@article{46be94cfe014400ab8764fe519861b4a,
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. ",
keywords = "Bayesian inference, Model-based cutoff finding, Next-generation sequencing, Sensitivity and specificity, Somatic mutation calling",
author = "Yu Fan and Liu Xi and Hughes, {Daniel S.T.} and Jianjun Zhang and Jianhua Zhang and Futreal, {P. Andrew} and Wheeler, {David A.} and Wenyi Wang",
note = "Funding Information: YF is partially supported by a training fellowship from the Keck Center of the Gulf Coast Consortia for the Computational Cancer Biology Training Program; the Cancer Prevention and Research Institute of Texas (CPRIT) RP140113, PI - Rathindra Bose; and the National Institutes of Health/National Cancer Institute through grant U24 CA143883 02S2 (to Dr. John N. Weinstein) and the Integrative Pipeline for Analysis & Translational Application of TCGA Data, grant 5U24CA143883-04 (to Dr. John N. Weinstein). WW is supported in part by the Cancer Prevention Research Institute of Texas through grant number RP130090 and by NCI through grant numbers 1R01CA174206-01 and P30 CA016672. YF and WW are supported in part by the US National Cancer Institute (NCI; MD Anderson TCGA Genome Data Analysis Center) through grant numbers CA143883, CA083639 and CA183793. JZ and PAF are supported by the Cancer Prevention and Research Institute of Texas through grant number R1205 01, the UT Systems Stars Award (PS100149), the Welch Foundation Robert A. Welch Distinguished University Chair Award (G-0040), the MD Anderson Physician Scientist Award, and the C.G. Johnson Advanced Scholar Award.",
year = "2016",
month = aug,
day = "24",
doi = "10.1186/s13059-016-1029-6",
language = "English (US)",
volume = "17",
pages = "178",
journal = "Genome biology",
issn = "1474-7596",
publisher = "BioMed Central",
number = "1",
}