Dataset Information

Machine Learning Reveals Missing Edges and Putative Interaction Mechanisms in Microbial Ecosystem Networks.

ABSTRACT: Microbes affect each other's growth in multiple, often elusive, ways. The ensuing interdependencies form complex networks, believed to reflect taxonomic composition as well as community-level functional properties and dynamics. The elucidation of these networks is often pursued by measuring pairwise interactions in coculture experiments. However, the combinatorial complexity precludes an exhaustive experimental analysis of pairwise interactions, even for moderately sized microbial communities. Here, we used a machine learning random forest approach to address this challenge. In particular, we show how partial knowledge of a microbial interaction network, combined with trait-level representations of individual microbial species, can provide accurate inference of missing edges in the network and putative mechanisms underlying the interactions. We applied our algorithm to three case studies: an experimentally mapped network of interactions between auxotrophic Escherichia coli strains, a community of soil microbes, and a large in silico network of metabolic interdependencies between 100 human gut-associated bacteria. For this last case, 5% of the network was sufficient to predict the remaining 95% with 80% accuracy, and the mechanistic hypotheses produced by the algorithm accurately reflected known metabolic exchanges. Our approach, broadly applicable to any microbial or other ecological network, may drive the discovery of new interactions and new molecular mechanisms, both for therapeutic interventions involving natural communities and for the rational design of synthetic consortia. IMPORTANCE Different organisms in a microbial community may drastically affect each other's growth phenotypes, significantly affecting the community dynamics, with important implications for human and environmental health. Novel culturing methods and the decreasing costs of sequencing will gradually enable high-throughput measurements of pairwise interactions in systematic coculturing studies. However, a thorough characterization of all interactions that occur within a microbial community is greatly limited both by the combinatorial complexity of possible assortments and by the limited biological insight that interaction measurements typically provide without laborious specific follow-ups. Here, we show how a simple and flexible formal representation of microbial pairs can be used for the classification of interactions via machine learning. The approach we propose predicts with high accuracy the outcome of yet-to-be performed experiments and generates testable hypotheses about the mechanisms of specific interactions.

SUBMITTER: DiMucci D

PROVIDER: S-EPMC6208640 | biostudies-other | 2018 Sep-Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Machine Learning Reveals Missing Edges and Putative Interaction Mechanisms in Microbial Ecosystem Networks.

DiMucci Demetrius D Kon Mark M Segrè Daniel D

mSystems 20180901 5

Microbes affect each other's growth in multiple, often elusive, ways. The ensuing interdependencies form complex networks, believed to reflect taxonomic composition as well as community-level functional properties and dynamics. The elucidation of these networks is often pursued by measuring pairwise interactions in coculture experiments. However, the combinatorial complexity precludes an exhaustive experimental analysis of pairwise interactions, even for moderately sized microbial communities. H ...[more]

PMID: 30417106

Similar Datasets

Project description:The incidence of type 2 diabetes (T2D) has been increasing globally, and a growing body of evidence links type 2 diabetes with altered microbiota composition. Type 2 diabetes is preceded by a long prediabetic state characterized by changes in various metabolic parameters. We tested whether the gut microbiome could have predictive potential for T2D development during the healthy and prediabetic disease stages. We used prospective data of 608 well-phenotyped Finnish men collected from the population-based Metabolic Syndrome in Men (METSIM) study to build machine learning models for predicting continuous glucose and insulin measures in a shorter (1.5 year) and longer (4 year) period. Our results show that the inclusion of the gut microbiome improves prediction accuracy for modeling T2D-associated parameters such as glycosylated hemoglobin and insulin measures. We identified novel microbial biomarkers and described their effects on the predictions using interpretable machine learning techniques, which revealed complex linear and nonlinear associations. Additionally, the modeling strategy carried out allowed us to compare the stability of model performance and biomarker selection, also revealing differences in short-term and long-term predictions. The identified microbiome biomarkers provide a predictive measure for various metabolic traits related to T2D, thus providing an additional parameter for personal risk assessment. Our work also highlights the need for robust modeling strategies and the value of interpretable machine learning.IMPORTANCE Recent studies have shown a clear link between gut microbiota and type 2 diabetes. However, current results are based on cross-sectional studies that aim to determine the microbial dysbiosis when the disease is already prevalent. In order to consider the microbiome as a factor in disease risk assessment, prospective studies are needed. Our study is the first study that assesses the gut microbiome as a predictive measure for several type 2 diabetes-associated parameters in a longitudinal study setting. Our results revealed a number of novel microbial biomarkers that can improve the prediction accuracy for continuous insulin measures and glycosylated hemoglobin levels. These results make the prospect of using the microbiome in personalized medicine promising.

Project description:Diabetes mellitus is a group of metabolic diseases in which blood sugar levels are too high. About 8.8% of the world was diabetic in 2017. It is projected that this will reach nearly 10% by 2045. The major challenge is that when machine learning-based classifiers are applied to such data sets for risk stratification, leads to lower performance. Thus, our objective is to develop an optimized and robust machine learning (ML) system under the assumption that missing values or outliers if replaced by a median configuration will yield higher risk stratification accuracy. This ML-based risk stratification is designed, optimized and evaluated, where: (i) the features are extracted and optimized from the six feature selection techniques (random forest, logistic regression, mutual information, principal component analysis, analysis of variance, and Fisher discriminant ratio) and combined with ten different types of classifiers (linear discriminant analysis, quadratic discriminant analysis, naïve Bayes, Gaussian process classification, support vector machine, artificial neural network, Adaboost, logistic regression, decision tree, and random forest) under the hypothesis that both missing values and outliers when replaced by computed medians will improve the risk stratification accuracy. Pima Indian diabetic dataset (768 patients: 268 diabetic and 500 controls) was used. Our results demonstrate that on replacing the missing values and outliers by group median and median values, respectively and further using the combination of random forest feature selection and random forest classification technique yields an accuracy, sensitivity, specificity, positive predictive value, negative predictive value and area under the curve as: 92.26%, 95.96%, 79.72%, 91.14%, 91.20%, and 0.93, respectively. This is an improvement of 10% over previously developed techniques published in literature. The system was validated for its stability and reliability. RF-based model showed the best performance when outliers are replaced by median values.

Dataset Information

Machine Learning Reveals Missing Edges and Putative Interaction Mechanisms in Microbial Ecosystem Networks.

Publications

Machine Learning Reveals Missing Edges and Putative Interaction Mechanisms in Microbial Ecosystem Networks.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets