Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study

PLoS One. 2018 Jun 25;13(6):e0198874. doi: 10.1371/journal.pone.0198874. eCollection 2018.


The biological pathways involved in amyotrophic lateral sclerosis (ALS) remain elusive and diagnostic decision-making can be challenging. Gene expression studies are valuable in overcoming such challenges since they can shed light on differentially regulated pathways and may ultimately identify valuable biomarkers. This two-stage transcriptome-wide study, including 397 ALS patients and 645 control subjects, identified 2,943 differentially expressed transcripts predominantly involved in RNA binding and intracellular transport. When batch effects between the two stages were overcome, three different models (support vector machines, nearest shrunken centroids, and LASSO) discriminated ALS patients from control subjects in the validation stage with high accuracy. The models' accuracy reduced considerably when discriminating ALS from diseases that mimic ALS clinically (N = 75), nor could it predict survival. We here show that whole blood transcriptome profiles are able to reveal biological processes involved in ALS. Also, this study shows that using these profiles to differentiate between ALS and mimic syndromes will be challenging, even when taking batch effects in transcriptome data into account.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / blood
  • Amyotrophic Lateral Sclerosis / diagnosis*
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / mortality
  • Biomarkers / analysis
  • Case-Control Studies
  • Cohort Studies
  • Diagnosis, Differential
  • Feasibility Studies
  • Female
  • Gene Expression Profiling / methods*
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Signal Transduction / genetics*
  • Support Vector Machine
  • Survival Analysis
  • Transcriptome / genetics*


  • Biomarkers

Grant support

The research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 259867 to LHvdB. This project was supported by ZONMW, under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases (PYRAMID) to JHV. This is an EU Joint Programme-Neurodegenerative Disease Research (JPND) project. The project is supported through ZonMW under the aegis of JPND (SOPHIA, STRENGTH). LHvdB received a grant from The Netherlands Organization for Health Research and Development (Vici scheme). MAvE is supported by NWO (Veni scheme), the Thierry Latran Foundation, the Dutch ALS Foundation and the Rudolf Magnus Brain Center Talent Fellowship. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.