JP2022517456A - 臓器健康および疾患をモニタリングするための方法およびシステム - Google Patents
臓器健康および疾患をモニタリングするための方法およびシステム Download PDFInfo
- Publication number
- JP2022517456A JP2022517456A JP2020572967A JP2020572967A JP2022517456A JP 2022517456 A JP2022517456 A JP 2022517456A JP 2020572967 A JP2020572967 A JP 2020572967A JP 2020572967 A JP2020572967 A JP 2020572967A JP 2022517456 A JP2022517456 A JP 2022517456A
- Authority
- JP
- Japan
- Prior art keywords
- cfdna
- sample
- tissue
- cell
- genome
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 126
- 210000000056 organ Anatomy 0.000 title claims abstract description 44
- 238000012544 monitoring process Methods 0.000 title claims abstract description 40
- 230000036541 health Effects 0.000 title claims abstract description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 39
- 201000010099 disease Diseases 0.000 title claims description 34
- 238000011002 quantification Methods 0.000 claims abstract description 34
- 210000001519 tissue Anatomy 0.000 claims description 111
- 239000000523 sample Substances 0.000 claims description 75
- 210000004027 cell Anatomy 0.000 claims description 50
- 108020004414 DNA Proteins 0.000 claims description 40
- 239000012472 biological sample Substances 0.000 claims description 31
- 239000012634 fragment Substances 0.000 claims description 29
- 238000012163 sequencing technique Methods 0.000 claims description 26
- 210000004369 blood Anatomy 0.000 claims description 23
- 239000008280 blood Substances 0.000 claims description 23
- 210000003734 kidney Anatomy 0.000 claims description 22
- 210000002381 plasma Anatomy 0.000 claims description 20
- 230000003321 amplification Effects 0.000 claims description 16
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 16
- 230000008816 organ damage Effects 0.000 claims description 14
- 239000012530 fluid Substances 0.000 claims description 12
- 210000004072 lung Anatomy 0.000 claims description 12
- 210000004185 liver Anatomy 0.000 claims description 10
- 230000000451 tissue damage Effects 0.000 claims description 10
- 238000000605 extraction Methods 0.000 claims description 9
- 230000008774 maternal effect Effects 0.000 claims description 9
- 102000053602 DNA Human genes 0.000 claims description 8
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 claims description 8
- 206010070863 Toxicity to various agents Diseases 0.000 claims description 8
- 238000009396 hybridization Methods 0.000 claims description 8
- 210000002700 urine Anatomy 0.000 claims description 8
- 206010036790 Productive cough Diseases 0.000 claims description 7
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 230000001605 fetal effect Effects 0.000 claims description 7
- 210000002216 heart Anatomy 0.000 claims description 7
- 208000017169 kidney disease Diseases 0.000 claims description 7
- 210000002966 serum Anatomy 0.000 claims description 7
- 210000003802 sputum Anatomy 0.000 claims description 7
- 208000024794 sputum Diseases 0.000 claims description 7
- 238000012408 PCR amplification Methods 0.000 claims description 6
- 210000003296 saliva Anatomy 0.000 claims description 6
- 210000001138 tear Anatomy 0.000 claims description 6
- 238000013382 DNA quantification Methods 0.000 claims description 5
- 210000003756 cervix mucus Anatomy 0.000 claims description 5
- 210000002751 lymph Anatomy 0.000 claims description 5
