The reverse-direction method links mass experimental data to human diseases

Arch Immunol Ther Exp (Warsz). 2014 Feb;62(1):41-5. doi: 10.1007/s00005-013-0255-9. Epub 2013 Aug 31.

Abstract

Genome-wide analyses such as DNA microarray, RNA sequencing and RNA interference-based high-throughput screening are prevalent to decipher a biological process of interest, and provide a large quantity of data to be processed. An ultimate goal for researchers must be extrapolation of their data to human diseases. We have conducted functional genome-wide screenings to elucidate molecular mechanisms of the inflammation amplifier, a NFκB/STAT3-dependent machinery that potently drives recruitment of immune cells to promote inflammation. Using a public database of genome-wide association studies (GWAS), we recently reported the reverse-direction method by which our mass screening data were successfully linked to many human diseases. As an example, the epiregulin-epidermal growth factor receptor pathway was identified as a regulator of the inflammation amplifier, and associated with human diseases by GWAS. In fact, serum epiregulin levels were higher in patients with chronic inflammatory disorders. The reverse-direction method can be a useful tool to narrow mass data down to focus on human disease-related genes.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Movement
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • Epiregulin
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Genome-Wide Association Study
  • High-Throughput Screening Assays
  • Humans
  • Immune System Diseases / diagnosis*
  • Immune System Diseases / immunology*
  • Inflammation Mediators / metabolism
  • Mass Screening / methods*
  • Mass Screening / trends
  • NF-kappa B / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Translational Research, Biomedical

Substances

  • EREG protein, human
  • Epiregulin
  • Inflammation Mediators
  • NF-kappa B
  • STAT3 Transcription Factor
  • Epidermal Growth Factor
  • EGFR protein, human
  • ErbB Receptors