JP6882373B2 - ターゲットシークエンシングパネルから変異を見つける方法 - Google Patents
ターゲットシークエンシングパネルから変異を見つける方法 Download PDFInfo
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Description
特に定義しない限り、本明細書で用いるすべての技術的および科学的用語は、本開示の属する分野における当業者に一般的に理解されるものと同じ意味を有する。本明細書に記載されるのと類似のまたは同等のいかなる方法および材料も本教示の実施または試験に用いることができるが、いくつかの代表的な方法および材料をここで記述する。
種々の実施形態を記載する前に、本開示の教示は記載した特定の実施形態に限定されず、そのため、当然ながら変更できることが理解されるであろう。また、本教示の範囲は添付の請求の範囲によってのみ限定されるものであるため、本明細書で使用する用語は、特定の実施形態を説明する目的のためにすぎず、限定することを意図するものではないことが理解されるであろう。
P(K>1|R1,...,Rn)=1−P(K=1|R1,...,Rn)
によって変異コールの確率を得る。
本出願は、米国特許仮出願第61/859,625号(2013年7月29日出願)の利益を主張するものであり、この出願全体が本明細書に参考として援用されている。
Claims (16)
- 配列変異を同定する方法であって、
(a)(i)ゲノム領域がエンリッチされたサンプルの複数の配列リードおよび(ii)ゲノム領域に対する参照配列を取得すること、
(b)BEST定理を用いて前記配列リードをアセンブリングして、それぞれが潜在的な変異に対応する複数の離散的な配列アセンブリを、複数の候補配列として得ること、
(c)複数の前記候補配列のそれぞれを構成する前記配列リードに基づいて、真の潜在的な変異を決定すること、
(d)前記真の潜在的な変異と、前記参照配列と関連すると分かっている突然変異とを比較すること、および
(e)前記サンプルが配列変異を含んでいるかどうかを示すレポートを出力することを含み、
前記真の潜在的な変異を決定することが、隠れマルコフモデルを用いて各前記潜在的な変異に尤度を割り当て、前記候補配列中の対立遺伝子に基づいて複数の前記潜在的な変異をフィルタリングで除外し、フィルタリング後の前記潜在的な変異のそれぞれのスコアをベイズの定理を用いて提供することを含む、方法。 - 前記ゲノム領域が癌と関連する、請求項1に記載の方法。
- 前記ゲノム領域が以下の遺伝子:PlK3CA、NRAS、KRAS、JAK2、HRAS、FGFR3、FGFR1、EGFR、CDK4、BRAF、RET、FGDFRA、KITおよびERBB2の少なくとも1つの少なくとも一部を含む、請求項1に記載の方法。
- 前記配列変異が、体細胞突然変異に対応する低頻度の配列変異である、請求項1に記載の方法。
- 前記ゲノム領域はヒトゲノムの領域である、請求項1に記載の方法。
- 前記エンリッチされるゲノム領域は、臨床検体から得た全DNAからエンリッチされる、請求項1に記載の方法。
- 前記臨床検体が生検である、請求項6に記載の方法。
- 前記レポートにより、前記サンプルが突然変異を含んでいるかどうかの指標および前記参照配列についての利用可能な公的情報が提供される、請求項1に記載の方法。
- 前記アセンブリングは、前記配列の信頼性が高いと思われる、前記配列リードのそれぞれの前記領域を分画することを含む、請求項1に記載の方法。
- 前記真の潜在的な変異を決定することは、配列のクオリティ、リードの数、ベースコールのクオリティおよびその前記参照配列へのマッチを調べ、前記潜在的な変異のそれぞれのスコアを提供することを含む、請求項1に記載の方法。
- 前記参照配列は、当技術分野において公知であり、シークエンシングリードが適当である変異を同定するためにアノテーションされる、請求項1に記載の方法。
- 前記アセンブリングは、前記アセンブリをアンカーするために前記参照配列からの配列および前記参照配列に固有の配列を用いる、請求項1に記載の方法。
- 前記方法は、変異コールの確率を提供する、請求項1に記載の方法。
- メモリを含むコンピュータシステムであって、
(a)ゲノム領域がエンリッチされたサンプルの配列リードデータベース、
(b)前記ゲノム領域の参照配列、および
(c)請求項1の前記方法を実行するために実行可能なプログラム
を含む、コンピュータシステム。 - 請求項1の前記方法を実行するための命令を含む、コンピュータ可読記憶媒体。
- 変異配列を同定する方法であって、
a)請求項1の前記方法を実行するための命令を含むプログラムを含むコンピュータシステムに配列情報を入力すること、
b)前記プログラムを実行すること、および
c)前記コンピュータシステムからの出力を受信すること
とを含む、方法。
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US11393557B2 (en) * | 2015-08-25 | 2022-07-19 | Nantomics, Llc | Systems and methods for high-accuracy variant calling |
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US20200176085A1 (en) * | 2016-01-18 | 2020-06-04 | Julian GOUGH | Determining phenotype from genotype |
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