- 210000004080 milk Anatomy 0.000 claims description 5
- 239000008267 milk Substances 0.000 claims description 5
- 235000013336 milk Nutrition 0.000 claims description 5
- -1 tears Substances 0.000 claims description 5
- 231100000827 tissue damage Toxicity 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 210000001742 aqueous humor Anatomy 0.000 claims description 4
- 210000004556 brain Anatomy 0.000 claims description 4
- 239000013610 patient sample Substances 0.000 claims description 4
- 206010046901 vaginal discharge Diseases 0.000 claims description 4
- 206010061818 Disease progression Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 208000004852 Lung Injury Diseases 0.000 claims description 3
- 206010069363 Traumatic lung injury Diseases 0.000 claims description 3
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims description 3
- 210000000601 blood cell Anatomy 0.000 claims description 3
- 230000005779 cell damage Effects 0.000 claims description 3
- 208000037887 cell injury Diseases 0.000 claims description 3
- 230000005750 disease progression Effects 0.000 claims description 3
- 210000003292 kidney cell Anatomy 0.000 claims description 3
- 231100000515 lung injury Toxicity 0.000 claims description 3
- 210000003205 muscle Anatomy 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 210000004204 blood vessel Anatomy 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 210000001185 bone marrow Anatomy 0.000 claims description 2
- 210000000845 cartilage Anatomy 0.000 claims description 2
- 210000000981 epithelium Anatomy 0.000 claims description 2
- 210000001508 eye Anatomy 0.000 claims description 2
- 210000004907 gland Anatomy 0.000 claims description 2
- 210000002865 immune cell Anatomy 0.000 claims description 2
- 210000000936 intestine Anatomy 0.000 claims description 2
- 210000002569 neuron Anatomy 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000003932 urinary bladder Anatomy 0.000 claims description 2
- 210000004127 vitreous body Anatomy 0.000 claims 3
- 108091092584 GDNA Proteins 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 37
- 238000009826 distribution Methods 0.000 description 35
- 206010028980 Neoplasm Diseases 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 18
- 150000007523 nucleic acids Chemical class 0.000 description 17
- 201000011510 cancer Diseases 0.000 description 14
- 102000039446 nucleic acids Human genes 0.000 description 13
- 108020004707 nucleic acids Proteins 0.000 description 13
- 208000020832 chronic kidney disease Diseases 0.000 description 12
- 238000010801 machine learning Methods 0.000 description 11
- 238000001574 biopsy Methods 0.000 description 10
- 238000004422 calculation algorithm Methods 0.000 description 10
- 230000030833 cell death Effects 0.000 description 10
- 238000001514 detection method Methods 0.000 description 10
- 208000014674 injury Diseases 0.000 description 9
- 238000003556 assay Methods 0.000 description 8
- 239000011159 matrix material Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 102000040430 polynucleotide Human genes 0.000 description 8
- 108091033319 polynucleotide Proteins 0.000 description 8
- 239000002157 polynucleotide Substances 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000012549 training Methods 0.000 description 5
- 230000008733 trauma Effects 0.000 description 5
- 206010067125 Liver injury Diseases 0.000 description 4
