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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod161

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod161 Module size 26 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 919 CD247 CD247 molecule 29126 CD274 CD274 molecule 940 CD28 CD28 molecule 915 CD3D CD3d molecule 916 CD3E CD3e molecule 917 CD3G CD3g molecule 920 CD4 CD4 molecule 921 CD5 CD5 molecule 941 CD80 CD80 molecule 942 CD86 CD86 molecule 925 CD8A CD8a molecule 926 CD8B CD8b molecule 1493 CTLA4 cytotoxic T-lymphocyte associated protein 4 8320 EOMES eomesodermin 2533 FYB FYN binding protein 1 9402 GRAP2 GRB2 related adaptor protein 2 3804 KIR2DL3 killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 3 83985 LAT sphingolipid transporter 1 (putative) 3937 LCP2 lymphocyte cytosolic protein 2 55824 PAG1 phosphoprotein membrane anchor with glycosphingolipid microdomains 1 5133 PDCD1 programmed cell death 1 80380 PDCD1LG2 programmed cell death 1 ligand 2 5551 PRF1 perforin 1 6452 SH3BP2 SH3 domain binding protein 2 84174 SLA2 Src like adaptor 2 50852 TRAT1 T cell receptor associated transmembrane adaptor 1

Functional annotation

Modules were tested for enrichment in functional and pathway annotations using two complementary approaches:
1. To select a small number of specific / non-redundant annotations for each module, a regression-based approach was used;
2. To obtain the complete set of enriched annotations, an extension of Fisher’s exact test that takes annotation bias into account was employed (Wallenius’ non-central hypergeometric distribution).

Most specific annotations for this module

Coeff.1 P-value.2 Source.3 Term.4 Class.5 2.20e-01 3.61e-19 GO T cell receptor complex cellular_component 1.22e-01 4.15e-12 GO positive regulation of interleukin-2 biosynthetic process biological_process 6.02e-02 1.07e-19 GO T cell costimulation biological_process 4.46e-02 4.78e-17 Reactome PD-1 signaling Immune System 3.93e-02 1.80e-18 Reactome Generation of second messenger molecules Immune System 3.84e-02 7.72e-16 GO T cell activation biological_process 3.16e-02 8.45e-12 GO coreceptor activity molecular_function 2.33e-02 5.76e-25 Reactome Costimulation by the CD28 family Immune System 1.31e-02 3.06e-10 GO positive regulation of signal transduction biological_process 1.07e-02 3.35e-09 GO negative regulation of T cell proliferation biological_process 7.93e-03 1.42e-10 GO SH3/SH2 adaptor activity molecular_function

¹Regression coefficient

²Fisher’s exact test nominal P-value

³Annotation source (Reactome, GO biological process (BP), molecular function (MF) and cellular component (CC))

⁴GO category or Reactome pathway

⁵High-level branch of annotation tree

Gene membership

All enriched annotations

Gene Ontology

P-value1 FDR2 Term 0e+00 0e+00 antigen receptor-mediated signaling pathway 0e+00 0e+00 immune response-activating signal transduction 0e+00 0e+00 positive regulation of immune response 0e+00 0e+00 T cell receptor signaling pathway 0e+00 0e+00 immune response-regulating signaling pathway 0e+00 0e+00 immune response-regulating cell surface receptor signaling pathway 0e+00 0e+00 immune response-activating cell surface receptor signaling pathway 0e+00 0e+00 T cell costimulation 0e+00 0e+00 regulation of cell-cell adhesion 0e+00 0e+00 positive regulation of cell-cell adhesion 0e+00 0e+00 lymphocyte costimulation 0e+00 0e+00 positive regulation of cell adhesion 0e+00 0e+00 positive regulation of T cell activation 0e+00 0e+00 positive regulation of cell activation 0e+00 0e+00 regulation of cell adhesion 0e+00 0e+00 regulation of cell activation 0e+00 0e+00 regulation of T cell activation 0e+00 0e+00 regulation of lymphocyte activation 0e+00 0e+00 T cell activation 0e+00 0e+00 external side of plasma membrane

