Crossing Gene Sets from GlyGen, GTEx and MoTrPAC Reveals G45495MK Associated with Aging and Exercise

Abstract

Biomedical omics resources are often treated as separate datasets, which fragments insight and limits discovery of shared mechanisms. By crossing geneset libraries from Common Fund programs we can reveal robust molecular programs that span distinct biological contexts. In this report we combined three complementary resources: the GlyGen Glycosylated Proteins library, which assembles proteins modified by glycans; the GTEx Tissue Specific Aging Signatures, which catalog genes whose expression declines in the esophagus with age; and the MoTrPAC Rat Endurance Exercise Training transcriptomics, which provides a consensus set of lung genes altered by endurance exercise. All possible three way combinations were evaluated and the top crossing, ranked 119 for its highly significant overlap, was selected because it contained the maximal set of genes shared across the three libraries. The intersecting set comprised five genes, CD40LG, JCHAIN, KLK6, LCN2 and PIGR, each present in all three source lists. Enrichment analysis highlighted a coherent immune signature, including CD40 signaling, immunoglobulin production, respiratory burst and pathways such as intestinal IgA production, NF kappa B and IL 17 signaling, with transcription factor regulators like RELA and STAT family members. Disease oriented enrichment linked the overlap to coronary atherosclerosis and pediatric autoimmune conditions. Together these findings illustrate how integrating GlyGen, GTEx and MoTrPAC data can uncover a unified immunological context that is consistently represented across glycosylation, aging and exercise responsive gene sets.