- 208000001647 Renal Insufficiency Diseases 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 238000013528 artificial neural network Methods 0.000 description 4
- 239000013060 biological fluid Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 201000000523 end stage renal failure Diseases 0.000 description 4
- 230000001973 epigenetic effect Effects 0.000 description 4
- 231100000753 hepatic injury Toxicity 0.000 description 4
- 201000006370 kidney failure Diseases 0.000 description 4
- 238000012417 linear regression Methods 0.000 description 4
- 230000035935 pregnancy Effects 0.000 description 4
- 238000002203 pretreatment Methods 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 210000005084 renal tissue Anatomy 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 208000031229 Cardiomyopathies Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 238000009534 blood test Methods 0.000 description 3
- 230000003822 cell turnover Effects 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 238000002790 cross-validation Methods 0.000 description 3
- 208000028208 end stage renal disease Diseases 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 230000003862 health status Effects 0.000 description 3
- 206010025135 lupus erythematosus Diseases 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000004055 small Interfering RNA Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000010200 validation analysis Methods 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 230000007067 DNA methylation Effects 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- 208000013875 Heart injury Diseases 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000021908 Myocardial disease Diseases 0.000 description 2
- 206010029260 Neuroblastoma Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 206010036590 Premature baby Diseases 0.000 description 2
- 206010061481 Renal injury Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 108091046869 Telomeric non-coding RNA Proteins 0.000 description 2
- 238000013473 artificial intelligence Methods 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004077 genetic alteration Effects 0.000 description 2
- 231100000118 genetic alteration Toxicity 0.000 description 2
- 208000016361 genetic disease Diseases 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 208000037806 kidney injury Diseases 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 238000007403 mPCR Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000013188 needle biopsy Methods 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 208000030761 polycystic kidney disease Diseases 0.000 description 2
- 238000009598 prenatal testing Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000000513 principal component analysis Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000013106 supervised machine learning method Methods 0.000 description 2
- 229940113082 thymine Drugs 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000013107 unsupervised machine learning method Methods 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 206010000234 Abortion spontaneous Diseases 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 208000006468 Adrenal Cortex Neoplasms Diseases 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 206010061692 Benign muscle neoplasm Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000004458 Myoma Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 208000009893 Nonpenetrating Wounds Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108020003224 Small Nucleolar RNA Proteins 0.000 description 1
