Fig. 3

Probabilistic causal network and functional biological context for the NK cell-mediated cytotoxicity PBMC module. A Probabilistic causal network and key driver analysis results for the NK cell-mediated cytotoxicity module. This PBMC transcriptome module was significantly enriched with PBMC asthma genes. The arrow indicates the overall causality flow with key drivers at 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. Selected non-key drivers are additionally labeled, as they are recognized to function with the upstream key drivers. B Functional biological context for the NK cell-mediated cytotoxicity module. Genes within purple boxes are key drivers and genes in purple font are module genes highlighted in A. Dashed arrows indicate causal relationships inferred from the causal network. NKG7 encodes natural killer cell granule protein 7, which regulates granule exocytosis in lymphocytes [48]. PRF1 encodes perforins that function with granzymes and granulysins to kill target cells [47]. Killer cell lectin-like receipt D1 encoded by KLRD1 forms heterodimers with NKG2 and can stimulate or inhibit cytotoxicity depending on NKG2 isoform [58, 59]. MBYL1, MYB proto-oncogene like 1, is a transcription activator [53]. The module genes GZMB, GZMA and GNLY encode granzymes and granulysin that kill target cells upon release [47, 49]