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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod13

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod13 Module size 35 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 257044 C1orf101 catsper channel auxiliary subunit epsilon 773 CACNA1A calcium voltage-gated channel subunit alpha1 A 774 CACNA1B calcium voltage-gated channel subunit alpha1 B 775 CACNA1C calcium voltage-gated channel subunit alpha1 C 776 CACNA1D calcium voltage-gated channel subunit alpha1 D 777 CACNA1E calcium voltage-gated channel subunit alpha1 E 778 CACNA1F calcium voltage-gated channel subunit alpha1 F 8913 CACNA1G calcium voltage-gated channel subunit alpha1 G 8912 CACNA1H calcium voltage-gated channel subunit alpha1 H 8911 CACNA1I calcium voltage-gated channel subunit alpha1 I 779 CACNA1S calcium voltage-gated channel subunit alpha1 S 781 CACNA2D1 calcium voltage-gated channel auxiliary subunit alpha2delta 1 9254 CACNA2D2 calcium voltage-gated channel auxiliary subunit alpha2delta 2 93589 CACNA2D4 calcium voltage-gated channel auxiliary subunit alpha2delta 4 782 CACNB1 calcium voltage-gated channel auxiliary subunit beta 1 783 CACNB2 calcium voltage-gated channel auxiliary subunit beta 2 784 CACNB3 calcium voltage-gated channel auxiliary subunit beta 3 785 CACNB4 calcium voltage-gated channel auxiliary subunit beta 4 786 CACNG1 calcium voltage-gated channel auxiliary subunit gamma 1 10368 CACNG3 calcium voltage-gated channel auxiliary subunit gamma 3 59285 CACNG6 calcium voltage-gated channel auxiliary subunit gamma 6 59284 CACNG7 calcium voltage-gated channel auxiliary subunit gamma 7 117144 CATSPER1 cation channel sperm associated 1 117155 CATSPER2 cation channel sperm associated 2 347732 CATSPER3 cation channel sperm associated 3 378807 CATSPER4 cation channel sperm associated 4 79820 CATSPERB cation channel sperm associated auxiliary subunit beta 257062 CATSPERD cation channel sperm associated auxiliary subunit delta 57828 CATSPERG cation channel sperm associated auxiliary subunit gamma 84329 HVCN1 hydrogen voltage gated channel 1 157855 KCNU1 potassium calcium-activated channel subfamily U member 1 5923 RASGRF1 Ras protein specific guanine nucleotide releasing factor 1 10125 RASGRP1 RAS guanyl releasing protein 1 25780 RASGRP3 RAS guanyl releasing protein 3 115727 RASGRP4 RAS guanyl releasing protein 4

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 7.34e-01 1.47e-25 Reactome Sperm Motility And Taxes Reproduction 3.89e-01 6.06e-52 GO voltage-gated calcium channel complex cellular_component 2.12e-01 1.47e-25 GO high voltage-gated calcium channel activity molecular_function 1.20e-01 3.79e-05 Reactome Activation of RAS in B cells Immune System 8.39e-02 3.44e-50 GO voltage-gated calcium channel activity molecular_function 7.82e-02 3.21e-23 GO L-type voltage-gated calcium channel complex cellular_component 6.96e-02 1.54e-06 GO diacylglycerol binding molecular_function 6.72e-02 3.98e-25 GO calcium ion import biological_process 3.67e-02 1.25e-35 Reactome Phase 2 - plateau phase Muscle contraction 2.06e-02 5.67e-06 GO positive regulation of Ras protein signal transduction biological_process 7.98e-03 1.66e-21 GO sperm-egg recognition biological_process 7.54e-04 1.33e-33 Reactome Phase 0 - rapid depolarisation Muscle contraction