- 102000042773 Small Nucleolar RNA Human genes 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 201000002454 adrenal cortex cancer Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008436 biogenesis Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000005189 cardiac health Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 108091092240 circulating cell-free DNA Proteins 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000013527 convolutional neural network Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013135 deep learning Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000002196 fr. b Anatomy 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 238000013412 genome amplification Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000006195 histone acetylation Effects 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 208000025854 malignant tumor of adrenal cortex Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000015994 miscarriage Diseases 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 238000001921 nucleic acid quantification Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000030266 primary brain neoplasm Diseases 0.000 description 1
- 201000003725 primary thrombocytopenia Diseases 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000000734 protein sequencing Methods 0.000 description 1
- 238000011155 quantitative monitoring Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 208000000995 spontaneous abortion Diseases 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000037964 urogenital cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6809—Methods for determination or identification of nucleic acids involving differential detection
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6881—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2537/00—Reactions characterised by the reaction format or use of a specific feature
- C12Q2537/10—Reactions characterised by the reaction format or use of a specific feature the purpose or use of
- C12Q2537/16—Assays for determining copy number or wherein the copy number is of special importance
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/112—Disease subtyping, staging or classification
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Description
本明細書に提供されるシステム、方法および組成物は、健康モニタリング、診断学、または細胞プロファイリングおよび解析のために、試料から遺伝子座特異的cfDNAコピー数シグナルを抽出するための方法に関する。具体的には、本システム、方法および組成物は、試料におけるセルフリーDNA(cfDNA)を解析して、試料における総cfDNAに対する組織または細胞型の相対的寄与を決定するための方法に関する。本明細書に提供される方法は、配列特異的cfDNAカバレッジ、強度またはコピー数シグナルを利用し、cfDNAにおけるメチル化状態の直接的な決定を含まない。
近年、セルフリーDNA(cfDNA)が、疾患診断学のためのバイオマーカー発見のための有望な供給源として現れた。特に、胎児cfDNAおよびインタクトな胎児細胞は、母体血液循環に進入することができる。結果的に、このような胎児の遺伝的材料の解析は、初期非侵襲的出生前検査(NIPT)を可能にすることができる。胎児cfDNAに関するNIPTの実行における重要な課題は、これが典型的には、母体cfDNAと混合されており、よって、cfDNAの解析が、母体の遺伝子型シグナルを説明する必要によって妨害されることである。さらに、cfDNAの解析は、がんの検出および診断のための診断ツールとして有用である。
本開示は、試料におけるcfDNAの組織および/または細胞特異的画分を定量するために、cfDNA遺伝子座特異的コピー数シグナルを抽出するための、試料におけるcfDNAを解析するためのシステム、方法および組成物に関する。
次の詳細な説明において、本明細書の一部を形成する添付の図面の参照が為される。図面において、文脈がそれ以外のことを指示しない限り、同様の記号は典型的に、同様の成分を識別する。詳細な説明、図面および特許請求の範囲に記載されている説明目的の実施形態は、限定を意味するものではない。本明細書に提示されている主題の精神または範囲から逸脱することなく、他の実施形態を利用することができ、他の変化を為すことができる。本明細書に概して記載され図中に説明されている本開示の態様を、その全てが本明細書に明確に企図される多種多様な異なる構成で配置し、置換し、組み合わせ、分離し、設計することができることが容易に理解されるであろう。
