Rapid Prediction of Bacterial Heterotrophic Fluxomics Using Machine Learning and Constraint Programming

PLoS Comput Biol. 2016 Apr 19;12(4):e1004838. doi: 10.1371/journal.pcbi.1004838. eCollection 2016 Apr.

Abstract

13C metabolic flux analysis (13C-MFA) has been widely used to measure in vivo enzyme reaction rates (i.e., metabolic flux) in microorganisms. Mining the relationship between environmental and genetic factors and metabolic fluxes hidden in existing fluxomic data will lead to predictive models that can significantly accelerate flux quantification. In this paper, we present a web-based platform MFlux (http://mflux.org) that predicts the bacterial central metabolism via machine learning, leveraging data from approximately 100 13C-MFA papers on heterotrophic bacterial metabolisms. Three machine learning methods, namely Support Vector Machine (SVM), k-Nearest Neighbors (k-NN), and Decision Tree, were employed to study the sophisticated relationship between influential factors and metabolic fluxes. We performed a grid search of the best parameter set for each algorithm and verified their performance through 10-fold cross validations. SVM yields the highest accuracy among all three algorithms. Further, we employed quadratic programming to adjust flux profiles to satisfy stoichiometric constraints. Multiple case studies have shown that MFlux can reasonably predict fluxomes as a function of bacterial species, substrate types, growth rate, oxygen conditions, and cultivation methods. Due to the interest of studying model organism under particular carbon sources, bias of fluxome in the dataset may limit the applicability of machine learning models. This problem can be resolved after more papers on 13C-MFA are published for non-model species.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Bacteria / metabolism*
  • Carbon Isotopes / metabolism
  • Computational Biology
  • Decision Trees
  • Machine Learning
  • Metabolic Flux Analysis / methods*
  • Metabolic Flux Analysis / statistics & numerical data
  • Metabolic Networks and Pathways
  • Models, Biological
  • Support Vector Machine
  • Systems Biology

Substances

  • Carbon Isotopes

Grants and funding

This work was funded by NSF DBI 1356669 http://www.nsf.gov/awardsearch/showAward?AWD_ID=1356669. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.