Combining tumor genome simulation with crowdsourcing to benchmark somatic single-nucleotide-variant detection.

TitleCombining tumor genome simulation with crowdsourcing to benchmark somatic single-nucleotide-variant detection.
Publication TypeJournal Article
Year of Publication2015
AuthorsEwing AD, Houlahan KE, Hu Y, Ellrott K, Caloian C, Yamaguchi TN, Bare CJ, P'ng C, Waggott D, Sabelnykova VY, Kellen MR, Norman TC, Haussler D, Friend SH, Stolovitzky G, Margolin AA, Stuart JM, Boutros PC
Refereed DesignationUnknown
Secondary Authorsparticipants ICGC-TCGADREAMSMCC, Xi L, Dewal N, Fan Y, Wang W, Wheeler D, Wilm A, Ting GH, Li C, Bertrand D, Nagarajan N, Chen Q-R, Hsu C-H, Hu Y, Yan C, Kibbe W, Meerzaman D, Cibulskis K, Rosenberg M, Bergelson L, Kiezun A, Radenbaugh A, Sertier A-S, Ferrari A, Tonton L, Bhutani K, Hansen NF, Wang D, Song L, Lai Z, Liao Y, Shi W, Carbonell-Caballero J, Dopazo J, Lau CCK, Guinney J
Journal TitleNature methods
Corporate Authorparticipants ICGC-TCGADREAMSMCC
Journal Date2015 May 18
Keywordscancer, NGS, variant calling
AbstractThe detection of somatic mutations from cancer genome sequences is key to understanding the genetic basis of disease progression, patient survival and response to therapy. Benchmarking is needed for tool assessment and improvement but is complicated by a lack of gold standards, by extensive resource requirements and by difficulties in sharing personal genomic information. To resolve these issues, we launched the ICGC-TCGA DREAM Somatic Mutation Calling Challenge, a crowdsourced benchmark of somatic mutation detection algorithms. Here we report the BAMSurgeon tool for simulating cancer genomes and the results of 248 analyses of three in silico tumors created with it. Different algorithms exhibit characteristic error profiles, and, intriguingly, false positives show a trinucleotide profile very similar to one found in human tumors. Although the three simulated tumors differ in sequence contamination (deviation from normal cell sequence) and in subclonality, an ensemble of pipelines outperforms the best individual pipeline in all cases. BAMSurgeon is available at
Alternate JournalNat. Methods