Crossing Gene Sets from GTEx, IDG and MoTrPAC Reveals Metformin Association with Cardiac and Metabolic Processes

Abstract

Biomedical omics resources are often treated as separate datasets, which fragments insight and limits discov- ery of shared mechanisms. Crossing gene sets from Common Fund programs can reveal coherent molecular programs, improve robustness, and connect diverse biological contexts. In this report we intersected three complementary gene sets: an upregulated signature from the GTEx Tissues library that captures genes with increased expression in the left ventricle of female donors aged 3039, a Metforminrelated signature from the IDG Drug Targets library that groups genes linked to the pharmacological action of Metformin, and a downreg- ulated signature from the MoTrPAC Rat Endurance Exercise Training Transcriptomics library that reflects genes reduced in brown adipose tissue of male eightweek subjects after endurance exercise. By crossing all possible combinations of one set from each library, the thirdranked overlap was selected because it contained the maximal number of genes common to all three sets. The intersection comprised four mitochondrial complex I genesNDUFA6, NDUFAB1, NDUFB3 and NDUFS1each appearing in every source set and highlighting a shared emphasis on oxidative phosphorylation. Enrichment analysis confirmed coordinated activation of aerobic respiration and electron transport, while the Metforminassociated gene set suggests that Metformin may be related to this mitochondrial pathway.