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 ion transmembrane transport 0e+00 0e+00 sperm-egg recognition 0e+00 0e+00 cell-cell recognition 0e+00 0e+00 cation transmembrane transport 0e+00 0e+00 metal ion transport 0e+00 0e+00 calcium ion transport 0e+00 0e+00 calcium ion transmembrane transport 0e+00 0e+00 action potential 0e+00 0e+00 divalent metal ion transport 0e+00 0e+00 regulation of membrane potential 0e+00 0e+00 membrane depolarization 0e+00 0e+00 membrane depolarization during action potential 0e+00 0e+00 cardiac conduction 0e+00 0e+00 regulation of heart contraction 0e+00 0e+00 transmembrane transporter complex 0e+00 0e+00 cation channel complex 0e+00 0e+00 ion channel complex 0e+00 0e+00 calcium channel complex 0e+00 0e+00 voltage-gated calcium channel complex

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 NCAM1 INTERACTIONS 0.00e+00 0.00e+00 NCAM SIGNALING FOR NEURITE OUT GROWTH 3.52e-11 1.32e-08 NCAM1 INTERACTIONS 2.89e-10 1.00e-07 NCAM SIGNALING FOR NEURITE OUT GROWTH 2.98e-08 6.21e-06 TRANSMISSION ACROSS CHEMICAL SYNAPSES 1.75e-07 3.32e-05 AXON GUIDANCE 5.81e-07 1.05e-04 NEURONAL SYSTEM 1.13e-06 2.54e-04 TRANSMISSION ACROSS CHEMICAL SYNAPSES 5.31e-06 1.06e-03 AXON GUIDANCE 6.59e-06 1.30e-03 NEURONAL SYSTEM 1.36e-04 2.04e-02 DEVELOPMENTAL BIOLOGY 3.89e-04 5.16e-02 INHIBITION OF INSULIN SECRETION BY ADRENALINE NORADRENALINE 1.45e-03 1.40e-01 INHIBITION OF INSULIN SECRETION BY ADRENALINE NORADRENALINE 2.61e-03 2.67e-01 DOWNSTREAM SIGNALING EVENTS OF B CELL RECEPTOR BCR 2.61e-03 2.35e-01 REGULATION OF INSULIN SECRETION 5.02e-03 4.12e-01 INTEGRATION OF ENERGY METABOLISM 5.34e-03 4.82e-01 REGULATION OF INSULIN SECRETION 7.23e-03 6.17e-01 SIGNALING BY THE B CELL RECEPTOR BCR 1.03e-02 8.15e-01 INTEGRATION OF ENERGY METABOLISM 1.36e-02 9.40e-01 DOWNSTREAM SIGNALING EVENTS OF B CELL RECEPTOR BCR

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 5.91e-08 9.55e-04 abnormal channel response 7.83e-07 7.32e-03 abnormal sperm physiology 5.61e-06 3.17e-02 abnormal muscle electrophysiology 1.16e-05 5.21e-02 abnormal sperm motility 2.82e-05 9.84e-02 abnormal discrimination learning 2.83e-05 9.84e-02 impaired sperm capacitation 3.33e-05 1.09e-01 abnormal CNS synaptic transmission 5.96e-05 1.60e-01 abnormal motor capabilities/coordination/movement 1.20e-04 2.54e-01 impaired acrosome reaction 1.52e-04 2.97e-01 decreased channel response intensity 1.55e-04 3.01e-01 abnormal spike wave discharge 1.93e-04 3.41e-01 asthenozoospermia 3.83e-04 5.20e-01 impaired social transmission of food preference 7.88e-04 7.83e-01 abnormal calcium ion homeostasis 9.73e-04 8.91e-01 impaired behavioral response to xenobiotic 1.25e-03 1.00e+00 abnormal brain wave pattern 1.33e-03 1.00e+00 decreased heart rate 1.93e-03 1.00e+00 abnormal fear/anxiety-related behavior 2.05e-03 1.00e+00 abnormal retinal inner plexiform layer morphology 2.07e-03 1.00e+00 clonic seizures

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

²FDR corrected p-value (Benjamini-Hochberg)