Genome-wide identification of allele-specific effects on gene expression for single and multiple individuals

• We developed a maximum likelihood model to characterize ASE based on RNA-seq data.
• Our method can identify ASE in multiple individuals.
• The fraction of ASE was stable and close to the fraction of experimental method.
• Simulations gave a better performance and robustness compared to binomial test.

The analysis of allele-specific gene expression (ASE) is essential for the mapping of genetic variants that affect gene regulation, and for the identification of alleles that modify disease risk. Although RNA sequencing offers the opportunity to measure expression at allele levels, the availability of powerful statistical methods for mapping ASE in single or multiple individuals is limited. We developed a maximum likelihood model to characterize ASE in the human genome. Approximately 17% of genes displayed an allele-specific effect on gene expression in a single individual. Simulations using our model gave a better performance and improved robustness when compared with the binomial test, with different coverage levels, allelic expression fractions and random noise. In addition, our method can identify ASE in multiple individuals, with enhanced performance. This is helpful in understanding the mechanism of genetic regulation leading to expression changes, alternative splicing variants and even disease susceptibility.