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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod103

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod103 Module size 60 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 248 ALPI alkaline phosphatase, intestinal 250 ALPP alkaline phosphatase, placental 251 ALPPL2 alkaline phosphatase, germ cell 653145 ANXA8 annexin A8 728113 ANXA8L1 annexin A8 like 1 432 ASGR1 asialoglycoprotein receptor 1 811 CALR calreticulin 821 CANX calnexin 4312 CLGN matrix metallopeptidase 1 10845 CLPX caseinolytic mitochondrial matrix peptidase chaperone subunit 78987 CRELD1 cysteine rich with EGF like domains 1 79174 CRELD2 cysteine rich with EGF like domains 2 54431 DNAJC10 DnaJ heat shock protein family (Hsp40) member C10 9695 EDEM1 ER degradation enhancing alpha-mannosidase like protein 1 55741 EDEM2 ER degradation enhancing alpha-mannosidase like protein 2 80267 EDEM3 ER degradation enhancing alpha-mannosidase like protein 3 57222 ERGIC1 endoplasmic reticulum-golgi intermediate compartment 1 51290 ERGIC2 ERGIC and golgi 2 51614 ERGIC3 ERGIC and golgi 3 30001 ERO1L endoplasmic reticulum oxidoreductase 1 alpha 56605 ERO1LB endoplasmic reticulum oxidoreductase 1 beta 10961 ERP29 endoplasmic reticulum protein 29 2548 GAA glucosidase alpha, acid 23193 GANAB glucosidase II alpha subunit 2595 GANC glucosidase alpha, neutral C 79158 GNPTAB N-acetylglucosamine-1-phosphate transferase subunits alpha and beta 150274 HSCB HscB mitochondrial iron-sulfur cluster cochaperone 7184 HSP90B1 heat shock protein 90 beta family member 1 23640 HSPBP1 HSPA (Hsp70) binding protein 1 23479 ISCU iron-sulfur cluster assembly enzyme 57462 KIAA1161 myogenesis regulating glycosidase (putative) 11253 MAN1B1 mannosidase alpha class 1B member 1 4125 MAN2B1 mannosidase alpha class 2B member 1 4126 MANBA mannosidase beta 124512 METTL23 methyltransferase like 23 84879 MFSD2A major facilitator superfamily domain containing 2A 8972 MGAM maltase-glucoamylase 9761 MLEC malectin 51237 MZB1 marginal zone B and B1 cell specific protein 4924 NUCB1 nucleobindin 1 4925 NUCB2 nucleobindin 2 5034 P4HB prolyl 4-hydroxylase subunit beta 2923 PDIA3 protein disulfide isomerase family A member 3 9601 PDIA4 protein disulfide isomerase family A member 4 10130 PDIA6 protein disulfide isomerase family A member 6 5479 PPIB peptidylprolyl isomerase B 5480 PPIC peptidylprolyl isomerase C 287134 PRKCSH N-acetylglucosamine-1-phosphate transferase subunit gamma 169714 QSOX2 quiescin sulfhydryl oxidase 2 6388 SDF2 stromal cell derived factor 2 23753 SDF2L1 stromal cell derived factor 2 like 1 11231 SEC63 SEC63 homolog, protein translocation regulator 6490 SI premelanosome protein 64374 SIL1 SIL1 nucleotide exchange factor 261729 STEAP2 STEAP2 metalloreductase 113419 TEX261 testis expressed 261 7038 TG thyroglobulin 56886 UGGT1 UDP-glucose glycoprotein glucosyltransferase 1 55757 UGGT2 UDP-glucose glycoprotein glucosyltransferase 2 10269 ZMPSTE24 zinc metallopeptidase STE24

