RT Journal Article
SR Electronic
T1 Clone decomposition based on mutation signatures provides novel insights into mutational processes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.08.443215
DO 10.1101/2021.05.08.443215
A1 Taro Matsutani
A1 Michiaki Hamada
YR 2021
UL http://biorxiv.org/content/early/2021/05/10/2021.05.08.443215.abstract
AB Intra-tumor heterogeneity is a phenomenon in which mutation profiles differ from cell to cell within the same tumor and is observed in almost all tumors. Understanding intra-tumor heterogeneity is essential from the clinical perspective. Numerous methods have been developed to predict this phenomenon based on variant allele frequency. Among the methods, CloneSig models the variant allele frequency and mutation signatures simultaneously and provides an accurate clone decomposition. However, this method has limitations in terms of clone number selection and modeling. We propose SigTracer, a novel hierarchical Bayesian approach for analyzing intra-tumor heterogeneity based on mutation signatures to tackle these issues. We show that SigTracer predicts more reasonable clone decompositions than the existing methods that use artificial data that mimic cancer genomes. We applied SigTracer to whole-genome sequences of blood cancer samples. The results were consistent with past findings that single base substitutions caused by a specific signature (previously reported as SBS9) related to the activation-induced cytidine deaminase intensively lie within immunoglobulin-coding regions for chronic lymphocytic leukemia samples. Furthermore, we showed that this signature mutates regions responsible for cell-cell adhesion. Accurate assignments of mutations to signatures by SigTracer can provide novel insights into signature origins and mutational processes.Competing Interest StatementThe authors have declared no competing interest.