Exon inclusion signatures enable accurate estimation of splicing factor activity.

ABSTRACT: Splicing factors control exon inclusion in messenger RNAs, shaping transcriptome and proteome diversity. Their catalytic activity is regulated by multiple layers, making single-omic measurements on their own fall short in identifying which splicing factors underlie a phenotype. Here, we posit that splicing factor activity can be estimated from changes in exon inclusion. To test this hypothesis, we benchmarked methods for constructing splicing factor→exon networks and estimating splicing factor activity. We found that combining RNA-seq perturbation-based networks with VIPER (Virtual Inference of Protein Activity by Enriched Regulon analysis) accurately captures splicing factor activation as modulated by multiple regulatory layers. This approach integrates splicing factor regulation into a s

SUBMITTER: Anglada-Girotto M 

PROVIDER: S-EPMC11230296 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature