title: Using gene expression signatures to identify novel treatment strategies in gulf war illness.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Psychological Studies, Nova Southeastern University, Fort Lauderdale, USA. tcraddock@nova.edu.|Graduate School of Computer and Information Sciences, Nova Southeastern University, Fort Lauderdale, USA. tcraddock@nova.edu.|Institute for Neuro-Immune Medicine, Nova Southeastern University, 3440 South University Drive, Fort Lauderdale, FL, 33328, USA. tcraddock@nova.edu.|College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, USA. tcraddock@nova.edu.|Department of Medicine, University of Alberta, Edmonton, Canada. tcraddock@nova.edu.
authors.forename: Travis J A
authors.initials: TJ
authors.lastname: Craddock
authors.affiliation: Miller School of Medicine, University of Miami, Miami, USA.
authors.forename: Jeanna M
authors.initials: JM
authors.lastname: Harvey
authors.affiliation: Institute for Neuro-Immune Medicine, Nova Southeastern University, 3440 South University Drive, Fort Lauderdale, FL, 33328, USA.|College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, USA.
authors.forename: Lubov
authors.initials: L
authors.lastname: Nathanson
authors.affiliation: Institute for Neuro-Immune Medicine, Nova Southeastern University, 3440 South University Drive, Fort Lauderdale, FL, 33328, USA.|College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, USA.|Miller School of Medicine, University of Miami, Miami, USA.|Miami Veterans Affairs Medical Center, Miami, USA.|Diabetes Research Institute, University of Miami, Miami, USA.
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Barnes
authors.affiliation: Institute for Neuro-Immune Medicine, Nova Southeastern University, 3440 South University Drive, Fort Lauderdale, FL, 33328, USA.|College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, USA.|Miller School of Medicine, University of Miami, Miami, USA.|Miami Veterans Affairs Medical Center, Miami, USA.
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Klimas
authors.affiliation: Institute for Neuro-Immune Medicine, Nova Southeastern University, 3440 South University Drive, Fort Lauderdale, FL, 33328, USA.|College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, USA.|Miller School of Medicine, University of Miami, Miami, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Fletcher
authors.affiliation: Center for Psychological Studies, Nova Southeastern University, Fort Lauderdale, USA.|Institute for Neuro-Immune Medicine, Nova Southeastern University, 3440 South University Drive, Fort Lauderdale, FL, 33328, USA.|College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, USA.|Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Broderick
mesh_terms: D000328:Adult; D030541:Databases, Genetic; D058492:Drug Repositioning; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008490:Medical Informatics / Q000379:methods*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D018923:Persian Gulf Syndrome / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics; D014728:Veterans