title: Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients.
abstract: BACKGROUND
  Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients.
  
  
  RESULTS
  Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%) showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA) was used to find disease-related networks (modules) and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls) and third dataset (63 patients and 63 controls), thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS.
  
  
  CONCLUSIONS
  This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands. c.g.j.saris@umcutrecht.nl
authors.forename: Christiaan G J
authors.initials: CG
authors.lastname: Saris
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Paul W J
authors.initials: PW
authors.lastname: van Vught
authors.forename: Michael A
authors.initials: MA
authors.lastname: van Es
authors.forename: Hylke M
authors.initials: HM
authors.lastname: Blauw
authors.forename: Tova F
authors.initials: TF
authors.lastname: Fuller
authors.forename: Peter
authors.initials: P
authors.lastname: Langfelder
authors.forename: Joseph
authors.initials: J
authors.lastname: DeYoung
authors.forename: John H J
authors.initials: JH
authors.lastname: Wokke
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
chemical_list: D012333:RNA, Messenger