A Bayesian model integration for mutation calling through data partitioning.

Motivation: Detection of somatic mutations from tumor and matched normal sequencing data has become among the most important analysis methods in cancer research. Some existing mutation callers have focused on additional information, e.g. heterozygous single-nucleotide polymorphisms (SNPs) nearby mutation candidates or overlapping paired-end read information. However, existing methods cannot take multiple information sources into account simultaneously. Existing Bayesian hierarchical model-based methods construct two generative models, the tumor model and error model, and limited information sources have been modeled.

Results: We proposed a Bayesian model integration framework named as partitioning-based model integration. In this framework, through introducing partitions for paired-end reads based on given information sources, we integrate existing generative models and utilize multiple information sources. Based on that, we constructed a novel Bayesian hierarchical model-based method named as OHVarfinDer. In both the tumor model and error model, we introduced partitions for a set of paired-end reads that cover a mutation candidate position, and applied a different generative model for each category of paired-end reads. We demonstrated that our method can utilize both heterozygous SNP information and overlapping paired-end read information effectively in simulation datasets and real datasets.

Availability And Implementation: https://github.com/takumorizo/OHVarfinDer.

Supplementary Information: Supplementary data are available at Bioinformatics online.