一般手順および方法
抽出
PCR増幅
配列決定
いくつかの数値
(実施例1)
凝集されたcfDNAシグナルプロファイルのモデル化
表1
乗法更新
反復加重線形回帰
モデルEPSの導出
教師なし機械学習
教師つき機械学習
(実施例3)
cfDNA研究
パイロット研究
混合物研究
完全研究
多様な臓器研究
多様な移植研究
Claims (33)
- 生体試料におけるセルフリーDNA(cfDNA)を解析する方法であって、
cfDNAを含む生体試料を得るステップと;
前記試料からcfDNAを抽出して、精製されたcfDNAを提供するステップであって、前記精製されたcfDNAが複数のcfDNA断片を含み、各断片が特異的な組織または細胞型に対応する、ステップと;
前記cfDNA断片を定量して、ゲノムワイドcfDNAコピー数プロファイルを生成するステップであって、前記ゲノムワイドcfDNAコピー数プロファイルが複数のコピー数シグナルを含み、各コピー数シグナルがcfDNA断片に対応する、ステップと;
前記ゲノムワイドcfDNAコピー数プロファイルを既知のcfDNAシグネチャーのセットと比較して、細胞損傷、組織損傷または臓器損傷を決定するステップと
を含む方法。 - 前記生体試料が、血液、血漿、血清、尿、脳脊髄液、唾液、リンパ液、房水、硝子体液、蝸牛液、涙、乳汁、痰、腟分泌物、またはこれらのいずれかの組合せを含む、請求項1に記載の方法。
- 定量するステップが、配列決定に基づくDNA分子計数を使用して、前記cfDNAを配列決定する工程を含む、請求項1に記載の方法。
- 目的のcfDNA断片を濃縮するステップをさらに含む、請求項1に記載の方法。
- 定量するステップが、ハイブリダイゼーションに基づくDNA定量化を実行する工程を含む、請求項1に記載の方法。
- 抽出するステップが、gDNAを除外し、かつcfDNA断片を濃縮するための、サイズに基づく濃縮を含む、請求項1に記載の方法。
- 濃縮するステップが、前記cfDNAの増幅を含む、請求項1に記載の方法。
- 増幅が、PCR増幅またはゲノムワイド増幅を含む、請求項7に記載の方法。
- 各コピー数シグナルが、特異的な組織または細胞型由来のcfDNAの相対的寄与を示す、請求項1に記載の方法。
- 前記組織型が、腎臓、筋肉、心臓、血管、肝臓、脳、眼、肺、脂肪、腺、骨、骨髄、軟骨、腸、胃、皮膚または膀胱である、請求項1に記載の方法。
- 前記細胞型が、血球細胞、ニューロン細胞、腎臓細胞、上皮、細胞外基質細胞、ベータ細胞または免疫細胞である、請求項1に記載の方法。
- 前記ゲノムワイドcfDNAプロファイルが、臓器または多臓器健康の査定を提供するために、多臓器由来のcfDNAの量を定量するために使用される、請求項1に記載の方法。
- 前記試料が、対象から定期的に得られ、かつ解析されて、経時的に健康をモニタリングする、請求項1に記載の方法。
- 経時的に臓器移植物をモニタリングするステップをさらに含む、請求項13に記載の方法。
- 前記ゲノムワイドcfDNAプロファイルが、臓器における薬物毒性または有効性を示す、請求項1に記載の方法。
- 前記試料が母体試料であり、前記ゲノムワイドcfDNAプロファイルが胎児健康を示す、請求項1に記載の方法。
- 様々な組織および細胞型に対応する参照cfDNAプロファイルのセットに前記ゲノムワイドcfDNAプロファイルを投射することにより、多臓器が、同時に定量される、請求項1に記載の方法。
- 前記ゲノムワイドcfDNAプロファイルからベースライン参照プロファイルを減算するステップをさらに含む、請求項1に記載の方法。
- 対象における疾患進行をモニタリングする方法であって、
前記対象から生体試料を得るステップであって、前記生体試料がセルフリーDNA(cfDNA)を含む、ステップと;
前記試料における前記cfDNAを定量して、複数のコピー数シグナルを含むゲノムワイドcfDNAプロファイルを得るステップであって、各コピー数シグナルが特異的な細胞型または組織型のcfDNA断片に対応する、ステップと;
前記複数のcfDNAコピー数シグナルを健康な対象の既知のコピー数シグナルのセットと比較するステップと
を含み、前記既知のコピー数シグナルと比較した、前記試料におけるコピー数シグナルの差が、前記対象における疾患進行と相関する、方法。 - 前記cfDNAを定量するステップの前に、総cfDNAが前記試料から濃縮される、請求項19に記載の方法。
- 前記複数のコピー数シグナルを、罹患患者試料の既知のコピー数シグナルのプロファイルと比較するステップをさらに含む、請求項19に記載の方法。
- 前記生体試料が、血液、血漿、血清、尿、脳脊髄液、唾液、リンパ液、房水、硝子体液、蝸牛液、涙、乳汁、痰、腟分泌物、またはこれらのいずれかの組合せを含む、請求項19に記載の方法。
- 定量するステップが、配列決定に基づくDNA分子計数を使用して、前記cfDNAを配列決定する工程を含む、請求項19に記載の方法。
- 定量するステップが、ハイブリダイゼーションに基づくDNA定量化を実行するステップを含む、請求項19に記載の方法。
- 前記疾患が、心不全、肺損傷、糖尿病、クローン病または腎臓疾患から選択される、請求項19に記載の方法。
- 濃縮するステップが、標的化された増幅またはゲノムワイド増幅により、前記cfDNAを増幅する工程を含む、請求項25に記載の方法。
- 対象における組織および臓器健康をモニタリングする方法であって、
前記対象から生体試料を得るステップであって、前記生体試料がセルフリーDNA(cfDNA)を含む、ステップと;
前記試料における前記cfDNAを定量して、複数のコピー数シグナルを含むゲノムワイドcfDNAプロファイルを得るステップであって、各コピー数シグナルが特異的な細胞型または組織型のcfDNA断片に対応する、ステップと;
前記複数のcfDNAコピー数シグナルを、健康な対象の既知のコピー数シグナルのセットと比較するステップと
を含み、前記既知のコピー数シグナルと比較した、前記試料におけるコピー数シグナルの差が、前記対象における臓器健康状態の変化と相関する、方法。 - 前記cfDNAを定量するステップの前に、総cfDNAが前記試料から濃縮される、請求項27に記載の方法。
- 前記複数のコピー数シグナルを、不良な組織または臓器健康を有する患者由来の試料の既知のコピー数シグナルのプロファイルと比較するステップをさらに含む、請求項27に記載の方法。
- 前記生体試料が、血液、血漿、血清、尿、脳脊髄液、唾液、リンパ液、房水、硝子体液、蝸牛液、涙、乳汁、痰、腟分泌物、またはこれらのいずれかの組合せを含む、請求項27に記載の方法。
- 定量するステップが、配列決定に基づくDNA分子計数を使用して、前記cfDNAを配列決定する工程を含む、請求項27に記載の方法。
- 定量するステップが、ハイブリダイゼーションに基づくDNA定量化を実行する工程を含む、請求項27に記載の方法。
- 濃縮するステップが、標的化された増幅またはゲノムワイド増幅により、前記cfDNAを増幅する工程を含む、請求項27に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962796481P | 2019-01-24 | 2019-01-24 | |
US62/796,481 | 2019-01-24 | ||
