KR102079976B1

KR102079976B1 - 치주질환 진단용 바이오마커

Info

Publication number: KR102079976B1
Application number: KR1020170100362A
Authority: KR
Inventors: 이태훈; 안선희
Original assignee: 전남대학교 산학협력단
Priority date: 2017-08-08
Filing date: 2017-08-08
Publication date: 2020-02-21
Also published as: KR20190016302A

Abstract

본 발명은 노인성 치주질환 진단용 조성물에 관한 것으로, 본 발명의 조성물은 노인성 치주염의 염증관련 질환의 예방을 위한 진단 및 약물 반응 진단, 치료용 물질의 타겟 및 치료 물질 개발 스크리닝을 위한 바이오마커로써 유용하게 활용될 수 있을 것으로 기대된다.

Description

치주질환 진단용 바이오마커{A biomarker for diagnosing periodontal disease}

본 발명은 치주질환 진단용 바이오마커에 관한 것이다.

치주질환은 흔히 풍치라고도 하는데, 병의 정도에 따라 치은염(gingivitis)과 치주염(periodontitis)으로 나뉜다. 비교적 가볍고 회복이 빠른 형태의 치주질환으로 잇몸 즉, 연조직에만 국한된 형태를 치은염이라고 하고, 이러한 염증이 잇몸과 잇몸뼈 주변까지 진행된 경우를 치주염이라고 한다.

치은(잇몸)과 치아 사이에는 V자 모양의 틈이 있는데, 이 홈(sulcus)의 잇몸 선 아래 부분을 박테리아가 공격하여 치주인대와 인접조직을 손상시키는 것이 치주질환이다. 염증이 진행되어 더 많은 조직이 손상되면서 홈이 치주낭(periodontal pocket)으로 발전하게 되며, 치주염이 심할수록 치주낭의 깊이가 깊어지게 된다. 치주낭이 깊어지면서 치주인대에 염증이 생기게 되고 골소실이 일어나게 되는 것이 치주질환이다.

치주질환의 직접적인 원인은 치아에 지속적으로 형성되는 플라크(plaque)라는 세균막이 원인이다. 플라크는 끈적끈적하고 무색이며, 이것이 제거되지 않고 단단해지면 치석이 된다. 플라크와 치석이 쌓이면 잇몸이 치아로부터 떨어지고, 이로 인해 틈이 벌어지면서 치아와 잇몸 사이에 치주낭이 형성된다. 치주낭이 발생하게 되면 세균이 더욱더 빠른 속도로 증식이 되며, 결국에는 치아를 둘러싸고 있는 치조골이 파괴되면서 치주염이 발생하게 된다.

치주질환은 연령과도 관계가 깊은데 20세 이상의 성인의 경우에는 과반수에서, 35세 이후에는 4명당 3명꼴로, 그리고 40세 이상의 장노년층의 경우 80~90%에서 잇몸질환이 발생한다. 노년기로 접어들면 침이 잘 분비되지 않아 세균번식에 유리한 환경이 되면서 잇몸질환과 노인성 충치가 더욱 심해진다. 치주염은 천천히 진행이 되기 때문에 질환을 인지하기에는 오랜 시간이 걸리기도 하며, 오랜 기간 동안 방치되어 있는 만큼 노인성 질환으로도 많이 불리고 있다. 또한, 노년기에는 잇몸이 점차 내려앉게 돼 치아뿌리가 노출되고 그로 인해 치근우식증(치아뿌리에 충치가 생기는 것)이 생길 수 있는데, 실제로 60세 이상 노인의 70% 가량이 치근우식증을 앓는 것으로 확인되고 있다.

하지만 치주질환도 조기 진단 및 치료를 통해 진행을 중지하거나, 이미 손상 받은 치아주위 조직도 조직재생치료를 통해 회복할 수 있다.

현재 치주질환의 진단은 환자의 자각증상, 방사선 촬영 후 치주낭 탐침기를 이용하여 치주낭 깊이, 잇몸의 퇴측 정도를 측정하여 치주염 진행 정도를 파악하거나, 세균감염 정도를 분석하는 것에 의존하고 있다. 하지만 치주질환의 효과적인 치료를 위해서는 조기 진단 및/또는 간편한 검사가 가능한 치주질환 진단 인자에 대한 개발이 필요하나 미비한 실정이다.

이에, 본 발명자들은 치주염의 염증관련 질환 진단을 위한 신뢰성 높은 바이오마커를 개발하던 중, 감염된 젊은 또는 노화된 구강세포에서 고발현되는 유전자군을 확인하고 본 발명을 완성하였다.

대한민국 등록특허공보 제10-1731764 호

본 발명은 치주염 진단용 조성물을 제공하는 것을 목적으로 한다.

또한, 본 발명은 치주염 진단을 위한 정보제공방법을 제공하는 것을 목적으로 한다.

또한, 본 발명은 치주염 치료제의 스크리닝 방법을 제공하는 것을 목적으로 한다.

1. PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICAM1(intercellular adhesion molecule 1), ICAM2(intercellular adhesion molecule 2), ICAM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP3(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymic stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하는 치주염 진단용 조성물.

2. 위 1에 있어서, 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하고, 상기 치주염은 노인성 치주염인, 조성물.

3. 위 1 또는 2의 조성물을 포함하는 치주염 진단용 키트.

4. 생물학적 시료에 존재하는 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICAM1(intercellular adhesion molecule 1), ICAM2(intercellular adhesion molecule 2), ICAM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP3(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymic stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하는, 치주염 진단을 위한 정보제공방법.

5. 위 4에 있어서, 생물학적 시료에 존재하는 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하고, 상기 치주염은 노인성 치주염인, 방법.

6. 위 4 또는 5에 있어서, 상기 생물학적 시료는 조직, 세포, 혈액, 혈청, 혈장, 타액 및 뇨로 이루어진 군으로부터 선택되는 것인, 방법.

7. 개체 내 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICAM1(intercellular adhesion molecule 1), ICAM2(intercellular adhesion molecule 2), ICAM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP3(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymic stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 감소시키는 물질을 선별하는 단계를 포함하는 치주염 치료제의 스크리닝 방법.

8. 위 7에 있어서, 개체 내 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 감소시키는 물질을 선별하는 단계를 포함하고, 상기 치주염은 노인성 치주염인, 방법.

도 1은 본 발명의 일 실시예에 따른 RNA-seq 분석 파이프라인을 나타낸 도이다.
도 2는 본 발명의 일 실시예에 따른 RNA-Seq 데이터의 분포를 나타낸 것으로, (A) 비감염 GF(P4) vs. 비감염 GF(P22), (B) 비감염 GF(P4) vs. F. n-감염 GF(P4), (C) 비감염 GF(P22) vs. F. n-감염 GF(P22), 및 (D) F. n-감염 GF(P4) vs. F. n-감염 GF(P22)를 Spearman 순위 상관 계수로 표시한 도이다.
도 3은 본 발명의 일 실시예에 따른 RNA-seq 데이터 분석 전략을 나타낸 것으로, (A) 인간 게놈으로 매핑된 DEGs 수, 및 (B) F. n 게놈으로 매핑된 RNA-seq 데이터를 표시한 도이다.
도 4는 본 발명의 일 실시예에 따라 유전자 발현 분석의 히트맵(Heat map)을 나타낸 것으로, (A) 비감염 GF(P4) vs. F. n-감염 GF(P4) 사이의 DEGs, (B) 비감염 GF(P22) vs. F. n-감염 GF(P22) 사이의 DEGs, 및 (C) F. n-감염 GF(P4) vs. F. n-감염 GF(P22) 사이의 DEGs의 히트맵을 나타낸 도이다. 이때, Benjamini-Hochberg 다중 검사 조정으로 q<0.05를 얻은 경우 유전자는 유의미하게 차별화된 것으로 간주되었다.
도 5는 본 발명의 일 실시예에 따른 거짓 발견률(FDR) < 5 %인 DEG의 중첩을 나타낸 벤다이어그램으로, (A) 감염에 대한 젊은 GF-특이적 반응, (B) 노화된 GF-특이적 반응, 및 (C) 젊은 GF 및 노화된 GF의 공통적인 유전자를 나타낸 도이다.
도 6은 본 발명의 일 실시예에 따라 DEG의 히트맵(Heat map)을 나타낸 것으로, (A) F. n-감염에 대한 젊은 GF-특이적 반응 유전자 히트맵, (B) F. n-감염에 대한 노화된 GF-특이적 반응 유전자 히트맵, 및 (C) F 감염에 대한 젊은 GF 및 노화된 GF의 공통 유전자 히트맵을 나타낸 도이다.
도 7은 본 발명의 일 실시예에 따라 감염에 대해 (A) 젊은 GF-특이적 반응하는 유전자, 및 (B) 노화된 GF-특이적 반응하는 유전자의 DEG IPA 네트워크 분석에서 IPA에 의해 예측된 네트워크를 나타낸 도이다.
도 8은 본 발명의 일 실시예에 따라 감염에 대해 (A) 젊은 GF-특이적 반응하는 유전자, 및 (B) 노화된 GF-특이적 반응하는 유전자의 DEG IPA 네트워크 분석에서 IPA에 의해 예측된 네트워크를 세포내 유전자발현 위치에 따라 나타낸 도이다.

이하 본 발명을 상세히 설명한다.

본 발명은 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICAM1(intercellular adhesion molecule 1), ICAM2(intercellular adhesion molecule 2), ICAM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP3(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymic stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하는 치주염 진단용 조성물을 제공한다.

본 발명은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 정도를 확인함으로써 치주염 발병 여부를 진단할 수 있다. 구체적으로, 본 발명자들은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 본 발명의 조성물은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하여, 그 발현 수준에 따라 치주염 발병 여부를 진단할 수 있다.

PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 또는 CSRNP1 유전자는 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 또는 CSRNP1 단백질을 암호화하는 게놈 DNA와 cDNA를 모두 포함한다. 상기 유전자는 치주염을 진단하기 위한 개체에 따라 뉴클레오티드 서열이 상이할 수 있으며, "개체"란 치주염이거나 치주염이 진행될 수 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 구체적인 예로, 인간을 포함한 포유동물일 수 있다.

인간인 경우 예를 들면 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자는 순서대로 서열번호 1 내지 31의 뉴클레오티드 서열일 수 있으며, 상기 유전자가 코딩하는 단백질은 순서대로 서열번호 32 내지 62의 아미노산 서열일 수 있다.

본 발명의 진단 대상 질병인 "치주염(periodontitis)"은 치주조직에 염증이 발생한 것을 의미하며, 특히, 염증이 잇몸(즉, 연조직)에만 국한된 것 이 아니라 잇몸뼈 주변까지 진행된 경우를 치주염이라고 한다.

본 발명은 상기 유전자 중 GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하는 노인성 치주염 진단용 조성물을 제공한다.

본 발명은 GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 정도를 확인함으로써 노인성 치주염 발병 여부를 진단할 수 있다. 구체적으로, 본 발명자들은 특히 노화된 구강세포에서 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 본 발명의 조성물은 GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하여, 그 발현 수준에 따라 노인성 치주염 발병 여부를 진단할 수 있다.

GADD45B, KLF10, ID1, TM4SF1 또는 CSRNP1 유전자는 GADD45B, KLF10, ID1, TM4SF1 또는 CSRNP1 단백질을 암호화하는 게놈 DNA와 cDNA를 모두 포함한다. 상기 유전자는 노인성 치주염을 진단하기 위한 개체에 따라 뉴클레오티드 서열이 상이할 수 있으며, "개체"란 치주염이거나 치주염이 진행될 수 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 구체적인 예로, 인간을 포함한 포유동물일 수 있다.

본 발명의 진단 대상 질병인 "노인성 치주염"은 노화에 따라 미생물의 감염과 그에 따른 염증 정도가 심각해지며, 결국 치아를 둘러싸고 있는 치조골이 파괴되면서 치주염이 발생한 것을 의미한다.

본 발명에서 "진단"이란 넓은 의미로는 환자의 병의 실태를 모든 면에 걸쳐서 판단하는 것을 의미한다. 판단의 내용은 병명, 병인, 병형, 경중, 병상의 상세한 양태, 합병증의 유무, 및 예후 등이다. 본 발명에서 진단은 치주염의 발병 여부 및 치주염 수준 등을 판단하는 것이다.

상기 mRNA 수준을 측정하는 제제는 mRNA에 상보적으로 결합하는 센스 및 안티센스 프라이머, 또는 프로브일 수 있으나, 이에 제한되는 것은 아니다.

본 발명에서 "프라이머"란 DNA 합성의 기시점이 되는 짧은 유전자 서열로써, 진단, DNA 시퀀싱 등에 이용할 목적으로 합성된 올리고뉴클레오티드를 의미한다. 상기 프라이머들은 통상적으로 15 내지 30 염기쌍의 길이로 합성하여 사용할 수 있으나, 사용 목적에 따라 달라질 수 있으며, 공지된 방법으로 메틸화, 캡화 등으로 변형시킬 수 있다.

본 발명에서 "프로브"란 효소 화학적인 분리정제 또는 합성과정을 거쳐 제작된 수 염기 내지 수백 염기길이의 mRNA와 특이적으로 결합할 수 있는 핵산을 의미한다. 방사성 동위원소나 효소 등을 표지하여 mRNA의 존재 유무를 확인할 수 있으며, 공지된 방법으로 디자인하고 변형시켜 사용할 수 있다.

상기 단백질 수준을 측정하는 제제는 유전자가 코딩하는 단백질에 특이적으로 결합하는 항체일 수 있으나, 이에 제한되는 것은 아니다.

본 발명에서 "항체"는 면역학적으로 특정 항원과 반응성을 갖는 면역글로불린 분자를 포함하며, 단클론(monoclonal) 항체 및 다클론(polyclonal) 항체를 모두 포함한다. 또한, 상기 항체는 키메라성 항체(예를 들면, 인간화 뮤린 항체) 및 이종결합항체(예를 들면, 양특이성 항체)와 같은 유전공학에 의해 생산된 형태를 포함한다. 단클론항체는 하이브리도마 세포를 이용한 방법, 또는 파지 항체 라이브러리 기술을 이용하여 제조할 수 있으며, 상기 과정에 필요한 기술은 당업계에 잘 알려져 있어 용이하게 실시할 수 있다. 다클론항체는 단백질 항원을 적합한 동물에게 주사하고, 이 동물로부터 항혈청을 수집한 다음, 공지의 친화성(affinity) 기술을 이용하여 항혈청으로부터 항체를 분리하여 얻을 수 있다.

또한, 본 발명은 상기 조성물을 포함하는 노인성 치주염 진단용 키트를 제공한다.

본 발명의 진단용 키트는 분석 방법에 적합한 한 종류 또는 그 이상의 다른 구성성분 조성물, 용액 또는 장치로 구성된다.

예컨대, 본 발명의 키트는 PCR을 수행하기 위해, 분석하고자 하는 시료로부터 유래된 게놈 DNA, 본 발명의 마커 유전자에 대해 특이적인 프라이머 세트, 적당량의 DNA 중합 효소, dNTP 혼합물, PCR 완충용액 및 물을 포함하는 키트일 수 있다. 상기 PCR 완충용액은 KCl, Tris-HCl 및 MgCl2를 함유할 수 있다. 이외에 PCR산물의 증폭 여부를 확인할 수 있는 전기영동 수행에 필요한 구성 성분들이 본 발명의 키트에 추가로 포함될 수 있다.

또한, 본 발명의 키트는 RT-PCR을 수행하기 위해 필요한 필수 요소를 포함하는 키트일 수 있다. RT-PCR키트는 마커 유전자에 대한 특이적인 각각의 프라이머 쌍 외에도 테스트 튜브 또는 다른 적절한 컨테이너, 반응 완충액, 데옥시뉴클레오티드(dNTPs), Taq-폴리머레이즈 및 역전사 효소와 같은 효소, DNase, RNase 억제제, DEPC-수(DEPC-water), 멸균수 등을 포함할 수 있다. 또한 정량 대조군으로 사용되는 유전자에 특이적인 프라이머 쌍을 포함할 수 있다.

또한, 본 발명의 키트는 DNA 칩을 수행하기 위해 필요한 필수 요소를 포함하는 키트일 수 있다. DNA 칩 키트는, 유전자 또는 그의 단편에 해당하는 cDNA가 프로브로 부착되어 있는 기판을 포함하고, 기판은 정량구조 유전자 또는 그의 단편에 해당하는 cDNA를 포함할 수 있다. 또한, 본 발명의 키트는 본 발명의 마커 유전자가 고정화되어 있는 기판을 갖는 마이크로어레이 형태일 수 있다. 또한, 본 발명의 키트는 ELISA를 수행하기 위해 필요한 필수 요소를 포함하는 것을 특징으로 하는 키트일 수 있다. ELISA 키트는 마커 단백질에 대한 특이적인 항체를 포함하며, 상기 단백질 수준을 측정하는 제제를 포함한다. 상기 ELISA 키트는 항원-항체 복합체를 형성한 항체를 검출할 수 있는 시약, 예를 들면 표지된 2차 항체, 발색단(chromopores), 효소, 및 그의 기질을 포함할 수 있다. 또한, 정량 대조군 단백질에 특이적인 항체를 포함할 수 있다.

본 발명에서 "항원-항체 복합체"란 유전자가 코딩하는 단백질과 이에 특이적인 항체의 결합물을 의미한다. 항원-항체 복합체의 형성량은 검출 라벨(detection label)의 시그널의 크기를 통해서 정량적으로 측정할 수 있다. 이러한 검출 라벨은 효소, 형광물, 리간드, 발광물, 미세입자(microparticle), 레독스 분자 및 방사선 동위원소로 이루어진 그룹 중에서 선택할 수 있으며, 이에 제한되는 것은 아니다.

또한, 본 발명은 생물학적 시료에 존재하는 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICAM1(intercellular adhesion molecule 1), ICAM2(intercellular adhesion molecule 2), ICAM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP3(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymic stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하는, 치주염 진단을 위한 정보제공방법을 제공한다.

본 발명자들은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 본 발명의 방법은 개체로부터 얻어진 생물학적 시료의 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하여 이를 정상 대조군과 비교함으로써, 해당 개체의 치주염 발병 여부를 진단하기 위한 정보를 제공할 수 있다.

본 발명은 상기 유전자 중 생물학적 시료에 존재하는 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하는, 노인성 치주염 진단을 위한 정보제공방법을 제공한다.

본 발명자들은 특히 노화된 구강세포에서 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 본 발명의 방법은 개체로부터 얻어진 생물학적 시료의 GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하여 이를 정상 대조군과 비교함으로써, 해당 개체의 노인성 치주염 발병 여부를 진단하기 위한 정보를 제공할 수 있다.

상기 생물학적 시료는 조직, 세포, 혈액, 혈청, 혈장, 타액 및 등을 포함할 수 있고, 보다 바람직하게는 혈액일 수 있으며, 더욱 바람직하게는 혈액 내 말초혈액단핵세포일 수 있으나, 이것으로 제한되는 것은 아니다.

상기 mRNA의 발현 수준을 측정하기 위한 방법은 중합효소반응(PCR), 역전사 중합효소반응(RT-PCR), 경쟁적 역전사 중합효소반응(Competitive RT-PCR), 실시간 역전사 중합효소반응(Realtime RT-PCR), RNase 보호 분석법(RPA;RNase protection assay), 노던 블랏팅(Northern blotting) 및 DNA 칩으로 이루어진 군으로부터 선택되는 1종 이상의 방법을 통해 측정될 수 있으나, 이에 제한되지 않는다.

상기 단백질의 발현 수준을 측정하기 위한 방법은 웨스턴 블롯, ELISA(enzyme linked immunosorbent assay), 방사선면역분석(RIA: Radioimmunoassay), 방사 면역 확산법(radioimmunodiffusion), 오우크테로니(Ouchterlony) 면역확산법, 로케트(rocket) 면역전기영동, 조직 면역 염색, 면역침전 분석법(Immunoprecipitation Assay), 보체 고정 분석법(Complement Fixation Assay), 유세포분석(Fluorescence Activated Cell Sorter, FACS) 및 단백질 칩(protein chip)으로 이루어진 군으로부터 선택되는 1종 이상의 방법을 통해 측정될 수 있으나, 이에 제한되지 않는다.

본 발명에서 "진단을 위한 정보제공방법"은 진단을 위한 예비적 단계로써 치주염(또는 노인성 치주염)의 진단을 위하여 필요한 객관적인 기초정보를 제공하는 것이며 의사의 임상학적 판단 또는 소견은 제외된다.

또한, 본 발명은 개체 내 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICAM1(intercellular adhesion molecule 1), ICAM2(intercellular adhesion molecule 2), ICAM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP3(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymic stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 증가시키는 물질을 선별하는 단계를 포함하는 치주염 치료제의 스크리닝 방법을 제공한다.

본 발명자들은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 대상 물질을 개체에 처리하여 개체의 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 발현 수준이 감소한다면 치주염이 치료되는 것이므로, 그러한 물질을 치주염 치료제로 선별할 수 있다.

이는 개체에 대상 물질 처리 전에 개체 내 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICAM1, ICAM2, ICAM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP3, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하고, 처리 후에 발현 수준을 측정하여 비교할 수도 있고, 여러 개체 중 일부 개체에 대상 물질을 처리하여 비교군과 상기 발현 수준을 비교할 수도 있다.

본 발명은 상기 유전자 중 개체 내 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 증가시키는 물질을 선별하는 단계를 포함하는 노인성 치주염 치료제의 스크리닝 방법을 제공한다.

본 발명자들은 특히 노화된 구강세포에서 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 대상 물질을 개체에 처리하여 개체의 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 발현 수준이 감소한다면 노인성 치주염이 치료되는 것이므로, 그러한 물질을 노인성 치주염 치료제로 선별할 수 있다.

이는 개체에 대상 물질 처리 전에 개체 내 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하고, 처리 후에 발현 수준을 측정하여 비교할 수도 있고, 여러 개체 중 일부 개체에 대상 물질을 처리하여 비교군과 상기 발현 수준을 비교할 수도 있다.

개체에 대상 물질을 처리하는 방법은 특별히 한정되지 않으며, 예를 들면 개체로부터 얻어진 생물학적 시료에 처리할 수 있다. 생물학적 시료는 전술한 바의 시료일 수도 있고, 인간 구강세포일 수도 있다.

유전자 및 단백질의 발현 수준은 전술한 방법에 의해 측정할 수 있다.

본 발명의 스크리닝 방법에서 "대상 물질"은 본 발명의 mRNA 또는 단백질의 발현량에 영향을 미치는지 여부를 검사하기 위하여 스크리닝에서 이용되는 미지의 물질을 의미한다. 상기 대상물질은 화학물질, 뉴클레오타이드, 안티센스-RNA, siRNA(small interference RNA) 및 천연물 추출물을 포함하나, 이에 한정되는 것은 아니다.

이하, 본 발명을 구체적으로 설명하기 위해 실시예를 들어 상세하게 설명하기로 한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.

[ 실험예 ]

1. 세포 배양

본 실험은 전남대학교 치과병원 기관 검토위원회(승인번호 CNUDH-20 13-001)의 승인을 받았다. 실험의 성격 및 가능한 결과에 대해 설명한 후 모든 피험자로부터 서면 동의서를 받았다. 모든 피험자는 치주질환이 없는 성인이었다.

2. 세포 배양 및 시약

일차 인간 구강섬유아세포 (gingival fibroblasts, GF)는 이전에 공지된 방법으로 제조하였다(Ahn SH et al., NOX1/2 activation in human gingival fibroblasts by Fusobacterium nucleatum facilitates attachment of Porphyromonas gingivalis, Arch Microbiol, 2016:198(6):573-83. doi: 10.1007/s00203-016-1223-7, PubMed PMID: 27071620 참조). 인간 치은 조직은 전술한 바와 같이 전남대학교 IRB의 승인을 받아 수집하였다. GF는 10 % 열-불활성화 소태아혈청(PAA Laboratories, Etobicoke, Ontario, Canada), 100 U/mL 페니실린, 및 100 μg/mL 스트렙토마이신(Gibco BRL)이 보충된 Dulbecco's modified Eagle's 배지(DMEM; Gibco BRL, Grand Island, NY, US)에서 5 % CO₂, 37 ℃ 조건으로 배양하였다. 0.25 % 트립신/0.02 % EDTA 용액(Sigma, MO, USA)을 사용하여 세포를 트립신화하고, 필요한 패시지(passage) 수에 도달할 때까지 1:3 비율로 계대배양하여 노화 현상을 관찰하였다.

하기 실험은 4 번째 계대(P4) 또는 22 번째 계대(P22)의 세포를 사용하였으며, 노화된 GF는 노화 관련 β-갈락토시다아제(SA-β-gal) 활성, 및 p53, p21 및 Cav-1과 같은 노화 마커의 발현으로 확인하였다.

3. 세균주 (Bacterial strains) 배양

F. nucleatum subsp . polymorphum(ATCC10953)을 37 ℃ 혐기성 챔버(85 % N₂, 5 % CO₂ 및 10 % H₂)에서 5 μg/mL hemin(Sigma, MO, USA)을 첨가한 TSB(tryptic soy broth)로 배양하였다. 박테리아를 원심분리(7,000xg, 10 분)하여 수집하고 인산염 완충 식염수로 세척한 후, 참고(reference) 표준에 대한 광학 밀도(OD)의 변경에 기초하여, 10⁸ CFU/mL로 조정하였다. 박테리아는 1.5 % agar(Sigma), 5 % 멸균 탈섬유소 양 혈액, 5 μg/mL hemin, 및 1 μg/mL 메나디온(menadione)이 첨가된 TSB 배지에서 혐기 배양에 의해 계수되었다.

4. RNA 분리 및 시퀀싱

RNeasy Mini Kit(QIAGEN, Hilden, Germany)을 사용하여 인간 GF로부터 RNA를 추출하였다. 분리된 RNA를 DNase Ⅰ로 처리하여 DNA 분해를 확인하였다. RNA 품질은 Agilent Technologies의 TapeStation system(Santa Clara, CA, USA)의 RNA screentape를 사용하여 평가하였으며, 모든 RNA 샘플의 RIN 점수는 7보다 높았다.

다음으로, Illumina TruSeq^TM RNA Sample Preparation Kit(Illumina, Inc., San Oiego, CA, USA)를 사용하여 mRNA-Seq 샘플을 얻었다. 즉, 총 RNA 샘플을 RiboZero Human kit 및 RiboZero bacteria kit(Epicentre)로 처리하여 박테리아 및 진핵세포 rRNA를 고갈시킨 후, 열 mRNA 단편화를 수행하였다. RNA 단편은 역전사 효소 및 랜덤 프라이머를 사용하여 첫 번째 가닥 cDNA로 전사되었다. 전사된 cDNA는 DNA Polymerase Ⅰ 및 RNase H를 사용하여 두 번째 가닥 cDNA로 합성되었다. 말단 수리 과정 후에, 하나의 'A' 염기를 단편에 첨가하고, 어댑터를 연결하여 흐름셀(flow cell) 상에 혼성화를 위한 cDNA를 준비하였다. 최종적으로 PCR 산물을 정제하고 농축시켜 cDNA 라이브러리(Macrogen, Seoul, Korea)를 만들었다. cDNA 라이브러리는 HiSeq 2000(Illumina)에서 시퀀싱되어, 약 10 억 쌍의 페어드 앤드 리드(paired-end reads, 2x101 bp)를 얻었다.

5. 전사체 분석

먼저, Trimmomatic(버전 0.33)을 사용하여 4 가지 시료의 RNA-seq 데이터를 사전 처리하여 어댑터 서열, 폴리-N 서열, 또는 낮은 품질의 염기(평균 Phred 점수 15 이하)를 제거한 깨끗한 판독 값(reads)을 얻었다. 손질된 판독 값은 기본 파라미터 하에서 Tophal2에 의해 인간 및 F. nucleatum 게놈으로 정렬되었다. 게놈 서열, 및 인간 돌연변이(GRCh38) 및 F. nucleatum의 주석(annotation)은 NCBI 게놈 데이터베이스 (https://www.ncbi.nlm.nih.gov/genome)에서 얻었다. mRNA 전사체의 정량을 위하여, 최종 손질된 판독 값을 Cufflinks(v2.2.1)에 넣었다. 달리 명시하지 않는 한, 분석에 사용된 모든 유전자 발현 수준은 FPKM(Fagment Per Kilobase of exon per Million fragments mapped) 단위로 표시된다. 차등 발현 분석은 Cufflinks(v2.2.1)를 사용하여 수행하였으며, 시각화는 R(R Development Core Team, R for Statistical Compllting, Vienna, Austria)에 의해 수행되었다.

본 분석의 절차는 도 1에 간결하게 설명되어 있다.

6. 유전자 존재론(Gene ontology, GO), 네트워크 및 경로 분석

각각 GATHER tool(http://gather.genome.duke.edu) 및 Ingenuity Pathway Analysis(IPA) 버전 8.0(Ingenuity® Systems, www.ingenuity.com)을 사용하여 차등 발현 유전자(Differentially Expressed Genes, DEGs)의 GO 및 기능적 경로 분석을 수행하였다.

GF 노화와 관련된 F. nucleatum 대사 경로의 독성 분석을 조사하기 위하여, KEGG 경로 비교 분석을 수행하였다.

[ 실시예 ]

1. RNA 시퀀싱 데이터 분석

F. nucleatum 감염 및 노화에 대한 구강섬유아세포(gingival fibroblasts, GF)의 변화를 확인하기 위하여, RNA-seq 기술을 사용하여 게놈 전체 전사체 분석을 수행함으로써 F. nucleatum 감염 또는 비감염 여부에 따른, 젊은 GF(P4) 및 노화된 GF(P22)의 유전자 발현 변화를 확인하였다. 생성된 원(RAW) 시퀀스 데이터를 손질(trimming)한 후, 각 샘플의 깨끗한 판독 값을 먼저 인간 게놈에 매핑하고, F. nucleatum 감염된(F. n-감염) 샘플에서 맵핑되지 않은 판독 값을 F. nucleatum 게놈에서 재매핑하였다.

그 결과, 표 1에 나타낸 바와 같이, 4 개의 샘플(비감염 GF(P4), F. n-감염 GF(P4), 비감염 GF(P22), 및 F. n-감염 GF(P22))로부터 전체 100 Gb의 원(raw) 시퀀스 데이터가 생성되었으며, F. n-감염 GF(P4) 및 GF(P22)에서 각각 총 433,937 건 및 109,468 건의 서열 판독 값이 F. nucleatum 게놈과 일치하였다. GC 함량은 인간 reference 게놈으로 매핑하여 얻어진 서열 판독 값의 백분율(각각 51.11 % 및 51.08 %)과 다른 유사성(각각 35.1 % 및 32.7 %)을 나타냈다. 이러한 결과는, 인간 DNA와 상동성이 없는 세균-특이적 서열이 잘 달성되었음을 의미한다.

Samples	Reference	Total reads (Raw data)	Total reads (w/o adaptor)	Aligned pairs	Multiple alignments	Concordant pair alignments
비감염 GF(P4)	Homo sapiens	240,914,330	240,59 1,122	109,770,915	4,661,202	108,834,930 (90.5%)^*
Fn-감염 GF(P4)	Homo sapiens F. nucleatum ATCC25586	249,525,110	249,311,972	107,274,408 473,131	3,153,643 39,194	106,723,775 (85.6%) 433,937 (0.1741%)
비감염 GF(P22)	Homo sapiens	266,758,386	266,438,682	124,654,404	2,965,534	123,496,658 (92.7%)
Fn-감염 GF(P22)	Homo sapiens F. nucleatum ATCC25586	266,580,404	259,574,938	121,806,945 111 ,166	4,613,353 1,698	120,318,603 (92.7%) 109,468 (0.0422%)

* Percentage of concordant pair alignment

또한, 정규화된 FPKM 값의 분포는 도 2에 나타내었으며, 1:1 비교하여 유전자 발현의 분포를 산점도(scatter plots)로 표시하였다. 전반적인 발현 양상은 서로 비슷하게 나타났다(R 값은 0.89에서 0.91까지).

2. 차등 발현 분석

먼저, 구강섬유아세포(GF)의 F. nucleatum 감염에 대한 노화-관련 변화를 확인하기 위하여, 감염 또는 노화 상태의 전사체 프로파일을 비교하였다. 먼저, 젊은(P4) 및 노화된 패시지(P22)에서, 비감염 GF 및 F. n-감염 GF 사이의 유전자 발현 양상을 확인하고, 다음으로 비감염 및 F. n-감염 조건에서, 젊은 GF(P4) 및 노화된 GF(P22) 사이의 유전자 발현 양상을 확인하였다.

그 결과, 도 3A에 나타낸 바와 같이, 먼저, 젊은 GF(P4) 및 노화된 GF(P22)에서 비감염 GF 및 F. n-감염에 따라 각각 차등 발현되는 88 개 및 40 개 유전자를 확인하였다. 이 유전자는 각각 젊은 GF 및 노화된 GF의 F. nucleatum에 대한 숙주 반응을 나타낸다. 또한, 비감염 상태에서는 GF(P4) 및 GF(P22) 사이에서 유의하게 변형된 유전자를 발견하지 못하였으나, F. n-감염 상태에서는 GF(P4) 및 GF(P22) 사이에서 유의하게 차등 발현되는 62 개의 유전자를 발견하였다. 이 유전자는 F. nucleatum 감염에 대한 숙주 반응의 노화 관련 변화를 의미한다.

차등 발현된 유전자의 전체 목록은 표 2 내지 4에 나타내었으며, 상기 결과를 종합하여 도 4에 나타내었다.

Gene Symbol	Uninfected GF(P4) (FPKM)	F. n-infected GF(P4) (FPKM)	Fold change	p-value	q-value	Description
PTX3	77.53	2761.75	35.62	5.0E-05	1.2E-02	pentraxin 3
CCL2	73.40	2676.51	36.47	5.0E-05	1.2E-02	chemokine (C-C motif) ligand 2
IL8	0.85	1630.11	1921.79	5.0E-05	1.2E-02	interleukin 8
CXCL1	1.95	1154.64	592.86	5.0E-05	1.2E-02	chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)
PTGS2	9.33	807.97	86.58	5.0E-05	1.2E-02	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)
LOC102723726,TNFAIP2	18.90	794.80	42.06	5.0E-05	1.2E-02	TNF alpha induced protein 2
TNFAIP6	14.53	684.66	47.12	5.0E-05	1.2E-02	TNF alpha induced protein 6
IL6	8.80	544.08	61.82	5.0E-05	1.2E-02	interleukin 6
SERPINE1	42.15	542.06	12.86	5.0E-05	1.2E-02	serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
TFPI2	17.18	329.22	19.17	5.0E-05	1.2E-02	tissue factor pathway inhibitor 2
CXCL2	0.96	308.47	321.45	5.0E-05	1.2E-02	chemokine (C-X-C motif) ligand 2
ERRFI1	33.28	246.56	7.41	1.5E-04	3.2E-02	ERBB receptor feedback inhibitor 1
SLC39A14	31.63	242.81	7.68	1.0E-04	2.3E-02	solute carrier family 39 (zinc transporter), member 14
G0S2	5.25	229.07	43.64	5.0E-05	1.2E-02	G0/G1 switch 2
ICAM1,ICAM4,ICAM5	8.03	228.69	28.48	5.0E-05	1.2E-02	toll-like receptor adaptor molecule
CXCL6	1.72	227.09	132.26	5.0E-05	1.2E-02	chemokine (C-X-C motif) ligand 6
TNFAIP3	1.48	219.88	149.07	5.0E-05	1.2E-02	TNF alpha induced protein 3
SPHK1	19.31	211.05	10.93	2.0E-04	4.0E-02	sphingosine kinase 1
MSC	17.45	197.21	11.30	1.0E-04	2.3E-02	musculin
MMP3	3.64	182.37	50.10	5.0E-05	1.2E-02	matrix metallopeptidase 3
NFKB1	17.76	160.54	9.04	5.0E-05	1.2E-02	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
NFKBIZ,NXPE3	20.42	150.94	7.39	1.0E-04	2.3E-02	uclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta\|neurexophilin and PC-esterase domain family member 3
NINJ1	13.12	135.72	10.34	5.0E-05	1.2E-02	ninjurin 1
IRF1	13.49	127.60	9.46	5.0E-05	1.2E-02	interferon regulatory factor 1
LOC102724685,NR4A3,STX17	18.70	126.23	6.75	5.0E-05	1.2E-02	nuclear receptor subfamily 4 group A member 3 , syntaxin 17
ACKR3	9.65	114.60	11.88	5.0E-05	1.2E-02	atypical chemokine receptor 3
ZC3H12A	3.18	113.34	35.61	5.0E-05	1.2E-02	zinc finger CCCH-type containing 12A
TNFAIP8	7.98	103.22	12.94	5.0E-05	1.2E-02	TNF alpha induced protein 8
RCAN1	11.62	100.04	8.61	5.0E-05	1.2E-02	regulator of calcineurin 1
BCL2A1	5.26	98.89	18.81	5.0E-05	1.2E-02	BCL2-related protein A1
GEM	5.79	79.34	13.71	5.0E-05	1.2E-02	GTP binding protein overexpressed in skeletal muscle
IFIT3	6.12	77.35	12.64	5.0E-05	1.2E-02	interferon induced protein with tetratricopeptide repeats 3
GBP1	11.34	64.85	5.72	2.5E-04	4.6E-02	immunoglobulin (CD79A) binding protein 1
BMP2	5.78	64.77	11.20	5.0E-05	1.2E-02	bone morphogenetic protein 2
PTGES	8.17	64.58	7.91	5.0E-05	1.2E-02	prostaglandin E synthase
TUBB2A	6.22	63.60	10.22	5.0E-05	1.2E-02	tubulin, beta 2A class IIa
NFKB2	7.87	60.73	7.71	5.0E-05	1.2E-02	nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)
PMAIP1	8.88	57.09	6.43	2.5E-04	4.6E-02	phorbol-12-myristate-13-acetate-induced protein 1
SMOX	6.76	56.12	8.30	5.0E-05	1.2E-02	spermine oxidase
NEDD9	3.49	55.23	15.83	5.0E-05	1.2E-02	neural precursor cell expressed, developmentally down-regulated 9
CH25H	1.16	54.79	47.16	5.0E-05	1.2E-02	cholesterol 25-hydroxylase
RELB	2.94	52.31	17.80	5.0E-05	1.2E-02	v-rel avian reticuloendotheliosis viral oncogene homolog B
IL11	2.97	50.93	17.16	5.0E-05	1.2E-02	interleukin 11
IL32	6.01	49.00	8.15	1.0E-04	2.3E-02	interleukin 32
CCRN4L	2.94	47.23	16.08	5.0E-05	1.2E-02	CCR4 carbon catabolite repression 4-like (S. cerevisiae)
ANGPTL4	4.82	45.73	9.50	5.0E-05	1.2E-02	angiopoietin like 4
HBEGF	0.82	41.38	50.63	5.0E-05	1.2E-02	heparin-binding EGF-like growth factor
GCH1	0.72	41.22	57.31	5.0E-05	1.2E-02	GTP cyclohydrolase 1
FZD8	2.10	40.85	19.46	5.0E-05	1.2E-02	frizzled class receptor 8
PDGFA	4.02	40.41	10.05	5.0E-05	1.2E-02	platelet-derived growth factor alpha polypeptide
SLC2A1	4.99	39.11	7.84	5.0E-05	1.2E-02	solute carrier family 2 (facilitated glucose transporter), member 1
HAS2	5.29	38.33	7.25	1.0E-04	2.3E-02	hyaluronan synthase 2
MAP2K3	5.21	36.72	7.05	2.5E-04	4.6E-02	mitogen-activated protein kinase kinase 3
SHB	4.10	35.31	8.62	5.0E-05	1.2E-02	Src homology 2 domain containing adaptor protein B
VCAM1	5.89	34.88	5.92	2.5E-04	4.6E-02	vascular cell adhesion molecule 1
RRAD	1.91	34.35	17.98	5.0E-05	1.2E-02	Ras-related associated with diabetes
ITPRIP	5.08	33.63	6.61	2.5E-04	4.6E-02	inositol 1,4,5-trisphosphate receptor interacting protein
ENC1	5.02	32.88	6.54	5.0E-05	1.2E-02	ectodermal-neural cortex 1 (with BTB domain)
IRAK2	3.02	31.65	10.50	5.0E-05	1.2E-02	interleukin 1 receptor associated kinase 2
GPR68	2.64	31.30	11.87	5.0E-05	1.2E-02	G protein-coupled receptor 68
FAM83G	3.89	25.65	6.59	1.5E-04	3.2E-02	family with sequence similarity 83 member G
MFSD2A	0.29	25.14	86.79	2.5E-04	4.6E-02	major facilitator superfamily domain containing 2A
SERPINB2	0.37	22.90	61.11	1.5E-04	3.2E-02	serpin peptidase inhibitor, clade B (ovalbumin), member 2
EREG	0.47	22.03	46.95	5.0E-05	1.2E-02	epiregulin
IFIT2	2.30	22.03	9.56	5.0E-05	1.2E-02	interferon induced protein with tetratricopeptide repeats 2
CD274	0.54	21.99	40.98	5.0E-05	1.2E-02	CD274 molecule
BCOR	2.40	21.85	9.10	5.0E-05	1.2E-02	BCL6 corepressor
TSLP	0.72	20.60	28.59	5.0E-05	1.2E-02	thymic stromal lymphopoietin
BIRC3	0.44	20.60	47.19	1.5E-04	3.2E-02	baculoviral IAP repeat containing 3
RASD1	2.38	20.20	8.49	1.0E-04	2.3E-02	RAS, dexamethasone-induced 1
NKX3-1	1.60	17.78	11.12	5.0E-05	1.2E-02	NK3 homeobox 1
JPH2	3.04	16.74	5.51	2.5E-04	4.6E-02	junctophilin 2
TRAF1	0.81	12.26	15.08	5.0E-05	1.2E-02	TNF receptor associated factor 1
EGR3	0.89	11.82	13.29	5.0E-05	1.2E-02	early growth response 3
NUAK2	0.83	10.67	12.91	1.0E-04	2.3E-02	NUAK family, SNF1-like kinase, 2
ZNF469	1.10	10.50	9.56	5.0E-05	1.2E-02	zinc finger protein 469
NFATC1	0.85	9.33	11.02	5.0E-05	1.2E-02	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
HUNK	0.51	6.05	11.87	2.5E-04	4.6E-02	hormonally up-regulated Neu-associated kinase
IL1A	0.00	1.63	-	5.0E-05	1.2E-02	interleukin 1 alpha
IFNB1	0.00	1.06	-	5.0E-05	1.2E-02	interferon, beta 1, fibroblast
ZFP42	0.00	0.15	-	5.0E-05	1.2E-02	ZFP42 zinc finger protein
TXNIP	110.14	1.57	0.01	5.0E-05	1.2E-02	thioredoxin interacting protein
ADAMTS15	17.87	1.86	0.10	5.0E-05	1.2E-02	ADAM metallopeptidase with thrombospondin type 1 motif 15
RP4-697P8.3	1.10	0.00	-	5.0E-05	1.2E-02	long noncoding RNA
LIF	2.48	328.35	132.61	5.0E-05	1.2E-02	leukemia inhibitory factor
NFKBIA	22.59	402.56	17.82	5.0E-05	1.2E-02	nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
MAP3K8	5.02	61.42	12.24	5.0E-05	1.2E-02	mitogen-activated protein kinase kinase kinase 8
NR4A1	5.52	49.98	9.05	5.0E-05	1.2E-02	nuclear receptor subfamily 4 group A member 1

