Using gene expression signatures to identify novel treatment strategies in gulf war illness

Travis J.A. Craddock, Jeanna M. Harvey, Lubov Nathanson, Zachary M. Barnes, Nancy G. Klimas, Mary Ann Fletcher, Gordon Broderick

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failure and a lengthy cycle time. Repurposing Food and Drug Administration approved drugs offers a cost-effective solution with a significantly abbreviated timeline. Methods: Here, we explore drug re-purposing opportunities in GWI by combining systems biology and bioinformatics techniques with pharmacogenomic information to find overlapping elements in gene expression linking GWI to successfully treated diseases. Gene modules were defined based on cellular function and their activation estimated from the differential expression of each module's constituent genes. These gene modules were then cross-referenced with drug atlas and pharmacogenomic databases to identify agents currently used successfully for treatment in other diseases. To explore the clinical use of these drugs in illnesses similar to GWI we compared gene expression patterns in modules that were significantly expressed in GWI with expression patterns in those same modules in other illnesses. Results: We found 19 functional modules with significantly altered gene expression patterns in GWI. Within these modules, 45 genes were documented drug targets. Illnesses with highly correlated gene expression patterns overlapping considerably with GWI were found in 18 of the disease conditions studied. Brain, muscular and autoimmune disorders composed the bulk of these. Conclusion: Of the associated drugs, immunosuppressants currently used in treating rheumatoid arthritis, and hormone based therapies were identified as the best available candidates for treating GWI symptoms.

Original languageEnglish (US)
Article number36
JournalBMC Medical Genomics
Volume8
Issue number1
DOIs
StatePublished - Jul 9 2015

Keywords

  • Bioinformatics
  • Complex chronic illness
  • Drug repurposing
  • Gulf war illness
  • Pharmacogenomics
  • Systems biology

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Craddock, T. J. A., Harvey, J. M., Nathanson, L., Barnes, Z. M., Klimas, N. G., Fletcher, M. A., & Broderick, G. (2015). Using gene expression signatures to identify novel treatment strategies in gulf war illness. BMC Medical Genomics, 8(1), [36]. https://doi.org/10.1186/s12920-015-0111-3