title: Importance of correlation between gene expression levels: application to the type I interferon signature in rheumatoid arthritis.
abstract: BACKGROUND
  The analysis of gene expression data shows that many genes display similarity in their expression profiles suggesting some co-regulation. Here, we investigated the co-expression patterns in gene expression data and proposed a correlation-based research method to stratify individuals.
  
  
  RESULTS
  Using blood from rheumatoid arthritis (RA) patients, we investigated the gene expression profiles from whole blood using Affymetrix microarray technology. Co-expressed genes were analyzed by a biclustering method, followed by gene ontology analysis of the relevant biclusters. Taking the type I interferon (IFN) pathway as an example, a classification algorithm was developed from the 102 RA patients and extended to 10 systemic lupus erythematosus (SLE) patients and 100 healthy volunteers to further characterize individuals. We developed a correlation-based algorithm referred to as Classification Algorithm Based on a Biological Signature (CABS), an alternative to other approaches focused specifically on the expression levels. This algorithm applied to the expression of 35 IFN-related genes showed that the IFN signature presented a heterogeneous expression between RA, SLE and healthy controls which could reflect the level of global IFN signature activation. Moreover, the monitoring of the IFN-related genes during the anti-TNF treatment identified changes in type I IFN gene activity induced in RA patients.
  
  
  CONCLUSIONS
  In conclusion, we have proposed an original method to analyze genes sharing an expression pattern and a biological function showing that the activation levels of a biological signature could be characterized by its overall state of correlation.
authors: Joint Unit Hospices Civils de Lyon - bioMérieux, Hôpital Edouard Herriot, Lyon, France.
authors: Frédéric
authors: F
authors: Reynier
authors: Fabien
authors: F
authors: Petit
authors: Malick
authors: M
authors: Paye
authors: Fanny
authors: F
authors: Turrel-Davin
authors: Pierre-Emmanuel
authors: PE
authors: Imbert
authors: Arnaud
authors: A
authors: Hot
authors: Bruno
authors: B
authors: Mougin
authors: Pierre
authors: P
authors: Miossec
mesh_terms: D000328:Adult; D000465:Algorithms; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000592:standards; D005786:Gene Expression Regulation; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic; D008297:Male; D008722:Methods; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged
chemical_list: D007370:Interferon Type I; D008727:Methotrexate