Crossing Gene Sets from GTEx, MoTrPAC and RummaGEO Reveals Azacitidine as a Potential Modulator of Brain Aging and Exercise Metabolism

Abstract

Biomedical omics resources are often treated as isolated collections, limiting the ability to see shared biological signals across studies. By crossing gene set libraries derived from the Common Fund Data Ecosystem, we can combine distinct experimental contexts and reveal robust molecular programs that appear in multiple conditions. In this work we selected three resources: the GTEx tissuespecific aging signatures that capture genes downregulated in the aging brain, the MoTrPAC rat endurance exercise transcriptomics that identify genes upregulated in brown adipose tissue after training, and the RummaGEO drug perturbation signatures that reflect genes induced by the azacitidine treatment. The three sets were intersected to find genes present in all of them, representing a maximal shared component among the many possible overlaps. The resulting nineteengene intersection highlighted a coherent network of immune receptor regulators, including PTPRC and CCR5, whose posttranslational modifications control signaling thresholds. Enrichment analysis linked these genes to immune functions such as superoxide production, myeloid cell immunity, antigen receptor signaling, and also to bone remodeling pathways. The inclusion of azacitidineresponsive genes underscores the relevance of this drugperturbation signature within the shared immune and remodeling axis.