Gene Symbol	Uninfected GF(P22) (FPKM)	F. n-infected GF(P22) (FPKM)	Fold change	p-value	q-value	Description
SEMA6B	0.00	0.24		5.0E-05	3.0E-02	sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B
PTPRD	0.01	0.55	95.69	5.0E-05	3.0E-02	protein tyrosine phosphatase, receptor type, D
EYA1	0.22	7.69	34.95	1.0E-04	4.9E-02	EYA transcriptional coactivator and phosphatase 1
SYTL2	0.58	9.20	15.94	5.0E-05	3.0E-02	synaptotagmin like 2
SFRP2	0.56	19.47	35.03	5.0E-05	3.0E-02	secreted frizzled-related protein 2
TRIB1	1.67	25.54	15.30	1.0E-04	4.9E-02	tribbles pseudokinase 1
PTGFRN	0.58	27.23	46.98	5.0E-05	3.0E-02	prostaglandin F2 receptor inhibitor
CHODL	0.13	34.46	268.50	1.0E-04	4.9E-02	chondrolectin
CPE	6.72	52.27	7.77	1.0E-04	4.9E-02	carboxypeptidase E
CSRNP1	3.98	59.50	14.94	5.0E-05	3.0E-02	cysteine-serine-rich nuclear protein 1
SMAD7	6.74	67.27	9.98	1.0E-04	4.9E-02	SMAD family member 7
BHLHE40	4.73	82.85	17.53	5.0E-05	3.0E-02	basic helix-loop-helix family member e40
TM4SF1	4.37	100.53	22.99	5.0E-05	3.0E-02	transmembrane 4 L six family member 1
NPTX1	3.39	102.91	30.37	5.0E-05	3.0E-02	neuronal pentraxin I
INSIG1	7.39	120.22	16.26	5.0E-05	3.0E-02	insulin induced gene 1
MAFF	15.23	136.42	8.96	5.0E-05	3.0E-02	v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F
KLF10	7.32	191.49	26.16	5.0E-05	3.0E-02	Kruppel-like factor 10
GADD45B	19.73	215.07	10.90	5.0E-05	3.0E-02	growth arrest and DNA damage inducible beta
DHRS3	23.01	253.13	11.00	5.0E-05	3.0E-02	dehydrogenase/reductase (SDR family) member 3
ID3	72.99	544.66	7.46	5.0E-05	3.0E-02	EP300 interacting inhibitor of differentiation 3
FLOT1,IER3	73.34	723.36	9.86	5.0E-05	3.0E-02	flotillin 1 , immediate early response 3
ID1	96.11	1162.16	12.09	1.0E-04	4.9E-02	inhibitor of DNA binding 1, dominant negative helix-loop-helix protein
SNORD3A	556.69	7878.18	14.15	5.0E-05	3.0E-02	small nucleolar RNA, C/D box 3A
SYNPO2	44.61	5.44	0.12	5.0E-05	3.0E-02	synaptopodin 2
POSTN	968.11	53.97	0.06	5.0E-05	3.0E-02	periostin, osteoblast specific factor
RPS16	579.07	30.73	0.05	5.0E-05	3.0E-02	ribosomal protein S16
CYTL1	359.00	28.69	0.08	5.0E-05	3.0E-02	cytokine like 1
NOV	194.08	18.44	0.10	5.0E-05	3.0E-02	nephroblastoma overexpressed
CST1,CST4	157.65	3.98	0.03	5.0E-05	3.0E-02	cystatin SN, cystatin S
SOD3	113.62	12.17	0.11	1.0E-04	4.9E-02	superoxide dismutase 3, extracellular
FMOD	72.51	7.13	0.10	5.0E-05	3.0E-02	fibromodulin
DIO2	59.95	0.98	0.02	5.0E-05	3.0E-02	deiodinase, iodothyronine, type II
HAPLN1	43.55	2.23	0.05	5.0E-05	3.0E-02	hyaluronan and proteoglycan link protein 1
CMKLR1	13.06	1.49	0.11	1.0E-04	4.9E-02	chemerin chemokine-like receptor 1
TMEM178B	8.27	0.28	0.03	5.0E-05	3.0E-02	transmembrane protein 178B
PLCXD3	6.07	0.23	0.04	1.0E-04	4.9E-02	phosphatidylinositol-specific phospholipase C, X domain containing 3
LIF	6.85	355.65	51.88	5.0E-05	3.0E-02	leukemia inhibitory factor
NFKBIA	15.76	299.90	19.03	5.0E-05	3.0E-02	nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
MAP3K8	2.81	27.68	9.83	5.0E-05	3.0E-02	mitogen-activated protein kinase kinase kinase 8
NR4A1	3.63	176.59	48.67	5.0E-05	3.0E-02	nuclear receptor subfamily 4 group A member 1

Gene Symbol	F. n-infected GF(P4) (FPKM)	F. n-infected GF(P22) (FPKM)	Fold change	p-value	q-value	Description
ID1	150.82	1044.03	6.92	5.0E-05	2.3E-02	inhibitor of DNA binding 1, dominant negative helix-loop-helix protein
GADD45B	14.03	196.62	14.01	5.0E-05	2.3E-02	growth arrest and DNA damage inducible beta
TIPARP	29.81	187.94	6.30	5.0E-05	2.3E-02	TCDD-inducible poly(ADP-ribose) polymerase
KLF10	23.13	172.26	7.45	5.0E-05	2.3E-02	Kruppel-like factor 10
SGK1	21.82	126.96	5.82	1.5E-04	4.8E-02	serum/glucocorticoid regulated kinase 1
IL8	1649.19	118.88	0.07	5.0E-05	2.3E-02	immediate early response 5-like
IER5L	20.17	114.75	5.69	5.0E-05	2.3E-02	immediate early response 5-like
FAM43A	11.41	104.09	9.12	5.0E-05	2.3E-02	family with sequence similarity 43 member A
TM4SF1	10.28	91.45	8.90	5.0E-05	2.3E-02	transmembrane 4 L six family member 1
PTX3	2807.05	85.64	0.03	5.0E-05	2.3E-02	pentraxin 3
HES1	1.10	83.41	75.81	5.0E-05	2.3E-02	hes family bHLH transcription factor 1
SNAI1	6.57	61.00	9.28	5.0E-05	2.3E-02	snail family zinc finger 1
CSRNP1	7.34	54.08	7.36	5.0E-05	2.3E-02	cysteine-serine-rich nuclear protein 1
STC2	8.20	53.56	6.53	5.0E-05	2.3E-02	stanniocalcin 2
CXCL1	1165.34	52.90	0.05	5.0E-05	2.3E-02	chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)
CXCL2	312.76	44.78	0.14	5.0E-05	2.3E-02	chemokine (C-X-C motif) ligand 2
LOC102723726,TNFAIP2	827.89	42.71	0.05	5.0E-05	2.3E-02	TNF alpha induced protein 2
PLEKHF1	1.99	39.78	19.96	1.0E-04	3.9E-02	pleckstrin homology and FYVE domain containing 1
IL6	567.62	36.27	0.06	5.0E-05	2.3E-02	interleukin 6
EPGN	4.01	30.82	7.68	1.5E-04	4.8E-02	epithelial mitogen
RPS16	798.43	27.75	0.03	5.0E-05	2.3E-02	ribosomal protein S16
ALDH3A1	0.72	25.92	35.90	5.0E-05	2.3E-02	aldehyde dehydrogenase 3 family member A1
NFKB1	163.17	21.69	0.13	5.0E-05	2.3E-02	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
GDF5	0.68	21.65	31.64	1.5E-04	4.8E-02	growth differentiation factor 5
SFRP2	113.42	17.60	0.16	1.5E-04	4.8E-02	secreted frizzled-related protein 2
G0S2	233.40	16.38	0.07	5.0E-05	2.3E-02	G0/G1 switch 2
CXCL3	334.75	14.81	0.04	5.0E-05	2.3E-02	chemokine (C-X-C motif) ligand 3
ICAM1,ICAM4,ICAM5	232.88	13.06	0.06	5.0E-05	2.3E-02	intercellular adhesion molecule
SOD3	87.29	10.87	0.12	5.0E-05	2.3E-02	superoxide dismutase 3, extracellular
EDNRB	81.38	9.82	0.12	5.0E-05	2.3E-02	endothelin receptor type B
PTGES	65.80	9.17	0.14	1.0E-04	3.9E-02	prostaglandin E synthase
CADM1	0.64	8.67	13.49	1.0E-04	3.9E-02	cell adhesion molecule 1
PMAIP1	58.03	6.99	0.12	1.5E-04	4.8E-02	phorbol-12-myristate-13-acetate-induced protein 1
SMOX	57.20	6.56	0.11	1.0E-04	3.9E-02	spermine oxidase
FMOD	39.71	6.48	0.16	1.5E-04	4.8E-02	fibromodulin
CCL20	162.09	5.74	0.04	5.0E-05	2.3E-02	chemokine (C-C motif) ligand 20
RIPK2	50.83	5.24	0.10	1.5E-04	4.8E-02	receptor interacting serine/threonine kinase 2
KLF6	35.51	5.05	0.14	1.0E-04	3.9E-02	Kruppel-like factor 6
HIVEP1	25.16	4.74	0.19	1.5E-04	4.8E-02	human immunodeficiency virus type I enhancer binding protein 1
TNFAIP6	695.14	4.64	0.01	5.0E-05	2.3E-02	TNF alpha induced protein 6
MMP3	185.18	4.15	0.02	5.0E-05	2.3E-02	matrix metallopeptidase 3
IFIT3	78.48	4.11	0.05	5.0E-05	2.3E-02	interferon induced protein with tetratricopeptide repeats 3
CXCL6	230.69	3.81	0.02	5.0E-05	2.3E-02	chemokine (C-X-C motif) ligand 6
GPC3	22.31	3.31	0.15	1.0E-04	3.9E-02	glypican 3
BIRC3	20.92	3.06	0.15	5.0E-05	2.3E-02	baculoviral IAP repeat containing 3
BCL2A1	100.23	3.00	0.03	5.0E-05	2.3E-02	BCL2-related protein A1
GCH1	41.93	2.98	0.07	1.5E-04	4.8E-02	GTP cyclohydrolase 1
BMP2	65.79	2.73	0.04	5.0E-05	2.3E-02	bone morphogenetic protein 2
CH25H	55.75	2.58	0.05	1.0E-04	3.9E-02	cholesterol 25-hydroxylase
CSF2	46.59	2.13	0.05	5.0E-05	2.3E-02	colony stimulating factor 2 (granulocyte-macrophage)
MXRA5	18.49	1.93	0.10	5.0E-05	2.3E-02	matrix-remodelling associated 5
SLC12A7	15.47	1.59	0.10	5.0E-05	2.3E-02	solute carrier family 12 (potassium/chloride transporter), member 7
MTRNR2L10	0.00	1.54	-	5.0E-05	2.3E-02	MT-RNR2-like 10
C11orf96	54.03	1.47	0.03	5.0E-05	2.3E-02	chromosome 11 open reading frame 96
TSLP	20.91	1.09	0.05	1.5E-04	4.8E-02	thymic stromal lymphopoietin
IGF2,INS,INS-IGF2	35.88	0.94	0.03	5.0E-05	2.3E-02	insulin like growth factor 2,
A2M	9.75	0.81	0.08	5.0E-05	2.3E-02	INS-IGF2 readthrough
IFIT2	22.36	0.73	0.03	5.0E-05	2.3E-02	interferon induced protein with tetratricopeptide repeats 2
GPR133	11.15	0.66	0.06	5.0E-05	2.3E-02	adhesion G protein-coupled receptor D1
PTPRD	6.89	0.50	0.07	5.0E-05	2.3E-02	protein tyrosine phosphatase, receptor type, D
HUNK	6.15	0.34	0.06	5.0E-05	2.3E-02	hormonally up-regulated Neu-associated kinase
KC6	0.00	0.22	-	1.5E-04	4.8E-02	Keratoconus gene 6

도 4를 참조하면, 젊은 GF(P4)에서는 단지 몇 개의 유전자(3 %, 88 개 중 3 개)만 감염에 의해 하향 조절되었고, 대부분의 차등 발현 유전자(97 %, 88 개 중 85 개)가 감염에 의해 상향 조절되었다(도 4A). 그러나, 노화된 GF(P22)에서는 차등 발현 유전자가 젊은 GF에 비해 상대적으로 더 높은 비율(32.5 %, 40 개 중 13 개)로 하향 조절되었고, 반대로 차등 발현 유전자의 67.5 %(40 개 중 27 개)는 감염에 의해 상향 조절되었다(도 4B). 또한, F. n-감염 상태에서 젊은 GF 및 노화된 GF를 직접 비교한 경우, 노화된 GF에서 차등 발현 유전자의 70 %(62 개 중 43 개)가 하향 조절되는 것을 확인하였다(도 4C).

다음으로, 숙주의 노화 상태에 대해 F. nucleatum가 어떻게 반응 하는지 확인하기 위하여, 인간 게놈으로부터 매핑되지 않은 서열 판독 값을 수집하고, 이를 F. nucleatum 게놈에 매핑한 후, GF의 노화 상태에 따라 고도로 발현된 F. nucleatum의 유전자를 동정하여 젊은 GF 및 노화된 GF에서 유전자 발현을 비교한 결과, 하기 표 5, 6에 나타낸 바와 같이, 높은 발현율(10 배 더 증가)을 보이는 유전자를 각각 젊은 GF에서 391 개, 노화된 GF에서 224 개씩 확인하였다.

GF(P4)
Gene	Locus	Fold change
FNr08	NC_003454.1:731536-734463	686.954
FNr01	NC_003454.1:444878-493887	167.562
FNr04	NC_003454.1:526874-529745	158.682
FNt02	NC_003454.1:85321-85397	139.414
FN0479	NC_003454.1:1127142-1127592	104.761
FN0083	NC_003454.1:721319-721604	81.042
FN0081	NC_003454.1:720174-720828	74.832
FN1636	NC_003454.1:100649-388096	70.750
FN0210	NC_003454.1:837137-837356	69.963
FNr07	NC_003454.1:729877-731379	63.754
rplS	NC_003454.1:1071500-1071851	60.578
FN1078	NC_003454.1:1724292-1724838	59.937
FN1635	NC_003454.1:100649-388096	59.072
FN1024	NC_003454.1:1678261-1678570	56.707
FN0211	NC_003454.1:837363-837630	56.357
FN1835	NC_003454.1:100649-388096	56.097
FN2037	NC_003454.1:546858-547227	55.561
FN0600	NC_003454.1:1255608-1256109	54.887
FN1637,rplP	NC_003454.1:100649-388096	54.617
FN1826	NC_003454.1:100649-388096	51.823
FN1203,FN1204	NC_003454.1:1862400-1863958	51.776
FN1916	NC_003454.1:412495-412906	50.650
FN1630	NC_003454.1:100649-388096	48.300
FN1627	NC_003454.1:100649-388096	47.988
FN1239	NC_003454.1:1896492-1897137	47.262
FN1309	NC_003454.1:1964995-1965190	47.168
FN1750	NC_003454.1:100649-388096	46.998
FN1093	NC_003454.1:1738354-1738783	46.660
FN1270	NC_003454.1:1926415-1926766	46.369
FN0377	NC_003454.1:1005432-1009256	46.336
FN1628	NC_003454.1:100649-388096	45.440
rplF	NC_003454.1:100649-388096	43.530
FN1451	NC_003454.1:2131717-2132800	43.421
FN2045	NC_003454.1:550463-550892	40.697
FN1350	NC_003454.1:2002448-2002933	40.207
FN0189,FN0190	NC_003454.1:813342-815773	39.543
FN1631	NC_003454.1:100649-388096	39.287
FN1833	NC_003454.1:100649-388096	39.143
FN2038	NC_003454.1:547273-547786	38.779
FN0149	NC_003454.1:777625-778525	37.646
FN2123	NC_003454.1:632297-633321	37.552
FN1118	NC_003454.1:1760698-1761028	37.055
rplE	NC_003454.1:100649-388096	36.963
FN0311	NC_003454.1:947264-949962	36.732
FNt06	NC_003454.1:85673-85751	36.600
FN1656	NC_003454.1:100649-388096	36.468
FN1657	NC_003454.1:100649-388096	35.978
secY	NC_003454.1:100649-388096	35.755
FN1825	NC_003454.1:100649-388096	35.371
FN0755	NC_003454.1:1414752-1415043	34.874
FN0085,FN0086	NC_003454.1:723409-724764	34.835
FN1879	NC_003454.1:100649-388096	33.771
tsf	NC_003454.1:100649-388096	33.176
FN1641	NC_003454.1:100649-388096	33.157
rplA	NC_003454.1:547939-548647	33.021
FN1437	NC_003454.1:2104669-2110868	32.908
FN0338	NC_003454.1:965238-972157	32.824
FN1911	NC_003454.1:403338-405375	32.778
FN0818	NC_003454.1:1476811-1477271	32.757
FN0039	NC_003454.1:678750-679302	32.733
FN1364	NC_003454.1:2010752-2017608	32.421
FN1828	NC_003454.1:100649-388096	32.174
FN0150	NC_003454.1:778592-778820	32.170
FN2121	NC_003454.1:629125-629818	31.881
FN0330	NC_003454.1:964722-965124	31.598
FN0556	NC_003454.1:1208469-1209090	31.561
FN1210	NC_003454.1:1869029-1870856	31.554
FN0528	NC_003454.1:1184372-1188753	31.053
FN1836	NC_003454.1:100649-388096	31.043
FN1241	NC_003454.1:1897870-1898602	30.768
FN1556	NC_003454.1:77614-79696	30.356
FN0536	NC_003454.1:1190095-1191241	30.061
rplB	NC_003454.1:100649-388096	29.991
FN0893	NC_003454.1:1553963-1554386	29.989
nadE	NC_003454.1:1861611-1862388	29.893
FN1432	NC_003454.1:2100518-2101670	29.579
FN1913	NC_003454.1:410143-411670	29.459
FN1643,rplD	NC_003454.1:100649-388096	29.398
FN1507	NC_003454.1:12311-12968	29.391
FN1809	NC_003454.1:100649-388096	29.107
FN1794	NC_003454.1:100649-388096	29.101
FN1639	NC_003454.1:100649-388096	29.095
FN1640	NC_003454.1:100649-388096	28.951
FN1914	NC_003454.1:411732-412080	28.746
FN1983	NC_003454.1:444878-493887	28.633
FN1625,FN1626	NC_003454.1:100649-388096	28.569
FN2040	NC_003454.1:548707-549133	27.966
FN0482	NC_003454.1:1128434-1128680	27.960
rplM	NC_003454.1:960770-964707	27.836
FN0585,FN0586	NC_003454.1:1239927-1241917	27.725
FN0756,FN0757	NC_003454.1:1415051-1416291	27.648
FN0758	NC_003454.1:1416303-1417365	27.457
rpsB	NC_003454.1:100649-388096	27.396
FN0798	NC_003454.1:1455915-1457943	27.262
secA	NC_003454.1:100649-388096	27.178
FN0113	NC_003454.1:746696-747752	27.112
FN1258	NC_003454.1:1913881-1914883	27.064
FN0367	NC_003454.1:996472-996991	27.023
rpsL	NC_003454.1:80239-80608	26.941
FN1375,FN1376,FN1377,FN1378,FN1379,FN1380	NC_003454.1:2021587-2028955	26.879
trmE	NC_003454.1:644644-646012	26.839
FN0332,FN0333,FN0334,FN0335,FN0336,FN0337	NC_003454.1:965238-972157	26.827
FN0358	NC_003454.1:988375-989764	26.732
FN1617,FN1618	NC_003454.1:100649-388096	26.312
FN0795,FN0796	NC_003454.1:1452527-1455889	26.290
FN0188	NC_003454.1:812415-813312	25.974
FN2032	NC_003454.1:537210-537405	25.971
FN0472	NC_003454.1:1117751-1118255	25.805
FN0480	NC_003454.1:1127593-1127899	25.706
FN1335	NC_003454.1:1988816-1989101	25.334
FN1645	NC_003454.1:100649-388096	25.124
FN0411	NC_003454.1:1048379-1048676	25.106
FN1622	NC_003454.1:100649-388096	25.034
FN2123	NC_003454.1:632297-633321	25.019
FN1646	NC_003454.1:100649-388096	24.768
FN1369	NC_003454.1:2018868-2019439	24.662
FN1509	NC_003454.1:14188-14266	24.591
FN0924,FN0925,FN0926	NC_003454.1:1579202-1597554	24.442
FN0108	NC_003454.1:743358-744375	24.439
FN0412	NC_003454.1:1048688-1049282	24.361
FN0776	NC_003454.1:1432083-1433067	24.019
FN1287	NC_003454.1:1944504-1944753	23.872
FN1282	NC_003454.1:1941358-1941709	23.790
asnC	NC_003454.1:679313-680897	23.669
FN1557	NC_003454.1:79741-80212	23.484
FN0283,FN0284	NC_003454.1:912778-914013	23.260
FN0785	NC_003454.1:1441285-1442461	22.956
FNt35	NC_003454.1:530229-530306	22.816
FN0101,FN0102,FN0103	NC_003454.1:736169-739667	22.780
FN0466	NC_003454.1:1111440-1112922	22.742
FN1283,rpsD	NC_003454.1:1941736-1943333	22.680
FN1517	NC_003454.1:20965-23545	22.673
FNt36	NC_003454.1:549944-550020	22.671
FN1238	NC_003454.1:1895283-1896381	22.658
FN0557	NC_003454.1:1209689-1210424	22.371
FN0820	NC_003454.1:1479499-1480879	22.165
tuf	NC_003454.1:76341-77526	21.599
FN1129	NC_003454.1:1774343-1777925	21.598
FN0302	NC_003454.1:936873-937638	21.547
FN0634	NC_003454.1:1292379-1294197	21.421
FN0364	NC_003454.1:993846-994503	21.397
FN0116	NC_003454.1:748392-750216	21.311
FN1091	NC_003454.1:1736054-1737398	21.280
FN0200	NC_003454.1:826262-826667	21.170
FN0501	NC_003454.1:1149676-1152028	20.993
FN0100	NC_003454.1:735208-735856	20.936
FN0488	NC_003454.1:1133196-1134516	20.928
rpmA	NC_003454.1:1761028-1761313	20.886
FN1359,FN1360,FN1361,FN1362,FN1363	NC_003454.1:2010752-2017608	20.866
FN1242	NC_003454.1:1898616-1899699	20.798
FN1240	NC_003454.1:1897146-1897869	20.520
FN1762	NC_003454.1:100649-388096	20.471
FN1812	NC_003454.1:100649-388096	20.387
FN1117	NC_003454.1:1760381-1760696	20.056
FN0311	NC_003454.1:947264-949962	19.963
nrdR	NC_003454.1:2171923-2172373	19.941
FN1332	NC_003454.1:1986155-1987253	19.910
thrS	NC_003454.1:1268498-1270361	19.853
FN1988,FN1989,tnaA	NC_003454.1:444878-493887	19.794
FN0718,FN0719,FN0720	NC_003454.1:1375755-1377679	19.689
FN2098	NC_003454.1:607462-608236	19.653
FN1423	NC_003454.1:2088942-2090160	19.557
FN2044	NC_003454.1:550046-550199	19.534
FN1808	NC_003454.1:100649-388096	19.487
FN1859	NC_003454.1:100649-388096	19.460
FN1924	NC_003454.1:421805-423083	19.446
FNt22	NC_003454.1:100649-388096	19.418
FN1285	NC_003454.1:1943372-1943762	19.334
FN1231	NC_003454.1:1887532-1888996	19.324
FN0360	NC_003454.1:990943-992446	19.283
FN1265	NC_003454.1:1921470-1922079	19.199
FN0376	NC_003454.1:1005432-1009256	19.193
FN0675	NC_003454.1:1330560-1332180	19.160
FN1435,FN1436,FN1438,FN1439,FN1440,FN1441	NC_003454.1:2104669-2110868	19.138
FN2126	NC_003454.1:636395-638315	19.095
FN1393	NC_003454.1:2049599-2050934	19.085
FN1092	NC_003454.1:1737406-1738321	19.056
FN0777	NC_003454.1:1433107-1434922	19.004
FN1533	NC_003454.1:45439-46411	19.001
FN1454	NC_003454.1:2134885-2135749	18.989
FN0295	NC_003454.1:928125-929055	18.959
FN0130	NC_003454.1:758725-759532	18.943
FN1977,FN1978	NC_003454.1:444878-493887	18.943
FN0865	NC_003454.1:1523129-1523855	18.867
FN0005	NC_003454.1:643895-644639	18.795
FN0579	NC_003454.1:1229942-1234778	18.736
gmk	NC_003454.1:537436-537994	18.717
FN0147,FN0148	NC_003454.1:775601-777586	18.647
FN1481	NC_003454.1:2162768-2163890	18.560
FN1623	NC_003454.1:100649-388096	18.527
FN1866	NC_003454.1:100649-388096	18.435
FN1941	NC_003454.1:441418-444013	18.417
glyQ	NC_003454.1:707948-708821	18.392
rpsM	NC_003454.1:1943807-1944164	18.337
FN1329	NC_003454.1:1983431-1983980	18.330
FN0736	NC_003454.1:1394747-1395503	18.245
FN1813	NC_003454.1:100649-388096	18.234
FN1811	NC_003454.1:100649-388096	18.189
FN0363	NC_003454.1:993523-993793	18.160
FN0359	NC_003454.1:990084-990933	18.150
FN0822	NC_003454.1:1481967-1482486	18.070
FN1985	NC_003454.1:444878-493887	17.989
FN0562,FN0563	NC_003454.1:1214986-1216427	17.842
FN1505	NC_003454.1:10535-11009	17.816
FN0285	NC_003454.1:914021-914261	17.751
FNt29	NC_003454.1:444878-493887	17.693
FN1428,FN1429,FN1430	NC_003454.1:2096949-2099292	17.657
FN0292	NC_003454.1:925100-926703	17.644
FN0151	NC_003454.1:778910-780152	17.570
FN0725	NC_003454.1:1384270-1384989	17.522
FN1424	NC_003454.1:2090184-2092095	17.419
FN1519	NC_003454.1:23552-24882	17.343
FN1205	NC_003454.1:1863968-1865252	17.267
FN0792	NC_003454.1:1448402-1450424	17.224
FN0092	NC_003454.1:728047-729166	17.160
FN0276	NC_003454.1:901835-903413	16.869
FN2125	NC_003454.1:633814-636250	16.812
FN0615	NC_003454.1:1273326-1275051	16.726
FN1354	NC_003454.1:2005485-2008055	16.702
FN0783	NC_003454.1:1439305-1440451	16.626
FN1483	NC_003454.1:2166100-2166613	16.619
FN0326,FN0327,FN0328,rplT	NC_003454.1:960770-964707	16.492
FN0658	NC_003454.1:1314979-1315765	16.453
FN0201	NC_003454.1:826681-827809	16.434
FN1824	NC_003454.1:100649-388096	16.404
engB	NC_003454.1:514157-514742	16.354
FN0462	NC_003454.1:1107323-1109255	16.326
FN0088,FN0089	NC_003454.1:725026-726444	16.324
FN1165,FN1166,mglC	NC_003454.1:1823037-1827649	16.262
FN1340	NC_003454.1:1993442-1994993	16.252
ychF	NC_003454.1:2010752-2017608	16.249
FN1972,FN1973,FN1974	NC_003454.1:444878-493887	16.237
FN0823	NC_003454.1:1482506-1484309	16.197
FN0494	NC_003454.1:1138916-1139648	16.125
FN0058	NC_003454.1:694046-695240	16.060
FN0203	NC_003454.1:828887-829691	16.010
FN0784	NC_003454.1:1440471-1441260	15.938
FN1765	NC_003454.1:100649-388096	15.899
FN1592,FN1593,FN1594,FN1595	NC_003454.1:100649-388096	15.865
FN1661	NC_003454.1:100649-388096	15.814
FN1717	NC_003454.1:100649-388096	15.813
FN1708	NC_003454.1:100649-388096	15.807
FN0309	NC_003454.1:944238-945921	15.795
glpQ	NC_003454.1:400685-401759	15.753
FN1800	NC_003454.1:100649-388096	15.693
FN1520	NC_003454.1:24891-26163	15.576
FN0306,FN0307	NC_003454.1:941239-943029	15.499
FN0454	NC_003454.1:1099606-1101082	15.414
FN1605	NC_003454.1:100649-388096	15.391
FN1077	NC_003454.1:1723843-1724095	15.371
FN0724	NC_003454.1:1383753-1384257	15.339
FN0263,FN0264,FN0265,FN0266,FN0267,FN0268,FN0269,FN0270	NC_003454.1:887665-897800	15.280
guaA	NC_003454.1:2111724-2113263	15.243
FN1781	NC_003454.1:100649-388096	15.235
asnC	NC_003454.1:679313-680897	15.075
FN1563	NC_003454.1:84866-85130	15.043
FN2088,FN2089,FN2090,FN2091,FN2092,FN2093	NC_003454.1:599937-603641	15.029
FN0079	NC_003454.1:717801-719169	14.982
FN1984	NC_003454.1:444878-493887	14.918
FN0009,FN0010,FN0011	NC_003454.1:649047-651680	14.912
FN0054	NC_003454.1:690975-692196	14.904
FN0262	NC_003454.1:887665-897800	14.873
smpB	NC_003454.1:1264400-1264847	14.866
FN1069	NC_003454.1:1714871-1717142	14.862
FN1315	NC_003454.1:1969010-1969544	14.753
FN0204	NC_003454.1:829711-831466	14.718
FN0022	NC_003454.1:660929-661211	14.676
FN1352	NC_003454.1:2003595-2004270	14.525
FN0602	NC_003454.1:1256788-1257499	14.471
FN0299	NC_003454.1:932532-934311	14.464
FN1138	NC_003454.1:1785608-1786040	14.461
FNt07	NC_003454.1:85759-85836	14.451
FN2035	NC_003454.1:538911-542871	14.364
FN0594	NC_003454.1:1248924-1249350	14.348
FN1383	NC_003454.1:2034544-2037946	14.330
FN0601	NC_003454.1:1256191-1256617	14.329
FN0522,FN0524	NC_003454.1:1173054-1179733	14.234
FN2008,FN2009,FN2010	NC_003454.1:507686-510392	14.189
FN1975	NC_003454.1:444878-493887	14.142
FN0927,FN0928,FN0929,FN0930,FN0931	NC_003454.1:1579202-1597554	14.089
FN0361,FN0362	NC_003454.1:992470-993483	14.081
FN1349	NC_003454.1:2000559-2002445	14.075
FN1211,FN1212	NC_003454.1:1870872-1873258	14.054
FN1025	NC_003454.1:1678713-1680021	14.047
FN0202	NC_003454.1:827919-828885	14.034
FN1763	NC_003454.1:100649-388096	14.030
FN2036	NC_003454.1:542906-546461	13.977
FN1994	NC_003454.1:497716-498151	13.930
FN1827	NC_003454.1:100649-388096	13.918
FN1172	NC_003454.1:1833701-1834804	13.916
FN1304	NC_003454.1:1960388-1960853	13.849
FN1298	NC_003454.1:1955080-1955716	13.839
FN1033	NC_003454.1:1686453-1687635	13.832
FN0109,FN0110	NC_003454.1:744422-746148	13.762
FN1121	NC_003454.1:1763209-1764730	13.732
FN1321	NC_003454.1:1976070-1977480	13.589
FN0186	NC_003454.1:810992-811646	13.550
FN0368,FN0369	NC_003454.1:997127-998985	13.533
FN2103	NC_003454.1:613342-614269	13.529
FN0065	NC_003454.1:700072-702244	13.360
FN1301	NC_003454.1:1957808-1959428	13.305
FN1229,FN1230	NC_003454.1:1886349-1887517	13.289
FN1900	NC_003454.1:388383-389376	13.243
FN1350	NC_003454.1:2002448-2002933	13.231
FN1252	NC_003454.1:1909507-1910194	13.196
FN0008	NC_003454.1:648149-649046	13.115
FN0321	NC_003454.1:957773-959597	13.105
FN1596	NC_003454.1:100649-388096	13.079
FN1171	NC_003454.1:1832454-1833651	13.066
FN1353	NC_003454.1:2004273-2005476	13.002
FN0749	NC_003454.1:1407801-1409019	12.970
FN1131,FN1132	NC_003454.1:1778962-1780314	12.950
FNt38	NC_003454.1:755222-755307	12.914
FN1782	NC_003454.1:100649-388096	12.913
FN1831	NC_003454.1:100649-388096	12.904
FN1896	NC_003454.1:100649-388096	12.822
FN0965,FN0966,FN0967	NC_003454.1:1618417-1621140	12.810
FN0322	NC_003454.1:959613-960640	12.754
FN0002	NC_003454.1:642687-643023	12.736
FN0162	NC_003454.1:790063-791404	12.727
FN1214,FN1215	NC_003454.1:1874255-1876257	12.678
FN2100	NC_003454.1:609125-610376	12.678
FN0310	NC_003454.1:945935-947006	12.655
FN1021,FN1022	NC_003454.1:1674727-1677561	12.645
FN0846	NC_003454.1:1504381-1505296	12.630
FN0297	NC_003454.1:930037-931261	12.596
FN2068	NC_003454.1:577534-579076	12.588
FN0843	NC_003454.1:1502911-1503476	12.560
FN0668	NC_003454.1:1324108-1325047	12.507
FN1810	NC_003454.1:100649-388096	12.502
FN2019	NC_003454.1:522019-522382	12.488
FN2082	NC_003454.1:593346-594981	12.412
FN0047	NC_003454.1:684566-685328	12.306
hppA	NC_003454.1:534118-536134	12.267
FN0977	NC_003454.1:1629179-1630670	12.212
FN1199	NC_003454.1:1859200-1860253	12.186
FN1873	NC_003454.1:100649-388096	12.177
FN0800	NC_003454.1:1460036-1460729	12.170
FN1224,FN1225,FN1226	NC_003454.1:1882629-1885593	12.124
FN1130	NC_003454.1:1777979-1778957	12.104
FN0207	NC_003454.1:833757-835086	12.095
FN1967,FN1968,FN1969,FN1970,FN1971	NC_003454.1:444878-493887	12.069
FN0741	NC_003454.1:1399080-1400046	12.063
FN2003,FN2004,FN2005	NC_003454.1:503871-506036	12.040
FN0976	NC_003454.1:1628235-1629153	12.031
FN0041	NC_003454.1:679313-680897	12.006
FN0731	NC_003454.1:1387859-1388393	11.994
FN0592,lpxC	NC_003454.1:1245851-1248903	11.849
FN0315	NC_003454.1:952073-952919	11.825
FN1506	NC_003454.1:11010-12120	11.728
FN1991	NC_003454.1:494762-496103	11.728
FN0388	NC_003454.1:1026689-1027520	11.728
engA	NC_003454.1:795350-796673	11.675
FN0174	NC_003454.1:799566-800523	11.592
FN1834	NC_003454.1:100649-388096	11.558
FN1487	NC_003454.1:2169648-2170110	11.541
FN1422	NC_003454.1:2083444-2088575	11.484
FN1030,FN1031	NC_003454.1:1683719-1685890	11.437
FN0316	NC_003454.1:953323-953779	11.414
FN1243	NC_003454.1:1899713-1900574	11.325
FN0322	NC_003454.1:959613-960640	11.286
upp	NC_003454.1:1128716-1129361	11.236
FN1392	NC_003454.1:2049285-2049549	11.194
FN1192	NC_003454.1:1854818-1855091	11.162
FN0558,FN0559,FN0560	NC_003454.1:1210821-1214279	11.066
FN0525	NC_003454.1:1179734-1181930	10.999
FN0999	NC_003454.1:1653893-1654937	10.945
FN1764	NC_003454.1:100649-388096	10.847
FN2079	NC_003454.1:590431-591208	10.726
FN0491	NC_003454.1:1136328-1137408	10.723
FN1619	NC_003454.1:100649-388096	10.702
FNt24	NC_003454.1:100649-388096	10.693
FN0375	NC_003454.1:1005432-1009256	10.606
FN1906	NC_003454.1:398506-399943	10.546
FN2016	NC_003454.1:517073-518938	10.498
FN1089,FN1090	NC_003454.1:1733181-1735810	10.477
FN1421	NC_003454.1:2083444-2088575	10.435
FN0475	NC_003454.1:1122259-1123567	10.424
FN1458,FN1459	NC_003454.1:2139066-2141450	10.355
FN0278	NC_003454.1:904395-905754	10.330
FN0576	NC_003454.1:1226252-1227362	10.323
FN0970	NC_003454.1:1622696-1623356	10.293
FN0932,FN0933,FN0934	NC_003454.1:1579202-1597554	10.263
FN0128,FN0129	NC_003454.1:756790-758430	10.196
FN1157,FN1158,glpX	NC_003454.1:1814042-1815911	10.176
FN0887	NC_003454.1:1547998-1549801	10.134
FN0084	NC_003454.1:721711-723154	10.107
FN0635	NC_003454.1:1294219-1295083	10.045
FN0294	NC_003454.1:927288-928101	10.034
FN0610	NC_003454.1:1264954-1268422	10.028
clpX	NC_003454.1:517073-518938	10.009

