MacLennan -

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Supplementary Materials for the Article:
Weighted Gene Coexpression Network Analysis
Identifies Biomarkers in Glycerol Kinase Deficient Mice

Nicole K. MacLennan¹, Jun Dong^2,3, Jason E. Aten^2,4, Steve Horvath^2,3, Lola Rahib⁵, Loren Ornelas¹, Katrina M. Dipple^1,2,5, Edward R.B. McCabe^1,2,5,6*.
¹Departments of Pediatrics, ²Human Genetics, and ⁴Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA; ³Departments of Biostatistics, School of Public Health at UCLA, Los Angeles, California 90095, USA; ⁵Biomedical Engineering Interdepartmental Program, and ⁶Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, UCLA, Los Angeles, California 90095, USA.
*Corresponding Author: Edward R.B. McCabe, Department of Pediatrics, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 22-412 MDCC, Los Angeles CA 90095-1752. Phone: (310) 825-5095; Fax: (310) 206-4584; Email: emccabe@mednet.ucla.edu
Citation
Presentation
Abstract
Additional Files
R Tutorial
Acknowledgement
Other Materials

Presentation Link to talks: PowerPoint Version PDF version Back to Top
Abstract Symptomatic glycerol kinase deficiency (GKD) is associated with episodic metabolic and central nervous system deterioration. We report here the first application of Weighted Gene Co-Expression Network Analysis (WGCNA) to investigate a knockout (KO) murine model of a human genetic disease. WGCNA identified networks and key hub transcripts from liver mRNA of glycerol kinase (Gyk) KO and wild type (WT) mice. Day of life 1 (dol1) samples from KO mice contained a network module enriched for organic acid metabolism before Gyk KO mice develop organic acidemia and die on dol3-4 and the module containing Gyk was enriched with apoptotic genes. Roles for the highly connected Acot, Psat and Plk3 transcripts were confirmed in cell cultures and subsequently validated by causality testing. We provide evidence that GK may have an apoptotic moonlighting role that is lost in GKD. This systems biology strategy has improved our understanding of GKD pathogenesis and suggests possible treatments. Back to Top
Additional Files Functional Enrichment Analysis (Gene Ontology) of the Mouse Gene Co-expression Modules (Download) Back to Top
R Tutorials For this application, please save all files to the same folder. R Tutorials: Network Generation: Microsoft word version (recommended) PDF version Network Overlap: Microsoft word version (recommended) PDF version Network Breakdown: Microsoft word version (recommended) PDF version Data Files: Mouse Microarray DataCustom made network R functions file 1 Back to Top
Acknowledgement We would like to acknowledge the help from everyone … … Back to Top

NO LINKS WORK IN THIS PAGE!!!
Supplementary Materials for the Article: Weighted Gene Coexpression Network Analysis Identifies Biomarkers in Glycerol Kinase Deficient Mice Nicole K. MacLennan¹, Jun Dong^2,3, Jason E. Aten^2,4, Steve Horvath^2,3, Lola Rahib⁵, Loren Ornelas¹, Katrina M. Dipple^1,2,5, Edward R.B. McCabe^1,2,5,6. ¹Departments of Pediatrics, ²Human Genetics, and ⁴Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA; ³Departments of Biostatistics, School of Public Health at UCLA, Los Angeles, California 90095, USA; ⁵Biomedical Engineering Interdepartmental Program, and ⁶Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, UCLA, Los Angeles, California 90095, USA. Corresponding Author: Edward R.B. McCabe, Department of Pediatrics, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 22-412 MDCC, Los Angeles CA 90095-1752. Phone: (310) 825-5095; Fax: (310) 206-4584; Email: emccabe@mednet.ucla.edu Citation Presentation Abstract Additional Files R Tutorial Acknowledgement Other Materials Presentation Link to talks: PowerPoint Version PDF version Back to Top
Abstract Symptomatic glycerol kinase deficiency (GKD) is associated with episodic metabolic and central nervous system deterioration. We report here the first application of Weighted Gene Co-Expression Network Analysis (WGCNA) to investigate a knockout (KO) murine model of a human genetic disease. WGCNA identified networks and key hub transcripts from liver mRNA of glycerol kinase (Gyk) KO and wild type (WT) mice. Day of life 1 (dol1) samples from KO mice contained a network module enriched for organic acid metabolism before Gyk KO mice develop organic acidemia and die on dol3-4 and the module containing Gyk was enriched with apoptotic genes. Roles for the highly connected Acot, Psat and Plk3 transcripts were confirmed in cell cultures and subsequently validated by causality testing. We provide evidence that GK may have an apoptotic moonlighting role that is lost in GKD. This systems biology strategy has improved our understanding of GKD pathogenesis and suggests possible treatments. Back to Top
Additional Files Functional Enrichment Analysis (Gene Ontology) of the Mouse Gene Co-expression Modules (Download) Back to Top
R Tutorials For this application, please save all files to the same folder. R Tutorials: Network Generation: Microsoft word version (recommended) PDF version Network Overlap: Microsoft word version (recommended) PDF version Network Breakdown: Microsoft word version (recommended) PDF version Data Files: Mouse Microarray DataCustom made network R functions file 1 Back to Top
Acknowledgement We would like to acknowledge the help from everyone … … Back to Top