Quantifying the influence of mutation detection on tumour subclonal reconstruction.
Quantifying the influence of mutation detection on tumour subclonal reconstruction.
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DOI：
10.1038/s41467-020-20055-w
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发表时间：
2020-12-07
影响因子：
16.6
通讯作者：
Boutros PC
中科院分区：
文献类型：
--
作者：
Liu LY;Bhandari V;Salcedo A;Espiritu SMG;Morris QD;Kislinger T;Boutros PC
全基因组测序可以用来估计肿瘤中的亚克隆群体，这种肿瘤内的异质性与临床结果有关。已经开发了许多用于亚克隆重建的算法，但它们的变异性和一致性在很大程度上是未知的。我们评估了16条用于从单个样本重建293例局限性前列腺癌的进化史的管道，以及18条用于多区域采样重建10个肿瘤的管道。我们表明，对亚克隆结构和体细胞突变时间的预测在不同的管道上有很大的不同。管道显示出一致类型的偏差，那些结合SomaticSniper和Btenberg的管道优先预测同质癌细胞群体，而那些使用MuTect的管道倾向于预测多个癌细胞群体。使用多区域采样的亚克隆重建证实，单样本重建系统地低估了肿瘤内的异质性，预测了平均不到多区域测序确定的癌细胞群体的一半。总体而言，这些偏见表明在解释特定的体系结构和亚克隆变体时要谨慎。不同的调用算法对分析肿瘤内异质性的影响还没有得到适当的量化。在这里，作者测量了22条管道的可变性，这些管道具有不同的变量调用者和亚克隆重建的聚类算法，以便为未来的分析提供信息。
Whole-genome sequencing can be used to estimate subclonal populations in tumours and this intra-tumoural heterogeneity is linked to clinical outcomes. Many algorithms have been developed for subclonal reconstruction, but their variabilities and consistencies are largely unknown. We evaluate sixteen pipelines for reconstructing the evolutionary histories of 293 localized prostate cancers from single samples, and eighteen pipelines for the reconstruction of 10 tumours with multi-region sampling. We show that predictions of subclonal architecture and timing of somatic mutations vary extensively across pipelines. Pipelines show consistent types of biases, with those incorporating SomaticSniper and Battenberg preferentially predicting homogenous cancer cell populations and those using MuTect tending to predict multiple populations of cancer cells. Subclonal reconstructions using multi-region sampling confirm that single-sample reconstructions systematically underestimate intra-tumoural heterogeneity, predicting on average fewer than half of the cancer cell populations identified by multi-region sequencing. Overall, these biases suggest caution in interpreting specific architectures and subclonal variants. The impact of variant calling algorithms on the analysis of intra-tumour heterogeneity has not been properly quantified. Here the authors measure the variability of 22 pipelines with different variant callers and clustering algorithms for subclonal reconstruction to inform future analyses.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
7
作者：
Ha G;Roth A;Khattra J;Ho J;Yap D;Prentice LM;Melnyk N;McPherson A;Bashashati A;Laks E;Biele J;Ding J;Le A;Rosner J;Shumansky K;Marra MA;Gilks CB;Huntsman DG;McAlpine JN;Aparicio S;Shah SP
通讯作者：
Shah SP
影响因子：
18.4
作者：
Alves JM;Prieto T;Posada D
通讯作者：
Posada D
影响因子：
5.4
作者：
Dentro, Stefan C.;Wedge, David C.;Van Loo, Peter
通讯作者：
Van Loo, Peter
影响因子：
64.8
作者：
Abbosh C;Birkbak NJ;Wilson GA;Jamal-Hanjani M;Constantin T;Salari R;Le Quesne J;Moore DA;Veeriah S;Rosenthal R;Marafioti T;Kirkizlar E;Watkins TBK;McGranahan N;Ward S;Martinson L;Riley J;Fraioli F;Al Bakir M;Grönroos E;Zambrana F;Endozo R;Bi WL;Fennessy FM;Sponer N;Johnson D;Laycock J;Shafi S;Czyzewska-Khan J;Rowan A;Chambers T;Matthews N;Turajlic S;Hiley C;Lee SM;Forster MD;Ahmad T;Falzon M;Borg E;Lawrence D;Hayward M;Kolvekar S;Panagiotopoulos N;Janes SM;Thakrar R;Ahmed A;Blackhall F;Summers Y;Hafez D;Naik A;Ganguly A;Kareht S;Shah R;Joseph L;Marie Quinn A;Crosbie PA;Naidu B;Middleton G;Langman G;Trotter S;Nicolson M;Remmen H;Kerr K;Chetty M;Gomersall L;Fennell DA;Nakas A;Rathinam S;Anand G;Khan S;Russell P;Ezhil V;Ismail B;Irvin-Sellers M;Prakash V;Lester JF;Kornaszewska M;Attanoos R;Adams H;Davies H;Oukrif D;Akarca AU;Hartley JA;Lowe HL;Lock S;Iles N;Bell H;Ngai Y;Elgar G;Szallasi Z;Schwarz RF;Herrero J;Stewart A;Quezada SA;Peggs KS;Van Loo P;Dive C;Lin CJ;Rabinowitz M;Aerts HJWL;Hackshaw A;Shaw JA;Zimmermann BG;TRACERx consortium;PEACE consortium;Swanton C
通讯作者：
Swanton C