PCT/US2020/014612 WO2020154402A1 (en) | 2019-01-24 | 2020-01-22 | Methods and systems for monitoring organ health and disease |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2024062693A Division JP2024074960A (ja) | 2019-01-24 | 2024-04-09 | 臓器健康および疾患をモニタリングするための方法およびシステム |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2022517456A true JP2022517456A (ja) | 2022-03-09 |
JPWO2020154402A5 JPWO2020154402A5 (ja) | 2023-01-30 |
Family
ID=69726743
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020572967A Pending JP2022517456A (ja) | 2019-01-24 | 2020-01-22 | 臓器健康および疾患をモニタリングするための方法およびシステム |
Country Status (12)
Country | Link |
---|---|
US (1) | US20210310067A1 (ja) |
EP (1) | EP3914731A1 (ja) |
JP (1) | JP2022517456A (ja) |
KR (1) | KR20210119282A (ja) |
CN (1) | CN112424372A (ja) |
AU (1) | AU2020210912A1 (ja) |
BR (1) | BR112020026133A2 (ja) |
CA (1) | CA3104153A1 (ja) |
IL (1) | IL279433A (ja) |
MX (1) | MX2020014095A (ja) |
SG (1) | SG11202012518WA (ja) |
WO (1) | WO2020154402A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116323978A (zh) * | 2020-10-20 | 2023-06-23 | 深圳华大基因股份有限公司 | 确定孕妇的孕期状态的方法 |
US20230175064A1 (en) * | 2021-02-09 | 2023-06-08 | Illumina, Inc. | Methods and systems for monitoring organ health and disease |
CA3219753A1 (en) * | 2021-05-21 | 2022-11-24 | Kristina KRUGLYAK | Methods and compositions for detecting cancer using fragmentomics |
CN113403395B (zh) * | 2021-06-03 | 2023-03-24 | 南京世和基因生物技术股份有限公司 | 房水cfDNA的提取方法、试剂盒以及在PVRL临床辅助检查中的应用 |
WO2023004204A2 (en) * | 2021-07-23 | 2023-01-26 | Georgetown University | Use of circulating cell-free methylated dna to detect tissue damage |
KR20240051739A (ko) * | 2022-10-13 | 2024-04-22 | 인하대학교 산학협력단 | cfDNA의 구조 변이 서열 검출을 통한 미세잔존질환 진단 방법 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG11201505515XA (en) * | 2012-01-27 | 2015-09-29 | Univ Leland Stanford Junior | Methods for profiling and quantitating cell-free rna |
JP2016512698A (ja) * | 2013-03-15 | 2016-05-09 | イムコア ジーティーアイ ダイアグノスティクス インコーポレイテッド | 尿中セルフリーdnaを用いて腎状態を評価するための方法および組成物 |
EP3165612B1 (en) * | 2014-07-02 | 2021-08-18 | DNA Chip Research Inc. | Method for counting number of nucleic acid molecules |
WO2016015058A2 (en) * | 2014-07-25 | 2016-01-28 | University Of Washington | Methods of determining tissues and/or cell types giving rise to cell-free dna, and methods of identifying a disease or disorder using same |
US10125399B2 (en) * | 2014-10-30 | 2018-11-13 | Personalis, Inc. | Methods for using mosaicism in nucleic acids sampled distal to their origin |
JP6931236B2 (ja) * | 2015-07-23 | 2021-09-01 | ザ チャイニーズ ユニバーシティ オブ ホンコン | 無細胞dnaの断片化パターンの分析 |
WO2018000031A1 (en) * | 2016-06-27 | 2018-01-04 | Olivia Newton-John Cancer Research Institute | Use of cell free dna as a measure of organ health following transplantation |
EP3481966B1 (en) * | 2016-07-06 | 2023-11-08 | Guardant Health, Inc. | Methods for fragmentome profiling of cell-free nucleic acids |
EP3497242A4 (en) * | 2016-08-10 | 2020-05-13 | Grail, Inc. | METHOD FOR ANALYZING NUCLEIC ACID FRAGMENTS |
EP3998350A1 (en) * | 2017-03-17 | 2022-05-18 | Sequenom, Inc. | Methods and processes for assessment of genetic mosaicism |
US11781188B2 (en) * | 2017-04-06 | 2023-10-10 | Cornell University | Methods of detecting cell-free DNA in biological samples |
-
2020
- 2020-01-22 BR BR112020026133-5A patent/BR112020026133A2/pt unknown
- 2020-01-22 MX MX2020014095A patent/MX2020014095A/es unknown
