Fig. 4

Probabilistic causal network and functional biological context for the interleukin production PBMC module. A Probabilistic causal network and key driver analysis results for the interleukin production module. This PBMC transcriptome module was significantly enriched with PBMC asthma genes. The arrow indicates the overall causality flow with the key drivers on the top level. Level indicates path length of the gene from a key driver. Genes on higher levels have greater causal impact on downstream genes. Color, shade, and shape indicate key driver, module membership, and PBMC asthma genes as summarized in the legend. Some genes downstream of key drivers are additionally highlighted given their recognized roles in immune-related functions. B Functional biological context for the interleukin production module. Genes highlighted within blue boxes are key drivers of the module. (1) CTSS, Cathepsin S, is a lysosomal cysteine proteinase that cleaves off the invariant chain on MHC class II molecules in the endolysosomal compartments for later antigen-MHC II formation [60]. ATP6AP2 encodes a protein involved in lysosomal proton-transporting V-type ATPase [55]. (2) TNFSF13 encodes a member of the tumor necrosis factor ligand superfamily important for B cell development [61]. (3) RAB3D encodes a member of the RAS oncogene family that regulates secretory granule maturation [56]. (4) PSAP encodes prosaposin, which yields Saposin B when cleaved [50]. Saposin B works with other enzymes to break down sphingolipids [52]. (5) CAPZA2, capping actin protein of muscle Z-line subunit alpha 2, is an F-actin capping protein that caps the barbed end of actin filaments [57]. (6) LCP1 encodes L-plastins (LPL) that bind F-actin. LPL also mediates sensitization of eosinophils [51]