VERSE: a varying effect regression for splicing elements discovery.

Identification of splicing regulatory elements (SREs) deserves special attention because these cis-acting short sequences are vital parts of splicing code. The fact that a variety of other biological signals cooperatively govern the splicing pattern indicates the necessity of developing novel tools to incorporate information from multiple sources to improve splicing factor binding sites prediction. Under this context, we proposed a Varying Effect Regression for Splicing Elements (VERSE) to discover intronic SREs in the proximity of exon junctions by integrating other biological features. As a result, 1562 intronic SREs were identified in 16 human tissues, many of which overlapped with experimentally verified binding motifs for several well-known splicing factors, including FOX-1, PTB, hnRNP A/B, hnRNP F/H, and so on. The discovered tissue, region, and conservation preferences of the putative motifs demonstrate that splice site selection is a complicated process that needs subtle and delicate regulation. VERSE may serve as a powerful tool to not only discover SREs by incorporating additional informative signals but also precisely quantify their varying contribution under different biological contexts.