- 2020-01-22 JP JP2020572967A patent/JP2022517456A/ja active Pending
- 2020-01-22 CA CA3104153A patent/CA3104153A1/en active Pending
- 2020-01-22 US US17/250,814 patent/US20210310067A1/en active Pending
- 2020-01-22 KR KR1020207037498A patent/KR20210119282A/ko unknown
- 2020-01-22 CN CN202080003539.6A patent/CN112424372A/zh active Pending
- 2020-01-22 AU AU2020210912A patent/AU2020210912A1/en active Pending
- 2020-01-22 SG SG11202012518WA patent/SG11202012518WA/en unknown
- 2020-01-22 WO PCT/US2020/014612 patent/WO2020154402A1/en unknown
- 2020-01-22 EP EP20708291.8A patent/EP3914731A1/en active Pending
- 2020-12-14 IL IL279433A patent/IL279433A/en unknown
Also Published As
Publication number | Publication date |
---|---|
EP3914731A1 (en) | 2021-12-01 |
MX2020014095A (es) | 2021-03-09 |
IL279433A (en) | 2021-01-31 |
WO2020154402A1 (en) | 2020-07-30 |
BR112020026133A2 (pt) | 2021-07-27 |
SG11202012518WA (en) | 2021-01-28 |
CN112424372A (zh) | 2021-02-26 |
US20210310067A1 (en) | 2021-10-07 |
KR20210119282A (ko) | 2021-10-05 |
CA3104153A1 (en) | 2020-07-30 |
AU2020210912A1 (en) | 2021-01-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2022517456A (ja) | 臓器健康および疾患をモニタリングするための方法およびシステム | |
Sim et al. | Precise detection of low-level somatic mutation in resected epilepsy brain tissue | |
Benigni et al. | Identification of miRNAs as potential biomarkers in cerebrospinal fluid from amyotrophic lateral sclerosis patients | |
US11776661B2 (en) | Determination of MAPK-AP-1 pathway activity using unique combination of target genes | |
CN110100013A (zh) | 用于肿瘤检测的方法和*** | |
CN105671181B (zh) | 用于检测肺癌的基因标志物、引物、探针及试剂盒 | |
KR102067607B1 (ko) | Y 염색체 메틸화 사이트의 전립선암 진단 마커로써의 응용 | |
WO2019074615A2 (en) | IN VITRO METHODS FOR DISCOVERING THERAPEUTIC COMPOUNDS FOR THE SKIN USING SKIN AGING BIOMARKERS | |
CN109136358B (zh) | 鉴别诊断NOA患者睾丸内残存***的试剂及miRNA在其中的应用 | |
WO2017120285A1 (en) | METHODS OF USING miRNA FROM BODILY FLUIDS FOR DIAGNOSIS AND MONITORING OF NEURODEVELOPMENTAL DISORDERS | |
TWI571514B (zh) | 評估罹患大腸直腸癌風險的方法 | |
EP3976810A1 (en) | Methods and systems for urine-based detection of urologic conditions | |
Chatterton et al. | Brain-derived circulating cell-free DNA defines the brain region and cell specific origins associated with neuronal atrophy | |
RU2818052C2 (ru) | Способы и системы мониторинга состояния здоровья и патологии органов | |
TWI758670B (zh) | 健康風險評估方法 | |
JP2024074960A (ja) | 臓器健康および疾患をモニタリングするための方法およびシステム | |
WO2022121960A1 (zh) | 泛癌症早筛预测方法 | |
US20230175064A1 (en) | Methods and systems for monitoring organ health and disease | |
CN113528635B (zh) | 一种印记基因的甲基化作为心脑血管疾病早期诊断的标志物 | |
WO2023063049A1 (ja) | がん検出のためのバイオマーカーセットの作製方法 | |
CN106834491B (zh) | 乳腺癌预后相关基因突变检测试剂盒及其使用方法 | |
CN118028450A (zh) | 一种对冠心病和脑卒中进行预警的数据处理装置、***及其应用 | |
JP2024043823A (ja) | 対象のがん罹患の可能性を分析する方法 | |
US20110275085A1 (en) | Method for detection of autoimmune diseases | |
Goel | Using Feature Selection and Ensemble Algorithms for Sophisticated Pancreatic Cancer Diagnosis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230119 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20230119 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20231227 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240110 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240409 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20240502 |