GF(P22)
Gene	Locus	Fold change
FNt16	NC_003454.1:100649-388096	296186
FNt45	NC_003454.1:1081919-1081996	48323.8
FN1821	NC_003454.1:100649-388096	34738.7
FNt14	NC_003454.1:100649-388096	31262.2
FN0702	NC_003454.1:1361014-1361092	24168
FN1633	NC_003454.1:100649-388096	23486.3
FN1681	NC_003454.1:100649-388096	21776.6
FN1674	NC_003454.1:100649-388096	18301.5
FNt01	NC_003454.1:85235-85313	17568.9
FN1634	NC_003454.1:100649-388096	8243.31
FN0231	NC_003454.1:857327-857441	4208.29
FN1952	NC_003454.1:444878-493887	3769.54
FNt13	NC_003454.1:100649-388096	2618.24
FN0797	NC_003454.1:1452527-1455889	620.822
FN1043	NC_003454.1:1694378-1694510	498.719
FN0919	NC_003454.1:1574388-1574625	484.425
FN1073	NC_003454.1:1720542-1721049	359.392
FN0051	NC_003454.1:688872-689351	289.453
FN0402	NC_003454.1:1040447-1040624	230.353
FN0575	NC_003454.1:1225470-1225644	224.712
FN0232	NC_003454.1:857910-858108	133.681
FN1084	NC_003454.1:1728800-1729058	126.776
FN0655	NC_003454.1:1313511-1313850	102.579
FN1957	NC_003454.1:444878-493887	99.7833
FN2114	NC_003454.1:624099-624297	98.4558
FN1852	NC_003454.1:100649-388096	98.33
FN1871	NC_003454.1:100649-388096	97.3719
FN0199	NC_003454.1:825922-826225	94.4385
FN1673	NC_003454.1:100649-388096	92.9704
FN1278,FN1279	NC_003454.1:1936871-1938360	86.9742
FN1188	NC_003454.1:1850919-1851417	82.8759
FN1302	NC_003454.1:1959508-1959727	82.8372
FN1545	NC_003454.1:59272-59557	80.6652
FN1583,FN1584	NC_003454.1:95128-96248	80.6124
FN1328	NC_003454.1:1983006-1983219	80.4023
FN0286	NC_003454.1:914272-914515	77.2394
FN0429	NC_003454.1:1071088-1071412	75.4542
FN0676	NC_003454.1:1332197-1332470	75.2102
FN2129	NC_003454.1:639689-639905	74.1361
FN0588	NC_003454.1:1242258-1242492	73.7762
FN1942	NC_003454.1:444089-444779	71.7464
FN1890	NC_003454.1:100649-388096	70.1143
FN0256	NC_003454.1:882347-882527	67.0627
FN1756	NC_003454.1:100649-388096	66.7586
FN1575	NC_003454.1:86282-86585	66.3147
FN0686	NC_003454.1:1342273-1342588	62.4737
FN1842	NC_003454.1:100649-388096	62.1048
FN1861	NC_003454.1:100649-388096	60.4914
FN0167	NC_003454.1:794245-794476	59.8087
FN1938	NC_003454.1:438038-438506	55.9081
FN1391	NC_003454.1:2048923-2049193	55.4497
FN0612	NC_003454.1:1270391-1270892	54.5937
FN0956	NC_003454.1:1612547-1612796	53.9226
FN1081	NC_003454.1:1727414-1727624	53.7403
FN0773	NC_003454.1:1429413-1429695	52.777
FN0980	NC_003454.1:1632617-1632875	52.6114
FN0139	NC_003454.1:771529-771700	50.9116
FN0663	NC_003454.1:1319425-1319857	49.7735
FN1296	NC_003454.1:1953721-1954231	48.473
FN0844	NC_003454.1:1503669-1503834	48.0724
FN1881	NC_003454.1:100649-388096	46.8453
FN1922	NC_003454.1:417722-419525	46.308
FN0845	NC_003454.1:1504074-1504284	46.3011
FN1193	NC_003454.1:1855191-1855461	45.8835
FN1796	NC_003454.1:100649-388096	45.6853
FN0584	NC_003454.1:1239583-1239877	44.5482
FN1257	NC_003454.1:1913310-1913754	44.4788
FN1740	NC_003454.1:100649-388096	43.8926
FN1885	NC_003454.1:100649-388096	42.1667
FN2076	NC_003454.1:587625-587856	41.863
FN0160	NC_003454.1:788418-788658	41.7649
FN0737	NC_003454.1:1395504-1395834	40.8342
FN1665	NC_003454.1:100649-388096	40.6129
FN1719	NC_003454.1:100649-388096	40.0705
FN0974	NC_003454.1:1626805-1627234	40.0415
FN1664	NC_003454.1:100649-388096	39.42
FN0861	NC_003454.1:1521827-1522049	39.1808
FN0365	NC_003454.1:994631-994949	38.9416
FN1816	NC_003454.1:100649-388096	38.9178
FN0134	NC_003454.1:769878-770190	38.7516
FN1795	NC_003454.1:100649-388096	38.6157
FN0551	NC_003454.1:1203415-1204805	38.2796
FN2124	NC_003454.1:633340-633802	38.0785
FN1248	NC_003454.1:1904689-1905304	37.6959
FN0401	NC_003454.1:1039994-1040240	37.2245
FN0698	NC_003454.1:1356750-1357167	37.1302
FN2113	NC_003454.1:623827-624022	37.057
FN1010	NC_003454.1:1664401-1664698	36.7644
FN1744	NC_003454.1:100649-388096	36.6508
FN1602	NC_003454.1:100649-388096	36.5205
FN0859	NC_003454.1:1520809-1521319	36.4966
FN1006	NC_003454.1:1661087-1661486	35.7727
FN1601	NC_003454.1:100649-388096	35.4601
FN0104	NC_003454.1:739707-739986	35.4003
FN1048	NC_003454.1:1698050-1699154	35.2476
FN0852	NC_003454.1:1510363-1510963	35.2267
FN1264	NC_003454.1:1920803-1921268	34.2273
FN1822	NC_003454.1:100649-388096	34.2236
FN1872	NC_003454.1:100649-388096	34.0814
FN1598	NC_003454.1:100649-388096	33.101
FN1683	NC_003454.1:100649-388096	32.9918
FN1720	NC_003454.1:100649-388096	32.4769
FN1966	NC_003454.1:444878-493887	32.4611
FN0895	NC_003454.1:1554998-1555463	32.202
FN1615	NC_003454.1:100649-388096	32.1823
FN0394	NC_003454.1:1032466-1033207	32.1653
FN1475	NC_003454.1:2157924-2158797	32.0673
FN0955	NC_003454.1:1612017-1612545	31.9155
FN1869	NC_003454.1:100649-388096	31.4823
FN1785	NC_003454.1:100649-388096	31.3492
FN0514	NC_003454.1:1163570-1163972	31.3418
FN2046	NC_003454.1:551000-551450	31.2184
FN0589	NC_003454.1:1242569-1242893	31.0438
FN0105	NC_003454.1:740346-740961	30.8145
FN1254	NC_003454.1:1910588-1911104	30.7056
FN0622	NC_003454.1:1281417-1282071	30.4443
FN1387	NC_003454.1:2042979-2043693	30.4287
FN0296	NC_003454.1:929111-929879	30.3646
FN1659	NC_003454.1:100649-388096	30.3245
FN1394	NC_003454.1:2050944-2051256	29.9854
FN1552	NC_003454.1:66290-67235	29.9157
FN1953	NC_003454.1:444878-493887	29.8956
FN1415	NC_003454.1:2075697-2076855	29.859
FN0106	NC_003454.1:741099-741522	29.8392
FN0640	NC_003454.1:1297528-1298410	29.7941
FN1647	NC_003454.1:100649-388096	29.7342
FN0135	NC_003454.1:770377-770665	29.3071
FN1680	NC_003454.1:100649-388096	29.2733
FN1832	NC_003454.1:100649-388096	28.998
FN1518	NC_003454.1:23552-24882	28.9337
FN0862	NC_003454.1:1522215-1522461	28.7948
FN0370	NC_003454.1:999061-999922	28.7619
FN1345	NC_003454.1:1998219-1999047	28.689
FN1666	NC_003454.1:100649-388096	28.5904
FN1479	NC_003454.1:2160792-2161359	28.5354
FN0633	NC_003454.1:1291067-1292312	28.4752
FN0406	NC_003454.1:1043599-1044664	28.2075
FN0626	NC_003454.1:1285624-1286182	28.1057
FN1347	NC_003454.1:1999733-2000390	27.9758
FN2112	NC_003454.1:623258-623753	27.9138
FN1134	NC_003454.1:1781634-1782102	27.9037
FN1829	NC_003454.1:100649-388096	27.7808
FN1007	NC_003454.1:1661657-1662542	27.676
FN1874	NC_003454.1:100649-388096	27.6067
FN2064	NC_003454.1:575302-575806	27.6029
FN1752	NC_003454.1:100649-388096	27.5611
FN0885	NC_003454.1:1544844-1545705	27.2795
FN0099	NC_003454.1:734821-735175	27.1855
FN0907	NC_003454.1:1565413-1566085	27.1701
FN0180	NC_003454.1:804935-805412	26.9446
FN1056	NC_003454.1:1703832-1704432	26.8213
FN0339	NC_003454.1:972174-972648	26.6597
FN0534	NC_003454.1:1188889-1189426	26.4741
FN0628	NC_003454.1:1287288-1288347	26.3039
FN1198	NC_003454.1:1857768-1859031	26.2149
FN1223	NC_003454.1:1882073-1882601	26.1522
FN1476	NC_003454.1:2158811-2159486	26.0342
FN1755	NC_003454.1:100649-388096	25.6512
FN1105	NC_003454.1:1750180-1750678	25.5813
FN1539	NC_003454.1:52600-53152	25.3244
FN1722	NC_003454.1:100649-388096	25.23
FN0185	NC_003454.1:809356-810559	25.2166
FN1308	NC_003454.1:1964279-1964921	25.2069
FN0120	NC_003454.1:752807-752981	24.7938
FN1803	NC_003454.1:100649-388096	24.7619
FN0191	NC_003454.1:815891-817325	24.7254
FN0034	NC_003454.1:675528-676179	24.6431
FN0035	NC_003454.1:676329-676992	24.5307
FN0765	NC_003454.1:1420931-1422020	24.3741
FN0209	NC_003454.1:836266-836860	24.073
FN0726	NC_003454.1:1385055-1385355	23.8308
FN0916	NC_003454.1:1572154-1572604	23.7657
FN0923	NC_003454.1:1577627-1579067	23.6697
FN0619	NC_003454.1:1278899-1279745	23.6635
FN0492,FN0493	NC_003454.1:1137543-1138642	23.6357567
FN0632	NC_003454.1:1290431-1290866	23.52
FN1333	NC_003454.1:1987253-1987670	23.5148
FN1901	NC_003454.1:389453-390107	23.1461
FN1195	NC_003454.1:1855693-1856329	23.1197
FN1368	NC_003454.1:2018246-2018861	23.1139
FN1780	NC_003454.1:100649-388096	22.7197
FN0788	NC_003454.1:1444029-1444449	22.4386
FN0922	NC_003454.1:1576677-1577616	22.3602
FN0678	NC_003454.1:1334108-1334711	22.014
FN1686	NC_003454.1:100649-388096	21.6872
FN1116	NC_003454.1:1759660-1760272	21.5224
FN0661	NC_003454.1:1317868-1318273	21.4653
FN1607	NC_003454.1:100649-388096	21.3926
FN0710	NC_003454.1:1369014-1369692	21.0041
FN0896	NC_003454.1:1555486-1555870	20.6374
FN1815	NC_003454.1:100649-388096	20.5528
FN0166	NC_003454.1:793871-794237	20.5513
FN0331	NC_003454.1:965238-972157	20.2373
FN0026	NC_003454.1:664424-664981	19.8545
FN1409	NC_003454.1:2069148-2070693	19.5984
FN1599	NC_003454.1:100649-388096	19.4607
FN0631	NC_003454.1:1289957-1290419	19.053
FN1741,FN1742	NC_003454.1:100649-388096	18.82696998
FN1878	NC_003454.1:100649-388096	18.6041
FN1710	NC_003454.1:100649-388096	18.3411
FN0059	NC_003454.1:695292-695679	18.07414877
FN1895	NC_003454.1:100649-388096	18.0624
FN0473	NC_003454.1:1118431-1119001	17.9177
FN1739	NC_003454.1:100649-388096	17.0717
FN0045,FN0046	NC_003454.1:683151-684325	16.86803782
FN1724	NC_003454.1:100649-388096	16.8544
FN0487	NC_003454.1:1131845-1132862	16.68169729
FN1721	NC_003454.1:100649-388096	16.6754
FN1405	NC_003454.1:2064426-2064996	16.5408
FN0449,FN0450	NC_003454.1:1092822-1094990	16.5277013
FN0960	NC_003454.1:1615214-1615709	15.6912
FN1541,FN1542	NC_003454.1:55354-57252	15.2105731
FN0836	NC_003454.1:1498941-1499238	15.1694
FN0464	NC_003454.1:1109814-1110147	14.4466
FN0030	NC_003454.1:667259-667736	14.1281
FN2111	NC_003454.1:622523-623183	13.9857
FN1342,FN1343	NC_003454.1:1996180-1997322	13.62975234
FN0407	NC_003454.1:1044743-1045268	13.41148985
FN0229	NC_003454.1:856414-857307	13.3563
FN1434	NC_003454.1:2102627-2104601	12.77477088
FN0260	NC_003454.1:886350-886728	12.70189693
cvrA	NC_003454.1:80966-82550	12.06494258
FN1374	NC_003454.1:2021587-2028955	11.05772237
FN2065,FN2066	NC_003454.1:575989-576833	10.82563193

또한, KEGG 데이터베이스를 사용하여 이들 유전자의 세균 경로를 분석한 결과, 노화된 GF(224 개 중 11 개)에 비하여 젊은 GF에서 상대적으로 많은 수의 F. nucleatum 유전자(391 개 중 65 개)가 신진 대사 경로에 매핑되었고, 젊은 GF에서 더 다양한 종류의 세균 경로가 검출되었다. 예를 들어, 젊은 GF에서는 해당 과정, 지방산 대사, 부틸레이트 대사 및 LPS/펩티도글리칸 생합성 경로가 밝혀졌지만, 노화된 GF에서는 이러한 경로가 전혀 나타나지 않았다.

3. GO 농축 분석

차등 발현 유전자(DEGs)의 생물학적 관련성을 조사하기 위하여 GATHER 데이터베이스를 사용하여 GO 분석을 수행하고, 각 차등 발현 유전자 세트의 상위 5 가지 주요 GO 주석(annotations)을 하기 표 7에 나타내었다.

Comparison groups	GO annotation	p-value^*	Genes
DEGs of uninfected GF(P4) vs. F. n-infected GF(P4)	GO:0006955 [4]: immune response	<0.0001	CCL2, CXCL1, CXCL2, CXCL6, GBP1, GEM, GPR68, IFIT2, IFIT3, IFNB1, 1L11, IL1A, IL32, IL6, IL8, IRAK2, IRF1, LIF, NFKB1, PDCD1LG1, PTGES, PTGS2, PTX3, TNF AIP6
	GO:0006952 [5]: defense response	<0.0001	CCL2, CXCL1, CXCL2, CXCL6, GBP1, GEM, GPR68, IFIT2, IFIT3, IFNB1, 1L11, IL1A, IL32, IL6, IL8, IRAK2, IRF1, LIF, NFKB1, PDCD1LG1, PTGES, PTGS2, PTX3, TNF AIP6
	GO:0009607 [4]: response to biotic stimulus	<0.0001	CCL2, CXCL1, CXCL2, CXCL6, GBP1, GEM, GPR68, IFIT2, IFIT3, IFNB1, 1L11, IL1A, IL32, IL6, IL8, IRAK2, IRF1, LIF, NFKB1, NFKBIA, PDCD1LG1, PTGES, PTGS2, PTX3, TNF AIP6
	GO:0051243 [5]: negative regulation of cellular physiological processes	<0.0001	ANGPTL4, BCL2A1, BIRC3, CCL2, CXCL1, IFNB1, IL1A, IL6, IL8, NFKB1, NFKBIA, SERPINB2, TNFAIP3, TNFAIP8
	GO:0006954 [5]: inflammatory response	<0.0001	CCL2, CXCL1, CXCL2, CXCL6, GPR68, IL1A, IL8, IRAK2, NFKB1, PTGS2, PTX3, TNFAIP6
DEGs of uninfected GF(P22) vs. F. n-infected GF(P22)	GO:0007179 [8]: transforming growth factor beta receptor signaling pathway	<0.0001	FMOD, KLFIO, SMAD7
	GO:0007178 [7] : transmembrane receptor protein serine/threonine kinase signaling pathway	0.0001	FMOD, KLFIO, SMAD7
	GO:0007167 [6]: enzyme-linked receptor protein signaling pathway	0.0004	FMOD, KLFIO, PTPRD, SMAD7
	GO:0007275 [2]: development	0.0008	CMKLR1, EYA1, GADD45B, ID1, ID3, IER3, KLFIO, LIF, NOV, NPTX1, POSTN, SEMA6B
	G0:000 1501 [5]: skeletal development	0.04	CMKLR1, KLF10, POSTN
DEGs of F. n-infected GF(P4) vs. F. n-infected GF(P22)	GO:0006954 [5]: inflammatory response	<0.0001	CCL20, CXCL1, CXCL2, CXCL3, CXCL6, IL8, NFKB1, PTX3, RIPK2, TNFAIP6
	GO:0009611 [5]: response to wounding	<0.0001	CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL6, IL8, NFKB1, PTX3, RIPK2, TNFAIP6
	GO:0006955 [4]: immune response	<0.0001	CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL6, IFIT2, IFIT3, IL6, IL8, KLF6, NFKB1, PTGES, PTX3, RIPK2, TNFAIP6
	GO:0009613 [5]: response to pest, pathogen, or parasite	<0.0001	CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL6, IL6, IL8, NFKB1, PTGES, PTX3, RIPK2, TNFAIP6
	GO:0043207 [5]: response to external biotic stimulus	<0.0001	CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL6, IL6, IL8, NFKB1, PTGES, PTX3, RIPK2, TNFAIP6

^*p-value is calculated using Fischer's exact test, which calculates the ratio of the pathway-associated genes in the experimental data to the total number of genes in that pathway.

상기 표 7에 나타낸 바와 같이, 감염에 대한 차등 발현 유전자의 생물학적 과정은 젊은 GF(P4) 및 노화된 GF(P22)에서 현저하게 다르게 나타났다. 예를 들어, 젊은 GF의 차등 발현 유전자 88 개는 면역 반응, 생체 자극에 대한 반응 및 염증 반응과 같은 세균 감염에 대한 숙주 방어에 더 많이 관여하는 것으로 나타난 반면, 노화된 GF의 차등 발현 유전자 44 개는 형질전환 생장 인자(transforming growth factor) 베타 수용체 신호 전달 경로 및 골격 발달과 같은 세포 유지에 매우 관여하는 것으로 나타났다. 또한, F. nucleatum-감염 젊은 GF 및 노화된 GF 사이의 공통적인 차등 발현 유전자 62 개는 염증 반응, 상처에 대한 반응 및 면역 반응과 같은 세균 감염에 대한 숙주 반응에 관여하는 것으로 나타났다.

4. 젊은 또는 노화된 GF -특이적 차등 발현 유전자( DEGs ) 분석

상기 실시예 3의 결과에 기초하여, 동정된 차등 발현 유전자의 F. nucleatum-감염에 대한 특이적 반응을 확인하였다.

먼저, 젊은 GF의 88 개 유전자와 노화된 GF의 40 개 유전자를 F. nucleatum-감염 젊은 GF 및 노화된 GF의 공통적인 62 개 유전자와 비교하였다. 그 결과, 도 5A 및 5B에 나타낸 바와 같이, 중첩 영역에서 각각 24 개 및 10 개의 유전자를 확인하였다. 이 유전자는 F. nucleatum 감염에 대하여 GF 노화의 정도에 따라 다르게 나타나는 유전자(각각 젊은 GF-특이적 유전자 및 노화된 GF-특이적 유전자 해당)를 의미한다.

또한, 젊은 GF의 88 개 유전자를 노화된 GF의 40 개 유전자와 직접 비교하였다. 그 결과, 도 5C에 나타낸 바와 같이, 중첩 영역에서 4 개의 유전자를 확인하였다. 이 유전자는 F. nucleatum 감염에 대한 GF-특이적 유전자를 의미한다.

상기 각 유전자는 표 8 내지 10에 나타내었다.

- F. nucleatum-감염 젊은 GF 및 노화된 GF의 공통적인 유전자와 젊은 GF(P4)에서 차등 발현되는 유전자의 중첩 분석

- F. nucleatum-감염 젊은 GF 및 노화된 GF의 공통적인 유전자와 노화된 GF(P22)에서 차등 발현되는 유전자의 중첩 분석

- GF(P4) 및 GF(P22)에서 차등 발현되는 유전자의 중첩 분석

또한, 이들 유전자의 발현 수준을 나타내는 Heatmap을 도 6에 나타내었다.

도 6에 나타낸 바와 같이, 24 및 10 유전자의 발현 수준은 F. nucleatum 감염 후, 젊은 GF 및 노화된 GF에서 각각 현저히 변화되었으며, 또한, 젊은 GF 및 노화된 GF 사이에서 유의미하게 차별적으로 발현되었다(도 6A 및 B). 또한, 4 개의 유전자는 젊은 GF 및 노화된 GF 모두에서 F. nucleatum 감염에 반응하는 동일한 발현 패턴을 나타내는 것을 확인하였다(도 6C). 이들 유전자는 F. nucleatum 감염에 대한 노화-독립적인 방식의 숙주 반응을 의미한다.

5. 차등 발현 유전자( DEGs )의 기능성 주석 분석

상기 실시예 4의 결과에 기초하여, 각 유전자 세트의 생물학적 관련성을 조사하기 위하여, 지식 데이터베이스 IPA를 사용하여 차등 발현 유전자에 기능적 주석을 달았다. 표 2, 3, 4, 7 및 8에 제시된 각 차등 발현 유전자 세트의 상위 10 개 세부 카테고리를 표 11에 나타내었다.

	Comparison groups	Categories	Diseases or Functions Annotation	p-value	# Molecules	Molecules
A	DEG of uninfected GF(P4) vs. F. n-infected GF(P4)	Cell Death and Survival	apoptosis	4.E-26	61	ANGPTL4,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL8,EGR3,ENC1,EREG,ERRFI1,G0S2,GEM,HAS2,HBEGF,HUNK,ICAM1,IFIT2,IFIT3,IFNB1,IL11,IL1A,IL32,IL6,IRAK2,IRF1,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NR4A1,NR4A3,NUAK2,PMAIP1,PTGES,PTGS2,RASD1,RCAN1,RELB,RRAD,SERPINE1,SLC2A1,SMOX,SPHK1,TFPI2,TNFAIP2,TNFAIP3,TNFAIP8,TRAF1,TSLP,TXNIP,ZC3H12A
		Cell Death and Survival	cell death	1.E-25	67	ACKR3,ANGPTL4,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL8,EGR3,ENC1,EREG,ERRFI1,G0S2,GCH1,GEM,HAS2,HBEGF,HUNK,ICAM1,IFIT2,IFIT3,IFNB1,IL11,IL1A,IL32,IL6,IRAK2,IRF1,ITPRIP,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NKX3-1,NR4A1,NR4A3,NUAK2,PMAIP1,PTGES,PTGS2,RASD1,RCAN1,RELB,RRAD,SERPINB2,SERPINE1,SLC2A1,SMOX,SPHK1,TFPI2,TNFAIP2,TNFAIP3,TNFAIP8,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A
		Cellular Growth and Proliferation	proliferation of cells	1.E-24	68	ACKR3,ADAMTS15,ANGPTL4,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL8,EGR3,ENC1,EREG,ERRFI1,FZD8,G0S2,GBP1,GCH1,GEM,HAS2,HBEGF,HUNK,ICAM1,IFIT3,IFNB1,IL11,IL1A,IL32,IL6,IRF1,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NINJ1,NKX3-1,NR4A1,NR4A3,PDGFA,PMAIP1,PTGES,PTGS2,PTX3,RASD1,RCAN1,RELB,RRAD,SERPINB2,SERPINE1,SHB,SLC2A1,SMOX,SPHK1,TFPI2,TNFAIP3,TNFAIP6,TNFAIP8,TRAF1,TSLP,TUBB2A,TXNIP,VCAM1
		Hematological System Development and Function, Tissue Morphology	quantity of leukocytes	4.E-24	38	ACKR3,BCL2A1,BIRC3,CCL2,CD274,CXCL2,CXCL6,CXCL8,EGR3,GPR68,HBEGF,ICAM1,IFNB1,IL11,IL1A,IL6,IRF1,LIF,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NR4A1,PTGS2,RELB,SERPINB2,SERPINE1,SLC2A1,SPHK1,TNFAIP3,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A
		Hematological System Development and Function, Tissue Morphology	quantity of blood cells	3.E-23	39	ACKR3,BCL2A1,BIRC3,CCL2,CD274,CXCL2,CXCL6,CXCL8,EGR3,GPR68,HBEGF,ICAM1,IFNB1,IL11,IL1A,IL6,IRF1,LIF,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NR4A1,PTGS2,RCAN1,RELB,SERPINB2,SERPINE1,SLC2A1,SPHK1,TNFAIP3,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A
		Cell Death and Survival	necrosis	7.E-23	58	ACKR3,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL8,EGR3,ENC1,EREG,G0S2,GCH1,GEM,HAS2,HBEGF,ICAM1,IFNB1,IL11,IL1A,IL32,IL6,IRAK2,IRF1,ITPRIP,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NR4A1,NR4A3,PMAIP1,PTGES,PTGS2,RASD1,RCAN1,RELB,RRAD,SERPINB2,SERPINE1,SLC2A1,SMOX,SPHK1,TFPI2,TNFAIP3,TNFAIP8,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A
		Cellular Movement	cell movement	9.E-23	53	ACKR3,ANGPTL4,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL6,CXCL8,EREG,ERRFI1,GBP1,GEM,HAS2,HBEGF,ICAM1,IFIT2,IFNB1,IL11,IL1A,IL32,IL6,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NKX3-1,NR4A1,NUAK2,PDGFA,PTGES,PTGS2,PTX3,RCAN1,RELB,SERPINB2,SERPINE1,SLC2A1,SPHK1,TFPI2,TNFAIP3,TNFAIP6,TNFAIP8,TSLP,VCAM1,ZC3H12A
		Tissue Morphology	quantity of cells	2.E-22	48	ACKR3,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL6,CXCL8,EGR3,ERRFI1,GPR68,HBEGF,ICAM1,IFNB1,IL11,IL1A,IL6,IRF1,LIF,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NKX3-1,NR4A1,NR4A3,PDGFA,PMAIP1,PTGES,PTGS2,RCAN1,RELB,SERPINB2,SERPINE1,SLC2A1,SPHK1,TNFAIP3,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A,ZFP42
		Cellular Movement	cellular infiltration	4.E-22	28	CCL2,CD274,CXCL2,CXCL8,GBP1,ICAM1,IL1A,IL32,IL6,LIF,MAP3K8,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NR4A1,PDGFA,PTGES,PTGS2,PTX3,SERPINE1,TNFAIP3,TNFAIP8,TSLP,VCAM1,ZC3H12A
		Cellular Movement	migration of cells	2.E-21	49	ACKR3,ANGPTL4,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL6,CXCL8,EREG,ERRFI1,HAS2,HBEGF,ICAM1,IFIT2,IFNB1,IL11,IL1A,IL32,IL6,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NKX3-1,NR4A1,PDGFA,PTGES,PTGS2,PTX3,RCAN1,SERPINB2,SERPINE1,SLC2A1,SPHK1,TFPI2,TNFAIP3,TNFAIP6,TNFAIP8,TSLP,VCAM1,ZC3H12A
B	DEG of uninfected GF(P22) vs. F. n-infected GF(P22)	Skeletal and Muscular System Development and Function	morphology of skeleton	6.E-10	10	DHRS3,EYA1,FMOD,HAPLN1,ID1,KLF10,LIF,NOV,POSTN,SFRP2
		Cellular Development, Connective Tissue Development and Function, Tissue Development	differentiation of connective tissue cells	2.E-09	13	CMKLR1,CYTL1,GADD45B,ID1,ID3,INSIG1,KLF10,LIF,NOV,NR4A1,POSTN,SFRP2,SMAD7
		Connective Tissue Disorders, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders, Skeletal and Muscular System Development and Function	abnormal morphology of skeleton	4.E-09	9	DHRS3,EYA1,FMOD,HAPLN1,ID1,KLF10,LIF,NOV,SFRP2
		Embryonic Development, Organismal Development	development of body axis	7.E-09	15	CSRNP1,CYTL1,DHRS3,DIO2,EYA1,FMOD,ID1,ID3,INSIG1,LIF,NFKBIA,POSTN,SFRP2,SMAD7,TM4SF1
		Embryonic Development, Organismal Development	development of head	3.E-08	14	CSRNP1,CYTL1,DHRS3,DIO2,EYA1,FMOD,ID1,ID3,INSIG1,LIF,NFKBIA,POSTN,SMAD7,TM4SF1
		Organismal Development	abnormal morphology of body cavity	3.E-08	15	BHLHE40,CMKLR1,DHRS3,EYA1,FMOD,ID1,ID3,LIF,MAP3K8,NFKBIA,NOV,POSTN,SMAD7,SYTL2,TRIB1
		Organismal Development	morphology of body cavity	5.E-08	16	BHLHE40,CMKLR1,DHRS3,EYA1,FMOD,ID1,ID3,LIF,MAP3K8,NFKBIA,NOV,NR4A1,POSTN,SMAD7,SYTL2,TRIB1
		Connective Tissue Development and Function, Skeletal and Muscular System Development and Function, Tissue Development	size of bone	1.E-07	8	EYA1,HAPLN1,ID1,KLF10,LIF,NOV,POSTN,SFRP2
		Cell Morphology, Tissue Morphology	morphology of connective tissue cells	1.E-07	8	ID1,INSIG1,KLF10,LIF,NOV,NR4A1,POSTN,TRIB1
		Cancer, Organismal Injury and Abnormalities, Reproductive System Disease	mammary tumor	2.E-07	17	BHLHE40,CPE,EYA1,GADD45B,ID1,KLF10,LIF,MAP3K8,NFKBIA,NPTX1,NR4A1,POSTN,PTPRD,SEMA6B,SFRP2,TM4SF1,TRIB1
C	DEG of F. n-infected GF(P4) vs F. n-infected GF(P22)	Cell Death and Survival	apoptosis	2.E-16	40	A2M,ALDH3A1,BCL2A1,BIRC3,BMP2,CADM1,CSF2,CSRNP1,CXCL1,CXCL2,CXCL8,EDNRB,FMOD,G0S2,GADD45B,GDF5,GPC3,HES1,HUNK,ICAM1,ID1,IFIT2,IFIT3,IGF2,IL6,KLF10,KLF6,MMP3,NFKB1,PLEKHF1,PMAIP1,PTGES,RIPK2,SFRP2,SGK1,SMOX,SNAI1,SOD3,TNFAIP2,TSLP
		Cell Death and Survival	cell death	6.E-16	44	A2M,ALDH3A1,BCL2A1,BIRC3,BMP2,CADM1,CSF2,CSRNP1,CXCL1,CXCL2,CXCL3,CXCL8,EDNRB,FMOD,G0S2,GADD45B,GCH1,GDF5,GPC3,HES1,HUNK,ICAM1,ID1,IFIT2,IFIT3,IGF2,IL6,KLF10,KLF6,MMP3,NFKB1,PLEKHF1,PMAIP1,PTGES,RIPK2,RPS16,SFRP2,SGK1,SLC12A7,SMOX,SNAI1,SOD3,TNFAIP2,TSLP
		Cell Death and Survival	necrosis	2.E-14	38	A2M,ALDH3A1,BCL2A1,BIRC3,BMP2,CADM1,CSF2,CXCL1,CXCL2,CXCL3,CXCL8,EDNRB,FMOD,G0S2,GADD45B,GCH1,GDF5,GPC3,HES1,ICAM1,ID1,IGF2,IL6,KLF10,KLF6,MMP3,NFKB1,PLEKHF1,PMAIP1,PTGES,RIPK2,RPS16,SFRP2,SGK1,SMOX,SNAI1,SOD3,TSLP
		Connective Tissue Disorders, Inflammatory Disease, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders	Rheumatic Disease	7.E-14	26	BMP2,CCL20,CSF2,CXCL1,CXCL2,CXCL3,CXCL6,CXCL8,EDNRB,FMOD,G0S2,GADD45B,GDF5,HES1,ICAM1,IL6,MMP3,NFKB1,PTGES,PTX3,RIPK2,RPS16,SGK1,SOD3,TNFAIP6,TSLP
		Cellular Growth and Proliferation, Tissue Development	proliferation of epithelial cells	2.E-13	18	BCL2A1,CSF2,CXCL3,CXCL8,EDNRB,EPGN,GDF5,GPC3,HES1,HUNK,ID1,IGF2,IL6,KLF10,NFKB1,SFRP2,TNFAIP6,TSLP
		Connective Tissue Disorders, Inflammatory Disease, Inflammatory Response, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders	inflammation of joint	3.E-13	24	BMP2,CCL20,CSF2,CXCL1,CXCL2,CXCL3,CXCL6,CXCL8,FMOD,G0S2,GADD45B,GDF5,HES1,ICAM1,IL6,MMP3,NFKB1,PTGES,PTX3,RIPK2,RPS16,SOD3,TNFAIP6,TSLP
		Cellular Growth and Proliferation	proliferation of cells	7.E-13	42	A2M,ALDH3A1,BCL2A1,BIRC3,BMP2,CADM1,CCL20,CSF2,CXCL1,CXCL2,CXCL3,CXCL8,EDNRB,EPGN,FMOD,G0S2,GADD45B,GCH1,GDF5,GPC3,HES1,HUNK,ICAM1,ID1,IFIT3,IGF2,IL6,KLF10,KLF6,MMP3,NFKB1,PMAIP1,PTGES,PTX3,RIPK2,SFRP2,SGK1,SMOX,SNAI1,STC2,TNFAIP6,TSLP
		Tissue Development	growth of epithelial tissue	8.E-13	20	BCL2A1,BMP2,CSF2,CXCL1,CXCL3,CXCL8,EDNRB,EPGN,GDF5,GPC3,HES1,HUNK,ID1,IGF2,IL6,KLF10,NFKB1,SFRP2,TNFAIP6,TSLP
		Cellular Movement	migration of cells	9.E-13	31	A2M,BMP2,CCL20,CSF2,CXCL1,CXCL2,CXCL3,CXCL6,CXCL8,EDNRB,FMOD,GDF5,GPC3,ICAM1,ID1,IFIT2,IGF2,IL6,KLF6,MMP3,NFKB1,PTGES,PTX3,RIPK2,SFRP2,SGK1,SNAI1,SOD3,TM4SF1,TNFAIP6,TSLP
		Cancer, Organismal Injury and Abnormalities	metastasis	3.E-12	21	BMP2,CSF2,CXCL1,CXCL2,CXCL3,CXCL6,CXCL8,EDNRB,GCH1,ICAM1,ID1,IGF2,IL6,KLF6,MMP3,NFKB1,PTX3,SLC12A7,SNAI1,SOD3,TM4SF1
D	Overlapping A and C	Gastrointestinal Disease, Inflammatory Disease, Organismal Injury and Abnormalities	esophagitis	1.E-12	7	BCL2A1,CXCL1,CXCL2,CXCL6,CXCL8,TNFAIP6,TSLP
		Connective Tissue Disorders, Inflammatory Disease, Inflammatory Response, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders	osteoarthritis	1.E-11	9	BMP2,CXCL2,CXCL6,ICAM1,IL6,MMP3,NFKB1,PTGES,PTX3
		Inflammatory Response	inflammatory response	3.E-11	13	BCL2A1,BIRC3,CXCL1,CXCL2,CXCL6,CXCL8,ICAM1,IL6,NFKB1,PTGES,PTX3,TNFAIP6,TSLP
		Connective Tissue Disorders, Inflammatory Disease, Inflammatory Response, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders	inflammation of joint	4.E-11	14	BMP2,CXCL1,CXCL2,CXCL6,CXCL8,G0S2,ICAM1,IL6,MMP3,NFKB1,PTGES,PTX3,TNFAIP6,TSLP
		Gastrointestinal Disease, Hematological Disease, Immunological Disease, Inflammatory Disease, Organismal Injury and Abnormalities	eosinophilia of esophagus	8.E-11	6	BCL2A1,CXCL1,CXCL2,CXCL6,TNFAIP6,TSLP
		Cellular Movement, Hematological System Development and Function, Immune Cell Trafficking, Inflammatory Response	influx of phagocytes	1.E-10	6	CXCL1,CXCL2,CXCL6,IL6,PTX3,TSLP
		Cell Death and Survival	apoptosis	2.E-10	19	BCL2A1,BIRC3,BMP2,CXCL1,CXCL2,CXCL8,G0S2,HUNK,ICAM1,IFIT2,IFIT3,IL6,MMP3,NFKB1,PMAIP1,PTGES,SMOX,TNFAIP2,TSLP
		Cellular Movement	influx of myeloid cells	2.E-10	6	CXCL1,CXCL2,CXCL6,IL6,PTX3,TSLP
		Digestive System Development and Function, Gastrointestinal Disease, Hepatic System Development and Function, Hepatic System Disease, Inflammatory Disease, Inflammatory Response, Organ Development, Organismal Injury and Abnormalities, Psychological Disorders	alcoholic hepatitis	3.E-10	5	CXCL1,CXCL2,CXCL6,CXCL8,IL6
		Cell Death and Survival	cell death of myeloid cells	5.E-10	8	BCL2A1,BIRC3,CXCL1,CXCL2,CXCL8,IL6,PMAIP1,TSLP
E	Overlapping B and C	Connective Tissue Disorders, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders, Skeletal and Muscular System Development and Function	abnormal morphology of skeleton	1.E-05	4	FMOD,ID1,KLF10,SFRP2
		Cellular Function and Maintenance, Tissue Development	function of chondrocytes	2.E-05	2	FMOD,SFRP2
		Connective Tissue Development and Function, Connective Tissue Disorders, Organ Morphology, Organismal Development, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders, Skeletal and Muscular System Development and Function, Tissue Development	abnormal morphology of limb bone	3.E-05	3	FMOD,KLF10,SFRP2
		Connective Tissue Development and Function, Skeletal and Muscular System Development and Function, Tissue Development	ossification of bone	4.E-05	3	FMOD,KLF10,SFRP2
		Skeletal and Muscular System Development and Function	morphogenesis of skeletal system	4.E-05	3	CSRNP1,FMOD,SFRP2
		Cancer, Cell Death and Survival, Organismal Injury and Abnormalities, Tumor Morphology	cell death of cancer cells	6.E-05	4	FMOD,KLF10,RPS16,SFRP2
		Connective Tissue Development and Function, Skeletal and Muscular System Development and Function	strength of bone	2.E-04	2	ID1,KLF10
		Cancer, Organismal Injury and Abnormalities	mucoepidermoid carcinoma	2.E-04	2	RPS16,SFRP2
		Hematological Disease, Immunological Disease, Organismal Injury and Abnormalities	abnormality of bone marrow cells	2.E-04	2	GADD45B,ID1
		Connective Tissue Development and Function, Skeletal and Muscular System Development and Function, Tissue Development	morphology of bone	3.E-04	4	FMOD,ID1,KLF10,SFRP2

상기 표 11에 나타낸 바와 같이, GO 분석과 비슷한 패턴을 나타내는 것을 확인하였다. 예를 들어, 젊은 GF의 차등 발현 유전자의 감염(세포 죽음, 및 세포 죽음, 세포 사멸 및 증식과 같은 생존 관련 기능)에 대한 반응에 있어서 생물학적 기능은 노화된 GF의 차등 발현 유전자의 감염(골격 및 골격의 형태학, 결합 조직 세포의 분화 및 골격의 비정상적인 형태와 같은 세포 발달 관련 기능)에 대한 기능과 구별되는 것을 확인하였다. 또한, F. n-감염 젊은 GF 및 노화된 GF 사이의 직접 비교에 의한 차등 발현 유전자는 세포 죽음 및 세포 죽음, 세포 사멸 및 괴사와 같은 생존 관련 기능을 나타내는 것을 확인하였다.

비슷한 맥락에서, 젊은 GF-특이적 차등 발현 유전자는 식도염, 골관절염 및 염증 반응과 같은 면역 반응에 관여하는 반면, 노화된 GF-특이적 차등 발현 유전자는 골격의 비정상 형태와 같은 결합 조직 장애 또는 발달, 및 사지 뼈의 비정상 형태에 관여하는 것으로 나타났다.

6. 차등 발현 유전자( DEGs )의 네트워크 분석

차등 발현된 유전자의 가능한 상호 작용을 확인하기 위하여, IPA를 사용하여 의해 젊은 GF-특이적 및 노화된 GF-특이적 차등 발현 유전자의 네트워크 분석을 수행하였다.

그 결과, 도 7에 나타낸 바와 같이, 젊은 GF-특이적 차등 발현 유전자는 위장병, 염증성 질환, 유기체 감염 및 비정상 경로(점수 33 및 집중 분자 13)의 네트워크와 밀접한 관련이 있었다. 즉, 노화된 GF와 비교하여 젊은 GF에서 이러한 차등 발현 유전자가 상향 조절되었고, 대다수의 유전자는 NF-kB 활성화 및 다양한 케모카인과 관련이 있었다.

또한, 노화된-GF 특이적 차등 발현 유전자는 자유 라디칼 소거, 세포주기 및 암 경로(점수 30 및 집중 분자 13)의 네트워크와 밀접한 관련이 있었다. 즉, 자유 라디칼 소거에 관여하는 유전자인 SOD3은 하향 조절되었지만, GADD45B, ID1, KLF10, CSRNP1 및 TM4SF1을 비롯한 세포주기 또는 암 관련 유전자는 젊은 GF와 비교하여 노화된 GF에서 상향 조절되었다.

나아가, 도 8에 나타낸 바와 같이, 젊은 GF에서 상향 조절된 차등 발현 유전자는 모두 핵과 세포질에 국한되어 있었으나, 노화된 GF에서 상향 조절된 차등 발현 유전자는 핵 내에 국한된 반면, 하향 조절된 차등 발현 유전자는 세포질에 국한되어 있는 것을 확인할 수 있었다.

상기 내용을 종합한 결과, 노화된 구강세포와 젊은 구강세포 모두에서 감염시 특이적으로 고발현되는 유전자군을 치주염 진단을 위하여 사용할 수 있을 것으로 기대되고, 특히, 노화된 구강세포에서 차별적으로 고발현되는 유전자군은 노인성 치주염 진단을 위하여 사용할 수 있을 것으로 기대된다.

