An evolutionary learning and network approach to identifying key metabolites for osteoarthritis

PLoS Comput Biol. 2018 Mar 1;14(3):e1005986. doi: 10.1371/journal.pcbi.1005986. eCollection 2018 Mar.

Abstract

Metabolomics studies use quantitative analyses of metabolites from body fluids or tissues in order to investigate a sequence of cellular processes and biological systems in response to genetic and environmental influences. This promises an immense potential for a better understanding of the pathogenesis of complex diseases. Most conventional metabolomics analysis methods exam one metabolite at a time and may overlook the synergistic effect of combining multiple metabolites. In this article, we proposed a new bioinformatics framework that infers the non-linear synergy among multiple metabolites using a symbolic model and subsequently, identify key metabolites using network analysis. Such a symbolic model is able to represent a complex non-linear relationship among a set of metabolites associated with osteoarthritis (OA) and is automatically learned using an evolutionary algorithm. Applied to the Newfoundland Osteoarthritis Study (NFOAS) dataset, our methodology was able to identify nine key metabolites including some known osteoarthritis-associated metabolites and some novel metabolic markers that have never been reported before. The results demonstrate the effectiveness of our methodology and more importantly, with further investigations, propose new hypotheses that can help better understand the OA disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Databases, Factual
  • Humans
  • Machine Learning
  • Metabolome* / genetics
  • Metabolome* / physiology
  • Metabolomics / methods*
  • Osteoarthritis / metabolism*
  • ROC Curve
  • Systems Biology

Grants and funding

This research is supported by the Research and Development Corporation of Newfoundland and Labrador (RDC) Ignite Grant 5404-1942-101 and the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN-2016-04699 to Ting Hu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.