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

Cytotoxic cell-like module (CCLM)

130

(115)

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

(88)

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

(49)

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

(PM)^a

114

(106)

Coagulation

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

(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

(13)

Mast cell and basophil function^b

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

(482)

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

(69)

Immune response-activating signal transduction

Positive regulation of immune response

Activation of immune response