<110> INDUSTRY FOUNDATION OF CHONNAM NATIONAL UNIVERSITY <120> A biomarker for diagnosing periodontal disease <130> 06048 <160> 62 <170> KopatentIn 2.0 <210> 1 <211> 1955 <212> RNA <213> NM_002852.3 Homo sapiens pentraxin 3 (PTX3), mRNA <400> 1 attcatcccc attcaggctt tcctcagcat ttattaagga ctctctgctc cagcctctca 60 ctctcactct cctccgctca aactcagctc acttgagagt ctcctcccgc cagctgtgga 120 aagaactttg cgtctctcca gcaatgcatc tccttgcgat tctgttttgt gctctctggt 180 ctgcagtgtt ggccgagaac tcggatgatt atgatctcat gtatgtgaat ttggacaacg 240 aaatagacaa tggactccat cccactgagg accccacgcc gtgcgcctgc ggtcaggagc 300 actcggaatg ggacaagctc ttcatcatgc tggagaactc gcagatgaga gagcgcatgc 360 tgctgcaagc cacggacgac gtcctgcggg gcgagctgca gaggctgcgg gaggagctgg 420 gccggctcgc ggaaagcctg gcgaggccgt gcgcgccggg ggctcccgca gaggccaggc 480 tgaccagtgc tctggacgag ctgctgcagg cgacccgcga cgcgggccgc aggctggcgc 540 gtatggaggg cgcggaggcg cagcgcccag aggaggcggg gcgcgccctg gccgcggtgc 600 tagaggagct gcggcagacg cgagccgacc tgcacgcggt gcagggctgg gctgcccgga 660 gctggctgcc ggcaggttgt gaaacagcta ttttattccc aatgcgttcc aagaagattt 720 ttggaagcgt gcatccagtg agaccaatga ggcttgagtc ttttagtgcc tgcatttggg 780 tcaaagccac agatgtatta aacaaaacca tcctgttttc ctatggcaca aagaggaatc 840 catatgaaat ccagctgtat ctcagctacc aatccatagt gtttgtggtg ggtggagagg 900 agaacaaact ggttgctgaa gccatggttt ccctgggaag gtggacccac ctgtgcggca 960 cctggaattc agaggaaggg ctcacatcct tgtgggtaaa tggtgaactg gcggctacca 1020 ctgttgagat ggccacaggt cacattgttc ctgagggagg aatcctgcag attggccaag 1080 aaaagaatgg ctgctgtgtg ggtggtggct ttgatgaaac attagccttc tctgggagac 1140 tcacaggctt caatatctgg gatagtgttc ttagcaatga agagataaga gagaccggag 1200 gagcagagtc ttgtcacatc cgggggaata ttgttgggtg gggagtcaca gagatccagc 1260 cacatggagg agctcagtat gtttcataaa tgttgtgaaa ctccacttga agccaaagaa 1320 agaaactcac acttaaaaca catgccagtt gggaaggtct gaaaactcag tgcataatag 1380 gaacacttga gactaatgaa agagagagtt gagaccaatc tttatttgta ctggccaaat 1440 actgaataaa cagttgaagg aaagacattg gaaaaagctt ttgaggataa tgttactaga 1500 ctttatgcca tggtgctttc agtttaatgc tgtgtctctg tcagataaac tctcaaataa 1560 ttaaaaagga ctgtattgtt gaacagaggg acaattgttt tacttttctt tggttaattt 1620 tgttttggcc agagatgaat tttacattgg aagaataaca aaataagatt tgttgtccat 1680 tgttcattgt tattggtatg taccttatta caaaaaaaag atgaaaacat atttatacta 1740 caaggtgact taacaactat aaatgtagtt tatgtgttat aatcgaatgt cacgtttttg 1800 agaagatagt catataagtt atattgcaaa agggatttgt attaatttaa gactattttt 1860 gtaaagctct actgtaaata aaatatttta taaaactagc tcacgtcatt taattataaa 1920 tttaagagat gttttggaaa aaaaaaaaaa aaaaa 1955 <210> 2 <211> 1184 <212> RNA <213> NM_001511.3 Homo sapiens C-X-C motif chemokine ligand 1 (CXCL1), transcript variant 1, mRN <400> 2 cacagagccc gggccgcagg cacctcctcg ccagctcttc cgctcctctc acagccgcca 60 gacccgcctg ctgagcccca tggcccgcgc tgctctctcc gccgccccca gcaatccccg 120 gctcctgcga gtggcactgc tgctcctgct cctggtagcc gctggccggc gcgcagcagg 180 agcgtccgtg gccactgaac tgcgctgcca gtgcttgcag accctgcagg gaattcaccc 240 caagaacatc caaagtgtga acgtgaagtc ccccggaccc cactgcgccc aaaccgaagt 300 catagccaca ctcaagaatg ggcggaaagc ttgcctcaat cctgcatccc ccatagttaa 360 gaaaatcatc gaaaagatgc tgaacagtga caaatccaac tgaccagaag ggaggaggaa 420 gctcactggt ggctgttcct gaaggaggcc ctgcccttat aggaacagaa gaggaaagag 480 agacacagct gcagaggcca cctggattgt gcctaatgtg tttgagcatc gcttaggaga 540 agtcttctat ttatttattt attcattagt tttgaagatt ctatgttaat attttaggtg 600 taaaataatt aagggtatga ttaactctac ctgcacactg tcctattata ttcattcttt 660 ttgaaatgtc aaccccaagt tagttcaatc tggattcata tttaatttga aggtagaatg 720 ttttcaaatg ttctccagtc attatgttaa tatttctgag gagcctgcaa catgccagcc 780 actgtgatag aggctggcgg atccaagcaa atggccaatg agatcattgt gaaggcaggg 840 gaatgtatgt gcacatctgt tttgtaactg tttagatgaa tgtcagttgt tatttattga 900 aatgatttca cagtgtgtgg tcaacatttc tcatgttgaa actttaagaa ctaaaatgtt 960 ctaaatatcc cttggacatt ttatgtcttt cttgtaaggc atactgcctt gtttaatggt 1020 agttttacag tgtttctggc ttagaacaaa ggggcttaat tattgatgtt ttcatagaga 1080 atataaaaat aaagcactta tagaaaaaac tcgtttgatt tttgggggga aacaagggct 1140 acctttactg gaaaatctgg tgatttataa aaaaaaaaaa aaaa 1184 <210> 3 <211> 1234 <212> RNA <213> NM_002089.3 Homo sapiens C-X-C motif chemokine ligand 2 (CXCL2), mRNA <400> 3 gagctccggg aatttccctg gcccgggact ccgggctttc cagccccaac catgcataaa 60 aggggttcgc cgttctcgga gagccacaga gcccgggcca caggcagctc cttgccagct 120 ctcctcctcg cacagccgct cgaaccgcct gctgagcccc atggcccgcg ccacgctctc 180 cgccgccccc agcaatcccc ggctcctgcg ggtggcgctg ctgctcctgc tcctggtggc 240 cgccagccgg cgcgcagcag gagcgcccct ggccactgaa ctgcgctgcc agtgcttgca 300 gaccctgcag ggaattcacc tcaagaacat ccaaagtgtg aaggtgaagt cccccggacc 360 ccactgcgcc caaaccgaag tcatagccac actcaagaat gggcagaaag cttgtctcaa 420 ccccgcatcg cccatggtta agaaaatcat cgaaaagatg ctgaaaaatg gcaaatccaa 480 ctgaccagaa ggaaggagga agcttattgg tggctgttcc tgaaggaggc cctgccctta 540 caggaacaga agaggaaaga gagacacagc tgcagaggcc acctggattg cgcctaatgt 600 gtttgagcat cacttaggag aagtcttcta tttatttatt tatttattta tttgtttgtt 660 ttagaagatt ctatgttaat attttatgtg taaaataagg ttatgattga atctacttgc 720 acactctccc attatattta ttgtttattt taggtcaaac ccaagttagt tcaatcctga 780 ttcatattta atttgaagat agaaggtttg cagatattct ctagtcattt gttaatattt 840 cttcgtgatg acatatcaca tgtcagccac tgtgatagag gctgaggaat ccaagaaaat 900 ggccagtgag atcaatgtga cggcagggaa atgtatgtgt gtctattttg taactgtaaa 960 gatgaatgtc agttgttatt tattgaaatg atttcacagt gtgtggtcaa catttctcat 1020 gttgaagctt taagaactaa aatgttctaa atatcccttg gacattttat gtctttcttg 1080 taaggcatac tgccttgttt aatgttaatt atgcagtgtt tccctctgtg ttagagcaga 1140 gaggtttcga tatttattga tgttttcaca aagaacagga aaataaaata tttaaaaata 1200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1234 <210> 4 <211> 4180 <212> RNA <213> NM_006291.2 Homo sapiens TNF alpha induced protein 2 (TNFAIP2), mRNA <400> 4 ccagggtgat gctgaagatg atgaccttct tccaaggcct ctagagccat cagcctgtgc 60 caggcaccct cgacttgcct agaggccccc aaaagttgca gtccacatca gaggcagagt 120 cagaggcctc catgtcggag gcctcctctg aggacctggt gccacccctg gaggctgggg 180 cagccccata tagggaggag gaagaggcgg cgaagaagaa gaaggagaag aagaagaagt 240 ccaaaggcct ggccaatgtg ttctgcgtct tcaccaaagg gaagaagaag aagggtcagc 300 ccagctcagc ggagcccgag gacgcagccg ggtccaggca ggggctggat ggcccgcccc 360 ccacagtgga ggagctgaag gcggcgctgg agcgcgggca gctggaggcg gcgcggccgc 420 tgctggcgct ggagcgggag ctggcggcgg cggcggcggc gggcggtgtg agcgaggagg 480 agctggtgcg gcgccagagc aaggtggagg cgctgtacga gctgctgcgc gaccaggtgc 540 tgggcgtgct gcggcggccg ctggaggcgc cgcccgagcg gctgcgccag gcgctggccg 600 tggtggcgga gcaggagcgc gaggaccgcc aggcggcggc ggcggggccg gggacctcgg 660 ggctggcggc cacgcgcccg cggcgctggc tgcagctgtg gcggcgcggc gtggcggagg 720 cggccgagga gcgcatgggc cagcggccgg ccgcgggcgc cgaggtcccc gagagcgtct 780 ttctgcactt gggccgcacc atgaaggagg acctggaggc cgtggtggag cggctgaagc 840 cgctgttccc cgccgagttc ggcgtcgtgg cggcctacgc cgagagctac caccagcact 900 tcgcggccca cctggccgcc gtggcgcagt tcgagctgtg cgagcgcgac acctacatgc 960 tgctgctctg ggtgcagaac ctctacccca atgacatcat caacagcccc aagctggtgg 1020 gtgagctgca gggtatgggg ctcgggagcc tcctgccccc caggcagatc cgactgctgg 1080 aggccacatt cctgtccagt gaggcggcca atgtgaggga gttgatggac cgagctctgg 1140 agctagaggc acggcgctgg gctgaggatg tgcctcccca gaggctggac ggccactgcc 1200 acagcgagct ggccatcgac atcatccaga tcacctccca ggcccaggcc aaggccgaga 1260 gcatcacgct ggacttgggc tcacagataa agcgggtgct gctggtggag ctgcctgcgt 1320 tcctgaggag ctaccagcgc gcctttaatg aatttctgga gagaggcaag cagctgacga 1380 attacagggc caatgttatt gccaacatca acaactgcct gtccttccgg atgtccatgg 1440 agcagaattg gcaggtaccc caggacaccc tgagcctcct gctgggcccc ctgggtgagc 1500 tcaagagcca cggctttgac accctgctcc agaacctgca tgaggacctg aagccactgt 1560 tcaagaggtt cacgcacacc cgctgggcgg cccctgtgga gaccctggaa aacatcatcg 1620 ccactgtaga cacgaggctg cctgagttct cagagctgca gggctgtttc cgggaggagc 1680 tcatggaggc cttgcacctg cacctggtga aggagtacat catccaactc agcaaggggc 1740 gcctggtcct caagacggcc gagcagcagc agcagctggc tgggtacatc ctggccaatg 1800 ctgacaccat ccagcacttc tgcacccagc acggctcccc ggcgacctgg ctgcagcctg 1860 ctctccctac gctggccgag atcattcgcc tgcaggaccc cagtgccatc aagattgagg 1920 tggccactta tgccacctgc taccctgact tcagcaaagg ccacctgagc gctatcctgg 1980 ccatcaaggg gaacctatcc aacagtgagg tcaagcgcat ccggagcatc ttggacgtca 2040 gcatgggggc gcaggagccc tcccggcccc tattttccct tataaaggtt ggttagcttt 2100 tcctgtggcc tgacctgcct gtgagtgccc agcaagcctt gggcacaccc cgctgggagc 2160 tgttaagagc agcgctggtt ctcggttcct cccgggtctc ctgtgctctg atgctacttc 2220 tgcctagccc tggcggaggt gcaggccctg tcagctggaa ctggacagac cttggtttgt 2280 ttacatgtcc gatgggggca ggagctccca tcctgggcag ccaaccaggc aacaccaagg 2340 actctttgta aacgatagct gatcgtgtgc acgcaaggaa agaaccagga gggagagtgc 2400 agccaggctc agggatcccc ggacacctct gtccagagcc cctccacagt cggcctcatg 2460 actgtcctcc tcgtgggtgg ggccgagggc cctcttcagc tctctggaga caggggccga 2520 gcctcaccca tctgccctct gcagcccagg gccgccgtga gcgggattca gcaatggtgg 2580 aatggaagac agaactggaa gagaaagaag gaaaagatga gctctcgtct ggcaggggct 2640 tttagggtcc tgtggcgagc tgtgagcacc gccagcatta gacgtcacat ccaggtggcc 2700 ccacggcccc tacaggctgg ccctgcaatg gggccctgag ccctccctct tcatccccca 2760 aggcctcaac tagagggtgg tcccccgagg gcttggtgtc tactaccgaa gggcccaaga 2820 cctcctgggt cctctcaggc tcccccttcc ccaaggcagg gacaggccct gggggtgcca 2880 ccgtgggccc tgccacccag aagtctggct gaggtctggg caggggcagg gcaagcttga 2940 cctctcactg ttgacccttt ggcctctgta tttgtttcct attgccgtga caggtttcca 3000 caaacttcgt ggatcaaaac gaggtcttcc agttctgcgg gtcagaaggc tgacccgggg 3060 ctcaaatctg ggtgtcggca gtcctgcact ccttctggag gctctagggg agaattcatt 3120 tctggccttt tcatttttag aggctgaccg taattcttga cttcaggctc ctccatcttc 3180 agagccagct gtgggtagtt gaatcttttt cccgtcacct cattgaggcc tcccctctcc 3240 tgcctccctc caccactttt tttttttttt ttttgagaca gggtcttgct gtgttgccca 3300 ggctggagtg cagtggcctg gtcatggcat caaggctcac tgcagcctgg acctcctggt 3360 tcaagtgatc ctcttgtctc agtcccctga gacaatcccc cacgcccagc tacatatttt 3420 ttgtggatac agggtctcat tctgttgcct aggcttgtct ggaactcctg ggctcaaggg 3480 atcttgtagc cttagcctcc taaagtgctg ggattatagg catgagtcac tgtacccggc 3540 ctgctctacc gcttttaagg acgcttatga tcacattgcg cctacccaga gaacccaggt 3600 cgtctttcta ttttcaggtc agctgattag ccaccttagt tccatctgca actttagttc 3660 ccactggctg tgtaacctaa catagtcaca ggctctgggg actgtcacgt ggacatcttt 3720 gggaggccgt tattctgccc accgcaccct ccgttcatcc cctgccctgc cgggcacctc 3780 gctctacccc aggaaaatgt gagctcgttt tcctgctcgg catgtgctcc ccctaaggct 3840 ctgctcctcc ctgggcctga aagttccttc tcagcctgag agggggccct tcggactcag 3900 gcatgactca gcccggctga tgcctctgca gtgctgagtc aggatttggg gccggctctc 3960 ttgggtccgt ccccttttcc caggtactgc cttacaaagc tgtggccagg aagtggccgg 4020 tataaaggat gcccaaggtc tttgtacgtg tgtaggagtt agcgtgtttg atattgttaa 4080 tataataata attatttttt agagtactgc ttttgtatgt atgttgaaca ggatccaggt 4140 ttttatagct tgatataaaa cagaattcaa aagtgaaaaa 4180 <210> 5 <211> 1718 <212> RNA <213> NM_000584.3 Homo sapiens C-X-C motif chemokine ligand 8 (CXCL8, IL8), mRNA <400> 5 gagggtgcat aagttctcta gtagggtgat gatataaaaa gccaccggag cactccataa 60 ggcacaaact ttcagagaca gcagagcaca caagcttcta ggacaagagc caggaagaaa 120 ccaccggaag gaaccatctc actgtgtgta aacatgactt ccaagctggc cgtggctctc 180 ttggcagcct tcctgatttc tgcagctctg tgtgaaggtg cagttttgcc aaggagtgct 240 aaagaactta gatgtcagtg cataaagaca tactccaaac ctttccaccc caaatttatc 300 aaagaactga gagtgattga gagtggacca cactgcgcca acacagaaat tattgtaaag 360 ctttctgatg gaagagagct ctgtctggac cccaaggaaa actgggtgca gagggttgtg 420 gagaagtttt tgaagagggc tgagaattca taaaaaaatt cattctctgt ggtatccaag 480 aatcagtgaa gatgccagtg aaacttcaag caaatctact tcaacacttc atgtattgtg 540 tgggtctgtt gtagggttgc cagatgcaat acaagattcc tggttaaatt tgaatttcag 600 taaacaatga atagtttttc attgtaccat gaaatatcca gaacatactt atatgtaaag 660 tattatttat ttgaatctac aaaaaacaac aaataatttt taaatataag gattttccta 720 gatattgcac gggagaatat acaaatagca aaattgaggc caagggccaa gagaatatcc 780 gaactttaat ttcaggaatt gaatgggttt gctagaatgt gatatttgaa gcatcacata 840 aaaatgatgg gacaataaat tttgccataa agtcaaattt agctggaaat cctggatttt 900 tttctgttaa atctggcaac cctagtctgc tagccaggat ccacaagtcc ttgttccact 960 gtgccttggt ttctccttta tttctaagtg gaaaaagtat tagccaccat cttacctcac 1020 agtgatgttg tgaggacatg tggaagcact ttaagttttt tcatcataac ataaattatt 1080 ttcaagtgta acttattaac ctatttatta tttatgtatt tatttaagca tcaaatattt 1140 gtgcaagaat ttggaaaaat agaagatgaa tcattgattg aatagttata aagatgttat 1200 agtaaattta ttttatttta gatattaaat gatgttttat tagataaatt tcaatcaggg 1260 tttttagatt aaacaaacaa acaattgggt acccagttaa attttcattt cagataaaca 1320 acaaataatt ttttagtata agtacattat tgtttatctg aaattttaat tgaactaaca 1380 atcctagttt gatactccca gtcttgtcat tgccagctgt gttggtagtg ctgtgttgaa 1440 ttacggaata atgagttaga actattaaaa cagccaaaac tccacagtca atattagtaa 1500 tttcttgctg gttgaaactt gtttattatg tacaaataga ttcttataat attatttaaa 1560 tgactgcatt tttaaataca aggctttata tttttaactt taagatgttt ttatgtgctc 1620 tccaaatttt ttttactgtt tctgattgta tggaaatata aaagtaaata tgaaacattt 1680 aaaatataat ttgttgtcaa agtaaaaaaa aaaaaaaa 1718 <210> 6 <211> 1197 <212> RNA <213> NM_000600.4 Homo sapiens interleukin 6 (IL6), transcript variant 1, mRNA <400> 6 gtctcaatat tagagtctca acccccaata aatataggac tggagatgtc tgaggctcat 60 tctgccctcg agcccaccgg gaacgaaaga gaagctctat ctcccctcca ggagcccagc 120 tatgaactcc ttctccacaa gcgccttcgg tccagttgcc ttctccctgg ggctgctcct 180 ggtgttgcct gctgccttcc ctgccccagt acccccagga gaagattcca aagatgtagc 240 cgccccacac agacagccac tcacctcttc agaacgaatt gacaaacaaa ttcggtacat 300 cctcgacggc atctcagccc tgagaaagga gacatgtaac aagagtaaca tgtgtgaaag 360 cagcaaagag gcactggcag aaaacaacct gaaccttcca aagatggctg aaaaagatgg 420 atgcttccaa tctggattca atgaggagac ttgcctggtg aaaatcatca ctggtctttt 480 ggagtttgag gtatacctag agtacctcca gaacagattt gagagtagtg aggaacaagc 540 cagagctgtg cagatgagta caaaagtcct gatccagttc ctgcagaaaa aggcaaagaa 600 tctagatgca ataaccaccc ctgacccaac cacaaatgcc agcctgctga cgaagctgca 660 ggcacagaac cagtggctgc aggacatgac aactcatctc attctgcgca gctttaagga 720 gttcctgcag tccagcctga gggctcttcg gcaaatgtag catgggcacc tcagattgtt 780 gttgttaatg ggcattcctt cttctggtca gaaacctgtc cactgggcac agaacttatg 840 ttgttctcta tggagaacta aaagtatgag cgttaggaca ctattttaat tatttttaat 900 ttattaatat ttaaatatgt gaagctgagt taatttatgt aagtcatatt tatattttta 960 agaagtacca cttgaaacat tttatgtatt agttttgaaa taataatgga aagtggctat 1020 gcagtttgaa tatcctttgt ttcagagcca gatcatttct tggaaagtgt aggcttacct 1080 caaataaatg gctaacttat acatattttt aaagaaatat ttatattgta tttatataat 1140 gtataaatgg tttttatacc aataaatggc attttaaaaa attcagcaaa aaaaaaa 1197 <210> 7 <211> 4093 <212> RNA <213> NM_003998.3 Homo sapiens nuclear factor kappa B subunit 1 (NFKB1) <400> 7 gtgagagagt gagcgagaca gaaagagaga gaagtgcacc agcgagccgg ggcaggaaga 60 ggaggtttcg ccaccggagc ggcccggcga cgcgctgaca gcttcccctg cccttcccgt 120 cggtcgggcc gccagccgcc gcagccctcg gcctgcacgc agccaccggc cccgctcccg 180 gagcccagcg ccgccgaggc cgcagccgcc cggccagtaa ggcggcgccg ccgcccggcc 240 accgcgcgcc ctgcgcttcc ctccgcccgc gctgcggcca tggcgcggcg ctgactggcc 300 tggcccggcc ccgccgcgct cccgctcgcc ccgacccgca ctcgggcccg cccgggctcc 360 ggcctgccgc cgcctcttcc ttctccagcc ggcaggcccg cgccgcttag gagggagagc 420 ccacccgcgc caggaggccg aacgcggact cgccacccgg cttcagaatg gcagaagatg 480 atccatattt gggaaggcct gaacaaatgt ttcatttgga tccttctttg actcatacaa 540 tatttaatcc agaagtattt caaccacaga tggcactgcc aacagcagat ggcccatacc 600 ttcaaatatt agagcaacct aaacagagag gatttcgttt ccgttatgta tgtgaaggcc 660 catcccatgg tggactacct ggtgcctcta gtgaaaagaa caagaagtct taccctcagg 720 tcaaaatctg caactatgtg ggaccagcaa aggttattgt tcagttggtc acaaatggaa 780 aaaatatcca cctgcatgcc cacagcctgg tgggaaaaca ctgtgaggat gggatctgca 840 ctgtaactgc tggacccaag gacatggtgg tcggcttcgc aaacctgggt atacttcatg 900 tgacaaagaa aaaagtattt gaaacactgg aagcacgaat gacagaggcg tgtataaggg 960 gctataatcc tggactcttg gtgcaccctg accttgccta tttgcaagca gaaggtggag 1020 gggaccggca gctgggagat cgggaaaaag agctaatccg ccaagcagct ctgcagcaga 1080 ccaaggagat ggacctcagc gtggtgcggc tcatgtttac agcttttctt ccggatagca 1140 ctggcagctt cacaaggcgc ctggaacccg tggtatcaga cgccatctat gacagtaaag 1200 cccccaatgc atccaacttg aaaattgtaa gaatggacag gacagctgga tgtgtgactg 1260 gaggggagga aatttatctt ctttgtgaca aagttcagaa agatgacatc cagattcgat 1320 tttatgaaga ggaagaaaat ggtggagtct gggaaggatt tggagatttt tcccccacag 1380 atgttcatag acaatttgcc attgtcttca aaactccaaa gtataaagat attaatatta 1440 caaaaccagc ctctgtgttt gtccagcttc ggaggaaatc tgacttggaa actagtgaac 1500 caaaaccttt cctctactat cctgaaatca aagataaaga agaagtgcag aggaaacgtc 1560 agaagctcat gcccaatttt tcggatagtt tcggcggtgg tagtggtgct ggagctggag 1620 gcggaggcat gtttggtagt ggcggtggag gagggggcac tggaagtaca ggtccagggt 1680 atagcttccc acactatgga tttcctactt atggtgggat tactttccat cctggaacta 1740 ctaaatctaa tgctgggatg aagcatggaa ccatggacac tgaatctaaa aaggaccctg 1800 aaggttgtga caaaagtgat gacaaaaaca ctgtaaacct ctttgggaaa gttattgaaa 1860 ccacagagca agatcaggag cccagcgagg ccaccgttgg gaatggtgag gtcactctaa 1920 cgtatgcaac aggaacaaaa gaagagagtg ctggagttca ggataacctc tttctagaga 1980 aggctatgca gcttgcaaag aggcatgcca atgccctttt cgactacgcg gtgacaggag 2040 acgtgaagat gctgctggcc gtccagcgcc atctcactgc tgtgcaggat gagaatgggg 2100 acagtgtctt acacttagca atcatccacc ttcattctca acttgtgagg gatctactag 2160 aagtcacatc tggtttgatt tctgatgaca ttatcaacat gagaaatgat ctgtaccaga 2220 cgcccttgca cttggcagtg atcactaagc aggaagatgt ggtggaggat ttgctgaggg 2280 ctggggccga cctgagcctt ctggaccgct tgggtaactc tgttttgcac ctagctgcca 2340 aagaaggaca tgataaagtt ctcagtatct tactcaagca caaaaaggca gcactacttc 2400 ttgaccaccc caacggggac ggtctgaatg ccattcatct agccatgatg agcaatagcc 2460 tgccatgttt gctgctgctg gtggccgctg gggctgacgt caatgctcag gagcagaagt 2520 ccgggcgcac agcactgcac ctggctgtgg agcacgacaa catctcattg gcaggctgcc 2580 tgctcctgga gggtgatgcc catgtggaca gtactaccta cgatggaacc acacccctgc 2640 atatagcagc tgggagaggg tccaccaggc tggcagctct tctcaaagca gcaggagcag 2700 atcccctggt ggagaacttt gagcctctct atgacctgga tgactcttgg gaaaatgcag 2760 gagaggatga aggagttgtg cctggaacca cgcctctaga tatggccacc agctggcagg 2820 tatttgacat attaaatggg aaaccatatg agccagagtt tacatctgat gatttactag 2880 cacaaggaga catgaaacag ctggctgaag atgtgaagct gcagctgtat aagttactag 2940 aaattcctga tccagacaaa aactgggcta ctctggcgca gaaattaggt ctggggatac 3000 ttaataatgc cttccggctg agtcctgctc cttccaaaac acttatggac aactatgagg 3060 tctctggggg tacagtcaga gagctggtgg aggccctgag acaaatgggc tacaccgaag 3120 caattgaagt gatccaggca gcctccagcc cagtgaagac cacctctcag gcccactcgc 3180 tgcctctctc gcctgcctcc acaaggcagc aaatagacga gctccgagac agtgacagtg 3240 tctgcgacag cggcgtggag acatccttcc gcaaactcag ctttaccgag tctctgacca 3300 gtggtgcctc actgctaact ctcaacaaaa tgccccatga ttatgggcag gaaggacctc 3360 tagaaggcaa aatttagcct gctgacaatt tcccacaccg tgtaaaccaa agccctaaaa 3420 ttccactgcg ttgtccacaa gacagaagct gaagtgcatc caaaggtgct cagagagccg 3480 gcccgcctga atcattctcg atttaactcg agaccttttc aacttggctt cctttcttgg 3540 ttcataaatg aattttagtt tggttcactt acagatagta tctagcaatc acaacactgg 3600 ctgagcggat gcatctgggg atgaggttgc ttactaagct ttgccagctg ctgctggatc 3660 acagctgctt tctgttgtca ttgctgttgt ccctctgcta cgttcctatt gtcattaaag 3720 gtatcacggt cgccacctgg cattccttct gaccacagca tcattttgca ttcaaattaa 3780 gggttaagaa aagagatatt ttaaaatgag agtcacttga tgtgccattt taaaaaaaaa 3840 ggcatattgc tttttctaat gtggttattt ctctgatttg caaaaaaaaa aaaaaaaaaa 3900 atacttgtca atatttaaac atggttacaa tcattgctga aaatggtatt ttcccccttt 3960 tctgcatttt gctattgtaa atatgttttt tagatcaaat actttaaagg aaaaaatgtt 4020 ggatttataa atgctatttt ttattttact tttataataa aaggaaaagc aaattgatga 4080 cctcaaaaaa aaa 4093 <210> 8 <211> 978 <212> RNA <213> NM_015714.3 Homo sapiens G0/G1 switch 2 (G0S2), mRNA <400> 8 tggctctgac cgcgctggcc tgggccggag agcccaggag gcgtgtctca gagaaaagat 60 ataagcggcc cccggacgct aaagcggtgc cagcggcgga gtctccaact gggagagctg 120 cagctgccga gaggaggaga acgctgaggt cggtcggacc aacggacgcg ctgaccgctg 180 ccaactgcag ctcgcgctgc ctcctgctcg cgccgtgcca ctaaggtcat tcccgcctcc 240 gagagcccag agccgagatg gaaacggtcc aggagctgat ccccctggcc aaggagatga 300 tggcccagaa gcgcaagggg aagatggtga agctgtacgt gctgggcagc gtgctggccc 360 tcttcggcgt ggtgctcggc ctgatggaga ctgtgtgcag ccccttcacg gccgccagac 420 gtctgcggga ccaggaggca gccgtggcgg agctgcaggc cgccctggag cgacaggctc 480 tccagaagca agccctgcag gagaaaggca agcagcagga cacggtcctc ggcggccggg 540 ccctgtccaa ccggcagcac gcctcctagg aactgtggga gaccagcgga gtgggaggga 600 gacgcagtag acagagacag accgagagag gaatggagag acagaggggg cgcgcgcaca 660 ggagcctgac tccgctggga gagtgcagga gcacgtgctg ttttttattt ggacttaact 720 tcagagaaac cgctgacatc tagaactgac ctaccacaag catccaccaa aggagtttgg 780 gattgagttt tgctgctgtg cagcactgca ttgtcatgac atttccaaca ctgtgtgaat 840 tatctaaatg cgtctaccat tttgcactag ggaggaagga taaatgcttt ttatgttatt 900 attattaatt attacaatga ccaccatttt gcattttgaa ataaaaaaac tttttatacc 960 ataaaaaaaa aaaaaaaa 978 <210> 9 <211> 3024 <212> RNA <213> BC015969.2 Homo sapiens intercellular adhesion molecule 1, mRNA (ICM1) <400> 9 ctataaagga tcacgcgccc cagtcgacgc tgagctcctc tgctactcag agttgcaacc 60 tcagcctcgc tatggctccc agcagccccc ggcccgcgct gcccgcactc ctggtcctgc 120 tcggggctct gttcccagga cctggcaatg cccagacatc tgtgtccccc tcaaaagtca 180 tcctgccccg gggaggctcc gtgctggtga catgcagcac ctcctgtgac cagcccaagt 240 tgttgggcat agagaccccg ttgcctaaaa aggagttgct cctgcctggg aacaaccgga 300 aggtgtatga actgagcaat gtgcaagaag atagccaacc aatgtgctat tcaaactgcc 360 ctgatgggca gtcaacagct aaaaccttcc tcaccgtgta ctggactcca gaacgggtgg 420 aactggcacc cctcccctct tggcagccag tgggcaagaa ccttacccta cgctgccagg 480 tggagggtgg ggcaccccgg gccaacctca ccgtggtgct gctccgtggg gagaaggagc 540 tgaaacggga gccagctgtg ggggagcccg ctgaggtcac gaccacggtg ctggtgagga 600 gagatcacca tggagccaat ttctcgtgcc gcactgaact ggacctgcgg ccccaagggc 660 tggagctgtt tgagaacacc tcggccccct accagctcca gacctttgtc ctgccagcga 720 ctcccccaca acttgtcagc ccccgggtcc tagaggtgga cacgcagggg accgtggtct 780 gttccctgga cgggctgttc ccagtctcgg aggcccaggt ccacctggca ctgggggacc 840 agaggttgaa ccccacagtc acctatggca acgactcctt ctcggccaag gcctcagtca 900 gtgtgaccgc agaggacgag ggcacccagc ggctgacgtg tgcagtaata ctggggaacc 960 agagccagga gacactgcag acagtgacca tctacagctt tccggcgccc aacgtgattc 1020 tgacgaagcc agaggtctca gaagggaccg aggtgacagt gaagtgtgag gcccacccta 1080 gagccaaggt gacgctgaat ggggttccag cccagccact gggcccgagg gcccagctcc 1140 tgctgaaggc caccccagag gacaacgggc gcagcttctc ctgctctgca accctggagg 1200 tggccggcca gcttatacac aagaaccaga cccgggagct tcgtgtcctg tatggccccc 1260 gactggacga gagggattgt ccgggaaact ggacgtggcc agaaaattcc cagcagactc 1320 caatgtgcca ggcttggggg aacccattgc ccgagctcaa gtgtctaaag gatggcactt 1380 tcccactgcc catcggggaa tcagtgactg tcactcgaga tcttgagggc acctacctct 1440 gtcgggccag gagcactcaa ggggaggtca cccgcaaggt gaccgtgaat gtgctctccc 1500 cccggtatga gattgtcatc atcactgtgg tagcagccgc agtcataatg ggcactgcag 1560 gcctcagcac gtacctctat aaccgccagc ggaagatcaa gaaatacaga ctacaacagg 1620 cccaaaaagg gacccccatg aaaccgaaca cacaagccac gcctccctga acctatcccg 1680 ggacagggcc tcttcctcgg ccttcccata ttggtggcag tggtgccaca ctgaacagag 1740 tggaagacat atgccatgca gctacaccta ccggccctgg gacgccggag gacagggcat 1800 tgtcctcagt cagatacaac agcatttggg gccatggtac ctgcacacct aaaacactag 1860 gccacgcatc tgatctgtag tcacatgact aagccaagag gaaggagcaa gactcaagac 1920 atgattgatg gatgttaaag tctagcctga tgagagggga agtggtgggg gagacatagc 1980 cccaccatga ggacatacaa ctgggaaata ctgaaacttg ctgcctattg ggtatgctga 2040 ggccccacag acttacagaa gaagtggccc tccatagaca tgtgtagcat caaaacacaa 2100 aggcccacac ttcctgacgg atgccagctt gggcactgct gtctactgac cccaaccctt 2160 gatgatatgt atttattcat ttgttatttt accagctatt tattgagtgt cttttatgta 2220 ggctaaatga acataggtct ctggcctcac ggagctccca gtcctaatca cattcaaggt 2280 caccaggtac agttgtacag gttgtacact gcaggagagt gcctggcaaa aagatcaaat 2340 ggggctggga cttctcattg gccaacctgc ctttccccag aaggagtgat ttttctatcg 2400 gcacaaaagc actatatgga ctggtaatgg ttacaggttc agagattacc cagtgaggcc 2460 ttattcctcc cttcccccca aaactgacac ctttgttagc cacctcccca cccacataca 2520 tttctgccag tgttcacaat gacactcagc ggtcatgtct ggacatgagt gcccagggaa 2580 tatgcccaag ctatgccttg tcctcttgtc ctgtttgcat ttcactggga gcttgcacta 2640 tgcagctcca gtttcctgca gtgatcaggg tcctgcaagc agtggggaag ggggccaagg 2700 tattggagga ctccctccca gctttggaag cctcatccgc gtgtgtgtgt gtgtgtatgt 2760 gtagacaagc tctcgctctg tcacccaggc tggagtgcag tggtgcaatc atggttcact 2820 gcagtcttga ccttttgagc tcaagtgatc ctcccacctc agcctcctga gtagctggga 2880 ccataggctc acaacaccac acctggcaaa tttgattttt tttttttttc cagagacggg 2940 gtcttgcaac attgcccaga cttcctttgt gttagttaat aaagctttct caactgccaa 3000 aaaaaaaaaa aaaaaaaaaa aaaa 3024 <210> 10 <211> 1051 <212> RNA <213> BC003097.1 Homo sapiens intercellular adhesion molecule 2, mRNA (ICM2) <400> 10 ctccctccag gcagcccttg gctggtccct gcgagcccgt ggagactgcc agagatgtcc 60 tctttcggtt acaggaccct gactgtggcc ctcttcaccc tgatctgctg tccaggatcg 120 gatgagaagg tattcgaggt acacgtgagg ccaaagaagc tggcggttga gcccaaaggg 180 tccctcgagg tcaactgcag caccacctgt aaccagcctg aagtgggtgg tctggagacc 240 tctctagata agattctgct ggacgaacag gctcagtgga aacattactt ggtctcaaac 300 atctcccatg acacggtcct ccaatgccac ttcacctgct ccgggaagca ggagtcaatg 360 aattccaacg tcagcgtgta ccagcctcca aggcaggtca tcctgacact gcaacccact 420 ttggtggctg tgggcaagtc cttcaccatt gagtgcaggg tgcccaccgt ggagcccctg 480 gacagcctca ccctcttcct gttccgtggc aatgagactc tgcactatga gaccttcggg 540 aaggcagccc ctgctccgca ggaggccaca gccacattca acagcacggc tgacagagag 600 gatggccacc gcaacttctc ctgcctggct gtgctggact tgatgtctcg cggtggcaac 660 atctttcaca aacactcagc cccgaagatg ttggagatct atgagcctgt gtcggacagc 720 cagatggtca tcatagtcac ggtggtgtcg gtgttgctgt ccctgttcgt gacatctgtc 780 ctgctctgct tcatcttcgg ccagcacttg cgccagcagc ggatgggcac ctacggggtg 840 cgagcggctt ggaggaggct gccccaggcc ttccggccat agcaaccatg agtggcatgg 900 ccaccaccac ggtggtcact ggaactcagt gtgactcctc agggttgagg tccagccctg 960 gctgaaggac tgtgacaggc agcagagact tgggacattg ccttttctag cccgaataca 1020 aacacctgga cttaaaaaaa aaaaaaaaaa a 1051 <210> 11 <211> 1771 <212> RNA <213> BC058903.1 Homo sapiens intercellular adhesion molecule 3, mRNA (ICM3) <400> 11 gtcagaatgg ccaccatggt accatccgtg ttgtggccca gggcctgctg gactctgctg 60 gtctgctgtc tgctgacccc aggtgtccag gggcaggagt tccttttgcg ggtggagccc 120 cagaaccctg tgctctctgc tggagggtcc ctgtttgtga actgcagtac tgattgtccc 180 agctctgaga aaatcgcctt ggagacgtcc ctatcaaagg agctggtggc cagtggcatg 240 ggctgggcag ccttcaatct cagcaacgtg actggcaaca gtcggatcct ctgctcagtg 300 tactgcaatg gctcccagat aacaggctcc tctaacatca ccgtgtacag gctcccggag 360 cgtgtggagc tggcacccct gcctccttgg cagccggtgg gccagaactt caccctgcgc 420 tgccaagtgg aggatgggtc gccccggacc agcctcacgg tggtgctgct tcgctgggag 480 gaggagctga gccggcagcc cgcagtggag gagccagcgg aggtcactgc cactgtgctg 540 gccagcagag acgaccacgg agcccctttc tcatgccgca cagaactgga catgcagccc 600 caggggctgg gactgttcgt gaacacctca gccccccgcc agctccgaac ctttgtcctg 660 cccgtgaccc ccccgcgcct cgtggccccc cggttcttgg aggtggaaac gtcgtggccg 720 gtggactgca ccctagacgg gctttttcca gcctcagagg cccaggtcta cctggcgctg 780 ggggaccaga tgctgaatgc gacagtcatg aaccacgggg acacgctaac ggccacagcc 840 acagccacgg cgcgcgcgga tcaggagggt gcccgggaga tcgtctgcaa cgtgacccta 900 gggggcgaga gacgggaggc ccgggagaac ttgacggtct ttagcttcct aggacccatt 960 gtgaacctca gcgagcccac cgcccatgag gggtccacag tgaccgtgag ttgcatggct 1020 ggggctcgag tccaggtcac gctggacgga gttccggccg cggccccggg gcagccagct 1080 caacttcagc taaatgctac cgagagtgac gacggacgca gcttcttctg cagtgccact 1140 ctcgaggtgg acggcgagtt cttgcacagg aacagtagcg tccagctgcg agtcctgtat 1200 ggtcccaaaa ttgaccgagc cacatgcccc cagcacttga aatggaaaga taaaacgaga 1260 cacgtcctgc agtgccaagc caggggcaac ccgtaccccg agctgcggtg tttgaaggaa 1320 ggctccagcc gggaggtgcc ggtggggatc ccgttcttcg tcaacgtaac acataatggt 1380 acttatcagt gccaagcgtc cagctcacga ggcaaataca ccctggtcgt ggtgatggac 1440 attgaggctg ggagctccca ctttgtcccc gtcttcgtgg cggtgttact gaccctgggc 1500 gtggtgacta tcgtactggc cttaatgtac gtcttcaggg agcaccaacg gagcggcagt 1560 taccatgtta gggaggagag cacctatctg cccctcacgt ctatgcagcc gacagaagca 1620 atgggggaag aaccgtccag agctgagtga cgctgggatc cgggatcaaa gttggcgggg 1680 gcttggctgt gccctcagat tccgcaccaa taaagccttc aaactcccta aaaaaaaaaa 1740 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 1771 <210> 12 <211> 1846 <212> RNA <213> BC008280.1 Homo sapiens prostaglandin E synthase, mRNA (PTGES) <400> 12 tgatcacacc cacagttgag ctgcgctggc cagagatgcc tgcccacagc ctggtgatga 60 gcagcccggc cctcccggcc ttcctgctct gcagcacgct gctggtcatc aagatgtacg 120 tggtggccat catcacgggc caagtgaggc tgcggaagaa ggcctttgcc aaccccgagg 180 atgccctgag acacggaggc ccccagtatt gcaggagcga ccccgacgtg gaacgctgcc 240 tcagggccca ccggaacgac atggagacca tctacccctt ccttttcctg ggcttcgtct 300 actcctttct gggtcctaac ccttttgtcg cctggatgca cttcctggtc ttcctcgtgg 360 gccgtgtggc acacaccgtg gcctacctgg ggaagctgcg ggcacccatc cgctccgtga 420 cctacaccct ggcccagctc ccctgcgcct ccatggctct gcagatcctc tgggaagcgg 480 cccgccacct gtgaccagca gctgatgcct ccttggccac cagaccatgg gccaagagcc 540 gccgtggcta tacctgggga cttgatgttc cttccagatt gtggtgggcc ctgagtcctg 600 gtttcctggc agcctgctgc gcgtgtgggt ctctgggcac agtgggcctg tgtgtgtgcc 660 cgtgtgtgtg tatgtgtatg tgtgtgtgta tgtttcttag ccccttggat tcctgcacga 720 agtggctgat gggaaccatt tcaagacaga ttgtgaagat tgatagaaaa tccttcagct 780 aaagtaacag agcatcaaaa acatcactcc ctctccctcc ctaacagtga aaagagagaa 840 gggagactct atttaagatt cccaaaccta atgatcatct gaatcccggg ctaagaatgc 900 agacttttca gactgacccc agaaattctg gcccagccaa tctagaggca agcctggcca 960 tctgtatttt tttttttcca agacagagtc ttgctctgtt gcccaagctg gagtgaagtg 1020 gtacaatctg gctcactgca gcctccgcct cccgggttca agcgattctc ccgcctcagc 1080 ctcctgagta gctgggatta caggcgcgta tcaccatacc cagctaattt ttgtattttt 1140 agtagagacg ggttcaccat gttgcccagg agggtctcga actcctggcc tcaagtgatc 1200 caccggcctc ggcctcccaa agtgctggga tgacaggcat gaatcactgt gctcagccac 1260 catctggagt tttaaaaggc tcccatgtga gtccctgtga tggccaggcc aggggacccc 1320 tgccagttct ctgtggaagc aaggctgggg tcttgggttc ctgtatggtg gaagctgggt 1380 gagccaagga cagggctggc tcctctgccc ccgctgacgc ttcccttgcc gttggctttg 1440 gatgtctttg ctgcagtctt ctctctggct caggtgtggg tgggaggggc ccacaggaag 1500 ctcagccttc tcctcccaag gtttgagtcc ctccaaaggg cagtgggtgg aggaccggga 1560 gctttgggtg accagccact caaaggaact ttctggtccc ttcagtatct tcaaggtttg 1620 gaaactgcaa atgtcccctt gatggggaat ccgtgtgtgt gtgtgtgtgt gtgtgtgtgt 1680 gtgtgtgtgt gtgtgttttc tcctagaccc gtgacctgag atgtgtgatt tttagtcatt 1740 aaatggaagt gtctgccaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1800 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 1846 <210> 13 <211> 1283 <212> RNA <213> BC032663.1 Homo sapiens phorbol-12-myristate-13-acetate-induced protein 1, mRNA (PMAIP1) <400> 13 ccacgcgtcc gcgtgtgtag ttggcatctc cgcgcgtccg gacacccgat cccagcatcc 60 ctgcctgcag gactgttcgt gttcagctcg cgtcctgcag ctgtccgagg tgctccagtt 120 ggaggctgag gttcccgggc tctgtagctg agtgggcggc ggcaccggcg gagatgcctg 180 ggaagaaggc gcgcaagaac gctcaaccga gccccgcgcg ggctccagca ggaccggcgg 240 gtacggcggg tacggcgagg gaccaagccg gatttgcgat tgggatgcag ctgcgtttca 300 ccaggggcaa aaagctcctt tcctcctctc tttcctcctc gccacttgcc cttccccggg 360 gccacgagga acaagtgcaa gtagctggaa gtcgagtgtg ctactcaact caggagattt 420 ggagacaaac tgaacttccg gcagaaactt ctgaatctga tatccaaact cttctgctca 480 ggaacctgac tgcatcaaaa acttgcatga ggggactcct tcaaaagagt tttctcagga 540 ggtgcacgtt tcatcaattt gaagaaagac tgcattgtaa ttgagaggaa tgtgaaggtg 600 cattcatggg tgcccttgga aacggaagat ggaatacatc aaagtgaatt tctgttcaag 660 ttttcccaga ttatcattct ttgggatgag agaacattat aaaaccactt tgtttatttt 720 aaagcaagaa tggaagaccc ttgaaaataa agaagtaatt attgacacat ttctttttta 780 cttagagaat cgttctagtg tttttgccga agattaccgc tggcctactg tgaagggaga 840 tgacctgtga ttagactggg cggctgggga gaaacagttc agtgcattgt tgttgttgct 900 gtttttggtg ttttgctttt cagtgccaac tcagcacatt gtatatgatt cggtttatac 960 atattacctt gttataatga aaaaactcat tctgagaaca ctgaaatgtt atactcagtg 1020 ttgatttctt cggtcactac acaacgtaaa atcatttgtt tcttttgact caaattgtat 1080 tgcttctgtt cagatgatct ttcattcaat gtgttcctgt tgggcgttac tagaaactat 1140 ggaaaactgg aaaataactt tgaaaaaatt ggataaagta taggagggtt acttggggcc 1200 agtaaatcag tagactgaac attcaatata ataaaagaac atggggattt tgtataacca 1260 gggataataa aaaaaaaaaa aaa 1283 <210> 14 <211> 1984 <212> RNA <213> BC000669.2 Homo sapiens spermine oxidase, mRNA (SMOX) <400> 14 gtcccggcgg cggctggagg aggaagccag gcggctggcg gaggaggaga gacggaggag 60 gccgagaccg gagcgccgct cgccgcagac ttacttcccc ggctcagcag ggaaaggttc 120 ctagaaggtg agcgcggacg gtatgcaaag ttgtgaatcc agtggtgaca gtgcggatga 180 ccctctcagt cgcggcctac ggagaagggg acagcctcgt gtggtggtga tcggcgccgg 240 cttggctggc ctggctgcag ccaaagcact tcttgagcag ggtttcacgg atgtcactgt 300 gcttgaggct tccagccaca tcggaggccg tgtgcagagt gtgaaacttg gacacgccac 360 ctttgagctg ggagccacct ggatccatgg ctcccatggg aaccctatct atcatctagc 420 agaagccaac ggcctcctgg aagagacaac cgatggggaa cgcagcgtgg gccgcatcag 480 cctctattcc aagaatggcg tggcctgcta ccttaccaac cacggccgca ggatccccaa 540 ggacgtggtt gaggaattca gcgatttata caacgaggtc tataacttga cccaggagtt 600 cttccggcac gataaaccag tcaatgctga aagtcaaaat agcgtggggg tgttcacccg 660 agaggaggtg cgtaaccgca tcaggaatga ccctgacgac ccagaggcta ccaagcgcct 720 gaagctcgcc atgatccagc agtacctgaa ggtggagagc tgtgagagca gctcacacag 780 catggacgag gtgtccctga gcgccttcgg ggagtggacc gagatccccg gcgctcacca 840 catcatcccc tcgggcttca tgcgggttgt ggagctgctg gcggagggca tccctgccca 900 cgtcatccag ctagggaaac ctgtccgctg cattcactgg gaccaggcct cagcccgccc 960 cagaggccct gagattgagc cccggggtgt gctaaagagg cagtacacca gtttcttccg 1020 gccaggcctg cccacagaga aggtggctgc catccaccgc ctgggcattg gcaccaccga 1080 caagatcttt ctggaattcg aggagccctt ctggggccct gagtgcaaca gcctacagtt 1140 tgtgtgggag gacgaagcgg agagccacac cctcacctac ccacctgagc tctggtaccg 1200 caagatctgc ggctttgatg tcctctaccc gcctgagcgc tacggccatg tgctgagcgg 1260 ctggatctgc ggggaggagg ccctcgtcat ggagaagtgt gatgacgagg cagtggccga 1320 gatctgcacg gagatgctgc gtcagttcac agggaacccc aacattccaa aacctcggcg 1380 aatcttgcgc tcggcctggg gcagcaaccc ttacttccgc ggctcctatt catacacgca 1440 ggtgggctcc agcggggcgg atgtggagaa gctggccaag cccctgccgt acacggagag 1500 ctcaaagaca gcgcccatgc aggtgctgtt ttccggtgag gccacccacc gcaagtacta 1560 ttccaccacc cacggtgctc tgctgtccgg ccagcgtgag gctgcccgcc tcattgagat 1620 gtaccgagac ctcttccagc aggggacctg agggctgtcc tcgctgctga gaagagccac 1680 taactcgtga cctccagcct gccccttgct gccgtgtgct cctgccttcc tgatcctctg 1740 tagaaaggat ttttatcttc tgtagagcta gccgccctga ctgccttcag acctggccct 1800 gtagcttttc tttttctcca ggctgggccg tgagcaggtg ggccgttgag ttacctctgt 1860 gctggatccc gtgcccccac ttgcctaccc tctgtcctgc cttgttattg taagtgcctt 1920 caatactttg cattttggga taataaaaaa ggctccctcc cctgcaaaaa aaaaaaaaaa 1980 aaaa 1984 <210> 15 <211> 1430 <212> RNA <213> BC030205.1 Homo sapiens tumor necrosis factor, alpha-induced protein 6, mRNA (TNFAIP6) <400> 15 gtgagcagcc cctaacaggc tgttacttca ctacaactga cgatatgatc atcttaattt 60 acttatttct cttgctatgg gaagacactc aaggatgggg attcaaggat ggaatttttc 120 ataactccat atggcttgaa cgagcagccg gtgtgtacca cagagaagca cggtctggca 180 aatacaagct cacctacgca gaagctaagg cggtgtgtga atttgaaggc ggccatctcg 240 caacttacaa gcagctagag gcagccagaa aaattggatt tcatgtctgt gctgctggat 300 ggatggctaa gggcagagtt ggatacccca ttgtgaagcc agggcccaac tgtggatttg 360 gaaaaactgg cattattgat tatggaatcc gtctcaatag gagtgaaaga tgggatgcct 420 attgctacaa cccacacgca aaggagtgtg gtggcgtctt tacagatcca aagcaaattt 480 ttaaatctcc aggcttccca aatgagtacg aagataacca aatctgctac tggcacatta 540 gactcaagta tggtcagcgt attcacctga gttttttaga ttttgacctt gaagatgacc 600 caggttgctt ggctgattat gttgaaatat atgacagtta cgatgatgtc catggctttg 660 tgggaagata ctgtggagat gagcttccag atgacatcat cagtacagga aatgtcatga 720 ccttgaagtt tctaagtgat gcttcagtga cagctggagg tttccaaatc aaatatgttg 780 caatggatcc tgtatccaaa tccagtcaag gaaaaaatac aagtactact tctactggaa 840 ataaaaactt tttagctgga