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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod272

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod272 Module size 67 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 80739 C6orf25 megakaryocyte and platelet inhibitory receptor G6b 55262 C7orf43 chromosome 7 open reading frame 43 914 CD2 CD2 molecule 51744 CD244 CD244 molecule 146722 CD300LF CD300 molecule like family member f 945 CD33 CD33 molecule 951 CD37 CD37 molecule 962 CD48 CD48 molecule 965 CD58 CD58 molecule 8832 CD84 CD84 molecule 29121 CLEC2D C-type lectin domain family 2 member D 116449 CLNK cytokine dependent hematopoietic cell linker 1445 CSK C-terminal Src kinase 352909 DAB1 dynein axonemal assembly factor 3 55816 DOK5 docking protein 5 345757 FAM174A family with sequence similarity 174 member A 64762 FAM59A GRB2 associated regulator of MAPK1 subtype 1 2204 FCAR Fc fragment of IgA receptor 2205 FCER1A Fc fragment of IgE receptor Ia 2207 FCER1G Fc fragment of IgE receptor Ig 2209 FCGR1A Fc fragment of IgG receptor Ia 2213 FCGR2B Fc fragment of IgG receptor IIb 2215 FCGR3A Fc fragment of IgG receptor IIIb 2215 FCGR3B Fc fragment of IgG receptor IIIb 115352 FCRL3 Fc receptor like 3 84824 FCRLA Fc receptor like A 2241 FER FER tyrosine kinase 2675 GFRA2 GDNF family receptor alpha 2 64096 GFRA4 GDNF family receptor alpha 4 23308 ICOSLG inducible T cell costimulator ligand 3702 ITK IL2 inducible T cell kinase 3820 KLRB1 killer cell lectin like receptor B1 10219 KLRG1 killer cell lectin like receptor G1 3903 LAIR1 leukocyte associated immunoglobulin like receptor 1 54900 LAX1 lymphocyte transmembrane adaptor 1 3932 LCK LCK proto-oncogene, Src family tyrosine kinase 54741 LEPROT leptin receptor overlapping transcript 23484 LEPROTL1 leptin receptor overlapping transcript like 1 79168 LILRA6 leukocyte immunoglobulin like receptor A6 11006 LILRB4 leukocyte immunoglobulin like receptor B4 54923 LIME1 Lck interacting transmembrane adaptor 1 4061 LY6E lymphocyte antigen 6 family member E 4063 LY9 lymphocyte antigen 9 4067 LYN LYN proto-oncogene, Src family tyrosine kinase 2206 MS4A2 membrane spanning 4-domains A2 150372 NFAM1 NFAT activating protein with ITAM motif 1 4902 NRTN neurturin 126014 OSCAR osteoclast associated, immunoglobulin-like receptor 29992 PILRA paired immunoglobin like type 2 receptor alpha 29990 PILRB paired immunoglobin-like type 2 receptor beta 403313 PPAPDC2 phospholipid phosphatase 6 5777 PTPN6 protein tyrosine phosphatase, non-receptor type 6 4068 SH2D1A SH2 domain containing 1A 54716 SIT1 solute carrier family 6 member 20 8631 SKAP1 src kinase associated phosphoprotein 1 6503 SLA Src like adaptor 6504 SLAMF1 signaling lymphocytic activation molecule family member 1 114836 SLAMF6 SLAM family member 6 6578 SLCO2A1 solute carrier organic anion transporter family member 2A1 9748 SLK STE20 like kinase 10809 STARD10 StAR related lipid transfer domain containing 10 6850 SYK spleen associated tyrosine kinase 9473 THEMIS2 thymocyte selection associated family member 2 757 TMEM50B transmembrane protein 50B 54209 TREM2 triggering receptor expressed on myeloid cells 2 340205 TREML1 triggering receptor expressed on myeloid cells like 1 7535 ZAP70 zeta chain of T cell receptor associated protein kinase 70

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 2.65e-01 2.17e-10 GO IgG binding molecular_function 1.10e-01 5.02e-06 GO regulation of B cell differentiation biological_process 6.14e-02 1.60e-09 GO SH2 domain binding molecular_function 5.83e-02 1.88e-05 GO positive regulation of interleukin-8 secretion biological_process 5.75e-02 3.43e-04 GO glial cell-derived neurotrophic factor receptor signaling pathway biological_process 5.31e-02 1.73e-10 GO non-membrane spanning protein tyrosine kinase activity molecular_function 5.01e-02 1.19e-05 GO regulation of release of sequestered calcium ion into cytosol biological_process 3.77e-02 2.68e-20 Reactome Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell Immune System 2.68e-02 2.80e-05 GO positive regulation of calcium-mediated signaling biological_process 2.34e-02 9.17e-06 Reactome PECAM1 interactions Hemostasis 2.25e-02 1.05e-07 Reactome GPVI-mediated activation cascade Hemostasis 2.06e-02 6.68e-04 GO negative regulation of JAK-STAT cascade biological_process 1.69e-02 4.09e-09 GO transmembrane receptor protein tyrosine kinase signaling pathway biological_process 1.44e-02 3.35e-05 GO MHC class I protein binding molecular_function 1.02e-02 4.40e-04 GO regulation of mast cell degranulation biological_process 5.10e-03 9.44e-04 GO negative regulation of protein localization to cell surface biological_process 3.85e-03 9.44e-04 GO positive regulation of interleukin-17 production biological_process 3.35e-03 5.48e-04 GO positive regulation of alpha-beta T cell differentiation biological_process 2.02e-04 1.10e-08 GO T cell receptor signaling pathway biological_process

