Crossing Gene Sets From GlyGen, GTEx, and LINCS Reveals CA4 As a Potential Modulator of Glycosylation and Aging

Abstract

Biomedical omics resources are often treated as isolated collections, which fragments insight and limits the discovery of shared mechanisms across physiological contexts. To overcome this limitation we leveraged the Common Fund Data Ecosystem to convert three complementary libraries: GlyGen Glycosylated Proteins, GTEx Tissue-Specific Aging Signatures, and LINCS L1000 CRISPR KO Perturbation Signaturesinto geneset libraries and examined every possible triple combination. By focusing on the crossing that exhibited the greatest inclusion of genes across all candidate overlaps, we extracted an intersecting set of eighteen genes present in every component library. Functional profiling of this core set revealed a coherent signature of circulating plasma glycoproteins that govern hemostasis, complement activation, and lipid handling, linking vascular tone, coagulation balance, and cholesterol metabolism. The enrichment of transcriptionfactor regulators such as CEBPA and ESR1 further underscores the convergence on metabolic and inflammatory control. The deepdive literature synthesis highlighted the roles of these proteins in transport, extracellular matrix stability, and antioxidant protection, providing a mechanistic basis for their shared involvement. Collectively, these findings illustrate how crossing Common Fund datasets can reveal robust, biologically meaningful intersections and clarify how the overlapping gene set is centrally involved in vascular tone, clotting, and lipid metabolism.