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OVarCall: Bayesian Mutation Calling Method Utilizing Overlapping Paired-End Reads.
IEEE Transactions on Nanobioscience 2017 March
Detection of somatic mutations from tumor and matched normal sequencing data has become a standard approach in cancer research. Although a number of mutation callers have been developed, it is still difficult to detect mutations with low allele frequency even in exome sequencing. We expect that overlapping paired-end read information is effective for this purpose, but no mutation caller has modeled overlapping information statistically in a proper form in exome sequence data. Here, we develop a Bayesian hierarchical method, OVar- Call (https://github.com/takumorizo/OVarCall), where overlapping paired-end read information improves the accuracy of low allele frequency mutation detection. Firstly, we construct two generative models: one is for reads with somatic variants generated from tumor cells and the other is for reads that does not have somatic variants but potentially includes sequence errors. Secondly, we calculate marginal likelihood for each model using a variational Bayesian algorithm to compute Bayes factor for the detection of somatic mutations. We empirically evaluated the performance of OVarCall and confirmed its better performance than other existing methods.
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