Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients


Saris CG, Horvath S, van Vught PW, van Es MA, Blauw HM, Fuller TF, Langfelder P, Deyoung J, Wokke JH, Veldink JH, van den Berg LH, Ophoff RA


Contact:
Roel Ophoff (ROphoff ..at.. mednet.ucla.edu) and Steve Horvath (shorvath ..at.. mednet.ucla.edu)

Article citation

Saris CG, Horvath S, van Vught PW, van Es MA, Blauw HM, Fuller TF, Langfelder P, Deyoung J, Wokke JH, Veldink JH, van den Berg LH, Ophoff RA (2009) Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients. BMC Genomics. 2009 Aug 27;10(1):405. PMID: 19712483

Link to article on BMC Genomics (link opens in a new tab/window)

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.


Data

Here we provide expression and sample annotation data that were used in the main article. All data is formated in plain text comma-separated value (csv) format which can be used by a variety of software. The following files are included:

  1. File ALS-SampleAnnotation-AllRounds.csv contains sample annotation (sample IDs, gender and age at onset);
  2. File ALS-ExpressionData-Rounds1And2-8000probeSets.csv contains expression data measured by 8000 probe sets for samples in rounds 1 and 2, as well as basic annotation for the probe sets. Each of the two rounds consists of 30 ALS and 30 control samples, for a total of 60 ALS and 60 control samples.
  3. File ALS-ExpressionData-Round3-22kProbeSets.csv contains expression data measured by over 22000 probe sets for samples in round 3, as well as basic annotation for the probe sets. This data sets contains 66 ALS cases and 66 controls.

Download the zipped data files:




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