TY - JOUR T1 - The impact of sex on alternative splicing JF - bioRxiv DO - 10.1101/490904 SP - 490904 AU - Guy Karlebach AU - Diogo F.T. Veiga AU - Anne Deslattes Mays AU - Anil K. Kesarwani AU - Daniel Danis AU - Georgios Kararigas AU - Xingmin Aaron Zhang AU - Joshy George AU - Guru Ananda AU - Robin Steinhaus AU - Peter Hansen AU - Dominik Seelow AU - Chris Bizon AU - Rebecca Boyles AU - Chris Ball AU - Julie A McMurry AU - Melissa A Haendel AU - Jeremy Yang AU - Tudor Oprea AU - Mitali Mukerji AU - Olga Anczukow AU - Jacques Banchereau AU - Peter N Robinson Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/12/10/490904.abstract N2 - Over 95% of human genes undergo alternative splicing (AS) in a developmental, tissue-specific, or signal transduction-dependent manner. A number of factors including binding of cis-acting sequences by RNA-binding proteins (RBPs) are known to affect AS, but the combinatorial mechanisms leading to the distribution of spliced isoforms remain largely unstudied. Here, in 9011 samples from 532 individuals across 53 tissues from the Genotype-Tissue Expression (GTEx) resource, we identified 4,135 genes with sex-biased expression and 5,925 sex-biased AS events. We find that factors including escape from X-chromosomal inactivation, presence of Alu elements, and oestrogen receptor binding sites affect sex-biased AS. We utilize hierarchical Bayesian modelling to characterize the interactions of exon skipping, gene expression, and RBPs, and demonstrate two categories of sex-biased AS that differ with respect to splice site scores, gene expression, RBP levels, and skipping/inclusion ratio. ER -