DCMD: Distance-based classification using mixture distributions on microbiome data

PLoS Comput Biol. 2021 Mar 12;17(3):e1008799. doi: 10.1371/journal.pcbi.1008799. eCollection 2021 Mar.

Abstract

Current advances in next-generation sequencing techniques have allowed researchers to conduct comprehensive research on the microbiome and human diseases, with recent studies identifying associations between the human microbiome and health outcomes for a number of chronic conditions. However, microbiome data structure, characterized by sparsity and skewness, presents challenges to building effective classifiers. To address this, we present an innovative approach for distance-based classification using mixture distributions (DCMD). The method aims to improve classification performance using microbiome community data, where the predictors are composed of sparse and heterogeneous count data. This approach models the inherent uncertainty in sparse counts by estimating a mixture distribution for the sample data and representing each observation as a distribution, conditional on observed counts and the estimated mixture, which are then used as inputs for distance-based classification. The method is implemented into a k-means classification and k-nearest neighbours framework. We develop two distance metrics that produce optimal results. The performance of the model is assessed using simulated and human microbiome study data, with results compared against a number of existing machine learning and distance-based classification approaches. The proposed method is competitive when compared to the other machine learning approaches, and shows a clear improvement over commonly used distance-based classifiers, underscoring the importance of modelling sparsity for achieving optimal results. The range of applicability and robustness make the proposed method a viable alternative for classification using sparse microbiome count data. The source code is available at https://github.com/kshestop/DCMD for academic use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • Gastrointestinal Microbiome / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Machine Learning*

Grants and funding

W.X. was funded by Natural Sciences and Engineering Research Council of Canada (NSERC Grant RGPIN-2017-06672), Crohn’s and Colitis Canada (CCC Grant CCC-GEMIII), and Helmsley Charitable Trust. K.S. was supported by CCC Grant CCC-GEMIII. M.D. was supported by NSERC Grant RGPIN-2017-06672 and CCC Grant CCC-GEMIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.