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Detection of Copy Number Alterations Using Single Cell Sequencing
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スケールされた単細胞ゲノム配列によるクローン分解とDNA複製状態
Emma Laks1, Andrew McPherson2, Hans Zahn3
1Department of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Genome Science and Technology Graduate Program, University of British Columbia, Vancouver, BC, Canada.
Cell
|November 16, 2019
まとめ
研究者は,腫瘍の進化を分析するために,スケーラブルな単細胞全ゲノムシーケンシングプラットフォーム (DLP+) を開発した. このプラットフォームはクローンゲノタイプと 変異過程の正確な測定を可能にし 癌の発達に関する理解を深めています
科学分野:
- ゲノミクス
- 癌 生物学
- バイオ情報学
背景:
- 腫瘍の進化を理解するには 個々の腫瘍細胞のゲノムを正確に分析する必要があります
- 既存の方法は,単細胞レベルでのクローン遺伝子型と変異過程の解明に限界があります.
研究 の 目的:
- 総合的な腫瘍分析のためのスケーラブルな単細胞全ゲノムシーケンシングプラットフォーム (DLP+) を開発し,検証する.
- 細胞形態学とプロイディ状態との相関関係に関するミトの誤差分離率の変動を調査する.
- 複隆性腫瘍集団におけるクローン型遺伝子型,系統型および染色体アヌプロイドの高解像度推論を可能にする.
主な方法:
- 商品機器,画像ベースのオブジェクト認識,オープンソースのコンピューティングツールを使用してDLP+プラットフォームの開発.
- 単細胞ゲノム51,926個の大規模データセットの生成と,さまざまなサンプルタイプからマッチした細胞画像.
- 細胞形態学とゲノムプロイディを相関させ,クローン構造を推論するためのゲノムと画像データの分析.
主要な成果:
- 大規模な単細胞ゲノム資源の生成に成功した.
- 異なる組織型と遺伝子型におけるミトス分離率の変動を特定する.
- 細胞形態学とゲノムプロイディ状態の間の相関が確立された.
- 複製番号プロファイルを共有した細胞を集約することによって推論された高解像度のクローン遺伝子型と系統型は,大量解像度の制限を克服します.
- クローン特異の染色体無積症の定義
結論:
- DLP+は,腫瘍の進化を研究するために不可欠な単細胞全ゲノム配列決定のためのスケーラブルで効果的なプラットフォームを提供します.
- このプラットフォームは,ミトスの誤り,細胞形態学とゲノムの関係,腫瘍内の複雑なクローン構造に関する新しい洞察を容易にする.
- このアプローチにより,前例のない解像度で腫瘍の異質性と進化の軌道を正確に特徴付けることができます.
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