title: Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease.
abstract: BACKGROUND
  This study aims to expand knowledge of the complex process of myocardial infarction (MI) through the application of a systems-based approach.
  
  
  METHODS
  We generated a gene co-expression network from microarray data originating from a mouse model of MI. We characterized it on the basis of connectivity patterns and independent biological information. The potential clinical novelty and relevance of top predictions were assessed in the context of disease classification models. Models were validated using independent gene expression data from mouse and human samples.
  
  
  RESULTS
  The gene co-expression network consisted of 178 genes and 7298 associations. The network was dissected into statistically and biologically meaningful communities of highly interconnected and co-expressed genes. Among the most significant communities, one was distinctly associated with molecular events underlying heart repair after MI (P < 0.05). Col5a2, a gene previously not specifically linked to MI response but responsible for the classic type of Ehlers-Danlos syndrome, was found to have many and strong co-expression associations within this community (11 connections with ρ > 0.85). To validate the potential clinical application of this discovery, we tested its disease discriminatory capacity on independently generated MI datasets from mice and humans. High classification accuracy and concordance was achieved across these evaluations with areas under the receiving operating characteristic curve above 0.8.
  
  
  CONCLUSIONS
  Network-based approaches can enable the discovery of clinically-interesting predictive insights that are accurate and robust. Col5a2 shows predictive potential in MI, and in principle may represent a novel candidate marker for the identification and treatment of ischemic cardiovascular disease.
authors.affiliation: Department of Translational Cardiovascular Research, CRP-Santé, Luxembourg, Luxembourg. francisco.azuaje@crp-sante.lu
authors.forename: Francisco
authors.initials: F
authors.lastname: Azuaje
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Céline
authors.initials: C
authors.lastname: Jeanty
authors.forename: Sarah-Lena
authors.initials: SL
authors.lastname: Puhl
authors.forename: Sophie
authors.initials: S
authors.lastname: Rodius
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Wagner
mesh_terms: D000818:Animals; D019540:Area Under Curve; D024062:Collagen Type V / Q000235:genetics*; D016208:Databases, Factual; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012372:ROC Curve
chemical_list: D024062:Collagen Type V