Network Analysis Reveals the Molecular Bases of Statin Pleiotropy That Vary with Genetic Background.

ABSTRACT: Many approved drugs are pleiotropic: for example, statins, whose main cholesterol-lowering activity is complemented by anticancer and prodiabetogenic mechanisms involving poorly characterized genetic interaction networks. We investigated these using the Saccharomyces cerevisiae genetic model, where most genetic interactions known are limited to the statin-sensitive S288C genetic background. We therefore broadened our approach by investigating gene interactions to include two statin-resistant genetic backgrounds: UWOPS87-2421 and Y55. Networks were functionally focused by selection of HMG1 and BTS1 mevalonate pathway genes for detection of genetic interactions. Networks, multilayered by genetic background, were analyzed for key genes using network centrality (degree, betweenne

SUBMITTER: Del Rio Hernandez CE 

PROVIDER: S-EPMC10100750 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature