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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod10

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod10 Module size 90 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 8647 ABCB11 ATP binding cassette subfamily B member 11 340273 ABCB5 ATP binding cassette subfamily B member 5 267 AMFR autocrine motility factor receptor 55139 ANKZF1 ankyrin repeat and zinc finger domain containing 1 84896 ATAD1 ATPase family, AAA domain containing 1 4287 ATXN3 ataxin 3 92552 ATXN3L ataxin 3 like 550 AUP1 AUP1, lipid droplet regulating VLDL assembly factor 25825 BACE2 beta-secretase 2 7917 BAG6 BCL2 associated athanogene 6 342346 C16orf96 chromosome 16 open reading frame 96 51526 C20orf111 oxidative stress responsive serine rich 1 51148 CERCAM cerebral endothelial cell adhesion molecule 55743 CHFR checkpoint with forkhead and ring finger domains 54982 CLN6 CLN6, transmembrane ER protein 9362 CPNE6 copine 6 54504 CPVL carboxypeptidase, vitellogenic like 5476 CTSA cathepsin A 1510 CTSE cathepsin E 79139 DERL1 derlin 1 51009 DERL2 derlin 2 91319 DERL3 derlin 3 27248 ERLEC1 endoplasmic reticulum lectin 1 11160 ERLIN2 ER lipid raft associated 2 23197 FAF2 Fas associated factor family member 2 84923 FAM104A family with sequence similarity 104 member A 51439 FAM8A1 family with sequence similarity 8 member A1 55137 FIGN fidgetin, microtubule severing factor 63979 FIGNL1 fidgetin like 1 2861 GPR37 G protein-coupled receptor 37 9709 HERPUD1 homocysteine inducible ER protein with ubiquitin like domain 1 79781 IQCA1 IQ motif containing with AAA domain 1 9812 KIAA0141 DAP3 binding cell death enhancer 1 55805 LRP2BP LRP2 binding protein 55016 MARCH1 membrane associated ring-CH-type finger 1 162333 MARCH10 membrane associated ring-CH-type finger 10 441061 MARCH11 membrane associated ring-CH-type finger 11 51257 MARCH2 membrane associated ring-CH-type finger 2 115123 MARCH3 membrane associated ring-CH-type finger 3 57574 MARCH4 membrane associated ring-CH-type finger 4 10299 MARCH6 membrane associated ring-CH-type finger 6 64844 MARCH7 membrane associated ring-CH-type finger 7 220972 MARCH8 membrane associated ring-CH-type finger 8 92979 MARCH9 membrane associated ring-CH-type finger 9 55666 NPLOC4 NPL4 homolog, ubiquitin recognition factor 55968 NSFL1C NSFL1 cofactor 10956 OS9 OS9, endoplasmic reticulum lectin 139562 OTUD6A OTU deubiquitinase 6A 51633 OTUD6B OTU domain containing 6B 643834 PGA3 pepsinogen 3, group I (pepsinogen A) 643847 PGA4 pepsinogen 4, group I (pepsinogen A) 5222 PGA5 pepsinogen 5, group I (pepsinogen A) 5225 PGC progastricsin 9373 PLAA phospholipase A2 activating protein 11236 RNF139 ring finger protein 139 153830 RNF145 ring finger protein 145 114804 RNF157 ring finger protein 157 51136 RNFT1 ring finger protein, transmembrane 1 84900 RNFT2 ring finger protein, transmembrane 2 59342 SCPEP1 serine carboxypeptidase 1 6400 SEL1L SEL1L, ERAD E3 ligase adaptor subunit 80343 SEL1L2 SEL1L2, ERAD E3 ligase adaptor subunit 23231 SEL1L3 SEL1L family member 3 65260 SELRC1 cytochrome c oxidase assembly factor 7 (putative) 6683 SPAST spastin 166378 SPATA5 spermatogenesis associated 5 79029 SPATA5L1 spermatogenesis associated 5 like 1 258010 SVIP small VCP interacting protein 84447 SYVN1 synoviolin 1 51669 TMEM66 store-operated calcium entry associated regulatory factor 7327 UBE2G2 ubiquitin conjugating enzyme E2 G2 51465 UBE2J1 ubiquitin conjugating enzyme E2 J1 118424 UBE2J2 ubiquitin conjugating enzyme E2 J2 9354 UBE4A ubiquitination factor E4A 22888 UBOX5 U-box domain containing 5 127733 UBXN10 UBX domain protein 10 91544 UBXN11 UBX domain protein 11 165324 UBXN2A UBX domain protein 2A 137886 UBXN2B UBX domain protein 2B 23190 UBXN4 UBX domain protein 4 80700 UBXN6 UBX domain protein 6 7353 UFD1L ubiquitin recognition factor in ER associated degradation 1 8975 USP13 ubiquitin specific peptidase 13 7415 VCP valosin containing protein 80124 VCPIP1 valosin containing protein interacting protein 1 51322 WAC WW domain containing adaptor with coiled-coil 55432 YOD1 YOD1 deubiquitinase 79752 ZFAND1 zinc finger AN1-type containing 1 90637 ZFAND2A zinc finger AN1-type containing 2A 130617 ZFAND2B zinc finger AN1-type containing 2B

