Metabolic pathway inference using multi-label classification with rich pathway features

PLoS Comput Biol. 2020 Oct 1;16(10):e1008174. doi: 10.1371/journal.pcbi.1008174. eCollection 2020 Oct.

Abstract

Metabolic inference from genomic sequence information is a necessary step in determining the capacity of cells to make a living in the world at different levels of biological organization. A common method for determining the metabolic potential encoded in genomes is to map conceptually translated open reading frames onto a database containing known product descriptions. Such gene-centric methods are limited in their capacity to predict pathway presence or absence and do not support standardized rule sets for automated and reproducible research. Pathway-centric methods based on defined rule sets or machine learning algorithms provide an adjunct or alternative inference method that supports hypothesis generation and testing of metabolic relationships within and between cells. Here, we present mlLGPR, multi-label based on logistic regression for pathway prediction, a software package that uses supervised multi-label classification and rich pathway features to infer metabolic networks in organismal and multi-organismal datasets. We evaluated mlLGPR performance using a corpora of 12 experimental datasets manifesting diverse multi-label properties, including manually curated organismal genomes, synthetic microbial communities and low complexity microbial communities. Resulting performance metrics equaled or exceeded previous reports for organismal genomes and identify specific challenges associated with features engineering and training data for community-level metabolic inference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Databases, Genetic
  • Genomics / methods*
  • Logistic Models
  • Machine Learning*
  • Metabolic Networks and Pathways / genetics*
  • Proteobacteria / genetics
  • Proteobacteria / metabolism
  • Software

Grants and funding

This work was performed under the auspices of Genome Canada, Genome British Columbia, the Natural Sciences and Engineering Research Council (NSERC) of Canada, and Compute/Calcul Canada through grants award to S.J.H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.