RT Journal Article
SR Electronic
T1 Accounting for tumor heterogeneity using a sample-specific error model improves sensitivity and specificity in mutation calling for sequencing data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 055467
DO 10.1101/055467
A1 Fan, Yu
A1 Liu, Xi
A1 Daniel S. T., Hughes
A1 Zhang, Jianjua
A1 Zhang, Jianhua
A1 Futreal, P. Andrew
A1 Wheeler, David A.
A1 Wenyi, Wang
YR 2016
UL http://biorxiv.org/content/early/2016/05/25/055467.abstract
AB Subclonal mutations reveal important features of the genetic architecture of tumors. However, accurate detection of mutations in genetically heterogeneous tumor cell populations using NGS remains challenging. We developed MuSE (http://bioinformatics.mdanderson.org/main/MuSE), mutation calling using a Markov substitution model for evolution, a novel approach 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 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 sequence.