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Bioinformatics
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HapMuC: somatic mutation calling using heterozygous germ line variants near candidate mutations

Authors: Naoto Usuyama; Yuichi Shiraishi; Yusuke Sato; Haruki Kume; Yukio Homma; Seishi Ogawa; Satoru Miyano; +1 Authors

HapMuC: somatic mutation calling using heterozygous germ line variants near candidate mutations

Abstract

Abstract Motivation: Identifying somatic changes from tumor and matched normal sequences has become a standard approach in cancer research. More specifically, this requires accurate detection of somatic point mutations with low allele frequencies in impure and heterogeneous cancer samples. Although haplotype phasing information derived by using heterozygous germ line variants near candidate mutations would improve accuracy, no somatic mutation caller that uses such information is currently available. Results: We propose a Bayesian hierarchical method, termed HapMuC, in which power is increased by using available information on heterozygous germ line variants located near candidate mutations. We first constructed two generative models (the mutation model and the error model). In the generative models, we prepared candidate haplotypes, considering a heterozygous germ line variant if available, and the observed reads were realigned to the haplotypes. We then inferred the haplotype frequencies and computed the marginal likelihoods using a variational Bayesian algorithm. Finally, we derived a Bayes factor for evaluating the possibility of the existence of somatic mutations. We also demonstrated that our algorithm has superior specificity and sensitivity compared with existing methods, as determined based on a simulation, the TCGA Mutation Calling Benchmark 4 datasets and data from the COLO-829 cell line. Availability and implementation: The HapMuC source code is available from http://github.com/usuyama/hapmuc. Contact: imoto@ims.u-tokyo.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online.

Related Organizations
Keywords

Heterozygote, DNA Mutational Analysis, Bayes Theorem, Original Papers, Polymorphism, Single Nucleotide, Gene Frequency, Haplotypes, Cell Line, Tumor, Neoplasms, Mutation, Humans, Algorithms

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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
19
Top 10%
Average
Top 10%
Green
gold