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 0.00e+00 0.00e+00 immune response-regulating cell surface receptor signaling pathway 0.00e+00 0.00e+00 non-membrane spanning protein tyrosine kinase activity 0.00e+00 0.00e+00 immunoglobulin binding 1.66e-18 1.59e-15 adaptive immune response 1.90e-13 1.77e-10 innate immune response 2.36e-12 2.17e-09 immune response-regulating signaling pathway 1.05e-10 8.69e-08 immune response-activating cell surface receptor signaling pathway 2.79e-10 1.62e-07 IgG binding 4.03e-10 3.14e-07 regulation of cell activation 4.67e-10 3.61e-07 positive regulation of immune response 7.87e-10 5.93e-07 immune response-activating signal transduction 1.11e-09 8.23e-07 peptidyl-tyrosine autophosphorylation 2.91e-09 2.04e-06 antigen receptor-mediated signaling pathway 7.55e-09 4.98e-06 leukocyte migration 1.16e-08 4.56e-06 extrinsic component of cytoplasmic side of plasma membrane 1.27e-08 8.16e-06 regulation of mast cell activation 2.21e-08 8.36e-06 cytoplasmic side of plasma membrane 2.99e-08 1.26e-05 SH2 domain binding 3.87e-08 1.42e-05 cytoplasmic side of membrane 3.93e-08 1.61e-05 protein tyrosine kinase activity

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 4.87e-08 9.88e-06 CELL SURFACE INTERACTIONS AT THE VASCULAR WALL 1.65e-07 4.17e-05 CELL SURFACE INTERACTIONS AT THE VASCULAR WALL 1.39e-05 2.03e-03 GPVI MEDIATED ACTIVATION CASCADE 2.06e-05 2.94e-03 PECAM1 INTERACTIONS 2.29e-05 3.23e-03 COSTIMULATION BY THE CD28 FAMILY 4.67e-05 7.84e-03 PECAM1 INTERACTIONS 6.10e-05 9.99e-03 COSTIMULATION BY THE CD28 FAMILY 6.41e-05 8.45e-03 PD1 SIGNALING 7.82e-05 1.24e-02 GPVI MEDIATED ACTIVATION CASCADE 8.87e-05 1.14e-02 REGULATION OF KIT SIGNALING 1.07e-04 1.35e-02 TCR SIGNALING 1.65e-04 2.42e-02 REGULATION OF KIT SIGNALING 1.97e-04 2.34e-02 GENERATION OF SECOND MESSENGER MOLECULES 2.63e-04 3.04e-02 NCAM1 INTERACTIONS 2.80e-04 3.86e-02 PD1 SIGNALING 4.30e-04 5.64e-02 TCR SIGNALING 6.49e-04 8.06e-02 GENERATION OF SECOND MESSENGER MOLECULES 6.85e-04 7.17e-02 PLATELET ACTIVATION SIGNALING AND AGGREGATION 6.90e-04 8.49e-02 NCAM1 INTERACTIONS 1.00e-03 1.00e-01 PLATELET ADHESION TO EXPOSED COLLAGEN

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.15e-08 2.85e-04 abnormal mast cell physiology 6.49e-06 3.43e-02 abnormal humoral immune response 7.16e-06 3.69e-02 decreased IgG level 9.38e-06 4.52e-02 decreased IgG1 level 4.12e-05 1.26e-01 abnormal immunoglobulin level 6.58e-05 1.72e-01 decreased T cell proliferation 6.62e-05 1.72e-01 decreased CD4-positive, alpha beta T cell number 7.74e-05 1.91e-01 increased susceptibility to type I hypersensitivity reaction 8.20e-05 1.99e-01 abnormal CD4-positive, alpha-beta T cell physiology 1.14e-04 2.46e-01 abnormal dendritic cell antigen presentation 1.28e-04 2.66e-01 increased IgE level 1.39e-04 2.82e-01 increased mature gamma-delta T cell number 1.93e-04 3.41e-01 abnormal parasympathetic postganglionic fiber morphology 1.98e-04 3.47e-01 abnormal NK T cell physiology 2.12e-04 3.61e-01 increased IgG1 level 2.49e-04 3.98e-01 abnormal CD8-positive, alpha-beta T cell differentiation 3.27e-04 4.72e-01 abnormal NK T cell morphology 4.28e-04 5.53e-01 decreased spleen germinal center size 4.60e-04 5.77e-01 increased immunoglobulin level 4.90e-04 5.99e-01 increased CD8-positive, alpha-beta memory T cell number

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

²FDR corrected p-value (Benjamini-Hochberg)