Interpreting tree ensemble machine learning models with endoR

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Tree ensemble machine learning models are increasingly used in microbiome science as they are compatible with the compositional, high-dimensional, and sparse structure of sequence-based microbiome data. While such models are often good at predicting phenotypes based on microbiome data, they only yield limited insights into how microbial taxa may be associated. We developed endoR, a method to interpret tree ensemble models. First, endoR simplifies the fitted model into a decision ensemble. Then, it extracts information on the importance of individual features and their pairwise interactions, displaying them as an interpretable network. Both the endoR network and importance scores provide insights into how features, and interactions between them, contribute to the predictive performance of the fitted model. Adjustable regularization and bootstrapping help reduce the complexity and ensure that only essential parts of the model are retained. We assessed endoR on both simulated and real metagenomic data. We found endoR to have comparable accuracy to other common approaches while easing and enhancing model interpretation. Using endoR, we also confirmed published results on gut microbiome differences between cirrhotic and healthy individuals. Finally, we utilized endoR to explore associations between human gut methanogens and microbiome components. Indeed, these hydrogen consumers are expected to interact with fermenting bacteria in a complex syntrophic network. Specifically, we analyzed a global metagenome dataset of 2203 individuals and confirmed the previously reported association between Methanobacteriaceae and Christensenellales. Additionally, we observed that Methanobacteriaceae are associated with a network of hydrogen-producing bacteria. Our method accurately captures how tree ensembles use features and interactions between them to predict a response. As demonstrated by our applications, the resultant visualizations and summary outputs facilitate model interpretation and enable the generation of novel hypotheses about complex systems.

OriginalsprogEngelsk
Artikelnummere1010714
TidsskriftPLOS Computational Biology
Vol/bind18
Udgave nummer12
Antal sider39
ISSN1553-734X
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
This work was supported by the Max Planck Society to AR, NY, and RL. NP was supported by a research grant (0069071) from Novo Nordisk Fonden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Sofia Esquivel-Elizondo for the discussions about hydrogenases and methanogens, and Jacobo de la Cuesta, Daphne Welter, and Brandon Seah for their feedback on the manuscript. We also thank the reviewers for their insights. We are grateful to all who make their data open and/or who contribute to open science. Open sharing of data enabled this project.

Publisher Copyright:
Copyright: © 2022 Ruaud et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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