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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod49

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod49 Module size 40 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 57406 ABHD6 abhydrolase domain containing 6 10369 CACNG2 calcium voltage-gated channel auxiliary subunit gamma 2 27092 CACNG4 calcium voltage-gated channel auxiliary subunit gamma 4 27091 CACNG5 calcium voltage-gated channel auxiliary subunit gamma 5 59283 CACNG8 calcium voltage-gated channel auxiliary subunit gamma 8 815 CAMK2A calcium/calmodulin dependent protein kinase II alpha 818 CAMK2G calcium/calmodulin dependent protein kinase II gamma 55450 CAMK2N1 calcium/calmodulin dependent protein kinase II inhibitor 1 29097 CNIH2 cornichon family AMPA receptor auxiliary protein 4 149111 CNIH3 cornichon family AMPA receptor auxiliary protein 3 2890 GRIA1 glutamate ionotropic receptor AMPA type subunit 1 2891 GRIA2 glutamate ionotropic receptor AMPA type subunit 2 2892 GRIA3 glutamate ionotropic receptor AMPA type subunit 3 2893 GRIA4 glutamate ionotropic receptor AMPA type subunit 4 2894 GRID1 glutamate ionotropic receptor delta type subunit 1 2895 GRID2 glutamate ionotropic receptor delta type subunit 2 2897 GRIK1 glutamate ionotropic receptor kainate type subunit 1 2898 GRIK2 glutamate ionotropic receptor kainate type subunit 2 2899 GRIK3 glutamate ionotropic receptor kainate type subunit 3 2900 GRIK4 glutamate ionotropic receptor kainate type subunit 4 2901 GRIK5 glutamate ionotropic receptor kainate type subunit 5 2902 GRIN1 glutamate ionotropic receptor NMDA type subunit 1 2903 GRIN2A glutamate ionotropic receptor NMDA type subunit 2A 2904 GRIN2B glutamate ionotropic receptor NMDA type subunit 2B 2905 GRIN2C glutamate ionotropic receptor NMDA type subunit 2C 2906 GRIN2D glutamate ionotropic receptor NMDA type subunit 2D 116443 GRIN3A glutamate ionotropic receptor NMDA type subunit 3A 116444 GRIN3B glutamate ionotropic receptor NMDA type subunit 3B 81832 NETO1 neuropilin and tolloid like 1 81831 NETO2 neuropilin and tolloid like 2 22871 NLGN1 neuroligin 1 51299 NRN1 neuritin 1 10439 OLFM1 olfactomedin 1 93145 OLFM2 olfactomedin 2 118427 OLFM3 olfactomedin 3 64840 PORCN porcupine O-acyltransferase 388336 SHISA6 shisa family member 6 729993 SHISA9 shisa family member 9 375567 VWC2 von Willebrand factor C domain containing 2 402117 VWC2L von Willebrand factor C domain containing 2 like

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 4.38e-01 2.01e-43 GO AMPA glutamate receptor complex cellular_component 3.03e-01 1.45e-45 GO ionotropic glutamate receptor signaling pathway biological_process 2.82e-01 1.84e-20 GO NMDA selective glutamate receptor complex cellular_component 2.82e-01 5.29e-14 GO kainate selective glutamate receptor activity molecular_function 1.12e-01 2.96e-26 Reactome Unblocking of NMDA receptor, glutamate binding and activation Neuronal System 6.03e-02 4.11e-24 GO glutamate receptor signaling pathway biological_process 4.90e-02 5.04e-23 GO synaptic transmission, glutamatergic biological_process 4.30e-02 5.21e-18 GO glutamate receptor activity molecular_function 3.68e-02 2.33e-03 Reactome WNT ligand secretion is abrogated by the PORCN inhibitor LGK974 Disease 2.75e-02 2.20e-19 GO regulation of AMPA receptor activity biological_process 1.84e-02 6.22e-16 GO modulation of chemical synaptic transmission biological_process 2.92e-03 1.67e-24 GO postsynaptic density membrane cellular_component

