JP6955035B2 - マイクロサテライト不安定性を決定するためのシステム及び方法 - Google Patents
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Description
本出願は、その開示があらゆる目的のために参照によりその全体が本明細書に組み入れられる2017年11月16日付けで出願された「MICROSATELLITE INSTABILITY ASSESSMENT TECHNIQUES」という表題の米国仮出願第62/587,350号の優先権と利益を主張する。本出願はまた、その開示があらゆる目的のために参照によりその全体が本明細書に組み入れられる2018年4月3日付けで出願された「MICROSATELLITE INSTABILITY ASSESSMENT TECHNIQUES WITH REDUCED BIAS」という表題の米国仮出願第62/652,151号の優先権と利益も主張する。
BL_n1=Pr[X=x]
BL_n2=Pr[X=x]
JS1=0.5×(合計(BL_n1×log(BL_n1/m1))+合計(BL_n1×log(BL_n1/m1)))
m1=0.5×(BL_n1+BL_n2)
d1=sqrt(JS1)。
BL_n=Pr[X=x]
T=Pr[X=x]
JS2=0.5×(合計(BL_n×log(BL_n/m2))+合計(T×log(T/m2)))
m2=0.5×(BL1+T)
d2=sqrt(JS2)。
MSI-H腫瘍:n=35(32個のCRC及び3個のUCEC)
MSS腫瘍:n=57(26個のCRC及び31個のUCEC)
総試験試料(92個の腫瘍+140個の正常=232個の試料)。
ΔJSD=平均(JSDbetween)-平均(JSDwithin)
各マイクロサテライト領域のデルタジェンセン-シャノン距離は、2つのグループ間の平均ジェンセン-シャノン距離及びグループ内の平均ジェンセン-シャノン距離の基準である。3又はそれより多くのグループ間の対としての比較を行ってもよい。この技術は、175個の部位(マイクロサテライト領域)を、各民族性グループの最小5個の試料につき少なくとも20個の支持リードで評価した。この分析に基づいて、3つの民族性グループ間の対としての比較に基づいて≧0.1のΔJSDを有する44個の部位を、高い民族学的な変動性を有するとして同定した。これらの部位を、参照試料データセットを生成するのに使用された配列データから除外した(例えば、消去又はマスクした)。
P_AFR(n=22)(アフリカ人)
P_AMR(n=25)(南米人)
P_EUR(n=8)(欧州人)
P_EAS(n=3)(東アジア人)。
14 マイクロサテライト領域
60 シーケンシングデバイス
62 試料処理デバイス
64 分析デバイス
70 試料スライド
72 画像化モジュール
74 プロセッサ
76 I/Oコントロール
78 内部バス
80 不揮発性メモリ
82 RAM
84 プロセッサ
86 I/Oコントロール
88 RAM
90 不揮発性メモリ
92 実行可能命令
94 内部バス、通信モジュール
96 ディスプレイ
100 マイクロサテライト不安定性を評価する方法
102、104、106、108、110、116、120 工程
112 配列データセット
150 腫瘍試料
154 正常試料
156 配列分析
158 腫瘍試料の配列データ
160 配列分析
162 正常試料の配列データ
164、166 マイクロサテライト不安定性分析技術
168 腫瘍のみのマイクロサテライト不安定性スコア
170 腫瘍/正常のマイクロサテライト不安定性スコア
200 方法
202、204、206、208、210 工程
Claims (15)
- プロセッサ;及び
命令を記憶するメモリ
を含むマイクロサテライト不安定性を決定するためのシステムであって、命令は、プロセッサによって実行されると、プロセッサに、
目的の試料のゲノム配列データにアクセスする工程であって、目的の試料は、マッチする正常試料が利用不可能な腫瘍試料由来であり、配列データは、複数のマイクロサテライト領域に関するヌクレオチド同一性情報を含む、工程;
目的の試料に関する試料情報を受け取る工程;
試料情報に基づいて、複数の参照試料データセットから、関連する参照試料データセットを選択する工程であって、関連する参照試料データセットは、複数のマイクロサテライト領域についてのヌクレオチド同一性情報及び複数の個体から生成される、マッチしない正常コホートである、工程;