agatttagcc acttataaaa aaaaaaaaag gatgatcaaa 900 acacacagtg tttatgttgg aatcttttgg aactcctttg atctcactgt tattattaac 960 atttatttat tatttttcta aatgtgaaag caatacataa tttagggaaa attggaaaat 1020 ataggaaact ttaaacgaga aaatgaaacc tctcataatc ccactgcata gaaataacaa 1080 gcgttaacat tttcatattt ttttctttca gtcatttttc tatttgtggt atatgtatat 1140 atgtacctat atgtatttgc atttgaaatt ttggaatcct gctctatgta cagttttgta 1200 ttatactttt taaatcttga actttataaa cattttctga aatcattgat tattctacaa 1260 aaacatgatt ttaaacagct gtaaaatatt ctatgatatg aatgttttat gcattattta 1320 agcctgtctc tattgttgga atttcaggtc attttcataa atattgttgc aataaatatc 1380 cttgaacaca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1430 <210> 16 <211> 1650 <212> RNA <213> BC069716.1 Homo sapiens matrix metallopeptidase 3 (stromelysin 1, progelatinase) <400> 16 acaaggaggc aggcaagaca gcaaggcata gagacaacat agagctaagt aaagccagtg 60 gaaatgaaga gtcttccaat cctactgttg ctgtgcgtgg cagtttgctc agcctatcca 120 ttggatggag ctgcaagggg tgaggacacc agcatgaacc ttgttcagaa atatctagaa 180 aactactacg acctcgaaaa agatgtgaaa cagtttgtta ggagaaagga cagtggtcct 240 gttgttaaaa aaatccgaga aatgcagaag ttccttggat tggaggtgac ggggaagctg 300 gactccgaca ctctggaggt gatgcgcaag cccaggtgtg gagttcctga cgttggtcac 360 ttcagaacct ttcctggcat cccgaagtgg aggaaaaccc accttacata caggattgtg 420 aattatacac cagatttgcc aaaagatgct gttgattctg ctgttgagaa agctctgaaa 480 gtctgggaag aggtgactcc actcacattc tccaggctgt atgaaggaga ggctgatata 540 atgatctctt ttgcagttag agaacatgga gacttttacc cttttgatgg acctggaaat 600 gttttggccc atgcctatgc ccctgggcca gggattaatg gagatgccca ctttgatgat 660 gatgaacaat ggacaaagga tacaacaggg accaatttat ttctcgttgc tgctcatgaa 720 attggccact ccctgggtct ctttcactca gccaacactg aagctttgat gtacccactc 780 tatcactcac tcacagacct gactcggttc cgcctgtctc aagatgatat aaatggcatt 840 cagtccctct atggacctcc ccctgactcc cctgagaccc ccctggtacc cacggaacct 900 gtccctccag aacctgggac gccagccaac tgtgatcctg ctttgtcctt tgatgctgtc 960 agcactctga ggggagaaat cctgatcttt aaagacaggc acttttggcg caaatccctc 1020 aggaagcttg aacctgaatt gcatttgatc tcttcatttt ggccatctct tccttcaggc 1080 gtggatgccg catatgaagt tactagcaag gacctcgttt tcatttttaa aggaaatcaa 1140 ttctgggcca tcagaggaaa tgaggtacga gctggatacc caagaggcat ccacacccta 1200 ggtttccctc caaccgtgag gaaaatcgat gcagccattt ctgataagga aaagaacaaa 1260 acatatttct ttgtagagga caaatactgg agatttgatg agaagagaaa ttccatggag 1320 ccaggctttc ccaagcaaat agctgaagac tttccaggga ttgactcaaa gattgatgct 1380 gtttttgaag aatttgggtt cttttatttc tttactggat cttcacagtt ggagtttgac 1440 ccaaatgcaa agaaagtgac acacactttg aagagtaaca gctggcttaa ttgttgaaag 1500 agatatgtag aaggcacaat atgggcactt taaatgaagc taataattct tcacctaagt 1560 ctctgtgaat tgaaatgttc gttttctcct gcctgtgctg tgactcgagt cacactcaag 1620 ggaacttgag cgtgaatctg tatcttgccg 1650 <210> 17 <211> 1971 <212> RNA <213> BC004977.1 Homo sapiens interferon-induced protein with tetratricopeptide repeats 3 <400> 17 caaaatcaac cgggacccca gcttttcaga actgcaggga aacagccatc atgagtgagg 60 tcaccaagaa ttccctggag aaaatccttc cacagctgaa atgccatttc acctggaact 120 tattcaagga agacagtgtc tcaagggatc tagaagatag agtgtgtaac cagattgaat 180 ctttaaacac tgagttcaaa gctacaatgt acaacttgtt ggcctacata aaacacctag 240 atggtaacaa cgaggcagcc ctggaatgct tacggcaagc tgaagagtta atccagcaag 300 aacatgctga ccaagcagaa atcagaagtc tagtcacttg gggaaactac gcctgggtct 360 actatcactt gggcagactc tcagatgctc agatttatgt agataaggtg aaacaaacct 420 gcaagaaatt ttcaaatcca tacagtattg agtattctga acttgactgt gaggaagggt 480 ggacacaact gaagtgtgga agaaatgaaa gggcgaaggt gtgttttgag aaggctctgg 540 aagaaaagcc caacaaccca gaattctcct ctggactggc aattgcgatg taccatctgg 600 ataatcaccc agagaaacag ttctctactg atgttttgaa gcaggccatt gagctgagtc 660 ctgataacca atacgtcaag gttctcttgg gcctgaaact gcagaagatg aataaagaag 720 ctgaaggaga gcagtttgtt gaagaagcct tggaaaagtc tccttgccaa acagatgtcc 780 tccgcagtgc agccaaattt tacagaagaa aaggtgacct agacaaagct attgaactgt 840 ttcaacgggt gttggaatcc acaccaaaca atggctacct ctatcaccag attgggtgct 900 gctacaaggc aaaagtaaga caaatgcaga atacaggaga atctgaagct agtggaaata 960 aagagatgat tgaagcacta aagcaatatg ctatggacta ttcgaataaa gctcttgaga 1020 agggactgaa tcctctgaat gcatactccg atctcgctga gttcctggag acggaatgtt 1080 atcagacacc attcaataag gaagtccctg atgctgaaaa gcaacaatcc catcagcgct 1140 actgcaacct tcagaaatat aatgggaagt ctgaagacac tgctgtgcaa catggtttag 1200 agggtttgtc cataagcaaa aaatcaactg acaaggaaga gatcaaagac caaccacaga 1260 atgtatctga aaatctgctt ccacaaaatg caccaaatta ttggtatctt caaggattaa 1320 ttcataagca gaatggagat ctgctgcaag cagccaaatg ttatgagaag gaactgggcc 1380 gcctgctaag ggatgcccct tcaggcatag gcagtatttt cctgtcagca tctgagcttg 1440 aggatggtag tgaggaaatg ggccagggcg cagtcagctc cagtcccaga gagctcctct 1500 ctaactcaga gcaactgaac tgagacagag gaggaaaaca gagcatcaga agcctgcagt 1560 ggtggttgtg acgggtagga cgataggaag acagggggcc ccaacctggg attgctgagc 1620 agggaagctt tgcatgttgc tctaaggtac atttttaaag agttgttttt tggccgggcg 1680 cagtggctca tgcctgtaat cccagcactt tgggaggccg aggtgggcgg atcacgaggt 1740 ctggagtttg agaccatcct ggctaacaca gtgaaatccc gtctctacta aaaatacaaa 1800 aaattagcca ggcgtggtgg ctggcacctg tagtcccagc tacttgggag gctgaggcag 1860 gagaatggcg tgaacctgga aggaagaggt tgcagtgagc caagattgcg cccctgcact 1920 ccagcctggg caacagagca agactccatc tcaaaaaaaa aaaaaaaaaa a 1971 <210> 18 <211> 1677 <212> RNA <213> NM_002993.3 Homo sapiens C-X-C motif chemokine ligand 6 (CXCL6), mRNA <400> 18 accccttctt tccacactgc cccctgagtt cagggaattt ccccagcatc ccaaagcttg 60 agtttcctgc cagtcgggag ggatgaatgc agataaaggg agtgcagaag gcacgaggaa 120 accaaagtgc tctgtatcct ccagtctccg cgcctccacc cagctcagga acccgcgaac 180 cctctcttga ccactatgag cctcccgtcc agccgcgcgg cccgtgtccc gggtccttcg 240 ggctccttgt gcgcgctgct cgcgctgctg ctcctgctga cgccgccggg gcccctcgcc 300 agcgctggtc ctgtctctgc tgtgctgaca gagctgcgtt gcacttgttt acgcgttacg 360 ctgagagtaa accccaaaac gattggtaaa ctgcaggtgt tccccgcagg cccgcagtgc 420 tccaaggtgg aagtggtagc ctccctgaag aacgggaagc aagtttgtct ggacccggaa 480 gccccttttc taaagaaagt catccagaaa attttggaca gtggaaacaa gaaaaactga 540 gtaacaaaaa agaccatgca tcataaaatt gcccagtctt cagcggagca gttttctgga 600 gatccctgga cccagtaaga ataagaagga agggttggtt tttttccatt ttctacatgg 660 attccctact ttgaagagtg tgggggaaag cctacgcttc tccctgaagt ttacagctca 720 gctaatgaag tactaatata gtatttccac tatttactgt tattttacct gataagttat 780 tgaacccttt ggcaattgac catattgtga gcaaagaatc actggttatt agtctttcaa 840 tgaatattga attgaagata actattgtat ttctatcata cattccttaa agtcttaccg 900 aaaaggctgt ggatttcgta tggaaataat gttttattag tgtgctgttg agggaggtat 960 cctgttgttc ttactcactc ttctcataaa ataggaaata ttttagttct gtttcttggg 1020 gaatatgtta ctctttaccc taggatgcta tttaagttgt actgtattag aacactgggt 1080 gtgtcatacc gttatctgtg cagaatatat ttccttattc agaatttcta aaaatttaag 1140 ttctgtaagg gctaatatat tctcttccta tggttttaga cgtttgatgt cttcttagta 1200 tggcataatg tcatgattta ctcattaaac tttgattttg tatgctattt tttcactata 1260 ggatgactat aattctggtc actaaatata cactttagat agatgaagaa gcccaaaaac 1320 agataaattc ctgattgcta atttacatag aaatgtattc tcttggtttt ttaaataaaa 1380 gcaaaattaa caatgatctg tgctctgaaa gttttgaaaa tatatttgaa caatttgaat 1440 ataaattcat catttagtcc tcaaaatata tatagcattg ctaagatttt cagatatcta 1500 ttgtggatct tttaaaggtt ttgaccattt tgttatgagg aattatacat gtatcacatt 1560 cactatatta aaattgcact tttatttttt cctgtgtgtc atgttggttt ttggtacttg 1620 tattgtcatt tggagaaaca ataaaagatt tctaaaccaa aaaaaaaaaa aaaaaaa 1677 <210> 19 <211> 6932 <212> RNA <213> NM_001165.4 Homo sapiens baculoviral IAP repeat containing 3 (BIRC3) <400> 19 gcatttaaaa gacagcgtga gactcgcgcc ctccggcacg gaaaaggcca ggcgacaggt 60 gtcgcttgaa aagactgggc ttgtccttgc tggtgcatgc gtcgtcggcc tctgggcagc 120 aggtttacaa aggaggaaaa cgacttcttc tagatttttt tttcagtttc ttctataaat 180 caaaacatct caaaatggag acctaaaatc cttaaaggga cttagtctaa tctcgggagg 240 tagttttgtg catgggtaaa caaattaagt attaactggt gttttactat ccaaagaatg 300 ctaattttat aaacatgatc gagttatata aggtatacca taatgagttt gattttgaat 360 ttgatttgtg gaaataaagg aaaagtgatt ctagctgggg catattgtta aagcattttt 420 ttcagagttg gccaggcagt ctcctactgg cacattctcc cattatgtag aatagaaata 480 gtacctgtgt ttgggaaaga ttttaaaatg agtgacagtt atttggaaca aagagctaat 540 aatcaatcca ctgcaaatta aagaaacatg cagatgaaag ttttgacaca ttaaaatact 600 tctacagtga caaagaaaaa tcaagaacaa agctttttga tatgtgcaac aaatttagag 660 gaagtaaaaa gataaatgtg atgattggtc aagaaattat ccagttattt acaaggccac 720 tgatatttta aacgtccaaa agtttgttta aatgggctgt taccgctgag aatgatgagg 780 atgagaatga tggttgaagg ttacatttta ggaaatgaag aaacttagaa aattaatata 840 aagacagtga tgaatacaaa gaagattttt ataacaatgt gtaaaatttt tggccaggga 900 aaggaatatt gaagttagat acaattactt acctttgagg gaaataattg ttggtaatga 960 gatgtgatgt ttctcctgcc acctggaaac aaagcattga agtctgcagt tgaaaagccc 1020 aacgtctgtg agatccagga aaccatgctt gcaaaccact ggtaaaaaaa aaaaaaaaaa 1080 aaaaaaaaag ccacagtgac ttgcttattg gtcattgcta gtattatcga ctcagaacct 1140 ctttactaat ggctagtaaa tcataattga gaaattctga attttgacaa ggtctctgct 1200 gttgaaatgg taaatttatt attttttttg tcatgataaa ttctggttca aggtatgcta 1260 tccatgaaat aatttctgac caaaactaaa ttgatgcaat ttgattatcc atcttagcct 1320 acagatggca tctggtaact tttgactgtt ttaaaaaata aatccactat cagagtagat 1380 ttgatgttgg cttcagaaac atttagaaaa acaaaagttc aaaaatgttt tcaggaggtg 1440 ataagttgaa taactctaca atgttagttc tttgaggggg acaaaaaatt taaaatcttt 1500 gaaaggtctt attttacagc catatctaaa ttatcttaag aaaattttta acaaagggaa 1560 tgaaatatat atcatgattc tgtttttcca aaagtaacct gaatatagca atgaagttca 1620 gttttgttat tggtagtttg ggcagagtct ctttttgcag cacctgttgt ctaccataat 1680 tacagaggac atttccatgt tctagccaag tatactatta gaataaaaaa acttaacatt 1740 gagttgcttc aacagcatga aactgagtcc aaaagaccaa atgaacaaac acattaatct 1800 ctgattattt attttaaata gaatatttaa ttgtgtaaga tctaatagta tcattatact 1860 taagcaatca tattcctgat gatctatggg aaataactat tatttaatta atattgaaac 1920 caggttttaa gatgtgttag ccagtcctgt tactagtaaa tctctttatt tggagagaaa 1980 ttttagattg ttttgttctc cttattagaa ggattgtaga aagaaaaaaa tgactaattg 2040 gagaaaaatt ggggatatat catatttcac tgaattcaaa atgtcttcag ttgtaaatct 2100 taccattatt ttacgtacct ctaagaaata aaagtgcttc taattaaaat atgatgtcat 2160 taattatgaa atacttcttg ataacagaag ttttaaaata gccatcttag aatcagtgaa 2220 atatggtaat gtattatttt cctcctttga gttaggtctt gtgctttttt ttcctggcca 2280 ctaaatttca caatttccaa aaagcaaaat aaacatattc tgaatatttt tgctgtgaaa 2340 cacttgacag cagagctttc caccatgaaa agaagcttca tgagtcacac attacatctt 2400 tgggttgatt gaatgccact gaaacattct agtagcctgg agaagttgac ctacctgtgg 2460 agatgcctgc cattaaatgg catcctgatg gcttaataca catcactctt ctgtgaaggg 2520 ttttaatttt caacacagct tactctgtag catcatgttt acattgtatg tataaagatt 2580 atacaaaggt gcaattgtgt atttcttcct taaaatgtat cagtatagga tttagaatct 2640 ccatgttgaa actctaaatg catagaaata aaaataataa aaaatttttc attttggctt 2700 ttcagcctag tattaaaact gataaaagca aagccatgca caaaactacc tccctagaga 2760 aaggctagtc ccttttcttc cccattcatt tcattatgaa catagtagaa aacagcatat 2820 tcttatcaaa tttgatgaaa agcgccaaca cgtttgaact gaaatacgac ttgtcatgtg 2880 aactgtaccg aatgtctacg tattccactt ttcctgctgg ggttcctgtc tcagaaagga 2940 gtcttgctcg tgctggtttc tattacactg gtgtgaatga caaggtcaaa tgcttctgtt 3000 gtggcctgat gctggataac tggaaaagag gagacagtcc tactgaaaag cataaaaagt 3060 tgtatcctag ctgcagattc gttcagagtc taaattccgt taacaacttg gaagctacct 3120 ctcagcctac ttttccttct tcagtaacaa attccacaca ctcattactt ccgggtacag 3180 aaaacagtgg atatttccgt ggctcttatt caaactctcc atcaaatcct gtaaactcca 3240 gagcaaatca agatttttct gccttgatga gaagttccta ccactgtgca atgaataacg 3300 aaaatgccag attacttact tttcagacat ggccattgac ttttctgtcg ccaacagatc 3360 tggcaaaagc aggcttttac tacataggac ctggagacag agtggcttgc tttgcctgtg 3420 gtggaaaatt gagcaattgg gaaccgaagg ataatgctat gtcagaacac ctgagacatt 3480 ttcccaaatg cccatttata gaaaatcagc ttcaagacac ttcaagatac acagtttcta 3540 atctgagcat gcagacacat gcagcccgct ttaaaacatt ctttaactgg ccctctagtg 3600 ttctagttaa tcctgagcag cttgcaagtg cgggttttta ttatgtgggt aacagtgatg 3660 atgtcaaatg cttttgctgt gatggtggac tcaggtgttg ggaatctgga gatgatccat 3720 gggttcaaca tgccaagtgg tttccaaggt gtgagtactt gataagaatt aaaggacagg 3780 agttcatccg tcaagttcaa gccagttacc ctcatctact tgaacagctg ctatccacat 3840 cagacagccc aggagatgaa aatgcagagt catcaattat ccattttgaa cctggagaag 3900 accattcaga agatgcaatc atgatgaata ctcctgtgat taatgctgcc gtggaaatgg 3960 gctttagtag aagcctggta aaacagacag ttcagagaaa aatcctagca actggagaga 4020 attatagact agtcaatgat cttgtgttag acttactcaa tgcagaagat gaaataaggg 4080 aagaggagag agaaagagca actgaggaaa aagaatcaaa tgatttatta ttaatccgga 4140 agaatagaat ggcacttttt caacatttga cttgtgtaat tccaatcctg gatagtctac 4200 taactgccgg aattattaat gaacaagaac atgatgttat taaacagaag acacagacgt 4260 ctttacaagc aagagaactg attgatacga ttttagtaaa aggaaatatt gcagccactg 4320 tattcagaaa ctctctgcaa gaagctgaag ctgtgttata tgagcattta tttgtgcaac 4380 aggacataaa atatattccc acagaagatg tttcagatct accagtggaa gaacaattgc 4440 ggagactaca agaagaaaga acatgtaaag tgtgtatgga caaagaagtg tccatagtgt 4500 ttattccttg tggtcatcta gtagtatgca aagattgtgc tccttcttta agaaagtgtc 4560 ctatttgtag gagtacaatc aagggtacag ttcgtacatt tctttcatga agaagaacca 4620 aaacatcgtc taaactttag aattaattta ttaaatgtat tataacttta acttttatcc 4680 taatttggtt tccttaaaat ttttatttat ttacaactca aaaaacattg ttttgtgtaa 4740 catatttata tatgtatcta aaccatatga acatatattt tttagaaact aagagaatga 4800 taggcttttg ttcttatgaa cgaaaaagag gtagcactac aaacacaata ttcaatcaaa 4860 atttcagcat tattgaaatt gtaagtgaag taaaacttaa gatatttgag ttaaccttta 4920 agaattttaa atattttggc attgtactaa taccgggaac atgaagccag gtgtggtggt 4980 atgtgcctgt agtcccaggc tgaggcaaga gaattacttg agcccaggag tttgaatcca 5040 tcctgggcag catactgaga ccctgccttt aaaaacaaac agaacaaaaa caaaacacca 5100 gggacacatt tctctgtctt ttttgatcag tgtcctatac atcgaaggtg tgcatatatg 5160 ttgaatgaca ttttagggac atggtgtttt tataaagaat tctgtgagaa aaaatttaat 5220 aaagcaacaa aaattactct tattcttcat tgctttattt caatgacatt ggatagttta 5280 gtcactccca gactctttcc ataccttctt aaagcctctc aaatattgaa ctacagttta 5340 tactccttcc cataagatgc ttcttcattg acacttgtag aacacggggt caacacatca 5400 taaaatctat tatggaatgc ctgagacaag aatcaaacag tccctttagt aagtttgttt 5460 attcacttct ctattgattc attcaagaag tctcatgcca gccccaccta ttggaagaag 5520 gtctgagttt tattcttatc tctttggtat taattctgaa acttagaaag tacactggtt 5580 agcaatgctt gggaccaaca ggttgttctg gtaaataaat ctgtttcata ttgtcagtgc 5640 aacaaaatgt ccccctctgc attatgttat tggtactcaa cacgtccgag tcataactct 5700 gtcctttgct tcttatagag gtattaggtc ttcaagagca gaagtaagac tgtaataggg 5760 aatactcagg ggaaggcagg caaaggctag tcatctaaac cagttctaga tgtctgtata 5820 ggggcagatg gctctgtaag ggcagaaggg aaagacccct tcataagggt cacagctgac 5880 aatcctataa caaaagacag gttaacaaga gaaaaactta acaaatttat ttaatcacag 5940 atttacatca ccggggagcc ttcgtaatga agatccaaaa ttacagggga aactgtgcat 6000 ttttatgctt aggtttgata atgaatggac agccctgaag aatagtgatt ggaaaaaaag 6060 gatatgatct aatgggaata gacacaggtt ggggacccag caaggcctgt ctgttcagat 6120 tattcttggt ctctgtgcag cattccttcc tcctggatat agggcagggc ctgtatggga 6180 tggggatatt ataacctgct atcaagcaag gtaggtcaga gaatttattt atggccagct 6240 cttacatagt taggtgagga aagattagag tactatcttt aagatgtaag tctggcattg 6300 tggaaagatg gttccagttt ctatgaccta ccttggggaa gaggaattca agtttctgtg 6360 gcttgccttc agggagaatg aggctgagac aggagggcag gataacatca gagaaaaact 6420 ttgcttctga ggccttcact ttgggttttc tgagccccaa catctgctag tgttgtaaag 6480 agaacaatta gggaccaagt gaggggagga aagaatccat ctctgcattc tgatgctggg 6540 agacttattt ccttgaaatg caattgattt tgcctctgct aagaggctct gctggctacc 6600 catgtactag ccagtgtcct gcatgggtgc taggctgaat tatttgtaat tgtgcttagg 6660 tgatttgtaa ctcaggtata gggtatttaa atagtaggca ccctttttgc accatgtgtt 6720 ttttttttta tctagttctt gtatactaca gataatattt gaactttgtc atctcactgt 6780 aaaacttttg ttcatttctc attatggtaa taaatagcta ttataaccaa cccatttatt 6840 caaatatgtt atttccctaa gtgttatttt gacattttgt tttggaaaaa ataaatcacc 6900 atagataata aaaaaaaaaa aaaaaaaaaa aa 6932 <210> 20 <211> 528 <212> RNA <213> CR541937.1 Homo sapiens BCL2-related protein A1 (BCL2A1) <400> 20 atgacagact gtgaatttgg atatatttac aggctggctc aggactatct gcagtgcgtc 60 ctacagatac cacaacctgg atcaggtcca agcaaaacgt ccagagtgct acaaaatgtt 120 gcgttctcag tccaaaaaga agtggaaaag aatctgaagt catgcttgga caatgttaat 180 gttgtgtccg tagacactgc cagaacacta ttcaaccaag tgatggaaaa ggagtttgaa 240 gacggcatca ttaactgggg aagaattgta accatatttg catttgaagg tattctcatc 300 aagaaacttc tacgacagca aattgccccg gatgtggata cctataagga gatttcatat 360 tttgttgcgg agttcataat gaataacaca ggagaatgga taaggcaaaa cggaggctgg 420 gaaaatggct ttgtaaagaa gtttgaacct aaatctggct ggatgacttt tctagaagtt 480 acaggaaaga tctgtgaaat gctatctctc ctgaagcaat actgttga 528 <210> 21 <211> 753 <212> RNA <213> CR536551.1 Homo sapiens GTP cyclohydrolase 1 (GCH1) <400> 21 atggagaagg gccctgtgcg ggcaccggcg gagaagccgc ggggcgccag gtgcagcaat 60 gggttccccg agcgggatcc gccgcggccc gggcccagca ggccggcgga gaagcccccg 120 cggcccgagg ccaagagcgc gcagcccgcg gacggctgga agggcgagcg gccccgcagc 180 gaggaggata acgagctgaa cctccctaac ctggcagccg cctactcgtc catcctgagc 240 tcgctgggcg agaaccccca gcggcaaggg ctgctcaaga cgccctggag ggcggcctcg 300 gccatgcagt tcttcaccaa gggctaccag gagaccatct cagatgtcct aaacgatgct 360 atatttgatg aagatcatga tgagatggtg attgtgaagg acatagacat gttttccatg 420 tgtgagcatc acttggttcc atttgttgga aaggtccata ttggttatct tcctaacaag 480 caagtccttg gcctcagcaa acttgcgagg attgtagaaa tctatagtag aagactacaa 540 gttcaggagc gccttacaaa acaaattgct gtagcaatca cggaagcctt gcggcctgct 600 ggagtcgggg tagtggttga agcaacacac atgtgtatgg taatgcgagg tgtacagaaa 660 atgaacagca aaactgtgac cagcacaatg ttgggtgtgt tccgggagga tccaaagact 720 cgggaagagt tcctgactct cattaggagc tga 753 <210> 22 <211> 3191 <212> RNA <213> NM_001200.3 Homo sapiens bone morphogenetic protein 2 (BMP2), mRNA <400> 22 ccacaaaggg cacttggccc cagggctagg agagcgaggg gagagcacag ccacccgcct 60 cggcggcccg ggactcggct cgactcgccg gagaatgcgc ccgaggacga cggggcgcca 120 gagccgcggt gctttcaact ggcgagcgcg aatgggggtg cactggagta aggcagagtg 180 atgcgggggg gcaactcgcc tggcaccgag atcgccgccg tgcccttccc tggacccggc 240 gtcgcccagg atggctgccc cgagccatgg gccgcggcgg agctagcgcg gagcgcccga 300 ccctcgaccc ccgagtcccg gagccggccc cgcgcggggc cacgcgtccc tcgggcgctg 360 gttcctaagg aggacgacag caccagcttc tcctttctcc cttcccttcc ctgccccgca 420 ctcctccccc tgctcgctgt tgttgtgtgt cagcacttgg ctggggactt cttgaacttg 480 cagggagaat aacttgcgca ccccactttg cgccggtgcc tttgccccag cggagcctgc 540 ttcgccatct ccgagcccca ccgcccctcc actcctcggc cttgcccgac actgagacgc 600 tgttcccagc gtgaaaagag agactgcgcg gccggcaccc gggagaagga ggaggcaaag 660 aaaaggaacg gacattcggt ccttgcgcca ggtcctttga ccagagtttt tccatgtgga 720 cgctctttca atggacgtgt ccccgcgtgc ttcttagacg gactgcggtc tcctaaaggt 780 cgaccatggt ggccgggacc cgctgtcttc tagcgttgct gcttccccag gtcctcctgg 840 gcggcgcggc tggcctcgtt ccggagctgg gccgcaggaa gttcgcggcg gcgtcgtcgg 900 gccgcccctc atcccagccc tctgacgagg tcctgagcga gttcgagttg cggctgctca 960 gcatgttcgg cctgaaacag agacccaccc ccagcaggga cgccgtggtg cccccctaca 1020 tgctagacct gtatcgcagg cactcaggtc agccgggctc acccgcccca gaccaccggt 1080 tggagagggc agccagccga gccaacactg tgcgcagctt ccaccatgaa gaatctttgg 1140 aagaactacc agaaacgagt gggaaaacaa cccggagatt cttctttaat ttaagttcta 1200 tccccacgga ggagtttatc acctcagcag agcttcaggt tttccgagaa cagatgcaag 1260 atgctttagg aaacaatagc agtttccatc accgaattaa tatttatgaa atcataaaac 1320 ctgcaacagc caactcgaaa ttccccgtga ccagactttt ggacaccagg ttggtgaatc 1380 agaatgcaag caggtgggaa agttttgatg tcacccccgc tgtgatgcgg tggactgcac 1440 agggacacgc caaccatgga ttcgtggtgg aagtggccca cttggaggag aaacaaggtg 1500 tctccaagag acatgttagg ataagcaggt ctttgcacca agatgaacac agctggtcac 1560 agataaggcc attgctagta acttttggcc atgatggaaa agggcatcct ctccacaaaa 1620 gagaaaaacg tcaagccaaa cacaaacagc ggaaacgcct taagtccagc tgtaagagac 1680 accctttgta cgtggacttc agtgacgtgg ggtggaatga ctggattgtg gctcccccgg 1740 ggtatcacgc cttttactgc cacggagaat gcccttttcc tctggctgat catctgaact 1800 ccactaatca tgccattgtt cagacgttgg tcaactctgt taactctaag attcctaagg 1860 catgctgtgt cccgacagaa ctcagtgcta tctcgatgct gtaccttgac gagaatgaaa 1920 aggttgtatt aaagaactat caggacatgg ttgtggaggg ttgtgggtgt cgctagtaca 1980 gcaaaattaa atacataaat atatatatat atatatattt tagaaaaaag aaaaaaacaa 2040 acaaacaaaa aaaccccacc ccagttgaca ctttaatatt tcccaatgaa gactttattt 2100 atggaatgga atggaaaaaa aaacagctat tttgaaaata tatttatatc tacgaaaaga 2160 agttgggaaa acaaatattt taatcagaga attattcctt aaagatttaa aatgtattta 2220 gttgtacatt ttatatgggt tcaaccccag cacatgaagt ataatggtca gatttatttt 2280 gtatttattt actattataa ccacttttta ggaaaaaaat agctaatttg tatttatatg 2340 taatcaaaag aagtatcggg tttgtacata attttccaaa aattgtagtt gttttcagtt 2400 gtgtgtattt aagatgaaaa gtctacatgg aaggttactc tggcaaagtg cttagcacgt 2460 ttgctttttt gcagtgctac tgttgagttc acaagttcaa gtccagaaaa aaaaagtgga 2520 taatccactc tgctgacttt caagattatt atattattca attctcagga atgttgcaga 2580 gtgattgtcc aatccatgag aatttacatc cttattaggt ggaatatttg gataagaacc 2640 agacattgct gatctattat agaaactctc ctcctgcccc ttaatttaca gaaagaataa 2700 agcaggatcc atagaaataa ttaggaaaac gatgaacctg caggaaagtg aatgatggtt 2760 tgttgttctt ctttcctaaa ttagtgatcc cttcaaaggg gctgatctgg ccaaagtatt 2820 caataaaacg taagatttct tcattattga tattgtggtc atatatattt aaaattgata 2880 tctcgtggcc ctcatcaagg gttggaaatt tatttgtgtt ttacctttac ctcatctgag 2940 agctctttat tctccaaaga acccagtttt ctaacttttt gcccaacacg cagcaaaatt 3000 atgcacatcg tgttttctgc ccaccctctg ttctctgacc tatcagcttg cttttctttc 3060 caaggttgtg tgtttgaaca catttctcca aatgttaaac ctatttcaga taataaatat 3120 caaatctctg gcatttcatt ctataaagtc caacctgtaa gagaaaaaaa aaaaaaaaaa 3180 aaaaaaaaaa a 3191 <210> 23 <211> 1378 <212> RNA <213> NM_003956.3 Homo sapiens cholesterol 25-hydroxylase (CH25H), mRNA <400> 23 agctgccttg cacagcctcg caatgagctg ccacaactgc tccgaccccc aggtcctttg 60 cagctccggg cagctgttcc tgcagcccct ctgggaccac ctgaggagct gggaggccct 120 cctacagtcg cccttcttcc cggtcatctt ctccatcacc acatacgtgg gcttttgcct 180 gcccttcgtg gtcctggata tcctgtgctc ctgggtgccc gccctgcggc gctacaagat 240 ccaccctgac ttctcgccat ccgcgcagca gctgctacct tgcctggggc agaccctcta 300 ccagcatgtg atgtttgtgt tccccgtgac gctgctgcat tgggcccgca gcccggccct 360 cctgccccac gaagctcccg agctgctcct gctgctgcac cacatcctgt tctgcctgct 420 actcttcgac atggagttct tcgtgtggca cctgctgcac cacaaggtgc cctggctgta 480 ccgcaccttc cacaaggtgc accaccagaa ctcgtcctcg ttcgcgctgg caacgcagta 540 tatgagcgtc tgggaactgt tttctttggg cttcttcgac atgatgaacg tcacactgct 600 cgggtgccac ccgctcacca ccctgacctt ccacgtggtc aacatctggc tttccgtgga 660 ggaccactcc ggctacaact tcccttggtc cactcacaga ctggtgccct tcgggtggta 720 cgggggtgtg gtgcaccacg acctgcatca ctctcacttt aactgcaact tcgctccgta 780 ctttacacac tgggacaaaa tactgggaac gctgcggact gcatctgtcc cagcgcggtg 840 atgtggctgc ggtgggtgcc cctaagactc gggactgctg tgcctttcac acttgaatga 900 agagaaacac ctgagctata tattttttta aagcaactaa cttattgctt tatgtttatc 960 tatgaaaacc atagataaaa tctgatgcat ttttgtaatc tgacaaagta atttacatac 1020 tgtttgtgta tcaatacaat tttgtgttct tggtattctt agtctagctc acctcaatag 1080 ccttgaatcc tgcatatgaa ttagacattc atcactggca tatttagaat atctctaaaa 1140 ggacttgttt gtagaataag gaattttcta tgtttcaaag tgttctaaaa cctggctaaa 1200 agaatgtatt tttgtggatg gtgttgactt ctgactctaa aagcaatcaa acatgtttct 1260 gctggacagt gaccaagaat tatagtacct tcttatattt ttttatagaa ctgtatattt 1320 attttgaaag aaatgttatt cgtgctttaa aaaggaaaaa aaaccatgaa tcaaataa 1378 <210> 24 <211> 2621 <212> RNA <213> BC040592.1 Homo sapiens thymic stromal lymphopoietin (TSLP), mRNA <400> 24 agagtggact tttttttcaa agaatgctgt ggtgactcga gtacaacaca tgaagaattc 60 cagaaaagag ccatttttga agtcagcggt gaatcagagg ttttctgacc ctctcgagtg 120 ccttctatga agaagagttc aactctggct ccagtttgtc ccctactctt ttcccgaatc 180 cctcgacatt ccttgctctt ttccccaggc accgcatggc ctgtgacatt tgctgggact 240 cacacacggc gtccaacctc ctttctccga gcgatgactc ctaggaactt cccaaggacc 300 agagcgatgc aggctccgac acgcgagggc ggggggcggg ggtgaggggt gcgatggacg 360 ggggagcgga agggaaagag agagagaggg gacctgggtg tagagagggc ccagggccgc 420 atgagccaag ccagggagga gcagggggtt catctcagca acctgatcgg tgtcggcctt 480 tccctccctt caaccctcca ttggtgttgc tggaactggg aagactgcta gacagacatc 540 ctctagggca ctctccctga ctcactttgc tgtgctttta agcgctcttt tctggatcaa 600 caagagtttg ctagtaaaaa tctgagcccg ccatctcgat gcttctcctg tctctaaaac 660 tggtgcccgg gctgaggccc caggtgacag acgttttcca gtctacgctg cgcggggcta 720 agcctctgcg aggcagagcg cactaaagcg tgcgccgcct ccgggagagc tgagctcagg 780 acagcatcgt ctccgtgcgg tcgccgctgg gcacccagca gcgcggtctg gctccgcttc 840 ttgtgtcgct ggccttaaga gtgggactgt gaaggtggct gggcgctgga atttgtggtt 900 ttaaaagttc ttgacacctg ctagaaagtg ctagaggact cttcagcccc taaggtgccc 960 ctagtcacca agagtaggcg ttttttcctg aaattgatat gggaaatttg aaaagtaggg 1020 tttttgagaa caagccacat cagatctttc cccacttatt tcaacctctt atcgttcctg 1080 cccctaaggt tctggtcacg gttgcacatt taatgctttc acatggaagt gctgtcgaag 1140 actgagactg caccccaccc tccaaagcat cccataagca agcacagttt cttactagcc 1200 aaggagaagg gaaagcacta gttgaaagtg gccacaggaa atgctcaaag atgttcagaa 1260 tgcatgggac atatgcaagg actccaaatc cttacagtgg ctgctggttt cagaaggtgt 1320 ttctcccaaa tagaaaggat tggtcacgga aatgccctgt aggagaaaga cactggtatc 1380 catttcttaa aggacattca cacttatgaa gtgtttaggg caaagcaaaa aggaggaagt 1440 ttctttcagg aaaatcttca tcttacaact tgtagggctg gtgttaactt acgacttcac 1500 taactgtgac tttgagaaga ttaaagcagc ctatctcagt actatttcta aagacctgat 1560 tacatatatg agtgggacca aaagtaccga gttcaacaac accgtctctt gtagcaatcg 1620 gccacattgc cttactgaaa tccagagcct aaccttcaat cccaccgccg gctgcgcgtc 1680 gctcgccaaa gaaatgttcg ccatgaaaac taaggctgcc ttagctatct ggtgcccagg 1740 ctattcggaa actcagataa atgctactca ggcaatgaag aagaggagaa aaaggaaagt 1800 cacaaccaat aaatgtctgg aacaagtgtc acaattacaa ggattgtggc gtcgcttcaa 1860 tcgaccttta ctgaaacaac agtaaaccat ctttattatg gtcatatttc acagcaccaa 1920 aataaatcat ctttattaag tagatgaaac attaactcta actgtgacaa agaagaccac 1980 aaatagttat cttttaatta cagaagagtt tcttaactta cttttgtaag tttttattgt 2040 gtaagtttat aatgcagggg aagtactact cctcaaatgt tgagggaagc ttccataaca 2100 ttgatgactg gcttcatggc agtaattctc ggctgtagtt gcataagcat tgctcaagag 2160 gaaaatccaa aagtgcagca ggagaactct tttccctgaa aaaggaaaaa tattgaactc 2220 aatgatagca cctaaactta catttaaaag acagacattc cttctacatg taatgacact 2280 tcttgtgtta aactaaaaat ttacaagaga agaaagtgaa agcaaatggg gtttcacaaa 2340 tagttgtaaa tatagtgaag caatttgaaa taattttcaa gcaaagtatt gtgaaagtat 2400 tctaagccaa gttttaaata ttatctaaca gacaagagtg gtatatacaa gtagatcctg 2460 agaagtacct ttgttacagc tactataaat atacatataa attatagaat ctactttaat 2520 ttattttgtg aacacttttg aaaatgtaca tgttcctttg taattgacac tatatatttc 2580 ttaataaaat aattctcaaa tttgcaaaaa aaaaaaaaaa a 2621 <210> 25 <211> 3505 <212> RNA <213> NM_001547.4 Homo sapiens IFIT2, mRNA <400> 25 agtttcactt tcccttttgt aacgtcagct gaagggaaac aaacaaaaag gaaccagagg 60 ccacttgtat atataggtct cttcagcatt tattggtggc agaagaggaa gatttctgaa 120 gagtgcagct gcctgaaccg agccctgccg aacagctgag aattgcactg caaccatgag 180 tgagaacaat aagaattcct tggagagcag cctacggcaa ctaaaatgcc atttcacctg 240 gaacttgatg gagggagaaa actccttgga tgattttgaa gacaaagtat tttaccggac 300 tgagtttcag aatcgtgaat tcaaagccac aatgtgcaac ctactggcct atctaaagca 360 cctcaaaggg caaaacgagg cagccctgga atgcttacgt aaagctgaag agttaatcca 420 gcaagagcat gctgaccagg cagaaatcag aagtctggtc acctggggaa actatgcctg 480 ggtctactat cacatgggcc gactctcaga cgttcagatt tatgtagaca aggtgaaaca 540 tgtctgtgag aagttttcca gtccctatag aattgagagt ccagagcttg actgtgagga 600 agggtggaca cggttaaagt gtggaggaaa ccaaaatgaa agagcgaagg tgtgctttga 660 gaaggctctg gaaaagaagc caaagaaccc agaattcacc tctggactgg caatagcaag 720 ctaccgtctg gacaactggc caccatctca gaacgccatt gaccctctga ggcaagccat 780 tcggctgaat cctgacaacc agtaccttaa agtcctcctg gctctgaagc ttcataagat 840 gcgtgaagaa ggtgaagagg aaggtgaagg agagaagtta gttgaagaag ccttggagaa 900 agccccaggt gtaacagatg ttcttcgcag tgcagccaag ttttatcgaa gaaaagatga 960 gccagacaaa gcgattgaac tgcttaaaaa ggctttagaa tacataccaa acaatgccta 1020 cctgcattgc caaattgggt gctgctatag ggcaaaagtc ttccaagtaa tgaatctaag 1080 agagaatgga atgtatggga aaagaaagtt actggaacta ataggacacg ctgtggctca 1140 tctgaagaaa gctgatgagg ccaatgataa tctcttccgt gtctgttcca ttcttgccag 1200 cctccatgct ctagcagatc agtatgaaga cgcagagtat tacttccaaa aggaattcag 1260 taaagagctt actcctgtag cgaaacaact gctccatctg cggtatggca actttcagct 1320 gtaccaaatg aagtgtgaag acaaggccat ccaccacttt atagagggtg taaaaataaa 1380 ccagaaatca agggagaaag aaaagatgaa agacaaactg caaaaaattg ccaaaatgcg 1440 actttctaaa aatggagcag attctgaggc tttgcatgtc ttggcattcc ttcaggagct 1500 gaatgaaaaa atgcaacaag cagatgaaga ctctgagagg ggtttggagt ctggaagcct 1560 catcccttca gcatcaagct ggaatgggga atgaagaata gagatgtggt gcccactagg 1620 ctactgctga aagggagctg aaattcctcc accaagttgg tattcaaaat atgtaatgac 1680 tggtatggca aaagattgga ctaagacact ggccatacca ctggacaggg ttatgttaac 1740 acctgaattg ctgggtcttg agagagccca aggagttctg ggagagggac cagattgggg 1800 ggtaggtcca cgggcttggt gatagaatta tttctcgatt gacttcttga gtgcaatttg 1860 aactgtaaca tttgcttagt cacctttagt ggagtaatct actgggcttg tttctatatt 1920 tatataaagc agccaaatcc ttcatgtaat attgaagtcc atttttgcaa tgttgttcca 1980 tacttggagt cattttgcat cccatagagg ttagtcctgc atagccagta atgtgctaag 2040 ttcatccaaa agctggcgga ccaaagtcta aatagggctc agtatccccc atcgcttatc 2100 tctgcctcct tcctcctcct tcccagtcta tcatcaacct tgagtattct acacaatgtg 2160 aattcaagtg cctgattaat tgaggtggca acatagtttg agacgagggc agagaacagg 2220 aagatacata gctagaagcg acgggtacaa aaagcaatgt gtacaagaag actttcagca 2280 agtatacaga gagttcacct ctactctgcc ctcctcatag tcataatgta gcaagtaaag 2340 aatgagaatg gattctgtac aatacactag aaaccaacat aatgtatttc tttaaaacct 2400 gtgtgaaaaa ataaatgttc caccagtagg gataggggaa aagtaaccaa aagagagaaa 2460 gagaaaggaa tgctggttta tctttgtaga ttgtaatcga atggagaaat ttgcagtatt 2520 ttagccacta ttaggaattt tttttttttg taaaatgaag actgaactct gttcaaatgc 2580 tttcatgaac ctggtttgag acggtaggaa agcaacaaaa cgtgggaacc tggtgactaa 2640 gggcctggtg caaggacttg ggaaatgtca ttgataatag atggtggggt tttcccccct 2700 ttagaaatgt tggatattaa gtgatataaa cacttctttt aactccgaaa atcttctgag 2760 aaatcacaaa attcacggta tgcttggaac gattgagatt ttctaggtag atgctgaata 2820 gcctagacat caaagttggt gtgaaccaaa atagagtcag ctgacccagc atcagccaca 2880 ctctgggttg gaaaatgttt gcctgttgga attaatttaa gcttaagtat atatcaacat 2940 tattttattg tgcaattaaa acaatacaaa ttcatggttt tttaaagtta aaaattctaa 3000 ccactgtaac aacagttttt gtgttatttt ctgtattaaa catcttgttg cacgcatttg 3060 aggtcatcag ggtgcaaaat ttgtattcct gaaaatgtca tatattttca ttaataaata 3120 acctaaatat gataaaacat aaagcagtgt tctggttcat ctggaatttt gctgtacttt 3180 aaatctttca gactcagcta ctgataaatg aaacgttaca caggtgtgaa ccaaatccaa 3240 ataacctcga ctggtctact atcataatca cctgaacaga acaaaacttt ttcctcagct 3300 ttaagagtcc agggcttcgg ataacagctg ccatctgcca cctgctacca ttgacctacg 3360 tgaacacaga cattctgtct ccaccttgat ggtgggtggg ctgctcccct tttctttgtt 3420 aaattttgtg ctttcatcac attttctcta ttctgacctc tgttatgaga aataaaagtc 3480 actgattcca ttttaaaaaa aaaaa 3505 <210> 26 <211> 7385 <212> RNA <213> NM_014586.1 Homo sapiens hormonally up-regulated Neu-associated kinase (HUNK), mRNA <400> 26 ggcgccgccg gaccgcgccc caccccgcgc gcccgagcag ggcgactgtc attagcttcc 60 tggacgggac ccggggcggg atcctggtgt cctgaaaggg gcccgggcga ccctaagagg 120 aagaactttt gggggcgggg tccccggtcc cgcgtcccct gggcagccgc tattgtctac 180 gcgcctcgct gggcggcgcg gggggcgtga tcgcggcggc cccgggctct gggtgcggag 240 acccaggcgg ggctgggccc agggcggcgg cgggagaagc cggggaagcc gaagagcctg 300 gggaggagga gctgcgagcg cgggagacga gcaggagccg cgcgggccgc ggcgagcgcg 360 atgccggcgg cggcggggga cgggctcctg ggggagccgg cggcgcctgg gggcggcggc 420 ggcgcggagg acgcggccag gcccgcggcg gcctgcgagg gaagtttcct gcctgcctgg 480 gtgagcggcg tgccccgcga gcggctccgc gacttccagc accacaagcg cgtgggcaac 540 tacctcatcg gcagcaggaa gctgggcgag ggctcctttg ccaaggtgcg cgaggggctg 600 cacgtgctga ccggggagaa ggtggccata aaagtcattg ataagaagag agccaaaaag 660 gacacctatg tcaccaaaaa cctgcggcga gagggtcaga tccagcagat gatccgccac 720 cccaatatca ctcagctcct tgatatttta gaaacggaaa acagctacta cctggtcatg 780 gagctgtgcc ctgggggcaa cctgatgcac aagatctatg agaagaagcg gctggaggag 840 tccgaagccc gcagatacat ccgacagctc atctctgccg tagagcacct gcaccgggcc 900 ggggtggtcc acagagactt gaagatagag aatttgctac tagatgaaga caataatatc 960 aagctgattg actttggttt gagcaactgc gcagggatcc tgggttactc ggatccgttc 1020 agcacacagt gtggcagccc tgcctacgct gcacctgaac tgctcgccag gaagaaatac 1080 ggccccaaaa tcgatgtctg gtccataggt gtgaacatgt atgccatgtt gaccgggacg 1140 ctgcctttca cggtggagcc tttcagcctg agggctttgt accagaagat ggtagacaaa 1200 gaaatgaacc ccctccccac tcagctctcc acaggtgcca tcagtttcct gcgctctctc 1260 ctggaaccgg atcctgtgaa gaggccaaat attcagcagg cactggcgaa tcgctggctt 1320 aatgagaatt acacgggcaa agtgccctgt aatgtcacct atcccaacag gatttctctg 1380 gaagatctga gcccgagcgt cgtgctgcac atgaccgaga agctgggtta caagaacagc 1440 gacgtgatca acactgtgct ctccaaccgc gcctgccaca tcctggccat ctacttcctc 1500 ttaaacaaga aactggagcg ctatttgtca gggaaatctg acatccagga cagcctctgc 1560 tacaagaccc ggctctacca gatagaaaag tacagggccc ccaaggagtc ctatgaggcc 1620 tctctggaca cctggacacg agatcttgaa ttccatgccg tgcaggataa aaagcccaaa 1680 gaacaagaaa aaagagggga ttttcttcat cgaccattct ccaagaagtt ggacaagaac 1740 ctgccctcgc acaaacagcc ctcaggctcg cttatgacac agattcagaa caccaaagcc 1800 ctcctgaagg accggaaggc ctccaagtcc agcttccccg acaaagattc ctttggctgc 1860 cgcaatattt tccgcaaaac ctcagattcc aattgtgtgg cttcttcttc catggagttc 1920 atccccgtgc caccgcccag gaccccgagg attgtgaaga aaccggagcc ccatcagcca 1980 gggcccggaa gcactggcat cccccacaag gaagaccccc tgatgctgga catggtgcgc 2040 tccttcgagt ctgtggatcg cgacgaccac gtagaagtgc tgtctccctc tcatcactac 2100 aggattctga actccccggt cagcttggct cgcagaaatt ccagcgagag gacgctgtcc 2160 ccgggtctgc catccggaag catgtcgcct ctccatactc ctttgcatcc aactctggtc 2220 tcttttgctc acgaagataa gaacagcccc ccaaaagagg agggcctgtg ttgcccacct 2280 ccggttccca gcaatggccc catgcagcct ctggggagcc ccaattgtgt gaaaagccga 2340 ggccggttcc ctatgatggg catcggacag atgttaagga agcgccatca gagtctgcag 2400 ccatctgcag ataggcccct ggaggccagc ctgcccccac tgcagcccct agcccctgtg 2460 aaccttgcct ttgacatggc cgatggggtc aagacccagt gctaacttgg gccagcgggg 2520 tttggggtat ctctagaaaa cagcaactga acagagctcc acacatctgt cagggtgtga 2580 gcactccaag gcctcgcgtg gagcatcctt agtcccacct gtagctgaat ccacagaccc 2640 aaagcctgca caacccaacc tcgcttaggg acccccagag atgctggaat cgctaggagg 2700 gttggctcca ggggcagcca attcctatca ttcagatctt ccttcctccc aagtactcac 2760 caaccccttc cacttcccac ttcccccagg cttgggggga aaacagggca tgagccttct 2820 ggggcactca gattatggac tgttaccaga tctttcttca cgctgtgcta catgtgtgcc 2880 tctcacagca gttggccaca gttacaggga gagaacaata tcacagtcat tcatccaggc 2940 cacgtttcct ctgcggagtg tagcagccct gcctttcata gcagggatta cctgaaggcc 3000 agcaggagcc gggggcaggc ccaggatcct cagaggaaga tggagaggag cttcggacca 3060 agatcaaacc aaacagtggg gaccccaaca gaagagaaag actgaaggag acactcattt 3120 cccaagcaag attttgatag atttttgttg ttgttgttgt tgaaacatgc taatgattga 3180 attatctttt ccaaagattt tttttaaatg tgatgtcggt aaattgaaat aacataattt 3240 tttaaaactt ggatggagag atgagaagca attccaccaa actcatgttt tcacaggagg 3300 gttcagtgtg gagagcaaaa aagctgactg tggtgatttg ctgagtgctg tggcccacag 3360 gcagggcaag tctcggtggc cctgtgttca tcctgttgtt taaggcatag ccctgatcct 3420 tctggaaggc atagaacacg gttacagctg gttctgtaga aagagggaaa agatgattgt 3480 gacaattcag agcataactc agatggcgag aaggcagcat tatctctgtg cgatgctgat 3540 ttcaagctgc ccacagaact ggtgcggctc agagctcggc gagtttgctg ggagctggga 3600 gcaggcttgc ctggcagaga acctgttcag atacaggcca gtttcttctt cgaggaaagc 3660 caagctcctc aaacagggtt cagtccacgt tgtgttttca cacctttctc caaggatcga 3720 accaaagatg tgtctccagt attgtgtctg tgcccctgtg tgtgttttgt ggacagccgt 3780 gttgtctgac tgtatccagc tggcacttga cagggtgcag tcattggtga gaagaatcag 3840 aaaaagaaga cccatcagca caggttggat aggggttagt gtaggagacc agttacagaa 3900 tggcctggag tcttcaactt ttgaccggtg caggtgtgac cagagaccac ctctgtggcc 3960 acctcagata gtcatctcag tccaaggatc ccaaaacaca aatctagaat tgcaaagcca 4020 gcctttattt ccctggcagg cagccttgcc agaaggcaga gaggcagttc tgaatcattc 4080 tctcattcac