¹1Nominal enrichment p-value (Wallenius’ noncentral hypergeometric distribution)

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 0.00e+00 0.00e+00 GENERATION OF SECOND MESSENGER MOLECULES 0.00e+00 0.00e+00 TCR SIGNALING 0.00e+00 0.00e+00 PD1 SIGNALING 0.00e+00 0.00e+00 COSTIMULATION BY THE CD28 FAMILY 0.00e+00 0.00e+00 GENERATION OF SECOND MESSENGER MOLECULES 0.00e+00 0.00e+00 TCR SIGNALING 0.00e+00 0.00e+00 PD1 SIGNALING 0.00e+00 0.00e+00 COSTIMULATION BY THE CD28 FAMILY 3.29e-11 9.41e-09 PHOSPHORYLATION OF CD3 AND TCR ZETA CHAINS 9.53e-10 2.33e-07 TRANSLOCATION OF ZAP 70 TO IMMUNOLOGICAL SYNAPSE 2.42e-09 5.64e-07 IMMUNOREGULATORY INTERACTIONS BETWEEN A LYMPHOID AND A NON LYMPHOID CELL 3.52e-09 8.08e-07 DOWNSTREAM TCR SIGNALING 5.44e-09 1.63e-06 PHOSPHORYLATION OF CD3 AND TCR ZETA CHAINS 1.37e-08 3.94e-06 IMMUNOREGULATORY INTERACTIONS BETWEEN A LYMPHOID AND A NON LYMPHOID CELL 1.84e-07 4.62e-05 TRANSLOCATION OF ZAP 70 TO IMMUNOLOGICAL SYNAPSE 1.05e-06 2.37e-04 DOWNSTREAM TCR SIGNALING 5.98e-06 9.28e-04 CD28 CO STIMULATION 7.85e-06 1.20e-03 THE ROLE OF NEF IN HIV1 REPLICATION AND DISEASE PATHOGENESIS 1.35e-05 1.97e-03 CD28 DEPENDENT VAV1 PATHWAY 7.65e-05 9.96e-03 CD28 DEPENDENT PI3K AKT SIGNALING

¹1Nominal enrichment p-value (Wallenius’ noncentral hypergeometric distribution)

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 2.52e-10 1.22e-05 decreased CD8-positive, alpha-beta T cell number 1.51e-08 3.46e-04 increased interferon-gamma secretion 1.70e-08 3.65e-04 decreased T cell proliferation 3.20e-08 5.96e-04 increased double-negative T cell number 3.39e-08 6.20e-04 abnormal T cell differentiation 4.29e-08 7.33e-04 decreased double-positive T cell number 5.80e-08 9.48e-04 abnormal T cell physiology 6.69e-08 1.03e-03 abnormal regulatory T cell physiology 1.16e-07 1.57e-03 abnormal double-negative T cell morphology 2.74e-07 3.16e-03 abnormal CD8-positive, alpha beta T cell morphology 4.35e-07 4.72e-03 arrested T cell differentiation 6.68e-07 6.54e-03 abnormal T cell morphology 9.60e-07 8.52e-03 abnormal T cell subpopulation ratio 1.22e-06 1.02e-02 decreased thymocyte number 1.24e-06 1.03e-02 abnormal cytotoxic T cell physiology 1.52e-06 1.19e-02 increased susceptibility to autoimmune diabetes 2.20e-06 1.57e-02 abnormal double-positive T cell morphology 5.15e-06 2.99e-02 decreased CD4-positive, alpha beta T cell number 5.74e-06 3.18e-02 abnormal cytokine secretion 6.87e-06 3.59e-02 increased activated T cell number

¹1Nominal enrichment p-value (Wallenius’ noncentral hypergeometric distribution)

²FDR corrected p-value (Benjamini-Hochberg)