Importance of correlation between gene expression levels: application to the type I interferon signature in rheumatoid arthritis

PLoS One. 2011;6(10):e24828. doi: 10.1371/journal.pone.0024828. Epub 2011 Oct 17.

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.

Methodology/principal findings: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics*
  • Case-Control Studies
  • Cluster Analysis
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Profiling / standards
  • Gene Expression Regulation*
  • Humans
  • Interferon Type I / antagonists & inhibitors
  • Interferon Type I / blood
  • Interferon Type I / genetics*
  • Lupus Erythematosus, Systemic
  • Male
  • Methods
  • Methotrexate / therapeutic use
  • Middle Aged

Substances

  • Interferon Type I
  • Methotrexate