cagtggtgac atccttcagt ccctcacatc tctgacagag cgggacagaa 4140 tggatatttg gctgaccttg gtgagacctg gagctgcctg tttcttccct aggggatcac 4200 cacggctcta gggcattcta ggatgaggtc agaccccttg gccattggtg ttattttttg 4260 tatagcttca gactgggttc cagaacttac cattgaaaac agagctttta ggccaggtgt 4320 ggtggctcac acctgtaatc ccagcacttt gggaggccga ggcaggtgga tcgcttgagc 4380 tcaggagttc gagagcagcc tgggcaacat ggtgaaagcc cgtctctacc gaaaaataca 4440 aaaaaaaata gctgggtgtg gtggtacgtg cctgtagtcc cagctacttc ggggactgag 4500 gtgggaggat cacttgaacc taggaggtcg aggctgcagt gagccaagat catgctactg 4560 cactccagct taggtggcaa agtgagaccc tgtctccaaa aaaagaaaat agagctttat 4620 aagcagagag aagaaaataa tcatctaaga ccatctctcc attcgacatg aagtgtacct 4680 tttctaaaga cggtttccag ctgcaacggc tccactttgc aggcttgcag ggtgtatacc 4740 tgcgcattgg gaacttgctg gaacccctga tgcattttcc ttgagagcag gggtacttcc 4800 gccttgccgt tagcttgtgg agaacgtgct tcttattcct ggcaggcttc aagaacagct 4860 gcacatgtgc cgctaactga ccgcgttgcc attggcgacc tggactctga actcaggttt 4920 attctaaacc cagtgagagg tgagggggag tgatgaaagg ggatcagctg tatttgtgtg 4980 tgtgtgtgtg tgtgagcacc tgacaaatct atgaaaccga gtgaaaggag aaatgttaga 5040 ttctttatta ttttattata tttatatgga aagctcgact ctccctttgg taagtccgaa 5100 gcatgttgtc tgttcgaccg tgactgtctt cctcagtctg tgcctgtgat tccagtcacc 5160 ctgtagttac tgacagaaat tgactggact gtcattgtgt gaagtctagg aggaaatgtc 5220 cattttaatt gtatgatttg gtcataagta aggactatat ttatgtcacc attattagat 5280 atatgtactt ttgtaatgac tgtgaaatac acttttccct cactacgact gcttctttat 5340 ttgctgataa atcttaaaac aactaagtac gttgcaaata atagtacagg taccatcttt 5400 tatgtgaagt tctttttctt tttttgagac agggtcttgc tctgtcaccc aggctggagt 5460 gcagtggcac aatcacagtt cactgcagcc tcaacctctc cagattcaag tgatcctccc 5520 atctcagcct cccaagtagc tgggactaca gttgtgcacc acaatgccta gctaattttt 5580 tttgtatttt gtagaaatgg ggtttcgcca tgttgctcag gctgatctca aactcctggg 5640 ctccaacgat ctgcccacct tggcctccca aagtgctgag attacaggcg tgagccactg 5700 tgcctggcct tatgtaaagc tcttgaccta gcatctgact ggaaacaagc gggaattgca 5760 ttggggggca ttttctgggc cagtttccct gccttatttt acctgcaata ggtgtgccta 5820 caaaagtctt tctgacatac acactgcagg tggcagttca agaagaatca acctttttca 5880 tttggggata ttaggatctt ccttggagac tctgaaaatg gcacacaaag aatggcagtt 5940 atgaacgtga cttctagatt ttgtccttgt aggaggcctt ggtcatggat aggggaagag 6000 ggatgatggg atggaatggg agggtgggat ctagatgacc tcttgaaatt gtcccagtta 6060 ctgcttcctt cataactgtt cacaaaacgt ttttcatata taccaccttg tttcccctgg 6120 gaagtgaggg gacgaagcct tagagggtga catagctaga aagtggagaa gctcactgtt 6180 cactgtgcaa agccccagta gtcggattcc ggggaaaaga acaagtatct agttttgatg 6240 acaatgtttt cttgtaagaa tcccaacact ttagaataga aaaggaccta agattctctg 6300 gctcagcccc agcctttctg aagaagggaa aactagggac ccagatggtt taaggacacc 6360 ccagagtccc cagatgagct ggcatttgag ctggtctgga gcagagtttc tccctcaaag 6420 aacacagaga aatcagagag tggctgccat ggtcagaggg ggatgtcaac aacagatcaa 6480 gccgtcatca caacaggtat ttctgaagtt cctgcaggga ctaggtcttg catttttaag 6540 tccttttcaa aactgtgcag cttcctgaac cttatgctgt ttgtcccatc cactcttgaa 6600 gctggggaaa gacagctttc tttgggaact ctgtctttct cagttgactt cccaagtaag 6660 cagcaaaccc ctggatagcc ttgttatcta ctttaggtat taagaggcta ttgggtttta 6720 ctagattaaa tcaataaaac atttcctata gagccatatc atacactgaa gcaaattcag 6780 aaagaatgca aaactgctat cttttggggg agtctggaag cctgttggtt agtgtattta 6840 ttttctttgt ggggtcttct gtgagctaca ggcacagtaa gaataattca gagcggtact 6900 gggagttggt tcaatttcat gtcatcactt ttcaatgaag ggagtgcatt tcctgagtag 6960 taaatgagta tattatttgt ggcagctttt ctgttaaggg agctttccag acatctggtt 7020 gcaaagacaa ataggatata tatttgtact tcttctctgt ggacatgttt ttgtgacaca 7080 cagttatctc taggagttga cgtctgtggg cactaaggga ctgaggttgg gggagaaagc 7140 tgaggaggct ttggaagaga aggtgaggag catttcagga tttgcagtcc ccctccacat 7200 gtatccacat ctgagctggt ggtgttccaa taatgaggca tttggggcaa ccaattttgg 7260 aaggatagaa tagctttatg tggagcaaac ttgaggatca attggagttg agtggtttaa 7320 aacttaaaga tggcacagga agctgtatca tttacaggtg aaaaaaataa atgggtctga 7380 cttca 7385 <210> 27 <211> 1393 <212> RNA <213> NM_015675.3 Homo sapiens growth arrest and DNA damage inducible beta (GADD45B), mRNA <400> 27 tcagatcgcc gaagcgtcgg actaccgttg gtttccgcaa cttcctggat tatcctcgcc 60 aaggactttg caatatattt ttccgccttt tctggaagga tttcgctgct tcccgaaggt 120 cttggacgag cgctctagct ctgtgggaag gttttgggct ctctggctcg gattttgcaa 180 tttctccctg gggactgccg tggagccgca tccactgtgg attataattg caacatgacg 240 ctggaagagc tcgtggcgtg cgacaacgcg gcgcagaaga tgcagacggt gaccgccgcg 300 gtggaggagc ttttggtggc cgctcagcgc caggatcgcc tcacagtggg ggtgtacgag 360 tcggccaagt tgatgaatgt ggacccagac agcgtggtcc tctgcctctt ggccattgac 420 gaggaggagg aggatgacat cgccctgcaa atccacttca cgctcatcca gtccttctgc 480 tgtgacaacg acatcaacat cgtgcgggtg tcgggcatgc agcgcctggc gcagctcctg 540 ggagagccgg ccgagaccca gggcaccacc gaggcccgag acctgcattg tctcctggtc 600 acgaaccctc acacggacgc ctggaagagc cacggcttgg tggaggtggc cagctactgc 660 gaagaaagcc ggggcaacaa ccagtgggtc ccctacatct ctcttcagga acgctgaggc 720 ccttcccagc agcagaatct gttgagttgc tgccacaaac aaaaaataca ataaatattt 780 gaaccccctc ccccccagca caaccccccc aaaacaaccc aacccacgag gaccatcggg 840 ggcagagtcg ttggagactg aagaggaaga ggaggaggag aaggggagtg agcggccgcc 900 cccagggcgg agatccagga gctggcggcc gccgatccga tggagaaggg gggacccagg 960 ccagcaggag acaggacccc cgaagctgag gccttgggat ggagcagaag ccggagtggc 1020 ggggcacgct gccgccttcc ccatcacgga gggtccagac tgtccactcg ggggtggagt 1080 gagactgact gcaagcccca ccctccttga gactggagct ggcgtctgca tacgagagac 1140 ttggttgaac ttggttggtc cttgtctgca ccctcgacaa gaccacactt tgggacttgg 1200 gagctggggc tgaagttgct ctgtacccat gaactcccag tttgcgaatt atagagacaa 1260 tctattttgt tacttgcact tgttattcga accactgaga gcgagatggg aagcatagat 1320 atctatattt ttatttctac tatgagggcc ttgtaataaa tttctaaagc ctctgaaaaa 1380 aaaaaaaaaa aaa 1393 <210> 28 <211> 2950 <212> RNA <213> BC095399.1 Homo sapiens Kruppel-like factor 10 (KLF10), mRNA <400> 28 agacggcgct gagcgcggcg gcggcgggag cggcgtcgag tgtctccgtg cgcccgtctg 60 tggccaagca gccagcagcc tagcagccag tcagcttgcc gccggcggcc aagcagccaa 120 ccatgctcaa cttcggtgcc tctctccagc agactgcgga ggaaagaatg gaaatgattt 180 ctgaaaggcc aaaagagagt atgtattcct ggaacaaaac tgcagagaaa agtgattttg 240 aagctgtaga agcacttatg tcaatgagct gcagttggaa gtctgatttt aagaaatacg 300 ttgaaaacag acctgttaca ccagtatctg atttgtcaga ggaagagaat ctgcttccgg 360 gaacacctga ttttcataca atcccagcat tttgtttgac tccaccttac agtccttctg 420 actttgaacc ctctcaagtg tcaaatctga tggcaccagc gccatctact gtacacttca 480 agtcactctc agatactgcc aaacctcaca ttgccgcacc tttcaaagag gaagaaaaga 540 gcccagtatc tgcccccaaa ctccccaaag ctcaggcaac aagtgtgatt cgtcatacag 600 ctgatgccca gctatgtaac caccagacct gcccaatgaa agcagccagc atcctcaact 660 atcagaacaa ttcttttaga agaagaaccc acctaaatgt tgaggctgca agaaagaaca 720 taccatgtgc cgctgtgtca ccaaacagat ccaaatgtga gagaaacaca gtggcagatg 780 ttgatgagaa agcaagtgct gcactttatg acttttctgt gccttcctca gagacggtca 840 tctgcaggtc tcagccagcc cctgtgtccc cacaacagaa gtcagtgttg gtctctccac 900 ctgcagtatc tgcaggggga gtgccaccta tgccggtcat ctgccagatg gttccccttc 960 ctgccaacaa ccctgttgtg acaacagtcg ttcccagcac tcctcccagc cagccaccag 1020 ccgtttgccc ccctgttgtg ttcatgggca cacaagtccc caaaggcgct gtcatgtttg 1080 tggtacccca gcccgttgtg cagagttcaa agcctccggt ggtgagcccg aatggcacca 1140 gactctctcc cattgcccct gctcctgggt tttccccttc agcagcaaaa gtcactcctc 1200 agattgattc atcaaggata aggagtcaca tctgtagcca cccaggatgt ggcaagacat 1260 actttaaaag ttcccatctg aaggcccaca cgaggacgca cacaggagaa aagcctttca 1320 gctgtagctg gaaaggttgt gaaaggaggt ttgcccgttc tgatgaactg tccagacaca 1380 ggcgaaccca cacgggtgag aagaaatttg cgtgccccat gtgtgaccgg cggttcatga 1440 ggagtgacca tttgaccaag catgcccggc gccatctatc agccaagaag ctaccaaact 1500 ggcagatgga agtgagcaag ctaaatgaca ttgctctacc tccaacccct gctcccacac 1560 agtgacagac cggaaagtga agagtcagaa ctaactttgg tctcagcggg agccagtggt 1620 gatgtaaaaa tgcttccact gcaagtctgt ggccccacaa cgtgggctta aagcagaagc 1680 cccacagcct ggcacgaagg ccccgcctgg gttaggtgac taaaagggct tcggccacag 1740 gcaggtcaca gaaaggcagg tttcatttct tatcacataa gagagatgag aaagctttta 1800 ttcctttgaa tattttttga aggtttcaga tgaggtcaac acaggtagca cagattttga 1860 atctgtgtgc atatttgtta ctttactttt gctgtttata cttgagacca acttttcaat 1920 gtgattcttc taaagcactg gtttcaagaa tatggaggct ggaaggaaat aaacattacg 1980 gtacagacat ggagatgtaa aatgagtttg tattattaca aatattgtca tctttttcta 2040 gagttatctt ctttattatt cctagtcttt ccagtcaaca tcgtggatgt agtgattaaa 2100 tatatctaga actatcattt ttacactatt gtgaatattt ggaattgaac gactgtatat 2160 tgctaagagg gcccaaagaa ttggaatcct ccttaattta attgctttga aacatagcta 2220 caatttgttt ttgcattttt gttttgaaag tttaacaaat gactgtatct aggcatttca 2280 ttatgctttg aactttagtt tgcctgcagt ttcttgtgta gatttgaaaa ttgtatacca 2340 atgtgttttc tgtagactct aagatacact gcactttgtt tagaaaaaaa actgaagatg 2400 aaatatatat tgtaaagaag ggatattaag aatcttagat aacttcttga aaaagatggc 2460 ttatgtcatc agtaaagtac ctttatgtta tgaggatata atgtgtgctt tattgaatta 2520 gaaaattagt gaccattatt cacaggtgga caaatgttga tgttgtcctg ttaatttata 2580 ggcgtttttt ggggatgtgg aggtagttgg gtagaaaaat tattagaaca ttcacttttg 2640 ttaacagtat ttctctttta ttctgttata tagtggatga tatacacagt ggcaaaacaa 2700 aagtacattg cttaaaatat atagtgaaaa atgtcactat atcttcccat ttaacattgt 2760 ttttgtatat tgggtgtaga tttctgacat caaaacttgg acccttggaa aacaaaagtt 2820 ttaattaaaa aaaatccttg tgacttacaa tttgcacaat atttcttttg ttgtacttta 2880 tatcttgttt acaataaaga attccctttg gtaaaaaaaa aaaaaaaaaa aaacaaaaaa 2940 aaaaaaaaaa 2950 <210> 29 <211> 926 <212> RNA <213> X77956.1 Homo sapiens Id1, mRNA <400> 29 ggggcccatt ctgtttcagc cagtcgccaa gaatcatgaa agtcgccagt ggcagcaccg 60 ccaccgccgc cgcgggcccc agctgcgcgc tgaaggccgg caagacagcg agcggtgcgg 120 gcgaggtggt gcgctgtctg tctgagcaga gcgtggccat ctcgcgctgc cggggcgccg 180 gggcgcgcct gcctgccctg ctggacgagc agcaggtaaa cgtgctgctc tacgacatga 240 acggctgtta ctcacgcctc aaggagctgg tgcccaccct gccccagaac cgcaaggtga 300 gcaaggtgga gattctccag cacgtcatcg actacatcag ggaccttcag ttggagctga 360 actcggaatc cgaagttggg acccccgggg gccgagggct gccggtccgg gctccgctca 420 gcaccctcaa cggcgagatc agcgccctga cggccgaggc ggcatgcgtt cctgcggacg 480 atcgcatctt gtgtcgctga agcgcctccc ccagggaccg gcggacccca gccatccagg 540 gggcaagagg aattacgtgc tctgtgggtc tcccccaacg cgcctcgccg gatctgaggg 600 agaacaagac cgatcggcgg ccactgcgcc cttaactgca tccagcctgg ggctgaggct 660 gaggcactgg cgaggagagg gcgctcctct ctgcacacct actagtcacc agagacttta 720 gggggtggga ttccactcgt gtgtttctat tttttgaaaa gcagacattt taaaaaatgg 780 tcacgtttgg tgcttctcag atttctgagg aaattgcttt gtattgtata ttacaatgat 840 caccgactga gaatattgtt ttacaatagt tctgtggggc tgtttttttg ttattaaaca 900 aataatttag atggtgaaaa aaaaaa 926 <210> 30 <211> 1675 <212> RNA <213> BC034145.1 Homo sapiens transmembrane 4 L six family member 1 (TM4SF1), mRNA <400> 30 agagcctgcc attaggacca atgaaagcaa agtacctcat cccctcagtg actaagaatt 60 gcagtattta agaggtagca ggaatgggct gagagtggtg tttgctttct ccaccagaag 120 ggcacacttt catctaattt ggggtatcac tgagctgaag acaaagagaa gggggagaaa 180 acctagcaga ccaccatgtg ctatgggaag tgtgcacgat gcatcggaca ttctctggtg 240 gggctcgccc tcctgtgcat cgcggctaat attttgcttt actttcccaa tggggaaaca 300 aagtatgcct ccgaaaacca cctcagccgc ttcgtgtggt tcttttctgg catcgtagga 360 ggtggcctgc tgatgctcct gccagcattt gtcttcattg ggctggaaca ggatgactgc 420 tgtggctgct gtggccatga aaactgtggc aaacgatgtg cgatgctttc ttctgtattg 480 gctgctctca ttggaattgc aggatctggc tactgtgtca ttgtggcagc ccttggctta 540 gcagaaggac cactatgtct tgattccctc ggccagtgga actacacctt tgccagcacc 600 gagggccagt accttctgga tacctccaca tggtccgagt gcactgaacc caagcacatt 660 gtggaatgga atgtatctct gttttctatc ctcttggctc ttggtggaat tgaattcatc 720 ttgtgtctta ttcaagtaat aaatggagtg cttggaggca tatgtggctt ttgctgctct 780 caccaacagc aaatgactgc taaaagaacc aacccaggac agagccacaa tcttcctcta 840 tttcattgta atttatatat ttcacttgta ttcatttgta aaactttgta ttagtgtaac 900 atactcccca cagtctactt ttacaaacgc ctgtaaagac tggcatcttc acaggatgtc 960 agtgtttaaa tttagtaaac ttcttttttg tttgtttatt tgtttttgtt tttttttaag 1020 gaatgaggaa acaaaccacc ctctgggggt agtttacaga ctgagtgaca gtactcagta 1080 tatctgagat aaactctata atgttttgga taaaaatagc attccaatca ctattgtata 1140 tatgtgcatg tattttttaa attaaagatg tctagttgct ttttataaga ccaagaagga 1200 gaaaatccga caacctggaa agatttttgt tttcactgct tgtatgatgt ttcccattca 1260 tacacctata aatctctaac aagaggccct ttgaactgcc ttgtgttctg tgagaaacaa 1320 atatttactt agagtggaag gactgattga gaatgttcca atccaaatga atgcatcaca 1380 acttacaatg ctgctcattg ttgtgagtac tatgagattc aaatttttct aacatatgga 1440 aagccttttg tcctccaaag atgagtacta gggatcatgt gtttaaaaaa agaaaggcta 1500 cgatgactgg gcaagaagaa agatgggaaa ctgaataaag cagttgatca gcatcattgg 1560 aacatgggga cgagtgacgg caggaggacc acgaggaaat accctcaaaa ctaacttgtt 1620 tacaacaaaa tagagtattc actaccaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 1675 <210> 31 <211> 3319 <212> RNA <213> NM_001320559.1 Homo sapiens cysteine and serine rich nuclear protein 1 (CSRNP1) <400> 31 ggaatggagg ccaacgtcaa agccagcctg ttccccagag tgcctggcta gcctggagca 60 agggcccgca gccctgcctg tgtgcagagt ggcgtgcctg tttggatgtg ctggaggagg 120 aggaggagga agcagagcca ccataccagg gccgtgcggg ctgtgcgggc tgtagggcgt 180 acacacacac acatacacac acacacacac acacacacag gcacacagat gcaagctgtg 240 tgaatcaccc agcctgtgag tcagcgccag gattcctgtc ggggaatgag tgagaccagg 300 ctgaggctgt ctgtccccag accccagagc acgtccggca ccaccatgac tgggctgttg 360 aagaggaaat ttgaccagct ggatgaggac aactcctcgg tctcctcctc ctcctcttcc 420 tctgggtgcc agtctcgctc ctgctcccca agctcttctg tctcccgtgc ctgggactca 480 gaggaggaag gcccctggga tcagatgccc ctgcctgacc gtgacttctg cggccccaga 540 agtttcaccc ccctgtctat cctgaagcgg gctcgccggg agcgcccagg ccgtgtagcc 600 tttgatggga tcaccgtctt ctacttcccc cgctgccagg gcttcaccag tgtgcccagc 660 cgtggtggct gtactctggg tatggccctt cgccacagtg cttgccgtcg cttctctttg 720 gctgagtttg cgcaggagca agcccgtgca cggcacgaga agctccgcca gcgcttgaaa 780 gaggagaagt tggagatgct gcagtggaag ctttcggcag ctggggtacc ccaggcagag 840 gcagggctgc cacctgtggt ggatgccatt gatgacgcct ctgtggagga ggacttggca 900 gtcgctgtgg caggtggccg gttggaagaa gtgagcttcc tacagcccta cccagcccgg 960 cgacgtcgag ctctgctgag ggcttcaggt gtgcgaagga tcgatcggga ggagaagcgg 1020 gagctgcagg cactgcgcca atcccgggag gattgtggct gtcactgcga taggatctgc 1080 gaccctgaga cctgcagctg cagcctggca ggcatcaagt gccagatgga ccacacagca 1140 ttcccctgtg gctgctgcag ggagggctgt gagaacccca tgggccgtgt ggaatttaat 1200 caggcaagag ttcagaccca tttcatccac acactcaccc gcctgcagtt ggaacaggag 1260 gctgagagct ttagggagct ggaggcccct gcccagggca gcccacccag ccctggtgag 1320 gaggccctgg tccctacttt cccactggcc aagcccccca tgaacaatga gctgggagac 1380 aacagctgca gcagcgacat gactgattct tctacagcat cttcatcagc atcgggcact 1440 agtgaggctc ctgactgccc cacccaccca ggcctgcctg gccctggctt ccagcctggc 1500 gttgatgatg acagcctggc acgcatcttg agtttcagtg actctgactt cggtggggag 1560 gaggaggaag aggaggaagg gagcgtgggg aacctggaca acctcagctg cttccatcca 1620 gctgacatct ttggtactag tgaccctggt ggcctggcca gctggaccca cagctattct 1680 ggctgtagct tcacatcagg cgtcctggat gagaatgcca acctggatgc cagctgcttc 1740 ctaaatggtg gccttgaagg gtcaagggaa ggcagccttc ctggcacctc agtgccaccc 1800 agcatggacg ctggccggag tagctcagtg gatctcagct tgtcttcttg tgactccttt 1860 gagttactcc aggctctgcc agattatagt ctggggcctc actacacatc acagaaggtg 1920 tctgacagcc tggacaacat cgaggcacct cacttccccc tgcctggcct gtctccacct 1980 ggggatgcca gcagttgctt cctggagtcc ctcatgggct tctccgagcc agccgccgaa 2040 gccctagatc cctttattga cagccagttt gaggacactg tcccagcatc tctaatggag 2100 cctgtgccgg tgtgaggacc aggatgtctt ttcccagccc caagagacct gttgctgctt 2160 tcttgtaatt atggggctcc ccagagtctg cgtaacagtc tcccactggc tggctcaccc 2220 acaggtgcca tgtgcacact cctggttttc aaacaattct ctggatttat ttatttgttt 2280 taacttttct gtgctgaaga gaggactggg gggagggggc ttcccctttc agctgcccgg 2340 ccccccacac ccacagcttg ctcttctatc tccacaacgt gagcctggaa gaggagaaaa 2400 tgtggctcct ctggagcttg gcagaccact tttcggtctt tgcgtgatgt tccttagccc 2460 aaagacggtg agacagggct gaaatcaggt ggcttctgcc accctgagcc ctagacccat 2520 gggtggctaa atccactgga ctgtgaagac tataatttat ttccataatt tatttggaga 2580 ttgaggaggc tttggttgca cttctttggc tggtgggtaa tgccaggggt ggggtgggca 2640 caggccctca agagcccctt ttgccttgta gtcctacacc ttgccctgcc tgggctttgg 2700 tgcagactag gtgtggattt gagctctgtg atctatgtct gctgcctggc tcctagatgg 2760 ctctgtgggc aggtgctggc caaggacatc atctaggcag ggggagagcc tgggctgaac 2820 agctgtgacc aaaactccct tctgccccac cctgccccct ccacttcctg ccctctgttc 2880 catcttcccc cttcccaaag gccacagcct ttattccagg cccagggatg taggaggggg 2940 aaggaggaaa caggaagccc agagagggca aagggcctac ctcggggcgc gaaccatgcc 3000 ccagactatt atctcagggc tttctgggca ctgcacttca gcgtggccca cctgcccatg 3060 ccctgaggcc agttggcgag gggtggctcc tgagggtttt tatacccttt gtttgctaat 3120 gtttaatttt gcatcataat ttctacattg tccctgagtg tcagaactat aatttattcc 3180 atttctctct gtgtctgtgc caagaaacgc aggctctggg cctgcccctt gcccaggagg 3240 ccttgccagc ctgtgtgctt gtgggaacac cttgtacctg agcttacagg taccaataaa 3300 gaggctttat ttttagcaa 3319 <210> 32 <211> 381 <212> PRT <213> NP_002843.2 pentraxin-related protein (PTX3) [Homo sapiens] <400> 32 Met His Leu Leu Ala Ile Leu Phe Cys Ala Leu Trp Ser Ala Val Leu 1 5 10 15 Ala Glu Asn Ser Asp Asp Tyr Asp Leu Met Tyr Val Asn Leu Asp Asn 20 25 30 Glu Ile Asp Asn Gly Leu His Pro Thr Glu Asp Pro Thr Pro Cys Ala 35 40 45 Cys Gly Gln Glu His Ser Glu Trp Asp Lys Leu Phe Ile Met Leu Glu 50 55 60 Asn Ser Gln Met Arg Glu Arg Met Leu Leu Gln Ala Thr Asp Asp Val 65 70 75 80 Leu Arg Gly Glu Leu Gln Arg Leu Arg Glu Glu Leu Gly Arg Leu Ala 85 90 95 Glu Ser Leu Ala Arg Pro Cys Ala Pro Gly Ala Pro Ala Glu Ala Arg 100 105 110 Leu Thr Ser Ala Leu Asp Glu Leu Leu Gln Ala Thr Arg Asp Ala Gly 115 120 125 Arg Arg Leu Ala Arg Met Glu Gly Ala Glu Ala Gln Arg Pro Glu Glu 130 135 140 Ala Gly Arg Ala Leu Ala Ala Val Leu Glu Glu Leu Arg Gln Thr Arg 145 150 155 160 Ala Asp Leu His Ala Val Gln Gly Trp Ala Ala Arg Ser Trp Leu Pro 165 170 175 Ala Gly Cys Glu Thr Ala Ile Leu Phe Pro Met Arg Ser Lys Lys Ile 180 185 190 Phe Gly Ser Val His Pro Val Arg Pro Met Arg Leu Glu Ser Phe Ser 195 200 205 Ala Cys Ile Trp Val Lys Ala Thr Asp Val Leu Asn Lys Thr Ile Leu 210 215 220 Phe Ser Tyr Gly Thr Lys Arg Asn Pro Tyr Glu Ile Gln Leu Tyr Leu 225 230 235 240 Ser Tyr Gln Ser Ile Val Phe Val Val Gly Gly Glu Glu Asn Lys Leu 245 250 255 Val Ala Glu Ala Met Val Ser Leu Gly Arg Trp Thr His Leu Cys Gly 260 265 270 Thr Trp Asn Ser Glu Glu Gly Leu Thr Ser Leu Trp Val Asn Gly Glu 275 280 285 Leu Ala Ala Thr Thr Val Glu Met Ala Thr Gly His Ile Val Pro Glu 290 295 300 Gly Gly Ile Leu Gln Ile Gly Gln Glu Lys Asn Gly Cys Cys Val Gly 305 310 315 320 Gly Gly Phe Asp Glu Thr Leu Ala Phe Ser Gly Arg Leu Thr Gly Phe 325 330 335 Asn Ile Trp Asp Ser Val Leu Ser Asn Glu Glu Ile Arg Glu Thr Gly 340 345 350 Gly Ala Glu Ser Cys His Ile Arg Gly Asn Ile Val Gly Trp Gly Val 355 360 365 Thr Glu Ile Gln Pro His Gly Gly Ala Gln Tyr Val Ser 370 375 380 <210> 33 <211> 107 <212> PRT <213> NP_001502.1 growth-regulated alpha protein (CXCL1) [Homo sapiens] <400> 33 Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu 1 5 10 15 Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala 20 25 30 Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr 35 40 45 Leu Gln Gly Ile His Pro Lys Asn Ile Gln Ser Val Asn Val Lys Ser 50 55 60 Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn 65 70 75 80 Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro Ile Val Lys Lys Ile 85 90 95 Ile Glu Lys Met Leu Asn Ser Asp Lys Ser Asn 100 105 <210> 34 <211> 107 <212> PRT <213> NP_002080.1 C-X-C motif chemokine 2 (CXCL2) [Homo sapiens] <400> 34 Met Ala Arg Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu 1 5 10 15 Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala 20 25 30 Ala Gly Ala Pro Leu Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr 35 40 45 Leu Gln Gly Ile His Leu Lys Asn Ile Gln Ser Val Lys Val Lys Ser 50 55 60 Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn 65 70 75 80 Gly Gln Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Lys Lys Ile 85 90 95 Ile Glu Lys Met Leu Lys Asn Gly Lys Ser Asn 100 105 <210> 35 <211> 654 <212> PRT <213> NP_006282.2 tumor necrosis factor alpha-induced protein 2 (TNFAIP2) [Homo sapiens] <400> 35 Met Ser Glu Ala Ser Ser Glu Asp Leu Val Pro Pro Leu Glu Ala Gly 1 5 10 15 Ala Ala Pro Tyr Arg Glu Glu Glu Glu Ala Ala Lys Lys Lys Lys Glu 20 25 30 Lys Lys Lys Lys Ser Lys Gly Leu Ala Asn Val Phe Cys Val Phe Thr 35 40 45 Lys Gly Lys Lys Lys Lys Gly Gln Pro Ser Ser Ala Glu Pro Glu Asp 50 55 60 Ala Ala Gly Ser Arg Gln Gly Leu Asp Gly Pro Pro Pro Thr Val Glu 65 70 75 80 Glu Leu Lys Ala Ala Leu Glu Arg Gly Gln Leu Glu Ala Ala Arg Pro 85 90 95 Leu Leu Ala Leu Glu Arg Glu Leu Ala Ala Ala Ala Ala Ala Gly Gly 100 105 110 Val Ser Glu Glu Glu Leu Val Arg Arg Gln Ser Lys Val Glu Ala Leu 115 120 125 Tyr Glu Leu Leu Arg Asp Gln Val Leu Gly Val Leu Arg Arg Pro Leu 130 135 140 Glu Ala Pro Pro Glu Arg Leu Arg Gln Ala Leu Ala Val Val Ala Glu 145 150 155 160 Gln Glu Arg Glu Asp Arg Gln Ala Ala Ala Ala Gly Pro Gly Thr Ser 165 170 175 Gly Leu Ala Ala Thr Arg Pro Arg Arg Trp Leu Gln Leu Trp Arg Arg 180 185 190 Gly Val Ala Glu Ala Ala Glu Glu Arg Met Gly Gln Arg Pro Ala Ala 195 200 205 Gly Ala Glu Val Pro Glu Ser Val Phe Leu His Leu Gly Arg Thr Met 210 215 220 Lys Glu Asp Leu Glu Ala Val Val Glu Arg Leu Lys Pro Leu Phe Pro 225 230 235 240 Ala Glu Phe Gly Val Val Ala Ala Tyr Ala Glu Ser Tyr His Gln His 245 250 255 Phe Ala Ala His Leu Ala Ala Val Ala Gln Phe Glu Leu Cys Glu Arg 260 265 270 Asp Thr Tyr Met Leu Leu Leu Trp Val Gln Asn Leu Tyr Pro Asn Asp 275 280 285 Ile Ile Asn Ser Pro Lys Leu Val Gly Glu Leu Gln Gly Met Gly Leu 290 295 300 Gly Ser Leu Leu Pro Pro Arg Gln Ile Arg Leu Leu Glu Ala Thr Phe 305 310 315 320 Leu Ser Ser Glu Ala Ala Asn Val Arg Glu Leu Met Asp Arg Ala Leu 325 330 335 Glu Leu Glu Ala Arg Arg Trp Ala Glu Asp Val Pro Pro Gln Arg Leu 340 345 350 Asp Gly His Cys His Ser Glu Leu Ala Ile Asp Ile Ile Gln Ile Thr 355 360 365 Ser Gln Ala Gln Ala Lys Ala Glu Ser Ile Thr Leu Asp Leu Gly Ser 370 375 380 Gln Ile Lys Arg Val Leu Leu Val Glu Leu Pro Ala Phe Leu Arg Ser 385 390 395 400 Tyr Gln Arg Ala Phe Asn Glu Phe Leu Glu Arg Gly Lys Gln Leu Thr 405 410 415 Asn Tyr Arg Ala Asn Val Ile Ala Asn Ile Asn Asn Cys Leu Ser Phe 420 425 430 Arg Met Ser Met Glu Gln Asn Trp Gln Val Pro Gln Asp Thr Leu Ser 435 440 445 Leu Leu Leu Gly Pro Leu Gly Glu Leu Lys Ser His Gly Phe Asp Thr 450 455 460 Leu Leu Gln Asn Leu His Glu Asp Leu Lys Pro Leu Phe Lys Arg Phe 465 470 475 480 Thr His Thr Arg Trp Ala Ala Pro Val Glu Thr Leu Glu Asn Ile Ile 485 490 495 Ala Thr Val Asp Thr Arg Leu Pro Glu Phe Ser Glu Leu Gln Gly Cys 500 505 510 Phe Arg Glu Glu Leu Met Glu Ala Leu His Leu His Leu Val Lys Glu 515 520 525 Tyr Ile Ile Gln Leu Ser Lys Gly Arg Leu Val Leu Lys Thr Ala Glu 530 535 540 Gln Gln Gln Gln Leu Ala Gly Tyr Ile Leu Ala Asn Ala Asp Thr Ile 545 550 555 560 Gln His Phe Cys Thr Gln His Gly Ser Pro Ala Thr Trp Leu Gln Pro 565 570 575 Ala Leu Pro Thr Leu Ala Glu Ile Ile Arg Leu Gln Asp Pro Ser Ala 580 585 590 Ile Lys Ile Glu Val Ala Thr Tyr Ala Thr Cys Tyr Pro Asp Phe Ser 595 600 605 Lys Gly His Leu Ser Ala Ile Leu Ala Ile Lys Gly Asn Leu Ser Asn 610 615 620 Ser Glu Val Lys Arg Ile Arg Ser Ile Leu Asp Val Ser Met Gly Ala 625 630 635 640 Gln Glu Pro Ser Arg Pro Leu Phe Ser Leu Ile Lys Val Gly 645 650 <210> 36 <211> 99 <212> PRT <213> NP_000575.1 interleukin-8 precursor (IL8) [Homo sapiens] <400> 36 Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu Ile Ser 1 5 10 15 Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu 20 25 30 Arg Cys Gln Cys Ile Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe 35 40 45 Ile Lys Glu Leu Arg Val Ile Glu Ser Gly Pro His Cys Ala Asn Thr 50 55 60 Glu Ile Ile Val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro 65 70 75 80 Lys Glu Asn Trp Val Gln Arg Val Val Glu Lys Phe Leu Lys Arg Ala 85 90 95 Glu Asn Ser <210> 37 <211> 136 <212> PRT <213> NP_001305024.1 interleukin-6 isoform 2 (IL6) [Homo sapiens] <400> 37 Met Cys Glu Ser Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu 1 5 10 15 Pro Lys Met Ala Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu 20 25 30 Glu Thr Cys Leu Val Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val 35 40 45 Tyr Leu Glu Tyr Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala 50 55 60 Arg Ala Val Gln Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln Lys 65 70 75 80 Lys Ala Lys Asn Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn 85 90 95 Ala Ser Leu Leu Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp 100 105 110 Met Thr Thr His Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser 115 120 125 Ser Leu Arg Ala Leu Arg Gln Met 130 135 <210> 38 <211> 969 <212> PRT <213> CAB94757.1 NFKB1 [Homo sapiens] <400> 38 Met Ala Glu Asp Asp Pro Tyr Leu Gly Arg Pro Glu Gln Met Phe His 1 5 10 15 Leu Asp Pro Ser Leu Thr His Thr Ile Phe Asn Pro Glu Val Phe Gln 20 25 30 Pro Gln Met Ala Leu Pro Thr Asp Gly Pro Tyr Leu Gln Ile Leu Glu 35 40 45 Gln Pro Lys Gln Arg Gly Phe Arg Phe Arg Tyr Val Cys Glu Gly Pro 50 55 60 Ser His Gly Gly Leu Pro Gly Ala Ser Ser Glu Lys Asn Lys Lys Ser 65 70 75 80 Tyr Pro Gln Val Lys Ile Cys Asn Tyr Val Gly Pro Ala Lys Val Ile 85 90 95 Val Gln Leu Val Thr Asn Gly Lys Asn Ile His Leu His Ala His Ser 100 105 110 Leu Val Gly Lys His Cys Glu Asp Gly Ile Cys Thr Val Thr Ala Gly 115 120 125 Pro Lys Asp Met Val Val Gly Phe Ala Asn Leu Gly Ile Leu His Val 130 135 140 Thr Lys Lys Lys Val Phe Glu Thr Leu Glu Ala Arg Met Thr Glu Ala 145 150 155 160 Cys Ile Arg Gly Tyr Asn Pro Gly Leu Leu Val His Pro Asp Leu Ala 165 170 175 Tyr Leu Gln Ala Glu Gly Gly Gly Asp Arg Gln Leu Gly Asp Arg Glu 180 185 190 Lys Glu Leu Ile Arg Gln Ala Ala Leu Gln Gln Thr Lys Glu Met Asp 195 200 205 Leu Ser Val Val Arg Leu Met Phe Thr Ala Phe Leu Pro Asp Ser Thr 210 215 220 Gly Ser Phe Thr Arg Arg Leu Glu Pro Val Val Ser Asp Ala Ile Tyr 225 230 235 240 Asp Ser Ser Glu Ala Pro Asn Ala Ser Asn Leu Lys Ile Val Arg Met 245 250 255 Asp Arg Thr Ala Gly Cys Val Thr Gly Gly Glu Glu Ile Tyr Leu Leu 260 265 270 Cys Asp Lys Val Gln Lys Asp Asp Ile Gln Ile Arg Phe Tyr Glu Glu 275 280 285 Glu Glu Asn Gly Gly Val Trp Glu Gly Phe Gly Asp Phe Ser Pro Thr 290 295 300 Asp Val His Arg Gln Phe Ala Ile Val Phe Lys Thr Pro Lys Tyr Lys 305 310 315 320 Asp Ile Asn Ile Thr Lys Pro Ala Ser Val Phe Val Gln Leu Arg Arg 325 330 335 Lys Ser Asp Leu Glu Thr Ser Glu Pro Lys Pro Phe Leu Tyr Tyr Pro 340 345 350 Glu Ile Lys Asp Lys Glu Glu Val Gln Arg Lys Arg Gln Lys Leu Met 355 360 365 Pro Asn Phe Ser Asp Ser Phe Gly Gly Gly Ser Gly Ala Gly Ala Gly 370 375 380 Gly Gly Gly Met Phe Gly Ser Gly Gly Gly Gly Gly Gly Thr Gly Ser 385 390 395 400 Thr Gly Pro Gly Tyr Ser Phe Pro His Tyr Gly Phe Pro Thr Tyr Gly 405 410 415 Gly Ile Thr Phe His Pro Gly Thr Thr Lys Ser Asn Ala Gly Met Lys 420 425 430 His Gly Thr Met Asp Thr Glu Ser Lys Lys Asp Pro Glu Gly Cys Asp 435 440 445 Lys Ser Asp Asp Lys Asn Thr Val Asn Leu Phe Gly Lys Val Ile Glu 450 455 460 Thr Thr Glu Gln Asp Gln Glu Pro Ser Glu Ala Thr Val Gly Asn Gly 465 470 475 480 Glu Val Thr Leu Thr Tyr Ala Thr Gly Thr Lys Glu Glu Ser Ala Gly 485 490 495 Val Gln Asp Asn Leu Phe Leu Glu Lys Ala Met Gln Leu Ala Lys Arg 500 505 510 His Ala Asn Ala Leu Phe Asp Tyr Ala Val Thr Gly Asp Val Lys Met 515 520 525 Leu Leu Ala Val Gln Arg His Leu Thr Ala Val Gln Asp Glu Asn Gly 530 535 540 Asp Ser Val Leu His Leu Ala Ser Ser His Leu His Ser Gln Leu Val 545 550 555 560 Arg Asp Leu Leu Glu Val Thr Ser Gly Leu Ile Ser Asp Asp Ile Ile 565 570 575 Asn Met Arg Asn Asp Leu Tyr Gln Thr Pro Leu His Leu Ala Val Ile 580 585 590 Thr Lys Gln Glu Asp Val Val Glu Asp Leu Leu Arg Ala Gly Ala Asp 595 600 605 Leu Ser Leu Leu Asp Arg Leu Gly Asn Ser Val Leu His Leu Ala Ala 610 615 620 Lys Glu Gly His Asp Lys Val Leu Ser Ile Leu Leu Lys His Lys Lys 625 630 635 640 Ala Ala Leu Leu Leu Asp His Pro Asn Gly Asp Gly Leu Asn Ala Ile 645 650 655 His Leu Ala Met Met Ser Asn Ser Leu Pro Cys Leu Leu Leu Leu Val 660 665 670 Ala Ala Gly Ala Asp Val Asn Ala Gln Glu Gln Lys Ser Gly Arg Thr 675 680 685 Ala Leu His Leu Ala Val Glu His Asp Asn Ile Ser Leu Ala Gly Cys 690 695 700 Leu Leu Leu Glu Gly Asp Ala His Val Asp Ser Thr Thr Tyr Asp Gly 705 710 715 720 Thr Thr Pro Leu His Ile Val Ala Gly Arg Gly Ser Thr Arg Leu Ala 725 730 735 Ala Leu Leu Lys Ala Ala Gly Ala Asp Pro Leu Val Glu Asn Phe Glu 740 745 750 Pro Leu Tyr Asp Leu Asp Asp Ser Trp Glu Asn Ala Gly Glu Asp Glu 755 760 765 Gly Val Val Pro Gly Thr Thr Pro Leu Asp Met Ala Thr Ser Trp Gln 770 775 780 Val Phe Asp Ile Leu Asn Gly Lys Pro Tyr Glu Pro Glu Phe Thr Ser 785 790 795 800 Asp Asp Leu Leu Ala Gln Gly Asp Met Lys Gln Leu Ala Glu Asp Val 805 810 815 Lys Leu Gln Leu Tyr Lys Leu Leu Glu Ile Pro Asp Pro Asp Lys Asn 820 825 830 Trp Ala Thr Leu Ala Gln Lys Leu Gly Leu Gly Ile Leu Asn Asn Ala 835 840 845 Phe Arg Leu Ser Pro Ala Pro Ser Lys Thr Leu Met Asp Asn Tyr Glu 850 855 860 Val Ser Gly Gly Thr Ile Arg Glu Leu Val Glu Ala Leu Arg Gln Met 865 870 875 880 Gly Tyr Thr Glu Ala Ile Glu Val Ile Gln Ala Ala Ser Ser Pro Val 885 890 895 Lys Thr Thr Ser Gln Ala His Ser Leu Pro Leu Ser Pro Ala Ser Thr 900 905 910 Arg Gln Gln Ile Asp Glu Leu Arg Asp Ser Asp Ser Val Cys Asp Thr 915 920 925 Gly Val Glu Thr Ser Phe Arg Lys Leu Ser Phe Thr Glu Ser Leu Thr 930 935 940 Ser Gly Ala Ser Leu Leu Thr Leu Asn Lys Met Pro His Asp Tyr Gly 945 950 955 960 Gln Glu Gly Pro Leu Glu Gly Lys Ile 965 <210> 39 <211> 103 <212> PRT <213> NP_056529.1 G0/G1 switch protein 2 (G0S2) [Homo sapiens] <400> 39 Met Glu Thr Val Gln Glu Leu Ile Pro Leu Ala Lys Glu Met Met Ala 1 5 10 15 Gln Lys Arg Lys Gly Lys Met Val Lys Leu Tyr Val Leu Gly Ser Val 20 25 30 Leu Ala Leu Phe Gly Val Val Leu Gly Leu Met Glu Thr Val Cys Ser 35 40 45 Pro Phe Thr Ala Ala Arg Arg Leu Arg Asp Gln Glu Ala Ala Val Ala 50 55 60 Glu Leu Gln Ala Ala Leu Glu Arg Gln Ala Leu Gln Lys Gln Ala Leu 65 70 75 80 Gln Glu Lys Gly Lys Gln Gln Asp Thr Val Leu Gly Gly Arg Ala Leu 85 90 95 Ser Asn Arg Gln His Ala Ser 100 <210> 40 <211> 532 <212> PRT <213> AAH15969.1 Intercellular adhesion molecule 1 (ICM1) [Homo sapiens] <400> 40 Met Ala Pro Ser Ser Pro Arg Pro Ala Leu Pro Ala Leu Leu Val Leu 1 5 10 15 Leu Gly Ala Leu Phe Pro Gly Pro Gly Asn Ala Gln Thr Ser Val Ser 20 25 30 Pro Ser Lys Val Ile Leu Pro Arg Gly Gly Ser Val Leu Val Thr Cys 35 40 45 Ser Thr Ser Cys Asp Gln Pro Lys Leu Leu Gly Ile Glu Thr Pro Leu 50 55 60 Pro Lys Lys Glu Leu Leu Leu Pro Gly Asn Asn Arg Lys Val Tyr Glu 65 70 75 80 Leu Ser Asn Val Gln Glu Asp Ser Gln Pro Met Cys Tyr Ser Asn Cys 85 90 95 Pro Asp Gly Gln Ser Thr Ala Lys Thr Phe Leu Thr Val Tyr Trp Thr 100 105 110 Pro Glu Arg Val Glu Leu Ala Pro Leu Pro Ser Trp Gln Pro Val Gly 115 120 125 Lys Asn Leu Thr Leu Arg Cys Gln Val Glu Gly Gly Ala Pro Arg Ala 130 135 140 Asn Leu Thr Val Val Leu Leu Arg Gly Glu Lys Glu Leu Lys Arg Glu 145 150 155 160 Pro Ala Val Gly Glu Pro Ala Glu Val Thr Thr Thr Val Leu Val Arg 165 170 175 Arg Asp His His Gly Ala Asn Phe Ser Cys Arg Thr Glu Leu Asp Leu 180 185 190 Arg Pro Gln Gly Leu Glu Leu Phe Glu Asn Thr Ser Ala Pro Tyr Gln 195 200 205 Leu Gln Thr Phe Val Leu Pro Ala Thr Pro Pro Gln Leu Val Ser Pro 210 215 220 Arg Val Leu Glu Val Asp Thr Gln Gly Thr Val Val Cys Ser Leu Asp 225 230 235 240 Gly Leu Phe Pro Val Ser Glu Ala Gln Val His Leu Ala Leu Gly Asp 245 250 255 Gln Arg Leu Asn Pro Thr Val Thr Tyr Gly Asn Asp Ser Phe Ser Ala 260 265 270 Lys Ala Ser Val Ser Val Thr Ala Glu Asp Glu Gly Thr Gln Arg Leu 275 280 285 Thr Cys Ala Val Ile Leu Gly Asn Gln Ser Gln Glu Thr Leu Gln Thr 290 295 300 Val Thr Ile Tyr Ser Phe Pro Ala Pro Asn Val Ile Leu Thr Lys Pro 305 310 315 320 Glu Val Ser Glu Gly Thr Glu Val Thr Val Lys Cys Glu Ala His Pro 325 330 335 Arg Ala Lys Val Thr Leu Asn Gly Val Pro Ala Gln Pro Leu Gly Pro 340 345 350 Arg Ala Gln Leu Leu Leu Lys Ala Thr Pro Glu Asp Asn Gly Arg Ser 355 360 365 Phe Ser Cys Ser Ala Thr Leu Glu Val Ala Gly Gln Leu Ile His Lys 370 375 380 Asn Gln Thr Arg Glu Leu Arg Val Leu Tyr Gly Pro Arg Leu Asp Glu 385 390 395 400 Arg Asp Cys Pro Gly Asn Trp Thr Trp Pro Glu Asn Ser Gln Gln Thr 405 410 415 Pro Met Cys Gln Ala Trp Gly Asn Pro Leu Pro Glu Leu Lys Cys Leu 420 425 430 Lys Asp Gly Thr Phe Pro Leu Pro Ile Gly Glu Ser Val Thr Val Thr 435 440 445 Arg Asp Leu Glu Gly Thr Tyr Leu Cys Arg Ala Arg Ser Thr Gln Gly 450 455 460 Glu Val Thr Arg Lys Val Thr Val Asn Val Leu Ser Pro Arg Tyr Glu 465 470 475 480 Ile Val Ile Ile Thr Val Val Ala Ala Ala Val Ile Met Gly Thr Ala 485 490 495 Gly Leu Ser Thr Tyr Leu Tyr Asn Arg Gln Arg Lys Ile Lys Lys Tyr 500 505 510 Arg Leu Gln Gln Ala Gln Lys Gly Thr Pro Met Lys Pro Asn Thr Gln 515 520 525 Ala Thr Pro Pro 530 <210> 41 <211> 275 <212> PRT <213> AAH03097.1 Intercellular adhesion molecule 2 (ICM2) [Homo sapiens] <400> 41 Met Ser Ser Phe Gly Tyr Arg Thr Leu Thr Val Ala Leu Phe Thr Leu 1 5 10 15 Ile Cys Cys Pro Gly Ser Asp Glu Lys Val Phe Glu Val His Val Arg 20 25 30 Pro Lys Lys Leu Ala Val Glu Pro Lys Gly Ser Leu Glu Val Asn Cys 35 40 45 Ser Thr Thr Cys Asn Gln Pro Glu Val Gly Gly Leu Glu Thr Ser Leu 50 55 60 Asp Lys Ile Leu Leu Asp Glu Gln Ala Gln Trp Lys His Tyr Leu Val 65 70 75 80 Ser Asn Ile Ser His Asp Thr Val Leu Gln Cys His Phe Thr Cys Ser 85 90 95 Gly Lys Gln Glu Ser Met Asn Ser Asn Val Ser Val Tyr Gln Pro Pro 100 105 110 Arg Gln Val Ile Leu Thr Leu Gln Pro Thr Leu Val Ala Val Gly Lys 115 120 125 Ser Phe Thr Ile Glu Cys Arg Val Pro Thr Val Glu Pro Leu Asp Ser 130 135 140 Leu Thr Leu Phe Leu Phe Arg Gly Asn Glu Thr Leu His Tyr Glu Thr 145 150 155 160 Phe Gly Lys Ala Ala Pro Ala Pro Gln Glu Ala Thr Ala Thr Phe Asn 165 170 175 Ser Thr Ala Asp Arg Glu Asp Gly His Arg Asn Phe Ser Cys Leu Ala 180 185 190 Val Leu Asp Leu Met Ser Arg Gly Gly Asn Ile Phe His Lys His Ser 195 200 205 Ala Pro Lys Met Leu Glu Ile Tyr Glu Pro Val Ser Asp Ser Gln Met 210 215 220 Val Ile Ile Val Thr Val Val Ser Val Leu Leu Ser Leu Phe Val Thr 225 230 235 240 Ser Val Leu Leu Cys Phe Ile Phe Gly Gln His Leu Arg Gln Gln Arg 245 250 255 Met Gly Thr Tyr Gly Val Arg Ala Ala Trp Arg Arg Leu Pro Gln Ala 260 265 270 Phe Arg Pro 275 <210> 42 <211> 547 <212> PRT <213> AAH58903.1 Intercellular adhesion molecule 3 (ICM3) [Homo sapiens] <400> 42 Met Ala Thr Met Val Pro Ser Val Leu Trp Pro Arg Ala Cys Trp Thr 1 5 10 15 Leu Leu Val Cys Cys Leu Leu Thr Pro Gly Val Gln Gly Gln Glu Phe 20 25 30 Leu Leu Arg Val Glu Pro Gln Asn Pro Val Leu Ser Ala Gly Gly Ser 35 40 45 Leu Phe Val Asn Cys Ser Thr Asp Cys Pro Ser Ser Glu Lys Ile Ala 50 55 60 Leu Glu Thr Ser Leu Ser Lys Glu Leu Val Ala Ser Gly Met Gly Trp 65 70 75 80 Ala Ala Phe Asn Leu Ser Asn Val Thr Gly Asn Ser Arg Ile Leu Cys 85 90 95 Ser Val Tyr Cys Asn Gly Ser Gln Ile Thr Gly Ser Ser Asn Ile Thr 100 105 110 Val Tyr Arg Leu Pro Glu Arg Val Glu Leu Ala Pro Leu Pro Pro Trp 115 120 125 Gln Pro Val Gly Gln Asn Phe Thr Leu Arg Cys Gln Val Glu Asp Gly 130 135 140 Ser Pro Arg Thr Ser Leu Thr Val Val Leu Leu Arg Trp Glu Glu Glu 145 150 155 160 Leu Ser Arg Gln Pro Ala Val Glu Glu Pro Ala Glu Val Thr Ala Thr 165 170 175 Val Leu Ala Ser Arg Asp Asp His Gly Ala Pro Phe Ser Cys Arg Thr 180 185 190 Glu Leu Asp Met Gln Pro Gln Gly Leu Gly Leu Phe Val Asn Thr Ser 195 200 205 Ala Pro Arg Gln Leu Arg Thr Phe Val Leu Pro Val Thr Pro Pro Arg 210 215 220 Leu Val Ala Pro Arg Phe Leu Glu Val Glu Thr Ser Trp Pro Val Asp 225 230 235 240 Cys Thr Leu Asp Gly Leu Phe Pro Ala Ser Glu Ala Gln Val Tyr Leu 245 250 255 Ala Leu Gly Asp Gln Met Leu Asn Ala Thr Val Met Asn His Gly Asp 260 265 270 Thr Leu Thr Ala Thr Ala Thr Ala Thr Ala Arg Ala Asp Gln Glu Gly 275 280 285 Ala Arg Glu Ile Val Cys Asn Val Thr Leu Gly Gly Glu Arg Arg Glu 290 295 300 Ala Arg Glu Asn Leu Thr Val Phe Ser Phe Leu Gly Pro Ile Val Asn 305 310 315 320 Leu