PAC: Highly accurate quantification of allelic gene expression for population and disease genetics

Abstract

Analysis of allele-specific gene expression (ASE) is a powerful approach for studying gene regulation. However, detection of ASE events relies on accurate alignment of RNA-sequencing reads, where challenges still remain. We have developed PAC, a method that combines multiple steps to improve the quantification of allelic reads, including personalised (i.e. diploid) read alignment with improved allocation of multi-mapping reads. We show that PAC outperforms standard alignment approaches for ASE detection in both accuracy and in the number of sites it can reliably quantify.