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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod256

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod256 Module size 32 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 10815 CPLX1 complexin 1 54808 DYM dymeclin 25924 MYRIP myosin VIIA and Rab interacting protein 150221 RIMBP3C RIMS binding protein 3C 22999 RIMS1 regulating synaptic membrane exocytosis 1 9699 RIMS2 regulating synaptic membrane exocytosis 2 57030 SLC17A7 solute carrier family 17 member 7 6571 SLC18A2 solute carrier family 18 member A2 6572 SLC18A3 solute carrier family 18 member A3 6616 SNAP25 synaptosome associated protein 25 29091 STXBP6 syntaxin binding protein 6 9145 SYNGR1 synaptogyrin 1 9143 SYNGR3 synaptogyrin 3 132204 SYNPR synaptoporin 6855 SYP synaptophysin 6856 SYPL1 synaptophysin like 1 6857 SYT1 synaptotagmin 1 23208 SYT11 synaptotagmin 11 83849 SYT15 synaptotagmin 15 51760 SYT17 synaptotagmin 17 127833 SYT2 synaptotagmin 2 84258 SYT3 synaptotagmin 3 6860 SYT4 synaptotagmin 4 6861 SYT5 synaptotagmin 5 9066 SYT7 synaptotagmin 7 90019 SYT8 synaptotagmin 8 84958 SYTL1 synaptotagmin like 1 54843 SYTL2 synaptotagmin like 2 94120 SYTL3 synaptotagmin like 3 94121 SYTL4 synaptotagmin like 4 94122 SYTL5 synaptotagmin like 5 123036 TC2N tandem C2 domains, nuclear

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 3.16e-01 7.20e-26 GO calcium ion-regulated exocytosis of neurotransmitter biological_process 3.04e-01 9.06e-37 GO exocytic vesicle cellular_component 6.23e-02 4.25e-09 GO neurexin family protein binding molecular_function 4.15e-02 8.32e-11 Reactome Acetylcholine Neurotransmitter Release Cycle Neuronal System 4.12e-02 1.90e-14 GO dense core granule cellular_component 3.55e-02 2.30e-15 GO positive regulation of dendrite extension biological_process 3.46e-02 1.15e-10 Reactome Serotonin Neurotransmitter Release Cycle Neuronal System 3.01e-02 1.78e-21 GO presynapse cellular_component 2.43e-02 1.15e-10 Reactome Norepinephrine Neurotransmitter Release Cycle Neuronal System 1.85e-02 3.56e-06 GO regulated exocytosis biological_process 1.80e-02 2.03e-08 GO integral component of synaptic vesicle membrane cellular_component 1.60e-02 1.13e-04 GO neurotransmitter transporter activity molecular_function 1.02e-03 2.85e-12 Reactome Neurotransmitter release cycle Neuronal System 1.54e-04 1.73e-19 GO synaptic vesicle exocytosis 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 0e+00 0e+00 chemical synaptic transmission 0e+00 0e+00 neurotransmitter secretion 0e+00 0e+00 neurotransmitter transport 0e+00 0e+00 regulation of neurotransmitter levels 0e+00 0e+00 vesicle organization 0e+00 0e+00 exocytosis 0e+00 0e+00 regulation of secretion 0e+00 0e+00 organelle localization 0e+00 0e+00 synaptic vesicle transport 0e+00 0e+00 regulated exocytosis 0e+00 0e+00 vesicle localization 0e+00 0e+00 establishment of vesicle localization 0e+00 0e+00 establishment of organelle localization 0e+00 0e+00 positive regulation of dendrite extension 0e+00 0e+00 regulation of regulated secretory pathway 0e+00 0e+00 regulation of vesicle-mediated transport 0e+00 0e+00 synaptic vesicle exocytosis 0e+00 0e+00 calcium ion-regulated exocytosis of neurotransmitter 0e+00 0e+00 calcium ion regulated exocytosis 0e+00 0e+00 regulation of exocytosis

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 2.58e-11 9.79e-09 NEUROTRANSMITTER RELEASE CYCLE 4.43e-10 1.13e-07 NEUROTRANSMITTER RELEASE CYCLE 1.16e-09 3.80e-07 NEURONAL SYSTEM 2.40e-09 7.51e-07 DOPAMINE NEUROTRANSMITTER RELEASE CYCLE 3.46e-09 1.06e-06 ACETYLCHOLINE NEUROTRANSMITTER RELEASE CYCLE 3.75e-09 1.14e-06 NOREPINEPHRINE NEUROTRANSMITTER RELEASE CYCLE 3.39e-08 7.03e-06 DOPAMINE NEUROTRANSMITTER RELEASE CYCLE 3.50e-08 9.56e-06 GLUTAMATE NEUROTRANSMITTER RELEASE CYCLE 4.07e-08 1.10e-05 TRANSMISSION ACROSS CHEMICAL SYNAPSES 4.76e-08 9.68e-06 NOREPINEPHRINE NEUROTRANSMITTER RELEASE CYCLE 5.41e-08 1.09e-05 ACETYLCHOLINE NEUROTRANSMITTER RELEASE CYCLE 7.54e-08 1.49e-05 NEURONAL SYSTEM 2.86e-07 5.33e-05 GLUTAMATE NEUROTRANSMITTER RELEASE CYCLE 9.39e-07 1.63e-04 BOTULINUM NEUROTOXICITY 1.67e-06 3.61e-04 BOTULINUM NEUROTOXICITY 2.35e-06 3.85e-04 TRANSMISSION ACROSS CHEMICAL SYNAPSES 6.76e-06 1.33e-03 GABA SYNTHESIS RELEASE REUPTAKE AND DEGRADATION 2.71e-05 3.79e-03 GABA SYNTHESIS RELEASE REUPTAKE AND DEGRADATION 3.99e-03 3.79e-01 REGULATION OF INSULIN SECRETION 6.60e-03 5.73e-01 INTEGRATION OF ENERGY METABOLISM

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 6.26e-07 6.25e-03 abnormal miniature excitatory postsynaptic currents 8.87e-07 7.97e-03 abnormal excitatory postsynaptic currents 2.08e-06 1.51e-02 abnormal CNS synaptic transmission 1.14e-05 5.13e-02 abnormal neurotransmitter secretion 3.36e-05 1.10e-01 enhanced paired-pulse facilitation 1.08e-04 2.39e-01 impaired coordination 1.71e-04 3.19e-01 abnormal neurotransmitter uptake 2.02e-04 3.52e-01 abnormal paired-pulse inhibition 4.90e-04 5.99e-01 abnormal inhibitory postsynaptic currents 7.33e-04 7.56e-01 abnormal endplate potential 1.03e-03 9.16e-01 decreased paired-pulse facilitation 1.07e-03 9.34e-01 decreased insulin secretion 1.25e-03 1.00e+00 abnormal dopamine level 1.36e-03 1.00e+00 abnormal neurotransmitter level 1.57e-03 1.00e+00 abnormal miniature endplate potential 1.97e-03 1.00e+00 unresponsive to tactile stimuli 2.11e-03 1.00e+00 infertility 2.35e-03 1.00e+00 abnormal pancreatic beta cell physiology 2.36e-03 1.00e+00 abnormal response to new environment 2.41e-03 1.00e+00 decreased vertical activity

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

²FDR corrected p-value (Benjamini-Hochberg)