Ser Glu Pro Thr Ala His Glu Gly Ser Thr Val Thr Val Ser Cys 325 330 335 Met Ala Gly Ala Arg Val Gln Val Thr Leu Asp Gly Val Pro Ala Ala 340 345 350 Ala Pro Gly Gln Pro Ala Gln Leu Gln Leu Asn Ala Thr Glu Ser Asp 355 360 365 Asp Gly Arg Ser Phe Phe Cys Ser Ala Thr Leu Glu Val Asp Gly Glu 370 375 380 Phe Leu His Arg Asn Ser Ser Val Gln Leu Arg Val Leu Tyr Gly Pro 385 390 395 400 Lys Ile Asp Arg Ala Thr Cys Pro Gln His Leu Lys Trp Lys Asp Lys 405 410 415 Thr Arg His Val Leu Gln Cys Gln Ala Arg Gly Asn Pro Tyr Pro Glu 420 425 430 Leu Arg Cys Leu Lys Glu Gly Ser Ser Arg Glu Val Pro Val Gly Ile 435 440 445 Pro Phe Phe Val Asn Val Thr His Asn Gly Thr Tyr Gln Cys Gln Ala 450 455 460 Ser Ser Ser Arg Gly Lys Tyr Thr Leu Val Val Val Met Asp Ile Glu 465 470 475 480 Ala Gly Ser Ser His Phe Val Pro Val Phe Val Ala Val Leu Leu Thr 485 490 495 Leu Gly Val Val Thr Ile Val Leu Ala Leu Met Tyr Val Phe Arg Glu 500 505 510 His Gln Arg Ser Gly Ser Tyr His Val Arg Glu Glu Ser Thr Tyr Leu 515 520 525 Pro Leu Thr Ser Met Gln Pro Thr Glu Ala Met Gly Glu Glu Pro Ser 530 535 540 Arg Ala Glu 545 <210> 43 <211> 152 <212> PRT <213> AAH08280.1 Prostaglandin E synthase (PTGES) [Homo sapiens] <400> 43 Met Pro Ala His Ser Leu Val Met Ser Ser Pro Ala Leu Pro Ala Phe 1 5 10 15 Leu Leu Cys Ser Thr Leu Leu Val Ile Lys Met Tyr Val Val Ala Ile 20 25 30 Ile Thr Gly Gln Val Arg Leu Arg Lys Lys Ala Phe Ala Asn Pro Glu 35 40 45 Asp Ala Leu Arg His Gly Gly Pro Gln Tyr Cys Arg Ser Asp Pro Asp 50 55 60 Val Glu Arg Cys Leu Arg Ala His Arg Asn Asp Met Glu Thr Ile Tyr 65 70 75 80 Pro Phe Leu Phe Leu Gly Phe Val Tyr Ser Phe Leu Gly Pro Asn Pro 85 90 95 Phe Val Ala Trp Met His Phe Leu Val Phe Leu Val Gly Arg Val Ala 100 105 110 His Thr Val Ala Tyr Leu Gly Lys Leu Arg Ala Pro Ile Arg Ser Val 115 120 125 Thr Tyr Thr Leu Ala Gln Leu Pro Cys Ala Ser Met Ala Leu Gln Ile 130 135 140 Leu Trp Glu Ala Ala Arg His Leu 145 150 <210> 44 <211> 136 <212> PRT <213> AAH32663.1 PMAIP1 protein (PMAIP1) [Homo sapiens] <400> 44 Met Pro Gly Lys Lys Ala Arg Lys Asn Ala Gln Pro Ser Pro Ala Arg 1 5 10 15 Ala Pro Ala Gly Pro Ala Gly Thr Ala Gly Thr Ala Arg Asp Gln Ala 20 25 30 Gly Phe Ala Ile Gly Met Gln Leu Arg Phe Thr Arg Gly Lys Lys Leu 35 40 45 Leu Ser Ser Ser Leu Ser Ser Ser Pro Leu Ala Leu Pro Arg Gly His 50 55 60 Glu Glu Gln Val Gln Val Ala Gly Ser Arg Val Cys Tyr Ser Thr Gln 65 70 75 80 Glu Ile Trp Arg Gln Thr Glu Leu Pro Ala Glu Thr Ser Glu Ser Asp 85 90 95 Ile Gln Thr Leu Leu Leu Arg Asn Leu Thr Ala Ser Lys Thr Cys Met 100 105 110 Arg Gly Leu Leu Gln Lys Ser Phe Leu Arg Arg Cys Thr Phe His Gln 115 120 125 Phe Glu Glu Arg Leu His Cys Asn 130 135 <210> 45 <211> 502 <212> PRT <213> AAH00669.1 Spermine oxidase (SMOX) [Homo sapiens] <400> 45 Met Gln Ser Cys Glu Ser Ser Gly Asp Ser Ala Asp Asp Pro Leu Ser 1 5 10 15 Arg Gly Leu Arg Arg Arg Gly Gln Pro Arg Val Val Val Ile Gly Ala 20 25 30 Gly Leu Ala Gly Leu Ala Ala Ala Lys Ala Leu Leu Glu Gln Gly Phe 35 40 45 Thr Asp Val Thr Val Leu Glu Ala Ser Ser His Ile Gly Gly Arg Val 50 55 60 Gln Ser Val Lys Leu Gly His Ala Thr Phe Glu Leu Gly Ala Thr Trp 65 70 75 80 Ile His Gly Ser His Gly Asn Pro Ile Tyr His Leu Ala Glu Ala Asn 85 90 95 Gly Leu Leu Glu Glu Thr Thr Asp Gly Glu Arg Ser Val Gly Arg Ile 100 105 110 Ser Leu Tyr Ser Lys Asn Gly Val Ala Cys Tyr Leu Thr Asn His Gly 115 120 125 Arg Arg Ile Pro Lys Asp Val Val Glu Glu Phe Ser Asp Leu Tyr Asn 130 135 140 Glu Val Tyr Asn Leu Thr Gln Glu Phe Phe Arg His Asp Lys Pro Val 145 150 155 160 Asn Ala Glu Ser Gln Asn Ser Val Gly Val Phe Thr Arg Glu Glu Val 165 170 175 Arg Asn Arg Ile Arg Asn Asp Pro Asp Asp Pro Glu Ala Thr Lys Arg 180 185 190 Leu Lys Leu Ala Met Ile Gln Gln Tyr Leu Lys Val Glu Ser Cys Glu 195 200 205 Ser Ser Ser His Ser Met Asp Glu Val Ser Leu Ser Ala Phe Gly Glu 210 215 220 Trp Thr Glu Ile Pro Gly Ala His His Ile Ile Pro Ser Gly Phe Met 225 230 235 240 Arg Val Val Glu Leu Leu Ala Glu Gly Ile Pro Ala His Val Ile Gln 245 250 255 Leu Gly Lys Pro Val Arg Cys Ile His Trp Asp Gln Ala Ser Ala Arg 260 265 270 Pro Arg Gly Pro Glu Ile Glu Pro Arg Gly Val Leu Lys Arg Gln Tyr 275 280 285 Thr Ser Phe Phe Arg Pro Gly Leu Pro Thr Glu Lys Val Ala Ala Ile 290 295 300 His Arg Leu Gly Ile Gly Thr Thr Asp Lys Ile Phe Leu Glu Phe Glu 305 310 315 320 Glu Pro Phe Trp Gly Pro Glu Cys Asn Ser Leu Gln Phe Val Trp Glu 325 330 335 Asp Glu Ala Glu Ser His Thr Leu Thr Tyr Pro Pro Glu Leu Trp Tyr 340 345 350 Arg Lys Ile Cys Gly Phe Asp Val Leu Tyr Pro Pro Glu Arg Tyr Gly 355 360 365 His Val Leu Ser Gly Trp Ile Cys Gly Glu Glu Ala Leu Val Met Glu 370 375 380 Lys Cys Asp Asp Glu Ala Val Ala Glu Ile Cys Thr Glu Met Leu Arg 385 390 395 400 Gln Phe Thr Gly Asn Pro Asn Ile Pro Lys Pro Arg Arg Ile Leu Arg 405 410 415 Ser Ala Trp Gly Ser Asn Pro Tyr Phe Arg Gly Ser Tyr Ser Tyr Thr 420 425 430 Gln Val Gly Ser Ser Gly Ala Asp Val Glu Lys Leu Ala Lys Pro Leu 435 440 445 Pro Tyr Thr Glu Ser Ser Lys Thr Ala Pro Met Gln Val Leu Phe Ser 450 455 460 Gly Glu Ala Thr His Arg Lys Tyr Tyr Ser Thr Thr His Gly Ala Leu 465 470 475 480 Leu Ser Gly Gln Arg Glu Ala Ala Arg Leu Ile Glu Met Tyr Arg Asp 485 490 495 Leu Phe Gln Gln Gly Thr 500 <210> 46 <211> 277 <212> PRT <213> AAH30205.1 Tumor necrosis factor, alpha-induced protein 6 (TNFAIP6) [Homo sapiens] <400> 46 Met Ile Ile Leu Ile Tyr Leu Phe Leu Leu Leu Trp Glu Asp Thr Gln 1 5 10 15 Gly Trp Gly Phe Lys Asp Gly Ile Phe His Asn Ser Ile Trp Leu Glu 20 25 30 Arg Ala Ala Gly Val Tyr His Arg Glu Ala Arg Ser Gly Lys Tyr Lys 35 40 45 Leu Thr Tyr Ala Glu Ala Lys Ala Val Cys Glu Phe Glu Gly Gly His 50 55 60 Leu Ala Thr Tyr Lys Gln Leu Glu Ala Ala Arg Lys Ile Gly Phe His 65 70 75 80 Val Cys Ala Ala Gly Trp Met Ala Lys Gly Arg Val Gly Tyr Pro Ile 85 90 95 Val Lys Pro Gly Pro Asn Cys Gly Phe Gly Lys Thr Gly Ile Ile Asp 100 105 110 Tyr Gly Ile Arg Leu Asn Arg Ser Glu Arg Trp Asp Ala Tyr Cys Tyr 115 120 125 Asn Pro His Ala Lys Glu Cys Gly Gly Val Phe Thr Asp Pro Lys Gln 130 135 140 Ile Phe Lys Ser Pro Gly Phe Pro Asn Glu Tyr Glu Asp Asn Gln Ile 145 150 155 160 Cys Tyr Trp His Ile Arg Leu Lys Tyr Gly Gln Arg Ile His Leu Ser 165 170 175 Phe Leu Asp Phe Asp Leu Glu Asp Asp Pro Gly Cys Leu Ala Asp Tyr 180 185 190 Val Glu Ile Tyr Asp Ser Tyr Asp Asp Val His Gly Phe Val Gly Arg 195 200 205 Tyr Cys Gly Asp Glu Leu Pro Asp Asp Ile Ile Ser Thr Gly Asn Val 210 215 220 Met Thr Leu Lys Phe Leu Ser Asp Ala Ser Val Thr Ala Gly Gly Phe 225 230 235 240 Gln Ile Lys Tyr Val Ala Met Asp Pro Val Ser Lys Ser Ser Gln Gly 245 250 255 Lys Asn Thr Ser Thr Thr Ser Thr Gly Asn Lys Asn Phe Leu Ala Gly 260 265 270 Arg Phe Ser His Leu 275 <210> 47 <211> 477 <212> PRT <213> AAH69716.1 Matrix metallopeptidase 3 (MMP) [Homo sapiens] <400> 47 Met Lys Ser Leu Pro Ile Leu Leu Leu Leu Cys Val Ala Val Cys Ser 1 5 10 15 Ala Tyr Pro Leu Asp Gly Ala Ala Arg Gly Glu Asp Thr Ser Met Asn 20 25 30 Leu Val Gln Lys Tyr Leu Glu Asn Tyr Tyr Asp Leu Glu Lys Asp Val 35 40 45 Lys Gln Phe Val Arg Arg Lys Asp Ser Gly Pro Val Val Lys Lys Ile 50 55 60 Arg Glu Met Gln Lys Phe Leu Gly Leu Glu Val Thr Gly Lys Leu Asp 65 70 75 80 Ser Asp Thr Leu Glu Val Met Arg Lys Pro Arg Cys Gly Val Pro Asp 85 90 95 Val Gly His Phe Arg Thr Phe Pro Gly Ile Pro Lys Trp Arg Lys Thr 100 105 110 His Leu Thr Tyr Arg Ile Val Asn Tyr Thr Pro Asp Leu Pro Lys Asp 115 120 125 Ala Val Asp Ser Ala Val Glu Lys Ala Leu Lys Val Trp Glu Glu Val 130 135 140 Thr Pro Leu Thr Phe Ser Arg Leu Tyr Glu Gly Glu Ala Asp Ile Met 145 150 155 160 Ile Ser Phe Ala Val Arg Glu His Gly Asp Phe Tyr Pro Phe Asp Gly 165 170 175 Pro Gly Asn Val Leu Ala His Ala Tyr Ala Pro Gly Pro Gly Ile Asn 180 185 190 Gly Asp Ala His Phe Asp Asp Asp Glu Gln Trp Thr Lys Asp Thr Thr 195 200 205 Gly Thr Asn Leu Phe Leu Val Ala Ala His Glu Ile Gly His Ser Leu 210 215 220 Gly Leu Phe His Ser Ala Asn Thr Glu Ala Leu Met Tyr Pro Leu Tyr 225 230 235 240 His Ser Leu Thr Asp Leu Thr Arg Phe Arg Leu Ser Gln Asp Asp Ile 245 250 255 Asn Gly Ile Gln Ser Leu Tyr Gly Pro Pro Pro Asp Ser Pro Glu Thr 260 265 270 Pro Leu Val Pro Thr Glu Pro Val Pro Pro Glu Pro Gly Thr Pro Ala 275 280 285 Asn Cys Asp Pro Ala Leu Ser Phe Asp Ala Val Ser Thr Leu Arg Gly 290 295 300 Glu Ile Leu Ile Phe Lys Asp Arg His Phe Trp Arg Lys Ser Leu Arg 305 310 315 320 Lys Leu Glu Pro Glu Leu His Leu Ile Ser Ser Phe Trp Pro Ser Leu 325 330 335 Pro Ser Gly Val Asp Ala Ala Tyr Glu Val Thr Ser Lys Asp Leu Val 340 345 350 Phe Ile Phe Lys Gly Asn Gln Phe Trp Ala Ile Arg Gly Asn Glu Val 355 360 365 Arg Ala Gly Tyr Pro Arg Gly Ile His Thr Leu Gly Phe Pro Pro Thr 370 375 380 Val Arg Lys Ile Asp Ala Ala Ile Ser Asp Lys Glu Lys Asn Lys Thr 385 390 395 400 Tyr Phe Phe Val Glu Asp Lys Tyr Trp Arg Phe Asp Glu Lys Arg Asn 405 410 415 Ser Met Glu Pro Gly Phe Pro Lys Gln Ile Ala Glu Asp Phe Pro Gly 420 425 430 Ile Asp Ser Lys Ile Asp Ala Val Phe Glu Glu Phe Gly Phe Phe Tyr 435 440 445 Phe Phe Thr Gly Ser Ser Gln Leu Glu Phe Asp Pro Asn Ala Lys Lys 450 455 460 Val Thr His Thr Leu Lys Ser Asn Ser Trp Leu Asn Cys 465 470 475 <210> 48 <211> 490 <212> PRT <213> AAH04977.1 IFIT3 [Homo sapiens] <400> 48 Met Ser Glu Val Thr Lys Asn Ser Leu Glu Lys Ile Leu Pro Gln Leu 1 5 10 15 Lys Cys His Phe Thr Trp Asn Leu Phe Lys Glu Asp Ser Val Ser Arg 20 25 30 Asp Leu Glu Asp Arg Val Cys Asn Gln Ile Glu Ser Leu Asn Thr Glu 35 40 45 Phe Lys Ala Thr Met Tyr Asn Leu Leu Ala Tyr Ile Lys His Leu Asp 50 55 60 Gly Asn Asn Glu Ala Ala Leu Glu Cys Leu Arg Gln Ala Glu Glu Leu 65 70 75 80 Ile Gln Gln Glu His Ala Asp Gln Ala Glu Ile Arg Ser Leu Val Thr 85 90 95 Trp Gly Asn Tyr Ala Trp Val Tyr Tyr His Leu Gly Arg Leu Ser Asp 100 105 110 Ala Gln Ile Tyr Val Asp Lys Val Lys Gln Thr Cys Lys Lys Phe Ser 115 120 125 Asn Pro Tyr Ser Ile Glu Tyr Ser Glu Leu Asp Cys Glu Glu Gly Trp 130 135 140 Thr Gln Leu Lys Cys Gly Arg Asn Glu Arg Ala Lys Val Cys Phe Glu 145 150 155 160 Lys Ala Leu Glu Glu Lys Pro Asn Asn Pro Glu Phe Ser Ser Gly Leu 165 170 175 Ala Ile Ala Met Tyr His Leu Asp Asn His Pro Glu Lys Gln Phe Ser 180 185 190 Thr Asp Val Leu Lys Gln Ala Ile Glu Leu Ser Pro Asp Asn Gln Tyr 195 200 205 Val Lys Val Leu Leu Gly Leu Lys Leu Gln Lys Met Asn Lys Glu Ala 210 215 220 Glu Gly Glu Gln Phe Val Glu Glu Ala Leu Glu Lys Ser Pro Cys Gln 225 230 235 240 Thr Asp Val Leu Arg Ser Ala Ala Lys Phe Tyr Arg Arg Lys Gly Asp 245 250 255 Leu Asp Lys Ala Ile Glu Leu Phe Gln Arg Val Leu Glu Ser Thr Pro 260 265 270 Asn Asn Gly Tyr Leu Tyr His Gln Ile Gly Cys Cys Tyr Lys Ala Lys 275 280 285 Val Arg Gln Met Gln Asn Thr Gly Glu Ser Glu Ala Ser Gly Asn Lys 290 295 300 Glu Met Ile Glu Ala Leu Lys Gln Tyr Ala Met Asp Tyr Ser Asn Lys 305 310 315 320 Ala Leu Glu Lys Gly Leu Asn Pro Leu Asn Ala Tyr Ser Asp Leu Ala 325 330 335 Glu Phe Leu Glu Thr Glu Cys Tyr Gln Thr Pro Phe Asn Lys Glu Val 340 345 350 Pro Asp Ala Glu Lys Gln Gln Ser His Gln Arg Tyr Cys Asn Leu Gln 355 360 365 Lys Tyr Asn Gly Lys Ser Glu Asp Thr Ala Val Gln His Gly Leu Glu 370 375 380 Gly Leu Ser Ile Ser Lys Lys Ser Thr Asp Lys Glu Glu Ile Lys Asp 385 390 395 400 Gln Pro Gln Asn Val Ser Glu Asn Leu Leu Pro Gln Asn Ala Pro Asn 405 410 415 Tyr Trp Tyr Leu Gln Gly Leu Ile His Lys Gln Asn Gly Asp Leu Leu 420 425 430 Gln Ala Ala Lys Cys Tyr Glu Lys Glu Leu Gly Arg Leu Leu Arg Asp 435 440 445 Ala Pro Ser Gly Ile Gly Ser Ile Phe Leu Ser Ala Ser Glu Leu Glu 450 455 460 Asp Gly Ser Glu Glu Met Gly Gln Gly Ala Val Ser Ser Ser Pro Arg 465 470 475 480 Glu Leu Leu Ser Asn Ser Glu Gln Leu Asn 485 490 <210> 49 <211> 114 <212> PRT <213> NP_002984.1 C-X-C motif chemokine 6 precursor (CXCL6) [Homo sapiens] <400> 49 Met Ser Leu Pro Ser Ser Arg Ala Ala Arg Val Pro Gly Pro Ser Gly 1 5 10 15 Ser Leu Cys Ala Leu Leu Ala Leu Leu Leu Leu Leu Thr Pro Pro Gly 20 25 30 Pro Leu Ala Ser Ala Gly Pro Val Ser Ala Val Leu Thr Glu Leu Arg 35 40 45 Cys Thr Cys Leu Arg Val Thr Leu Arg Val Asn Pro Lys Thr Ile Gly 50 55 60 Lys Leu Gln Val Phe Pro Ala Gly Pro Gln Cys Ser Lys Val Glu Val 65 70 75 80 Val Ala Ser Leu Lys Asn Gly Lys Gln Val Cys Leu Asp Pro Glu Ala 85 90 95 Pro Phe Leu Lys Lys Val Ile Gln Lys Ile Leu Asp Ser Gly Asn Lys 100 105 110 Lys Asn <210> 50 <211> 604 <212> PRT <213> NP_892007.1 baculoviral IAP repeat-containing protein 3 (BIRC3) [Homo sapiens] <400> 50 Met Asn Ile Val Glu Asn Ser Ile Phe Leu Ser Asn Leu Met Lys Ser 1 5 10 15 Ala Asn Thr Phe Glu Leu Lys Tyr Asp Leu Ser Cys Glu Leu Tyr Arg 20 25 30 Met Ser Thr Tyr Ser Thr Phe Pro Ala Gly Val Pro Val Ser Glu Arg 35 40 45 Ser Leu Ala Arg Ala Gly Phe Tyr Tyr Thr Gly Val Asn Asp Lys Val 50 55 60 Lys Cys Phe Cys Cys Gly Leu Met Leu Asp Asn Trp Lys Arg Gly Asp 65 70 75 80 Ser Pro Thr Glu Lys His Lys Lys Leu Tyr Pro Ser Cys Arg Phe Val 85 90 95 Gln Ser Leu Asn Ser Val Asn Asn Leu Glu Ala Thr Ser Gln Pro Thr 100 105 110 Phe Pro Ser Ser Val Thr Asn Ser Thr His Ser Leu Leu Pro Gly Thr 115 120 125 Glu Asn Ser Gly Tyr Phe Arg Gly Ser Tyr Ser Asn Ser Pro Ser Asn 130 135 140 Pro Val Asn Ser Arg Ala Asn Gln Asp Phe Ser Ala Leu Met Arg Ser 145 150 155 160 Ser Tyr His Cys Ala Met Asn Asn Glu Asn Ala Arg Leu Leu Thr Phe 165 170 175 Gln Thr Trp Pro Leu Thr Phe Leu Ser Pro Thr Asp Leu Ala Lys Ala 180 185 190 Gly Phe Tyr Tyr Ile Gly Pro Gly Asp Arg Val Ala Cys Phe Ala Cys 195 200 205 Gly Gly Lys Leu Ser Asn Trp Glu Pro Lys Asp Asn Ala Met Ser Glu 210 215 220 His Leu Arg His Phe Pro Lys Cys Pro Phe Ile Glu Asn Gln Leu Gln 225 230 235 240 Asp Thr Ser Arg Tyr Thr Val Ser Asn Leu Ser Met Gln Thr His Ala 245 250 255 Ala Arg Phe Lys Thr Phe Phe Asn Trp Pro Ser Ser Val Leu Val Asn 260 265 270 Pro Glu Gln Leu Ala Ser Ala Gly Phe Tyr Tyr Val Gly Asn Ser Asp 275 280 285 Asp Val Lys Cys Phe Cys Cys Asp Gly Gly Leu Arg Cys Trp Glu Ser 290 295 300 Gly Asp Asp Pro Trp Val Gln His Ala Lys Trp Phe Pro Arg Cys Glu 305 310 315 320 Tyr Leu Ile Arg Ile Lys Gly Gln Glu Phe Ile Arg Gln Val Gln Ala 325 330 335 Ser Tyr Pro His Leu Leu Glu Gln Leu Leu Ser Thr Ser Asp Ser Pro 340 345 350 Gly Asp Glu Asn Ala Glu Ser Ser Ile Ile His Phe Glu Pro Gly Glu 355 360 365 Asp His Ser Glu Asp Ala Ile Met Met Asn Thr Pro Val Ile Asn Ala 370 375 380 Ala Val Glu Met Gly Phe Ser Arg Ser Leu Val Lys Gln Thr Val Gln 385 390 395 400 Arg Lys Ile Leu Ala Thr Gly Glu Asn Tyr Arg Leu Val Asn Asp Leu 405 410 415 Val Leu Asp Leu Leu Asn Ala Glu Asp Glu Ile Arg Glu Glu Glu Arg 420 425 430 Glu Arg Ala Thr Glu Glu Lys Glu Ser Asn Asp Leu Leu Leu Ile Arg 435 440 445 Lys Asn Arg Met Ala Leu Phe Gln His Leu Thr Cys Val Ile Pro Ile 450 455 460 Leu Asp Ser Leu Leu Thr Ala Gly Ile Ile Asn Glu Gln Glu His Asp 465 470 475 480 Val Ile Lys Gln Lys Thr Gln Thr Ser Leu Gln Ala Arg Glu Leu Ile 485 490 495 Asp Thr Ile Leu Val Lys Gly Asn Ile Ala Ala Thr Val Phe Arg Asn 500 505 510 Ser Leu Gln Glu Ala Glu Ala Val Leu Tyr Glu His Leu Phe Val Gln 515 520 525 Gln Asp Ile Lys Tyr Ile Pro Thr Glu Asp Val Ser Asp Leu Pro Val 530 535 540 Glu Glu Gln Leu Arg Arg Leu Gln Glu Glu Arg Thr Cys Lys Val Cys 545 550 555 560 Met Asp Lys Glu Val Ser Ile Val Phe Ile Pro Cys Gly His Leu Val 565 570 575 Val Cys Lys Asp Cys Ala Pro Ser Leu Arg Lys Cys Pro Ile Cys Arg 580 585 590 Ser Thr Ile Lys Gly Thr Val Arg Thr Phe Leu Ser 595 600 <210> 51 <211> 175 <212> PRT <213> CAG46735.1 BCL2A1 [Homo sapiens] <400> 51 Met Thr Asp Cys Glu Phe Gly Tyr Ile Tyr Arg Leu Ala Gln Asp Tyr 1 5 10 15 Leu Gln Cys Val Leu Gln Ile Pro Gln Pro Gly Ser Gly Pro Ser Lys 20 25 30 Thr Ser Arg Val Leu Gln Asn Val Ala Phe Ser Val Gln Lys Glu Val 35 40 45 Glu Lys Asn Leu Lys Ser Cys Leu Asp Asn Val Asn Val Val Ser Val 50 55 60 Asp Thr Ala Arg Thr Leu Phe Asn Gln Val Met Glu Lys Glu Phe Glu 65 70 75 80 Asp Gly Ile Ile Asn Trp Gly Arg Ile Val Thr Ile Phe Ala Phe Glu 85 90 95 Gly Ile Leu Ile Lys Lys Leu Leu Arg Gln Gln Ile Ala Pro Asp Val 100 105 110 Asp Thr Tyr Lys Glu Ile Ser Tyr Phe Val Ala Glu Phe Ile Met Asn 115 120 125 Asn Thr Gly Glu Trp Ile Arg Gln Asn Gly Gly Trp Glu Asn Gly Phe 130 135 140 Val Lys Lys Phe Glu Pro Lys Ser Gly Trp Met Thr Phe Leu Glu Val 145 150 155 160 Thr Gly Lys Ile Cys Glu Met Leu Ser Leu Leu Lys Gln Tyr Cys 165 170 175 <210> 52 <211> 250 <212> PRT <213> CAG38788.1 GCH1 [Homo sapiens] <400> 52 Met Glu Lys Gly Pro Val Arg Ala Pro Ala Glu Lys Pro Arg Gly Ala 1 5 10 15 Arg Cys Ser Asn Gly Phe Pro Glu Arg Asp Pro Pro Arg Pro Gly Pro 20 25 30 Ser Arg Pro Ala Glu Lys Pro Pro Arg Pro Glu Ala Lys Ser Ala Gln 35 40 45 Pro Ala Asp Gly Trp Lys Gly Glu Arg Pro Arg Ser Glu Glu Asp Asn 50 55 60 Glu Leu Asn Leu Pro Asn Leu Ala Ala Ala Tyr Ser Ser Ile Leu Ser 65 70 75 80 Ser Leu Gly Glu Asn Pro Gln Arg Gln Gly Leu Leu Lys Thr Pro Trp 85 90 95 Arg Ala Ala Ser Ala Met Gln Phe Phe Thr Lys Gly Tyr Gln Glu Thr 100 105 110 Ile Ser Asp Val Leu Asn Asp Ala Ile Phe Asp Glu Asp His Asp Glu 115 120 125 Met Val Ile Val Lys Asp Ile Asp Met Phe Ser Met Cys Glu His His 130 135 140 Leu Val Pro Phe Val Gly Lys Val His Ile Gly Tyr Leu Pro Asn Lys 145 150 155 160 Gln Val Leu Gly Leu Ser Lys Leu Ala Arg Ile Val Glu Ile Tyr Ser 165 170 175 Arg Arg Leu Gln Val Gln Glu Arg Leu Thr Lys Gln Ile Ala Val Ala 180 185 190 Ile Thr Glu Ala Leu Arg Pro Ala Gly Val Gly Val Val Val Glu Ala 195 200 205 Thr His Met Cys Met Val Met Arg Gly Val Gln Lys Met Asn Ser Lys 210 215 220 Thr Val Thr Ser Thr Met Leu Gly Val Phe Arg Glu Asp Pro Lys Thr 225 230 235 240 Arg Glu Glu Phe Leu Thr Leu Ile Arg Ser 245 250 <210> 53 <211> 396 <212> PRT <213> NP_001191.1 bone morphogenetic protein 2 preproprotein (BMP2) [Homo sapiens] <400> 53 Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 1 5 10 15 Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 20 25 30 Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 35 40 45 Val Leu Ser Glu Phe Glu Leu Arg Leu Leu Ser Met Phe Gly Leu Lys 50 55 60 Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 65 70 75 80 Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 85 90 95 His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 100 105 110 His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 115 120 125 Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 130 135 140 Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 145 150 155 160 Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 165 170 175 Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 180 185 190 Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 195 200 205 Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 210 215 220 Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 225 230 235 240 Lys Arg His Val Arg Ile Ser Arg Ser Leu His Gln Asp Glu His Ser 245 250 255 Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 260 265 270 Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 275 280 285 Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 290 295 300 Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 305 310 315 320 His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 325 330 335 Leu Asn Ser Thr Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val 340 345 350 Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 355 360 365 Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Asn 370 375 380 Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 385 390 395 <210> 54 <211> 272 <212> PRT <213> NP_003947.1 cholesterol 25-hydroxylase (CH25H) [Homo sapiens] <400> 54 Met Ser Cys His Asn Cys Ser Asp Pro Gln Val Leu Cys Ser Ser Gly 1 5 10 15 Gln Leu Phe Leu Gln Pro Leu Trp Asp His Leu Arg Ser Trp Glu Ala 20 25 30 Leu Leu Gln Ser Pro Phe Phe Pro Val Ile Phe Ser Ile Thr Thr Tyr 35 40 45 Val Gly Phe Cys Leu Pro Phe Val Val Leu Asp Ile Leu Cys Ser Trp 50 55 60 Val Pro Ala Leu Arg Arg Tyr Lys Ile His Pro Asp Phe Ser Pro Ser 65 70 75 80 Ala Gln Gln Leu Leu Pro Cys Leu Gly Gln Thr Leu Tyr Gln His Val 85 90 95 Met Phe Val Phe Pro Val Thr Leu Leu His Trp Ala Arg Ser Pro Ala 100 105 110 Leu Leu Pro His Glu Ala Pro Glu Leu Leu Leu Leu Leu His His Ile 115 120 125 Leu Phe Cys Leu Leu Leu Phe Asp Met Glu Phe Phe Val Trp His Leu 130 135 140 Leu His His Lys Val Pro Trp Leu Tyr Arg Thr Phe His Lys Val His 145 150 155 160 His Gln Asn Ser Ser Ser Phe Ala Leu Ala Thr Gln Tyr Met Ser Val 165 170 175 Trp Glu Leu Phe Ser Leu Gly Phe Phe Asp Met Met Asn Val Thr Leu 180 185 190 Leu Gly Cys His Pro Leu Thr Thr Leu Thr Phe His Val Val Asn Ile 195 200 205 Trp Leu Ser Val Glu Asp His Ser Gly Tyr Asn Phe Pro Trp Ser Thr 210 215 220 His Arg Leu Val Pro Phe Gly Trp Tyr Gly Gly Val Val His His Asp 225 230 235 240 Leu His His Ser His Phe Asn Cys Asn Phe Ala Pro Tyr Phe Thr His 245 250 255 Trp Asp Lys Ile Leu Gly Thr Leu Arg Thr Ala Ser Val Pro Ala Arg 260 265 270 <210> 55 <211> 159 <212> PRT <213> AAH40592.1 TSLP protein [Homo sapiens] <400> 55 Met Lys Cys Leu Gly Gln Ser Lys Lys Glu Glu Val Ser Phe Arg Lys 1 5 10 15 Ile Phe Ile Leu Gln Leu Val Gly Leu Val Leu Thr Tyr Asp Phe Thr 20 25 30 Asn Cys Asp Phe Glu Lys Ile Lys Ala Ala Tyr Leu Ser Thr Ile Ser 35 40 45 Lys Asp Leu Ile Thr Tyr Met Ser Gly Thr Lys Ser Thr Glu Phe Asn 50 55 60 Asn Thr Val Ser Cys Ser Asn Arg Pro His Cys Leu Thr Glu Ile Gln 65 70 75 80 Ser Leu Thr Phe Asn Pro Thr Ala Gly Cys Ala Ser Leu Ala Lys Glu 85 90 95 Met Phe Ala Met Lys Thr Lys Ala Ala Leu Ala Ile Trp Cys Pro Gly 100 105 110 Tyr Ser Glu Thr Gln Ile Asn Ala Thr Gln Ala Met Lys Lys Arg Arg 115 120 125 Lys Arg Lys Val Thr Thr Asn Lys Cys Leu Glu Gln Val Ser Gln Leu 130 135 140 Gln Gly Leu Trp Arg Arg Phe Asn Arg Pro Leu Leu Lys Gln Gln 145 150 155 <210> 56 <211> 472 <212> PRT <213> NP_001538.4 IFIT2 [Homo sapiens] <400> 56 Met Ser Glu Asn Asn Lys Asn Ser Leu Glu Ser Ser Leu Arg Gln Leu 1 5 10 15 Lys Cys His Phe Thr Trp Asn Leu Met Glu Gly Glu Asn Ser Leu Asp 20 25 30 Asp Phe Glu Asp Lys Val Phe Tyr Arg Thr Glu Phe Gln Asn Arg Glu 35 40 45 Phe Lys Ala Thr Met Cys Asn Leu Leu Ala Tyr Leu Lys His Leu Lys 50 55 60 Gly Gln Asn Glu Ala Ala Leu Glu Cys Leu Arg Lys Ala Glu Glu Leu 65 70 75 80 Ile Gln Gln Glu His Ala Asp Gln Ala Glu Ile Arg Ser Leu Val Thr 85 90 95 Trp Gly Asn Tyr Ala Trp Val Tyr Tyr His Met Gly Arg Leu Ser Asp 100 105 110 Val Gln Ile Tyr Val Asp Lys Val Lys His Val Cys Glu Lys Phe Ser 115 120 125 Ser Pro Tyr Arg Ile Glu Ser Pro Glu Leu Asp Cys Glu Glu Gly Trp 130 135 140 Thr Arg Leu Lys Cys Gly Gly Asn Gln Asn Glu Arg Ala Lys Val Cys 145 150 155 160 Phe Glu Lys Ala Leu Glu Lys Lys Pro Lys Asn Pro Glu Phe Thr Ser 165 170 175 Gly Leu Ala Ile Ala Ser Tyr Arg Leu Asp Asn Trp Pro Pro Ser Gln 180 185 190 Asn Ala Ile Asp Pro Leu Arg Gln Ala Ile Arg Leu Asn Pro Asp Asn 195 200 205 Gln Tyr Leu Lys Val Leu Leu Ala Leu Lys Leu His Lys Met Arg Glu 210 215 220 Glu Gly Glu Glu Glu Gly Glu Gly Glu Lys Leu Val Glu Glu Ala Leu 225 230 235 240 Glu Lys Ala Pro Gly Val Thr Asp Val Leu Arg Ser Ala Ala Lys Phe 245 250 255 Tyr Arg Arg Lys Asp Glu Pro Asp Lys Ala Ile Glu Leu Leu Lys Lys 260 265 270 Ala Leu Glu Tyr Ile Pro Asn Asn Ala Tyr Leu His Cys Gln Ile Gly 275 280 285 Cys Cys Tyr Arg Ala Lys Val Phe Gln Val Met Asn Leu Arg Glu Asn 290 295 300 Gly Met Tyr Gly Lys Arg Lys Leu Leu Glu Leu Ile Gly His Ala Val 305 310 315 320 Ala His Leu Lys Lys Ala Asp Glu Ala Asn Asp Asn Leu Phe Arg Val 325 330 335 Cys Ser Ile Leu Ala Ser Leu His Ala Leu Ala Asp Gln Tyr Glu Asp 340 345 350 Ala Glu Tyr Tyr Phe Gln Lys Glu Phe Ser Lys Glu Leu Thr Pro Val 355 360 365 Ala Lys Gln Leu Leu His Leu Arg Tyr Gly Asn Phe Gln Leu Tyr Gln 370 375 380 Met Lys Cys Glu Asp Lys Ala Ile His His Phe Ile Glu Gly Val Lys 385 390 395 400 Ile Asn Gln Lys Ser Arg Glu Lys Glu Lys Met Lys Asp Lys Leu Gln 405 410 415 Lys Ile Ala Lys Met Arg Leu Ser Lys Asn Gly Ala Asp Ser Glu Ala 420 425 430 Leu His Val Leu Ala Phe Leu Gln Glu Leu Asn Glu Lys Met Gln Gln 435 440 445 Ala Asp Glu Asp Ser Glu Arg Gly Leu Glu Ser Gly Ser Leu Ile Pro 450 455 460 Ser Ala Ser Ser Trp Asn Gly Glu 465 470 <210> 57 <211> 714 <212> PRT <213> NP_055401.1 hormonally up-regulated neu tumor-associated kinase (HUNK) [Homo sapiens] <400> 57 Met Pro Ala Ala Ala Gly Asp Gly Leu Leu Gly Glu Pro Ala Ala Pro 1 5 10 15 Gly Gly Gly Gly Gly Ala Glu Asp Ala Ala Arg Pro Ala Ala Ala Cys 20 25 30 Glu Gly Ser Phe Leu Pro Ala Trp Val Ser Gly Val Pro Arg Glu Arg 35 40 45 Leu Arg Asp Phe Gln His His Lys Arg Val Gly Asn Tyr Leu Ile Gly 50 55 60 Ser Arg Lys Leu Gly Glu Gly Ser Phe Ala Lys Val Arg Glu Gly Leu 65 70 75 80 His Val Leu Thr Gly Glu Lys Val Ala Ile Lys Val Ile Asp Lys Lys 85 90 95 Arg Ala Lys Lys Asp Thr Tyr Val Thr Lys Asn Leu Arg Arg Glu Gly 100 105 110 Gln Ile Gln Gln Met Ile Arg His Pro Asn Ile Thr Gln Leu Leu Asp 115 120 125 Ile Leu Glu Thr Glu Asn Ser Tyr Tyr Leu Val Met Glu Leu Cys Pro 130 135 140 Gly Gly Asn Leu Met His Lys Ile Tyr Glu Lys Lys Arg Leu Glu Glu 145 150 155 160 Ser Glu Ala Arg Arg Tyr Ile Arg Gln Leu Ile Ser Ala Val Glu His 165 170 175 Leu His Arg Ala Gly Val Val His Arg Asp Leu Lys Ile Glu Asn Leu 180 185 190 Leu Leu Asp Glu Asp Asn Asn Ile Lys Leu Ile Asp Phe Gly Leu Ser 195 200 205 Asn Cys Ala Gly Ile Leu Gly Tyr Ser Asp Pro Phe Ser Thr Gln Cys 210 215 220 Gly Ser Pro Ala Tyr Ala Ala Pro Glu Leu Leu Ala Arg Lys Lys Tyr 225 230 235 240 Gly Pro Lys Ile Asp Val Trp Ser Ile Gly Val Asn Met Tyr Ala Met 245 250 255 Leu Thr Gly Thr Leu Pro Phe Thr Val Glu Pro Phe Ser Leu Arg Ala 260 265 270 Leu Tyr Gln Lys Met Val Asp Lys Glu Met Asn Pro Leu Pro Thr Gln 275 280 285 Leu Ser Thr Gly Ala Ile Ser Phe Leu Arg Ser Leu Leu Glu Pro Asp 290 295 300 Pro Val Lys Arg Pro Asn Ile Gln Gln Ala Leu Ala Asn Arg Trp Leu 305 310 315 320 Asn Glu Asn Tyr Thr Gly Lys Val Pro Cys Asn Val Thr Tyr Pro Asn 325 330 335 Arg Ile Ser Leu Glu Asp Leu Ser Pro Ser Val Val Leu His Met Thr 340 345 350 Glu Lys Leu Gly Tyr Lys Asn Ser Asp Val Ile Asn Thr Val Leu Ser 355 360 365 Asn Arg Ala Cys His Ile Leu Ala Ile Tyr Phe Leu Leu Asn Lys Lys 370 375 380 Leu Glu Arg Tyr Leu Ser Gly Lys Ser Asp Ile Gln Asp Ser Leu Cys 385 390 395 400 Tyr Lys Thr Arg Leu Tyr Gln Ile Glu Lys Tyr Arg Ala Pro Lys Glu 405 410 415 Ser Tyr Glu Ala Ser Leu Asp Thr Trp Thr Arg Asp Leu Glu Phe His 420 425 430 Ala Val Gln Asp Lys Lys Pro Lys Glu Gln Glu Lys Arg Gly Asp Phe 435 440 445 Leu His Arg Pro Phe Ser Lys Lys Leu Asp Lys Asn Leu Pro Ser His 450 455 460 Lys Gln Pro Ser Gly Ser Leu Met Thr Gln Ile Gln Asn Thr Lys Ala 465 470 475 480 Leu Leu Lys Asp Arg Lys Ala Ser Lys Ser Ser Phe Pro Asp Lys Asp 485 490 495 Ser Phe Gly Cys Arg Asn Ile Phe Arg Lys Thr Ser Asp Ser Asn Cys 500 505 510 Val Ala Ser Ser Ser Met Glu Phe Ile Pro Val Pro Pro Pro Arg Thr 515 520 525 Pro Arg Ile Val Lys Lys Pro Glu Pro His Gln Pro Gly Pro Gly Ser 530 535 540 Thr Gly Ile Pro His Lys Glu Asp Pro Leu Met Leu Asp Met Val Arg 545 550 555 560 Ser Phe Glu Ser Val Asp Arg Asp Asp His Val Glu Val Leu Ser Pro 565 570 575 Ser His His Tyr Arg Ile Leu Asn Ser Pro Val Ser Leu Ala Arg Arg 580 585 590 Asn Ser Ser Glu Arg Thr Leu Ser Pro Gly Leu Pro Ser Gly Ser Met 595 600 605 Ser Pro Leu His Thr Pro Leu His Pro Thr Leu Val Ser Phe Ala His 610 615 620 Glu Asp Lys Asn Ser Pro Pro Lys Glu Glu Gly Leu Cys Cys Pro Pro 625 630 635 640 Pro Val Pro Ser Asn Gly Pro Met Gln Pro Leu Gly Ser Pro Asn Cys 645 650 655 Val Lys Ser Arg Gly Arg Phe Pro Met Met Gly Ile Gly Gln Met Leu 660 665 670 Arg Lys Arg His Gln Ser Leu Gln Pro Ser Ala Asp Arg Pro Leu Glu 675 680 685 Ala Ser Leu Pro Pro Leu Gln Pro Leu Ala Pro Val Asn Leu Ala Phe 690 695 700 Asp Met Ala Asp Gly Val Lys Thr Gln Cys 705 710 <210> 58 <211> 160 <212> PRT <213> NP_056490.2 GADD45B [Homo sapiens] <400> 58 Met Thr Leu Glu Glu Leu Val Ala Cys Asp Asn Ala Ala Gln Lys Met 1 5 10 15 Gln Thr Val Thr Ala Ala Val Glu Glu Leu Leu Val Ala Ala Gln Arg 20 25 30 Gln Asp Arg Leu Thr Val Gly Val Tyr Glu Ser Ala Lys Leu Met Asn 35 40 45 Val Asp Pro Asp Ser Val Val Leu Cys Leu Leu Ala Ile Asp Glu Glu 50 55 60 Glu Glu Asp Asp Ile Ala Leu Gln Ile His Phe Thr Leu Ile Gln Ser 65 70 75 80 Phe Cys Cys Asp Asn Asp Ile Asn Ile Val Arg Val Ser Gly Met Gln 85 90 95 Arg Leu Ala Gln Leu Leu Gly Glu Pro Ala Glu Thr Gln Gly Thr Thr 100 105 110 Glu Ala Arg Asp Leu His Cys Leu Leu Val Thr Asn Pro His Thr Asp 115 120 125 Ala Trp Lys Ser His Gly Leu Val Glu Val Ala Ser Tyr Cys Glu Glu 130 135 140 Ser Arg Gly Asn Asn Gln Trp Val Pro Tyr Ile Ser Leu Gln Glu Arg 145 150 155 160 <210> 59 <211> 480 <212> PRT <213> AAH95399.1 Kruppel-like factor 10 (KLF10) [Homo sapiens] <400> 59 Met Leu Asn Phe Gly Ala Ser Leu Gln Gln Thr Ala Glu Glu Arg Met 1 5 10 15 Glu Met Ile Ser Glu Arg Pro Lys Glu Ser Met Tyr Ser Trp Asn Lys 20 25 30 Thr Ala Glu Lys Ser Asp Phe Glu Ala Val Glu Ala Leu Met Ser Met 35 40 45 Ser Cys Ser Trp Lys Ser Asp Phe Lys Lys Tyr Val Glu Asn Arg Pro 50 55 60 Val Thr Pro Val Ser Asp Leu Ser Glu Glu Glu Asn Leu Leu Pro Gly 65 70 75 80 Thr Pro Asp Phe His Thr Ile Pro Ala Phe Cys Leu Thr Pro Pro Tyr 85 90 95 Ser Pro Ser Asp Phe Glu Pro Ser Gln Val Ser Asn Leu Met Ala Pro 100 105 110 Ala Pro Ser Thr Val His Phe Lys Ser Leu Ser Asp Thr Ala Lys Pro 115 120 125 His Ile Ala Ala Pro Phe Lys Glu Glu Glu Lys Ser Pro Val Ser Ala 130 135 140 Pro Lys Leu Pro Lys Ala Gln Ala Thr Ser Val Ile Arg His Thr Ala 145 150 155 160 Asp Ala Gln Leu Cys Asn His Gln Thr Cys Pro Met Lys Ala Ala Ser 165 170 175 Ile Leu Asn Tyr Gln Asn Asn Ser Phe Arg Arg Arg Thr His Leu Asn 180 185 190 Val Glu Ala Ala Arg Lys Asn Ile Pro Cys Ala Ala Val Ser Pro Asn 195 200 205 Arg Ser Lys Cys Glu Arg Asn Thr Val Ala Asp Val Asp Glu Lys Ala 210 215 220 Ser Ala Ala Leu Tyr Asp Phe Ser Val Pro Ser Ser Glu Thr Val Ile 225 230 235 240 Cys Arg Ser Gln Pro Ala Pro Val Ser Pro Gln Gln Lys Ser Val Leu 245 250 255 Val Ser Pro Pro Ala Val Ser Ala Gly Gly Val Pro Pro Met Pro Val 260 265 270 Ile Cys Gln Met Val Pro Leu Pro Ala Asn Asn Pro Val Val Thr Thr 275 280 285 Val Val Pro Ser Thr Pro Pro Ser Gln Pro Pro Ala Val Cys Pro Pro 290 295 300 Val Val Phe Met Gly Thr Gln Val Pro Lys Gly Ala Val Met Phe Val 305 310 315 320 Val Pro Gln Pro Val Val Gln Ser Ser Lys Pro Pro Val Val Ser Pro 325 330 335 Asn Gly Thr Arg Leu Ser Pro Ile Ala Pro Ala Pro Gly Phe Ser Pro 340 345 350 Ser Ala Ala Lys Val Thr Pro Gln Ile Asp Ser Ser Arg Ile Arg Ser 355 360 365 His Ile Cys Ser His Pro Gly Cys Gly Lys Thr Tyr Phe Lys Ser Ser 370 375 380 His Leu Lys Ala His Thr Arg Thr His Thr Gly Glu Lys Pro Phe Ser 385 390 395 400 Cys Ser Trp Lys Gly Cys Glu Arg Arg Phe Ala Arg Ser Asp Glu Leu 405 410 415 Ser Arg His Arg Arg Thr His Thr Gly Glu Lys Lys Phe Ala Cys Pro 420 425 430 Met Cys Asp Arg Arg Phe Met Arg Ser Asp His Leu Thr Lys His Ala 435 440 445 Arg Arg His Leu Ser Ala Lys Lys Leu Pro Asn Trp Gln Met Glu Val 450 455 460 Ser Lys Leu Asn Asp Ile Ala Leu Pro Pro Thr Pro Ala Pro Thr Gln 465 470 475 480 <210> 60 <211> 154 <212> PRT <213> CAA54920.1 Id1 [Homo sapiens] <400> 60 Met Lys Val Ala Ser Gly Ser Thr Ala Thr Ala Ala Ala Gly Pro Ser 1 5 10 15 Cys Ala Leu Lys Ala Gly Lys Thr Ala Ser Gly Ala Gly Glu Val Val 20 25 30 Arg Cys Leu Ser Glu Gln Ser Val Ala Ile Ser Arg Cys Arg Gly Ala 35 40 45 Gly Ala Arg Leu Pro Ala Leu Leu Asp Glu Gln Gln Val Asn Val Leu 50 55 60 Leu Tyr Asp Met Asn Gly Cys Tyr Ser Arg Leu Lys Glu Leu Val Pro 65 70 75 80 Thr Leu Pro Gln Asn Arg Lys Val Ser Lys Val Glu Ile Leu Gln His 85 90 95 Val Ile Asp Tyr Ile Arg Asp Leu Gln Leu Glu Leu Asn Ser Glu Ser 100 105 110 Glu Val Gly Thr Pro Gly Gly Arg Gly Leu Pro Val Arg Ala Pro Leu 115 120 125 Ser Thr Leu Asn Gly Glu Ile Ser Ala Leu Thr Ala Glu Ala Ala Cys 130 135 140 Val Pro Ala Asp Asp Arg Ile Leu Cys Arg 145 150 <210> 61 <211> 232 <212> PRT <213> AAH34145.1 TM4SF1 protein [Homo sapiens] <400> 61 Met Cys Tyr Gly Lys Cys Ala Arg Cys Ile Gly His Ser Leu Val Gly 1 5 10 15 Leu Ala Leu Leu Cys Ile Ala Ala Asn Ile Leu Leu Tyr Phe Pro Asn 20 25 30 Gly Glu Thr Lys Tyr Ala Ser Glu Asn His Leu Ser Arg Phe Val Trp 35 40 45 Phe Phe Ser Gly Ile Val Gly Gly Gly Leu Leu Met Leu Leu Pro Ala 50 55 60 Phe Val Phe Ile Gly Leu Glu Gln Asp Asp Cys Cys Gly Cys Cys Gly 65 70 75 80 His Glu Asn Cys Gly Lys Arg Cys Ala Met Leu Ser Ser Val Leu Ala 85 90 95 Ala Leu Ile Gly Ile Ala Gly Ser Gly Tyr Cys Val Ile Val Ala Ala 100 105 110 Leu Gly Leu Ala Glu Gly Pro Leu Cys Leu Asp Ser Leu Gly Gln Trp 115 120 125 Asn Tyr Thr Phe Ala Ser Thr Glu Gly Gln Tyr Leu Leu Asp Thr Ser 130 135 140 Thr Trp Ser Glu Cys Thr Glu Pro Lys His Ile Val Glu Trp Asn Val 145 150 155 160 Ser Leu Phe Ser Ile Leu Leu Ala Leu Gly Gly Ile Glu Phe Ile Leu 165 170 175 Cys Leu Ile Gln Val Ile Asn Gly Val Leu Gly Gly Ile Cys Gly Phe 180 185 190 Cys Cys Ser His Gln Gln Gln Met Thr Ala Lys Arg Thr Asn Pro Gly 195 200 205 Gln Ser His Asn Leu Pro Leu Phe His Cys Asn Leu Tyr Ile Ser Leu 210 215 220 Val Phe Ile Cys Lys Thr Leu Tyr 225 230 <210> 62 <211> 609 <212> PRT <213> NP_001307488.1 cysteine/serine-rich nuclear protein 1 isoform a (CSRNP1) [Homo sapiens] <400> 62 Met Ser Glu Thr Arg Leu Arg Leu Ser Val Pro Arg Pro Gln Ser Thr 1 5 10 15 Ser Gly Thr Thr Met Thr Gly Leu Leu Lys Arg Lys Phe Asp Gln Leu 20 25 30 Asp Glu Asp Asn Ser Ser Val Ser Ser Ser Ser Ser Ser Ser Gly Cys 35 40 45 Gln Ser Arg Ser Cys Ser Pro Ser Ser Ser Val Ser Arg Ala Trp Asp 50 55 60 Ser Glu Glu Glu Gly Pro Trp Asp Gln Met Pro Leu Pro Asp Arg Asp 65 70 75 80 Phe Cys Gly Pro Arg Ser Phe Thr Pro Leu Ser Ile Leu Lys Arg Ala 85 90 95 Arg Arg Glu Arg Pro Gly Arg Val Ala Phe Asp Gly Ile Thr Val Phe 100 105 110 Tyr Phe Pro Arg Cys Gln Gly Phe Thr Ser Val Pro Ser Arg Gly Gly 115 120 125 Cys Thr Leu Gly Met Ala Leu Arg His Ser Ala Cys Arg Arg Phe Ser 130 135 140 Leu Ala Glu Phe Ala Gln Glu Gln Ala Arg Ala Arg His Glu Lys Leu 145 150 155 160 Arg Gln Arg Leu Lys Glu Glu Lys Leu Glu Met Leu Gln Trp Lys Leu 165 170 175 Ser Ala Ala Gly Val Pro Gln Ala Glu Ala Gly Leu Pro Pro Val Val 180 185 190 Asp Ala Ile Asp Asp Ala Ser Val Glu Glu Asp Leu Ala Val Ala Val 195 200 205 Ala Gly Gly Arg Leu Glu Glu Val Ser Phe Leu Gln Pro Tyr Pro Ala 210 215 220 Arg Arg Arg Arg Ala Leu Leu Arg Ala Ser Gly Val Arg Arg Ile Asp 225 230 235 240 Arg Glu Glu Lys Arg Glu Leu Gln Ala Leu Arg Gln Ser Arg Glu Asp 245 250 255 Cys Gly Cys His Cys Asp Arg Ile Cys Asp Pro Glu Thr Cys Ser Cys 260 265 270 Ser Leu Ala Gly Ile Lys Cys Gln Met Asp His Thr Ala Phe Pro Cys 275 280 285 Gly Cys Cys Arg Glu Gly Cys Glu Asn Pro Met Gly Arg Val Glu Phe 290 295 300 Asn Gln Ala Arg Val Gln Thr His Phe Ile His Thr Leu Thr Arg Leu 305 310 315 320 Gln Leu Glu Gln Glu Ala Glu Ser Phe Arg Glu Leu Glu Ala Pro Ala 325 330 335 Gln Gly Ser Pro Pro Ser Pro Gly Glu Glu Ala Leu Val Pro Thr Phe 340 345 350 Pro Leu Ala Lys Pro Pro Met Asn Asn Glu Leu Gly Asp Asn Ser Cys 355 360 365 Ser Ser Asp Met Thr Asp Ser Ser Thr Ala Ser Ser Ser Ala Ser Gly 370 375 380 Thr Ser Glu Ala Pro Asp Cys Pro Thr His Pro Gly Leu Pro Gly Pro 385 390 395 400 Gly Phe Gln Pro Gly Val Asp Asp Asp Ser Leu Ala Arg Ile Leu Ser 405 410 415 Phe Ser Asp Ser Asp Phe Gly Gly Glu Glu Glu Glu Glu Glu Glu Gly 420 425 430 Ser Val Gly Asn Leu Asp Asn Leu Ser Cys Phe His Pro Ala Asp Ile 435 440 445 Phe Gly Thr Ser Asp Pro Gly Gly Leu Ala Ser Trp Thr His Ser Tyr 450 455 460 Ser Gly Cys Ser Phe Thr Ser Gly Val Leu Asp Glu Asn Ala Asn Leu 465 470 475 480 Asp Ala Ser Cys Phe Leu Asn Gly Gly Leu Glu Gly Ser Arg Glu Gly 485 490 495 Ser Leu Pro Gly Thr Ser Val Pro Pro Ser Met Asp Ala Gly Arg Ser 500 505 510 Ser Ser Val Asp Leu Ser Leu Ser Ser Cys Asp Ser Phe Glu Leu Leu 515 520 525 Gln Ala Leu Pro Asp Tyr Ser Leu Gly Pro His Tyr Thr Ser Gln Lys 530 535 540 Val Ser Asp Ser Leu Asp Asn Ile Glu Ala Pro His Phe Pro Leu Pro 545 550 555 560 Gly Leu Ser Pro Pro Gly Asp Ala Ser Ser Cys Phe Leu Glu Ser Leu 565 570 575 Met Gly Phe Ser Glu Pro Ala Ala Glu Ala Leu Asp Pro Phe Ile Asp 580 585 590 Ser Gln Phe Glu Asp Thr Val Pro Ala Ser Leu Met Glu Pro Val Pro 595 600 605 Val

