title: MuSE: accounting for tumor heterogeneity using a sample-specific error model improves sensitivity and specificity in mutation calling from sequencing data.
abstract: Subclonal mutations reveal important features of the genetic architecture of tumors. However, accurate detection of mutations in genetically heterogeneous tumor cell populations using next-generation sequencing remains challenging. We develop MuSE ( http://bioinformatics.mdanderson.org/main/MuSE ), Mutation calling using a Markov Substitution model for Evolution, a novel approach for modeling the evolution of the allelic composition of the tumor and normal tissue at each reference base. MuSE adopts a sample-specific error model that reflects the underlying tumor heterogeneity to greatly improve the overall accuracy. We demonstrate the accuracy of MuSE in calling subclonal mutations in the context of large-scale tumor sequencing projects using whole exome and whole genome sequencing.
authors: Department of Bioinformatics and Computational Biology - Unit 1410, The University of Texas MD Anderson Cancer Center, P. O. Box 301402, Houston, 77230-1402, TX, USA.
authors: Yu
authors: Y
authors: Fan
authors: Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Alkek N1419, Houston, 77030-3411, TX, USA.
authors: Liu
authors: L
authors: Xi
authors: Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Alkek N1419, Houston, 77030-3411, TX, USA.
authors: Daniel S T
authors: DS
authors: Hughes
authors: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA.
authors: Jianjun
authors: J
authors: Zhang
authors: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA.
authors: Jianhua
authors: J
authors: Zhang
authors: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA.
authors: P Andrew
authors: PA
authors: Futreal
authors: Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Alkek N1419, Houston, 77030-3411, TX, USA.
authors: David A
authors: DA
authors: Wheeler
authors: Department of Bioinformatics and Computational Biology - Unit 1410, The University of Texas MD Anderson Cancer Center, P. O. Box 301402, Houston, 77230-1402, TX, USA. wwang7@mdanderson.org.
authors: Wenyi
authors: 0000-0003-0617-9438
authors: W
authors: Wang
mesh_terms: D000465:Algorithms; D000483:Alleles; D019295:Computational Biology; D059472:Exome / Q000235:genetics; D018740:Genetic Heterogeneity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D012680:Sensitivity and Specificity; D012984:Software
keywords: Bayesian inference; Model-based cutoff finding; Next-generation sequencing; Sensitivity and specificity; Somatic mutation calling