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 4.31e-01 8.67e-16 GO endoplasmic reticulum chaperone complex cellular_component 2.67e-01 6.52e-07 GO alkaline phosphatase activity molecular_function 2.19e-01 6.24e-05 Reactome Lysosomal oligosaccharide catabolism Metabolism 2.04e-01 3.52e-09 GO mannosyl-oligosaccharide 1,2-alpha-mannosidase activity molecular_function 1.96e-01 1.16e-21 Reactome Calnexin/calreticulin cycle Metabolism of proteins 1.16e-01 1.30e-09 GO protein disulfide isomerase activity molecular_function 7.03e-02 3.22e-22 Reactome N-glycan trimming in the ER and Calnexin/Calreticulin cycle Metabolism of proteins 3.00e-02 4.62e-04 Reactome Digestion of dietary carbohydrate Digestion and absorption 1.29e-02 2.53e-15 GO protein folding biological_process 1.24e-02 5.64e-04 GO adenyl-nucleotide exchange factor activity molecular_function 1.00e-02 9.43e-07 GO integral component of Golgi membrane cellular_component 9.33e-03 1.84e-09 GO protein folding in endoplasmic reticulum biological_process 3.64e-03 2.92e-10 GO carbohydrate binding molecular_function 3.62e-03 5.32e-06 GO ER-associated misfolded protein catabolic process biological_process 2.83e-03 1.44e-06 GO chaperone-mediated protein folding 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 response to endoplasmic reticulum stress 0.00e+00 0.00e+00 protein folding 0.00e+00 0.00e+00 endoplasmic reticulum lumen 0.00e+00 0.00e+00 endoplasmic reticulum chaperone complex 0.00e+00 0.00e+00 hydrolase activity, hydrolyzing O-glycosyl compounds 0.00e+00 0.00e+00 hydrolase activity, acting on glycosyl bonds 2.10e-11 1.86e-08 protein deglycosylation 4.45e-11 3.82e-08 N-glycan processing 7.41e-11 3.88e-08 endoplasmic reticulum-Golgi intermediate compartment 1.31e-10 1.07e-07 protein alpha-1,2-demannosylation 1.76e-10 1.04e-07 protein disulfide isomerase activity 2.19e-10 1.76e-07 ERAD pathway 2.97e-10 2.35e-07 cellular response to topologically incorrect protein 5.03e-10 3.88e-07 glycoprotein ERAD pathway 5.03e-10 3.88e-07 mannose trimming involved in glycoprotein ERAD pathway 6.17e-10 2.84e-07 melanosome 9.93e-10 5.28e-07 mannosidase activity 1.93e-09 8.40e-07 endoplasmic reticulum quality control compartment 2.91e-09 1.44e-06 glucosidase activity 4.33e-09 2.96e-06 endoplasmic reticulum mannose trimming

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 ASPARAGINE N LINKED GLYCOSYLATION 0.00e+00 0.00e+00 POST TRANSLATIONAL PROTEIN MODIFICATION 0.00e+00 0.00e+00 N GLYCAN TRIMMING IN THE ER AND CALNEXIN CALRETICULIN CYCLE 0.00e+00 0.00e+00 CALNEXIN CALRETICULIN CYCLE 0.00e+00 0.00e+00 ASPARAGINE N LINKED GLYCOSYLATION 0.00e+00 0.00e+00 POST TRANSLATIONAL PROTEIN MODIFICATION 0.00e+00 0.00e+00 N GLYCAN TRIMMING IN THE ER AND CALNEXIN CALRETICULIN CYCLE 0.00e+00 0.00e+00 CALNEXIN CALRETICULIN CYCLE 1.80e-05 3.28e-03 ANTIGEN PRESENTATION FOLDING ASSEMBLY AND PEPTIDE LOADING OF CLASS I MHC 8.27e-05 1.07e-02 DIABETES PATHWAYS 9.83e-05 1.53e-02 DIABETES PATHWAYS 1.16e-04 1.45e-02 UNFOLDED PROTEIN RESPONSE 1.44e-04 2.15e-02 UNFOLDED PROTEIN RESPONSE 2.46e-04 2.86e-02 ANTIGEN PRESENTATION FOLDING ASSEMBLY AND PEPTIDE LOADING OF CLASS I MHC 3.17e-04 4.31e-02 ER PHAGOSOME PATHWAY 3.64e-04 4.86e-02 ACTIVATION OF CHAPERONE GENES BY ATF6 ALPHA 4.62e-04 5.05e-02 DIGESTION OF DIETARY CARBOHYDRATE 6.91e-04 8.50e-02 ACTIVATION OF CHAPERONES BY ATF6 ALPHA 8.43e-04 8.63e-02 ACTIVATION OF CHAPERONE GENES BY ATF6 ALPHA 9.93e-04 1.00e-01 ACTIVATION OF CHAPERONES BY ATF6 ALPHA

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 8.50e-05 2.04e-01 decreased trabecular bone volume 2.18e-04 3.67e-01 decreased compact bone area 1.04e-03 9.21e-01 abnormal thyroid follicle morphology 1.04e-03 9.21e-01 increased glycogen level 1.37e-03 1.00e+00 abnormal Kupffer cell morphology 1.57e-03 1.00e+00 abnormal Z lines 1.77e-03 1.00e+00 abnormal lysosome physiology 2.70e-03 1.00e+00 progressive muscle weakness 2.85e-03 1.00e+00 abnormal lysosome morphology 3.17e-03 1.00e+00 abnormal skeleton morphology 3.24e-03 1.00e+00 fragile skeleton 5.14e-03 1.00e+00 abnormal sarcomere morphology 5.63e-03 1.00e+00 decreased femur compact bone thickness 7.03e-03 1.00e+00 osteoporosis 7.24e-03 1.00e+00 dilated heart right ventricle 7.49e-03 1.00e+00 enlarged thyroid gland 7.52e-03 1.00e+00 rib fractures 8.28e-03 1.00e+00 kyphosis 8.56e-03 1.00e+00 abnormal femur morphology 9.35e-03 1.00e+00 epidermal atrophy

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

²FDR corrected p-value (Benjamini-Hochberg)