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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod47

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod47 Module size 28 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 125981 ACER1 alkaline ceramidase 1 340485 ACER2 alkaline ceramidase 2 427 ASAH1 N-acylsphingosine amidohydrolase 1 56624 ASAH2 N-acylsphingosine amidohydrolase 2 64781 CERK ceramide kinase 10715 CERS1 ceramide synthase 1 29956 CERS2 ceramide synthase 2 204219 CERS3 ceramide synthase 3 79603 CERS4 ceramide synthase 4 91012 CERS5 ceramide synthase 5 253782 CERS6 ceramide synthase 6 8560 DEGS1 delta 4-desaturase, sphingolipid 1 123099 DEGS2 delta 4-desaturase, sphingolipid 2 2581 GALC galactosylceramidase 57704 GBA2 glucosylceramidase beta 2 8611 PPAP2A phospholipid phosphatase 1 8613 PPAP2B phospholipid phosphatase 3 8612 PPAP2C phospholipid phosphatase 2 259230 SGMS1 sphingomyelin synthase 1 166929 SGMS2 sphingomyelin synthase 2 81537 SGPP1 sphingosine-1-phosphate phosphatase 1 130367 SGPP2 sphingosine-1-phosphate phosphatase 2 6610 SMPD2 sphingomyelin phosphodiesterase 2 55512 SMPD3 sphingomyelin phosphodiesterase 3 55627 SMPD4 sphingomyelin phosphodiesterase 4 8877 SPHK1 sphingosine kinase 1 56848 SPHK2 sphingosine kinase 2 7368 UGT8 UDP glycosyltransferase 8

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 4.02e-01 1.74e-11 GO N-acylsphingosine amidohydrolase activity molecular_function 3.34e-01 3.48e-17 GO sphingosine N-acyltransferase activity molecular_function 1.22e-01 3.63e-29 GO ceramide biosynthetic process biological_process 1.09e-01 6.51e-60 Reactome Sphingolipid metabolism Metabolism 8.77e-02 4.66e-38 Reactome Sphingolipid de novo biosynthesis Metabolism 8.29e-02 9.50e-08 GO sphingomyelin phosphodiesterase activity molecular_function 4.27e-02 5.94e-07 GO lipid phosphorylation biological_process 3.25e-02 3.04e-05 Reactome TNFR1-mediated ceramide production Signal Transduction

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 membrane lipid metabolic process 0.00e+00 0.00e+00 sphingolipid biosynthetic process 0.00e+00 0.00e+00 sphingolipid metabolic process 0.00e+00 0.00e+00 sphingosine metabolic process 0.00e+00 0.00e+00 lipid biosynthetic process 0.00e+00 0.00e+00 amide biosynthetic process 0.00e+00 0.00e+00 cellular amide metabolic process 0.00e+00 0.00e+00 ceramide biosynthetic process 0.00e+00 0.00e+00 ceramide metabolic process 0.00e+00 0.00e+00 glycosphingolipid metabolic process 0.00e+00 0.00e+00 sphingosine N-acyltransferase activity 1.77e-12 1.63e-09 sphingolipid catabolic process 4.90e-12 4.46e-09 membrane lipid catabolic process 2.35e-11 2.07e-08 glycolipid metabolic process 1.65e-10 1.34e-07 sphingomyelin metabolic process 1.22e-09 6.39e-07 ceramidase activity 7.27e-09 4.81e-06 sphingosine biosynthetic process 8.17e-09 5.37e-06 sphingoid biosynthetic process 9.13e-09 4.19e-06 N-acyltransferase activity 1.61e-07 5.98e-05 lipid kinase activity

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 SPHINGOLIPID DE NOVO BIOSYNTHESIS 0.00e+00 0.00e+00 PHOSPHOLIPID METABOLISM 0.00e+00 0.00e+00 SPHINGOLIPID METABOLISM 0.00e+00 0.00e+00 GLYCOSPHINGOLIPID METABOLISM 0.00e+00 0.00e+00 SPHINGOLIPID DE NOVO BIOSYNTHESIS 0.00e+00 0.00e+00 SPHINGOLIPID METABOLISM 0.00e+00 0.00e+00 PHOSPHOLIPID METABOLISM 2.79e-09 6.47e-07 GLYCOSPHINGOLIPID METABOLISM 2.36e-02 1.00e+00 ASSOCIATION OF TRIC CCT WITH TARGET PROTEINS DURING BIOSYNTHESIS 4.33e-02 1.00e+00 PROTEIN FOLDING

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 ceramide level 7.12e-11 4.12e-06 abnormal lipid level 3.89e-09 1.13e-04 abnormal sphingomyelin level 6.92e-04 7.31e-01 abnormal lipid homeostasis 2.12e-03 1.00e+00 tremors 2.23e-03 1.00e+00 abnormal brain white matter morphology 2.96e-03 1.00e+00 abnormal macrophage morphology 5.12e-03 1.00e+00 abnormal long bone metaphysis morphology 5.63e-03 1.00e+00 nervous 7.16e-03 1.00e+00 decreased bone trabecula number 7.19e-03 1.00e+00 abnormal myelin sheath morphology 7.20e-03 1.00e+00 impaired skin barrier function 8.11e-03 1.00e+00 increased insulin sensitivity 9.99e-03 1.00e+00 decreased circulating insulin-like growth factor I level 1.01e-02 1.00e+00 abnormal cytokine level 1.01e-02 1.00e+00 abnormal femur morphology 1.06e-02 1.00e+00 hindlimb paralysis 1.12e-02 1.00e+00 decreased thyrotroph cell number 1.12e-02 1.00e+00 muscle twitch 1.16e-02 1.00e+00 astrocytosis

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

²FDR corrected p-value (Benjamini-Hochberg)