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 regulation of ion transport 0e+00 0e+00 regulation of neurotransmitter receptor activity 0e+00 0e+00 regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity 0e+00 0e+00 regulation of ion transmembrane transport 0e+00 0e+00 regulation of glutamate receptor signaling pathway 0e+00 0e+00 regulation of membrane potential 0e+00 0e+00 regulation of receptor activity 0e+00 0e+00 regulation of cation channel activity 0e+00 0e+00 regulation of synaptic plasticity 0e+00 0e+00 modulation of synaptic transmission 0e+00 0e+00 chemical synaptic transmission 0e+00 0e+00 regulation of postsynaptic membrane potential 0e+00 0e+00 excitatory postsynaptic potential 0e+00 0e+00 glutamate receptor signaling pathway 0e+00 0e+00 ionotropic glutamate receptor signaling pathway 0e+00 0e+00 chemical synaptic transmission, postsynaptic 0e+00 0e+00 AMPA glutamate receptor complex 0e+00 0e+00 transmembrane transporter complex 0e+00 0e+00 receptor complex 0e+00 0e+00 synaptic 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 NEUROTRANSMITTER RECEPTOR BINDING AND DOWNSTREAM TRANSMISSION IN THE POSTSYNAPTIC CELL 0.00e+00 0.00e+00 NEURONAL SYSTEM 0.00e+00 0.00e+00 TRAFFICKING OF AMPA RECEPTORS 0.00e+00 0.00e+00 TRANSMISSION ACROSS CHEMICAL SYNAPSES 0.00e+00 0.00e+00 UNBLOCKING OF NMDA RECEPTOR GLUTAMATE BINDING AND ACTIVATION 0.00e+00 0.00e+00 ACTIVATION OF NMDA RECEPTOR UPON GLUTAMATE BINDING AND POSTSYNAPTIC EVENTS 0.00e+00 0.00e+00 NEUROTRANSMITTER RECEPTOR BINDING AND DOWNSTREAM TRANSMISSION IN THE POSTSYNAPTIC CELL 0.00e+00 0.00e+00 NEURONAL SYSTEM 0.00e+00 0.00e+00 TRAFFICKING OF AMPA RECEPTORS 0.00e+00 0.00e+00 TRANSMISSION ACROSS CHEMICAL SYNAPSES 0.00e+00 0.00e+00 UNBLOCKING OF NMDA RECEPTOR GLUTAMATE BINDING AND ACTIVATION 0.00e+00 0.00e+00 ACTIVATION OF NMDA RECEPTOR UPON GLUTAMATE BINDING AND POSTSYNAPTIC EVENTS 1.27e-10 3.43e-08 CREB PHOSPHORYLATION THROUGH THE ACTIVATION OF CAMKII 1.89e-10 5.03e-08 RAS ACTIVATION UOPN CA2 INFUX THROUGH NMDA RECEPTOR 2.05e-10 7.25e-08 CREB PHOSPHORYLATION THROUGH THE ACTIVATION OF CAMKII 8.92e-10 2.96e-07 RAS ACTIVATION UOPN CA2 INFUX THROUGH NMDA RECEPTOR 2.86e-09 6.62e-07 CREB PHOSPHORYLATION THROUGH THE ACTIVATION OF RAS 3.27e-09 1.00e-06 IONOTROPIC ACTIVITY OF KAINATE RECEPTORS 6.39e-09 1.43e-06 POST NMDA RECEPTOR ACTIVATION EVENTS 9.91e-09 2.18e-06 IONOTROPIC ACTIVITY OF KAINATE RECEPTORS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 0.00e+00 0.00e+00 abnormal CNS synaptic transmission 0.00e+00 0.00e+00 abnormal excitatory postsynaptic currents 2.62e-10 1.23e-05 reduced long term potentiation 3.81e-10 1.62e-05 abnormal AMPA-mediated synaptic currents 1.09e-08 2.74e-04 abnormal miniature excitatory postsynaptic currents 8.17e-08 1.19e-03 absent long term depression 4.57e-07 4.91e-03 abnormal glutamate-mediated receptor currents 4.68e-07 4.99e-03 decreased vertical activity 1.75e-06 1.33e-02 abnormal CNS synapse formation 2.95e-06 1.99e-02 impaired coordination 3.14e-06 2.07e-02 decreased chemical nociceptive threshold 5.08e-06 2.96e-02 reduced AMPA-mediated synaptic currents 8.10e-06 4.02e-02 abnormal NMDA-mediated synaptic currents 9.70e-06 4.64e-02 hyperactivity 1.02e-05 4.76e-02 abnormal excitatory postsynaptic potential 1.13e-05 5.11e-02 abnormal long term potentiation 1.35e-05 5.72e-02 abnormal social investigation 1.74e-05 6.94e-02 increased startle reflex 3.09e-05 1.05e-01 decreased paired-pulse facilitation 4.05e-05 1.24e-01 jumpy

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

²FDR corrected p-value (Benjamini-Hochberg)