SL-scan identifies synthetic lethal interactions in cancer using metabolic networks

Abstract

Exploiting synthetic lethality is a promising strategy for developing targeted cancer therapies. However, identifying clinically significant synthetic lethal (SL) interactions among a large number of gene combinations is a challenging computational task. In this study, we developed the SL-scan pipeline based on metabolic network modeling to discover SL interaction. The SL-scan pipeline identifies the association between simulated Flux Balance Analysis knockout scores and mutation data across cancer cell lines and predicts putative SL interactions. We assessed the concordance of the SL pairs predicted by SL-scan with those of obtained from analysis of the CRISPR, shRNA, and PRISM datasets. Our results demonstrate that the SL-scan pipeline outperformed existing SL prediction approaches based on metabolic networks in identifying SL pairs in various cancers. This study emphasizes the importance of integrating multiple data sources, particularly mutation data, when identifying SL pairs for targeted cancer therapies. The findings of this study may lead to the development of novel targeted cancer therapies.