Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.
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DOI：
10.1038/s41467-020-18151-y
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发表时间：
2020-09-21
影响因子：
16.6
通讯作者：
PCAWG Consortium
中科院分区：
文献类型：
--
作者：
Bailey MH;Meyerson WU;Dursi LJ;Wang LB;Dong G;Liang WW;Weerasinghe A;Li S;Li Y;Kelso S;MC3 Working Group;PCAWG novel somatic mutation calling methods working group;Saksena G;Ellrott K;Wendl MC;Wheeler DA;Getz G;Simpson JT;Gerstein MB;Ding L;PCAWG Consortium
癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）分别使用全外显子组测序（WES）和全基因组测序（WGS）来策划共有体细胞突变调用。在这里，作为ICGC/TCGA泛癌症全基因组分析（PCAWG）联盟的一部分，该联盟汇总了来自38种肿瘤类型的2，658种癌症的全基因组测序数据，我们比较了来自746个TCGA样本的WES和WGS，发现约80%的突变在覆盖的外显子区域重叠。我们估计，低变异等位基因分数（VAF < 15%）和克隆异质性贡献了高达68%的私人WGS突变和71%的私人WES突变。我们观察到，约30%的私有WGS突变可追溯到WES共识努力中由单个变体调用者识别的突变。WGS捕获外显子区域中约50%的变异和具有可变GC含量的基因座中未观察到的突变。总之，我们的分析突出了两个可重复的体细胞变异检测工作之间的技术分歧。随着大型泛癌症全外显子组和全基因组测序项目的产生，问题仍然是这些数据集的可比性如何。在这里，使用作为全基因组泛癌症分析项目的一部分分析的癌症基因组图谱样本，作者探索了全外显子组测序和全基因组测序技术所称的突变的一致性。
The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts. With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
64.8
作者：
Nik-Zainal S;Davies H;Staaf J;Ramakrishna M;Glodzik D;Zou X;Martincorena I;Alexandrov LB;Martin S;Wedge DC;Van Loo P;Ju YS;Smid M;Brinkman AB;Morganella S;Aure MR;Lingjærde OC;Langerød A;Ringnér M;Ahn SM;Boyault S;Brock JE;Broeks A;Butler A;Desmedt C;Dirix L;Dronov S;Fatima A;Foekens JA;Gerstung M;Hooijer GK;Jang SJ;Jones DR;Kim HY;King TA;Krishnamurthy S;Lee HJ;Lee JY;Li Y;McLaren S;Menzies A;Mustonen V;O'Meara S;Pauporté I;Pivot X;Purdie CA;Raine K;Ramakrishnan K;Rodríguez-González FG;Romieu G;Sieuwerts AM;Simpson PT;Shepherd R;Stebbings L;Stefansson OA;Teague J;Tommasi S;Treilleux I;Van den Eynden GG;Vermeulen P;Vincent-Salomon A;Yates L;Caldas C;van't Veer L;Tutt A;Knappskog S;Tan BK;Jonkers J;Borg Å;Ueno NT;Sotiriou C;Viari A;Futreal PA;Campbell PJ;Span PN;Van Laere S;Lakhani SR;Eyfjord JE;Thompson AM;Birney E;Stunnenberg HG;van de Vijver MJ;Martens JW;Børresen-Dale AL;Richardson AL;Kong G;Thomas G;Stratton MR
通讯作者：
Stratton MR
影响因子：
9.9
作者：
Auslander N;Cunningham CE;Toosi BM;McEwen EJ;Yizhak K;Vizeacoumar FS;Parameswaran S;Gonen N;Freywald T;Bhanumathy KK;Freywald A;Vizeacoumar FJ;Ruppin E
通讯作者：
Ruppin E
影响因子：
5.8
作者：
McLaren, William;Pritchard, Bethan;Cunningham, Fiona
通讯作者：
Cunningham, Fiona