Predicting synthetic lethal genetic interactions in Saccharomyces cerevisiae using short polypeptide clusters

Background: Protein synthetic lethal genetic interactions are useful to define functional relationships between proteins and pathways. However, the molecular mechanism of synthetic lethal genetic interactions remains unclear. Results: In this study we used the clusters of short polypeptide sequences, which are typically shorter than the classically defined protein domains, to characterize the functionalities of proteins. We developed a framework to identify significant short polypeptide clusters from yeast protein sequences, and then used these short polypeptide clusters as features to predict yeast synthetic lethal genetic interactions. The short polypeptide clusters based approach provides much higher coverage for predicting yeast synthetic lethal genetic interactions. Evaluation using experimental data sets showed that the short polypeptide clusters based approach is superior to the previous protein domain based one. Conclusion: We were able to achieve higher performance in yeast synthetic lethal genetic interactions prediction using short polypeptide clusters as features. Our study suggests that the short polypeptide cluster may help better understand the functionalities of proteins.