SPP1 Inflammatory Activation

Gene co-expression module in Endothelial

View this module in SCUBA

Why this annotation

This module has the strongest inflammation signal in the batch (delta_UC=0.851, delta_CD=0.729) with marked reversal in UC remission (-0.676), indicating a highly inflammation-specific program. SPP1 (osteopontin) is a major pro-inflammatory glycoprotein and integrin ligand upregulated in IBD endothelium and macrophages, driving leukocyte recruitment. ADAM15 is a metalloprotease mediating leukocyte adhesion and transendothelial migration. GJC1 (connexin 45) is a gap junction protein expressed in vascular endothelium. FKBP5 is a glucocorticoid/stress-responsive immunophilin upregulated in inflammatory states. EIF2AK4 (GCN2) is an integrated stress response kinase activated by nutrient deprivation and inflammation. PAXX and MGMT suggest concurrent DNA damage/repair activity in inflamed endothelium. NAPRT supports NAD biosynthesis under inflammatory stress. ATG4A links to autophagy. The combination of SPP1 + ADAM15 + FKBP5 + EIF2AK4 defines an inflammatory activation and stress response program, the most acute inflammatory module in this batch.

Genes

ADAM15, ATG4A, C1orf54, C7orf50, C9orf40, CPXM2, EBF3, EIF2AK4, FKBP5, GJC1, MGMT, NAPRT, PAXX, PCDH17, PDE8A, SLC29A1, SNAP25, SPP1

Module annotations were drafted by a large language model from the module's genes, then reviewed and approved by a domain expert. See sources & licences.