Table 1 The top 10 overlapping co-expression genes and the corresponding functions in the top two significant GO/KEGG pathways

KEGG_PATHWAY hsa04060: Cytokine-cytokine receptor interaction

CSF2RB

Colony-stimulating factor 2 (granulocyte, macrophage), IL3, IL5 receptor common subunit beta (high affinity), critical for the activation of both the JAK/STAT (JAK2, STAT5) and MAP kinase pathways, involved in LYN binding.

0.72

CCL5

C-C motif chemokine ligand 5, chemoattractant for blood monocytes, memory T-helper cells and eosinophils, may activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5.

0.80

CXCR3

C-X-C motif chemokine receptor 3, binding CXCL9/Mig, CXCL10/IP10 and CXCL11/I-TAC induce cellular responses that are involved in leukocyte traffic, most notably integrin activation, cytoskeletal changes and chemotactic migration.

0.75

LTB

Lymphotoxin beta, a type II membrane protein of the TNF family, and an inducer of the inflammatory response and involved in normal development of lymphoid tissue.

0.55

CD27

A member of the TNF-receptor superfamily, is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis.

0.68

Others

IL10RA, IL3RA, IL12RB1, CSF1R, CCR5.

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KEGG_PATHWAY hsa04514: Cell adhesion molecules (CAMs)

PECAM1

Platelet and endothelial cell adhesion molecule 1, makes up a large portion of endothelial cell intercellular junctions, and might involve in leukocyte migration, angiogenesis, and integrin activation.

0.77

CD4

This gene encodes a membrane glycoprotein of T lymphocytes that interacts with MHC II antigens and initiates or augments the early phase of T-cell activation.

0.74

CD2

The protein encoded by this gene is a surface antigen found on all peripheral blood T-cells. The encoded protein interacts with LFA3 (CD58) on antigen presenting cells to optimize immune recognition.

0.80

ITGB2

Integrin subunit beta 2, combines with multiple different alpha chains to form different integrin heterodimers. Integrins are cell-surface proteins that participate in cell adhesion as well as cell-surface mediated signaling.

0.75

ITGAL

Integrin subunit alpha L, combines with ITGB2 to form integrins.

0.73

Others

SELPLG, CD86, HLA-DPB1, HLA-DPA1, CD40LG.

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GOTERM_BP_DIRECT GO:0007165 ~ signal transduction

PECAM1

As presented above.

0.77

RASAL3

RAS Protein Activator Like 3, a Ras GTPase-activating protein, plays an important role in the expansion and functions of natural killer T cells in the liver by negatively regulating RAS activity and the down-stream ERK signaling pathway.

0.75

TYROBP

TYRO protein tyrosine kinase binding protein, non-covalently associates with activating receptors of the CD300 family. Cross-linking of CD300-TYROBP complexes results in cellular activation, involves in neutrophil activation mediated by integrin.

0.91

DOK2

Docking Protein 2 provides a docking platform for the assembly of multimolecular signaling complexes, may modulate the cellular proliferation induced by IL-4, IL-2 and IL-3. DOK2 may involve in modulating Bcr-Abl signaling and inhibit EGF-stimulated MAP kinase activation.

0.79

ARHGAP9

Rho GTPase Activating Protein 9, a member of the Rho-GAP family of GTPase activating proteins, has substantial GAP activity towards several Rho-family GTPases, converting them to an inactive GDP-bound state. It implicates in regulating adhesion of hematopoietic cells to the extracellular matrix.

0.79

Others

ARHGAP15, CD4, CD48, CD79B, CD33.

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GOTERM_BP_DIRECT GO:0006955 ~ immune response

CD4

As presented above.

0.74

CST7

Cystatin-7, a cysteine protease inhibitor with a role in immune regulation through inhibition of the hematopoietic system. Additionally, CST7 promotes metastasis in various cancers.

0.71

WAS

WASP actin nucleation promoting factor, involves in transduction of signals from receptors on the cell surface to the actin cytoskeleton. WAS associates with the small GTPase, Cdc42 (regulates formation of actin filaments) and the cytoskeletal organizing complex, Arp2/3.

0.81

CCL5

As presented above.

0.80

VAV1

Vav guanine nucleotide exchange factor 1, activates pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. VAV1 is important in hematopoiesis, T-cell and B-cell development and activation.

0.53

Others

CD79B, LST1, NCF4, S1PR4, LCP2.

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GOTERM_CC_DIRECT GO:0005886 ~ plasma membrane

HCST

Hematopoietic cell signal transducer, associates with KLRK1 to trigger cytotoxicity against target cells. KLRK1-HCST receptor plays a role in immune surveillance against tumors and is required for cytolysis of tumors cells, tumor cells that do not express HCST escape from immune surveillance mediated by NK cell.

0.86

TYROBP

As presented above.

0.91

PECAM1

As presented above.

0.77

CD2

As presented above.

0.80

CORO1A

Coronin 1A, a crucial component of the cytoskeleton of highly motile cells, functioning in the invagination and protrusions of plasma membrane involved in cell locomotion. CORO1A involves in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation.

0.71

Others

CD3D, CD3E, CD79B, GNGT2, KLRB1.

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GOTERM_MF_DIRECT GO:0005515 ~ protein binding

HCST

As presented above.

0.86

TNFAIP8L2

TNF alpha-induced protein 8-like protein 2, acts as a negative regulator of innate and adaptive immunity by maintaining immune homeostasis, negatively regulates Toll-like receptor and T-cell receptor function. TNFAIP8L2 inhibits JUN/AP1 and NF-kappa-B activation, promotes Fas-induced apoptosis.

0.88

SPI1

Spi-1 proto-oncogene, is a member of the Ets transcription factor family and plays a vital role in development and maturation of the myeloid and lymphoid lineages.

0.86

WAS

As presented above.

0.81

PECAM1

As presented above.

0.77

Others

LAPTM5, CD37, GPSM3, ARHGAP9, TYROBP.

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