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 2.91e-01 2.56e-23 GO retrograde protein transport, ER to cytosol biological_process 1.69e-01 1.11e-37 GO ubiquitin-dependent ERAD pathway biological_process 1.51e-01 2.96e-16 GO ERAD pathway biological_process 1.38e-01 2.88e-06 GO multivesicular body lumen cellular_component 1.07e-01 1.34e-05 GO microtubule-severing ATPase activity molecular_function 9.80e-02 9.77e-06 GO protein K11-linked deubiquitination biological_process 9.54e-02 8.14e-15 GO Derlin-1 retrotranslocation complex cellular_component 8.36e-02 7.75e-10 GO aspartic-type endopeptidase activity molecular_function 5.86e-02 1.89e-10 GO protein catabolic process biological_process 5.26e-02 2.01e-14 GO ubiquitin binding molecular_function 3.46e-02 1.76e-08 GO transferase activity molecular_function 3.18e-02 8.38e-14 GO endoplasmic reticulum mannose trimming biological_process 2.66e-02 1.78e-05 Reactome Josephin domain DUBs Metabolism of proteins 1.65e-02 2.31e-05 GO ubiquitin-ubiquitin ligase activity molecular_function 1.43e-02 1.67e-05 GO Golgi stack cellular_component 5.60e-03 2.98e-11 GO ubiquitin-specific protease binding molecular_function 3.65e-03 7.36e-08 GO protein N-linked glycosylation via asparagine biological_process 2.78e-03 8.89e-06 GO digestion 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 proteasome-mediated ubiquitin-dependent protein catabolic process 0e+00 0e+00 protein exit from endoplasmic reticulum 0e+00 0e+00 protein catabolic process 0e+00 0e+00 retrograde protein transport, ER to cytosol 0e+00 0e+00 cellular protein catabolic process 0e+00 0e+00 ER-associated ubiquitin-dependent protein catabolic process 0e+00 0e+00 modification-dependent protein catabolic process 0e+00 0e+00 proteolysis involved in cellular protein catabolic process 0e+00 0e+00 response to endoplasmic reticulum stress 0e+00 0e+00 ERAD pathway 0e+00 0e+00 ubiquitin-dependent protein catabolic process 0e+00 0e+00 proteasomal protein catabolic process 0e+00 0e+00 negative regulation of retrograde protein transport, ER to cytosol 0e+00 0e+00 regulation of retrograde protein transport, ER to cytosol 0e+00 0e+00 negative regulation of protein catabolic process 0e+00 0e+00 regulation of protein exit from endoplasmic reticulum 0e+00 0e+00 negative regulation of ERAD pathway 0e+00 0e+00 regulation of ERAD pathway 0e+00 0e+00 cellular response to topologically incorrect protein 0e+00 0e+00 Derlin-1 retrotranslocation complex

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 1.72e-05 3.16e-03 ANTIGEN PROCESSING UBIQUITINATION PROTEASOME DEGRADATION 3.06e-05 5.36e-03 CLASS I MHC MEDIATED ANTIGEN PROCESSING PRESENTATION 9.01e-05 1.16e-02 ANTIGEN PROCESSING UBIQUITINATION PROTEASOME DEGRADATION 1.16e-04 1.45e-02 CLASS I MHC MEDIATED ANTIGEN PROCESSING PRESENTATION 1.57e-03 1.50e-01 UNFOLDED PROTEIN RESPONSE 8.74e-03 7.19e-01 UNFOLDED PROTEIN RESPONSE 9.68e-03 7.14e-01 ACTIVATION OF GENES BY ATF4 1.00e-02 7.32e-01 PRE NOTCH PROCESSING IN GOLGI 1.13e-02 8.10e-01 PERK REGULATED GENE EXPRESSION 1.17e-02 9.02e-01 ACTIVATION OF GENES BY ATF4 1.33e-02 9.97e-01 PERK REGULATED GENE EXPRESSION 1.51e-02 1.00e+00 DIABETES PATHWAYS 2.04e-02 1.00e+00 SYNTHESIS OF BILE ACIDS AND BILE SALTS VIA 7ALPHA HYDROXYCHOLESTEROL 2.10e-02 1.00e+00 RECYCLING OF BILE ACIDS AND SALTS 2.41e-02 1.00e+00 DIABETES PATHWAYS 2.50e-02 1.00e+00 RECYCLING OF BILE ACIDS AND SALTS 2.87e-02 1.00e+00 SYNTHESIS OF BILE ACIDS AND BILE SALTS VIA 7ALPHA HYDROXYCHOLESTEROL 2.93e-02 1.00e+00 PRE NOTCH PROCESSING IN GOLGI 2.96e-02 1.00e+00 SYNTHESIS OF BILE ACIDS AND BILE SALTS 3.32e-02 1.00e+00 SYNTHESIS OF BILE ACIDS AND BILE SALTS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 2.68e-03 1e+00 seizures 2.78e-03 1e+00 abnormal dendritic cell antigen presentation 5.62e-03 1e+00 abnormal ureteric bud elongation 7.48e-03 1e+00 abnormal bile canaliculus morphology 7.48e-03 1e+00 skeletal muscle endomysial fibrosis 7.48e-03 1e+00 abnormal blood vessel elastic tissue morphology 7.48e-03 1e+00 absent lacrimal glands 8.98e-03 1e+00 abnormal cell physiology 9.34e-03 1e+00 enhanced AMPA-mediated synaptic currents 9.34e-03 1e+00 increased circulating interleukin-18 level 9.34e-03 1e+00 impaired branching involved in terminal bronchiole morphogenesis 1.12e-02 1e+00 intrahepatic cholestasis 1.12e-02 1e+00 liver cirrhosis 1.19e-02 1e+00 impaired coordination 1.24e-02 1e+00 enlarged liver 1.31e-02 1e+00 absent lateral semicircular canal 1.31e-02 1e+00 increased kidney cell proliferation 1.49e-02 1e+00 neuronal intranuclear inclusions 1.68e-02 1e+00 abnormal membranous labyrinth morphology 1.68e-02 1e+00 abnormal substantia nigra morphology

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

²FDR corrected p-value (Benjamini-Hochberg)