BBmix: a Bayesian beta-binomial mixture model for accurate genotyping from RNA-sequencing
Elena Vigorito, Anne Barton, Costantino Pitzalis, Myles J Lewis, Chris Wallace- Computational Mathematics
- Computational Theory and Mathematics
- Computer Science Applications
- Molecular Biology
- Biochemistry
- Statistics and Probability
Abstract
Motivation
While many pipelines have been developed for calling genotypes using RNA-sequencing (RNA-Seq) data, they all have adapted DNA genotype callers that do not model biases specific to RNA-Seq such as allele-specific expression (ASE).
Results
Here, we present Bayesian beta-binomial mixture model (BBmix), a Bayesian beta-binomial mixture model that first learns the expected distribution of read counts for each genotype, and then deploys those learned parameters to call genotypes probabilistically. We benchmarked our model on a wide variety of datasets and showed that our method generally performed better than competitors, mainly due to an increase of up to 1.4% in the accuracy of heterozygous calls, which may have a big impact in reducing false positive rate in applications sensitive to genotyping error such as ASE. Moreover, BBmix can be easily incorporated into standard pipelines for calling genotypes. We further show that parameters are generally transferable within datasets, such that a single learning run of less than 1 h is sufficient to call genotypes in a large number of samples.
Availability and implementation
We implemented BBmix as an R package that is available for free under a GPL-2 licence at https://gitlab.com/evigorito/bbmix and https://cran.r-project.org/package=bbmix with accompanying pipeline at https://gitlab.com/evigorito/bbmix_pipeline.