Claims

ID1(inhibitor of DNA binding 1) 및 HUNK(hormonally upregulated Neu-associated kinase) 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하는 치주염 진단용 조성물.
청구항 1에 있어서, GADD45B(growth arrest and DNA damage inducible beta), PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICAM(intercellular adhesion molecule), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP3(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymic stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), KLF10(kruppel-like factor 10), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 더 포함하는 치주염 진단용 조성물.
청구항 1에 있어서, GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 더 포함하고, 상기 치주염은 노인성 치주염인, 조성물.
청구항 1 내지 3 중 어느 한 항의 조성물을 포함하는 치주염 진단용 키트.
생물학적 시료 내 구강 섬유아세포에 존재하는 ID1(inhibitor of DNA binding 1) 및 HUNK(hormonally upregulated Neu-associated kinase) 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하는, 치주염 진단을 위한 정보제공방법.
청구항 5에 있어서, 상기 mRNA 및 단백질의 발현 수준을 측정하는 단계에서 생물학적 시료 내 구강 섬유아세포에 존재하는 GADD45B(growth arrest and DNA damage inducible beta), PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICAM1(intercellular adhesion molecule 1), ICAM2(intercellular adhesion molecule 2), ICAM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP3(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymic stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), KLF10(kruppel-like factor 10), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 더 측정하는, 치주염 진단을 위한 정보제공방법.
청구항 5에 있어서, 상기 mRNA 및 단백질의 발현 수준을 측정하는 단계에서 생물학적 시료 내 구강 섬유아세포에 존재하는 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 더 측정하고, 상기 치주염은 노인성 치주염인, 방법.
청구항 5 내지 7 중 어느 한 항에 있어서, 상기 생물학적 시료는 구강 내 조직, 세포, 혈액, 혈청, 혈장 및 타액으로 이루어진 군으로부터 선택되는 것인, 방법.
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