Functional dynamics of protein interactome induced by alternative splicing: An in silico approach
The critical role of alternative splicing (AS) in cell functioning has recently become apparent, whether in studying tissue- or cell-specific regulation, or understanding molecular mechanisms governing a complex disorder. Studying the rewiring, or edgetic, effects of alternatively spliced isoforms on protein interactome can provide system-wide insights into these questions. Yet, high-throughput experiments for such studies are expensive and time-consuming, motivating the need for an in-silico approach. We present ALT-IN Tool, a method to determine disruptions to protein-protein interaction (PPI) networks induced by alternative splicing. We describe application of our method to the transcriptomic data obtained from the brain and liver tissues of a healthy mouse and western diet fed mouse that developed type two diabetes (T2D). We demonstrated that the edgetic effects of differentially expressed transcripts associated with the disease condition are system-wide, involve regulatory pathways (e.g., PI3-Akt) and unlikely to be detected on the gene-specific expression levels. The magnitude of changes to PPIs of western diet fed mouse shows the impact environment can have on molecular regulatory mechanisms.