目的の試料からの配列データを、関連する参照試料データセットと比較することに基づいて、目的の試料のマイクロサテライト不安定性を分類する工程;及び
分類に基づいて、目的の試料のマイクロサテライト不安定性を代表する指示を提供する工程
を行わせる、システム。 - 試料情報が、目的の試料の起源の情報を含み、複数の参照試料データセットが、起源に基づいて互いに異なり、関連する参照試料データセットが、目的の試料の起源の情報と、関連する参照試料データセットの起源との間のマッチに基づいて選択される、請求項1に記載のシステム。
- 関連する参照試料データセットが、複数の個体由来のFFPE試料から生成され、目的の試料が、FFPE試料である、請求項1又は2に記載のシステム。
- 関連する参照試料データセットが、複数の個体由来の新しい凍結した試料から生成され、目的の試料が、新しい凍結した試料である、請求項1又は2に記載のシステム。
- 関連する参照試料データセットが、複数の個体由来の細胞株から生成され、目的の試料が、細胞株である、請求項1又は2に記載のシステム。
- 試料情報が、組織タイプの情報を含み、複数の参照試料データセットが、組織タイプに基づいて互いに異なっており、関連する参照試料データセットが、前記組織タイプの情報と、関連する参照試料データセットの組織タイプとのマッチに基づいて更に選択される、請求項1から5のいずれか一項に記載のシステム。
- 試料情報が、配列データを生成するのに使用されたシーケンシングパネル情報を含み、複数の参照試料データセットが、参照試料データセットを生成するのに使用されたシーケンシングパネルに基づいて互いに異なっており、関連する参照試料データセットが、前記シーケンシングパネル情報と、関連する参照試料データセットを生成するのに使用されたシーケンシングパネルとの間のマッチに基づいて更に選択される、請求項1から6のいずれか一項に記載のシステム。
- 関連する参照試料データセットが、複数の個体由来のプールしたデータセットである、請求項1から7のいずれか一項に記載のシステム。
- マッチしない正常コホートが、万能なマッチする試料である、請求項1から8のいずれか一項に記載のシステム。
- 複数のマイクロサテライト領域の個々のマイクロサテライト領域に関する、シーケンシング深さに基づく、品質測定基準を使用して、関連する参照試料データセットに関する、個々のマイクロサテライト領域を選択することを含む、請求項1から9のいずれか一項に記載のシステム。
- 目的の試料中のマイクロサテライト不安定性を検出するための、コンピューターにより実施される方法であって、
目的の試料の配列データを提供する工程であって、目的の試料は、マッチする正常試料が利用不可能な腫瘍試料由来であり、配列データは、複数のマイクロサテライト領域に関するヌクレオチド同一性情報を含む、工程;
目的の試料に関する試料情報を提供する工程;
試料情報に基づいて、複数の参照試料データセットから、関連する参照試料データセットを選択する工程であって、関連する参照試料データセットは、複数のマイクロサテライト領域のヌクレオチド同一性情報及び複数の個体から生成される、マッチしない正常コホートである、工程;及び
目的の試料からの配列データを、関連する参照試料データセットと、コンピューターによる実施によって比較することに基づいて、目的の試料のマイクロサテライト不安定性を評価する工程
を含む、方法。 - マッチしない正常コホートが、万能なマッチする試料である、請求項11に記載の方法。
- 複数のマイクロサテライト領域の個々のマイクロサテライト領域に関する、シーケンシング深さに基づく、品質測定基準を使用して、関連する参照試料データセットに関する、個々のマイクロサテライト領域を選択することを含む、請求項11又は12に記載の方法。
- 請求項1から10のいずれか一項に記載のシステムを使用する、請求項11に記載の方法。
- 目的の試料中のマイクロサテライト不安定性を検出するため、及び/又は目的の試料におけるマイクロサテライト不安定性のタイプを決定するための、請求項1から10のいずれか一項に記載のシステムの使用であって、試料は、マッチする正常試料が利用不可能な腫瘍試料由来である、使用。
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