Crossing Gene Sets from LINCS, Metabolomics and MoTrPAC Reveals CLEC12A as a Potential Modulator of Energy Metabolism and Adrenal Hormone Regulation

Abstract

Biomedical omics resources are often treated as isolated collections, limiting the ability to see shared molec- ular programs across diverse perturbations. To overcome this limitation we crossed three complementary gene set libraries drawn from the Common Fund Data Ecosystem: the LINCS L1000 CRISPR knockout sig- natures that capture the transcriptional response to loss of CLEC12A, the Metabolomics enzymemetabolite associations that enumerate enzymes linked to the metabolite coenzyme A, and the MoTrPAC rat endurance exercise transcriptomics that record genes downregulated in adrenal tissue of female rats after eight weeks of training. By intersecting these sets we identified a small but highly significant core of four genes that appear in all three libraries: ACAA2, ELOVL6, FASN and HMGCS2. This threeway crossing was selected because it represents a robust shared biological signal. Enrichment analysis with Enrichr confirmed that these genes converge on lipidrelated pathways including fattyacid elongation, biosynthesis, degradation and ketonebody metabolism and pointed to transcriptional regulators such as PPARD and PPARG. The appearance of a thiazide diureticrelated glucose response among the enriched phenotypes indicates a link to metabolic regulation.