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Table 1 Immune module gene content and putative biological function based on GO terms (top three shown) and literature

From: An interaction map of circulating metabolites, immune gene networks, and their genetic regulation

Module Size GO terms Literature-based immune-related function of genes
Cytotoxic cell-like module (CCLM) 130
Immune system process
Defense response
Immune response
Cytotoxic effectors (GZMA, GZMB, GZMM, CTSW, PRF1 [66]); surface receptors (IL2RB, SLAMF6, CD8A, CD8B, CD2, CD247, KLRD1, KLRG1 [66,67,68]); T and NK cell differentiation (ID2 and EOMES [69, 70]), activation (ZAP70 and CBLB [71, 72]), and recruitment (CX3CR1, CCL5, CCL4L2 [73])
Viral response module (VRM) 95
Response to virus
Type I interferon signaling pathway
Response to biotic stimulus
Type I interferon-induced antiviral activity (IFITM1, IFIT1, IFIT2, IFIT3, IFIT5, IFI44, IFI44L, IFI6, MX1, ISG15, ISG20, HERC5 [74, 75]); viral RNA degradation (OAS1, OAS2, OAS3, OASL, DDX60 [30]); type 1 interferon-signaling pathway (IRF9, STAT1, STAT2 [76, 77])
B-cell activity module (BCM) 54
Immune system process
Immune response
B cell activation
B cell surface markers (CD79A, CD79B, CD22 [33, 78]); B cell activation (BANK1, BTLA, CD40, TNFRSF13B, TNFRSF13C [79]), development (POU2AF1, BCL11A, RASGRP3 [80]), migration (CXCR5, CCR6 [80, 81]), and their regulation (CD83, FCER2, FCRL5 [82]); antigen presentation (HLA-DOA, HLA-DOB [83])
Platelet module
Blood coagulation
Cell activation
Platelet receptor signaling, activation, and coagulation (GP6, GP9, ITGA2B, ITGB3, ITGB5, MGLL, MPL, MMRN1, PTK2, VCL, THBS1, F13A1, VWF, [84]); regulating platelet activity (SEPT5, TSPAN9 [85, 86])
Neutrophil module (NM)a 26
Killing of cells of other organism
Cell killing
Response to fungus
Anti-microbial, -fungal, and -viral activity (DEFA1, DEFA1B, DEFA3, DEFA4, ELANE, BPI, RNASE2, RNASE3 [87,88,89,90]); neutrophil-mediated activity (AZU1, LCN2, MPO, CEACAM6, CEACAM8, OLFM4 [90, 91]) and its regulation (LCN2, CAMP, OLR1 [49, 92, 93])
Lipid-leukocyte module (LLM)a 13
Mast cell and basophil functionb Mast cell and basophil related immune response and allergic inflammation (FCER1A, HDC, GATA2, SLC45A3, CPA3, MS4A3 [13, 94, 95])
General immune module A (GIMA) 509
Immune system process
Defense response
Regulation of response to stimulus
These modules contain genes involved in a broad range of immune processes and their regulation such as signaling; cell death; defense response to stress, inflammation, and external stimuli; leukocyte activation, migration, and adhesion
General immune module B (GIMB) 74
Immune response-activating signal transduction
Positive regulation of immune response
Activation of immune response
  1. Size refers to the number of core genes in each module and the subset of these core genes with GO term annotations are listed in parentheses. Functions were assigned to each of these modules based on GO enrichments and literature-based searches for genes in the modules.
  2. a Modules previously reported to have immune related function
  3. b The LLM was not significantly enriched for any GO term