Dataset Information

A Dirichlet-tree multinomial regression model for associating dietary nutrients with gut microorganisms.

ABSTRACT: Understanding the factors that alter the composition of the human microbiota may help personalized healthcare strategies and therapeutic drug targets. In many sequencing studies, microbial communities are characterized by a list of taxa, their counts, and their evolutionary relationships represented by a phylogenetic tree. In this article, we consider an extension of the Dirichlet multinomial distribution, called the Dirichlet-tree multinomial distribution, for multivariate, over-dispersed, and tree-structured count data. To address the relationships between these counts and a set of covariates, we propose the Dirichlet-tree multinomial regression model for which we develop a penalized likelihood method for estimating parameters and selecting covariates. For efficient optimization, we adopt the accelerated proximal gradient approach. Simulation studies are presented to demonstrate the good performance of the proposed procedure. An analysis of a data set relating dietary nutrients with bacterial counts is used to show that the incorporation of the tree structure into the model helps increase the prediction power.

SUBMITTER: Wang T

PROVIDER: S-EPMC5587402 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Dirichlet-tree multinomial regression model for associating dietary nutrients with gut microorganisms.

Wang Tao T Zhao Hongyu H

Biometrics 20170123 3

Understanding the factors that alter the composition of the human microbiota may help personalized healthcare strategies and therapeutic drug targets. In many sequencing studies, microbial communities are characterized by a list of taxa, their counts, and their evolutionary relationships represented by a phylogenetic tree. In this article, we consider an extension of the Dirichlet multinomial distribution, called the Dirichlet-tree multinomial distribution, for multivariate, over-dispersed, and ...[more]

PMID: 28112797

Similar Datasets

Project description:Studying the human microbiome has gained substantial interest in recent years, and a common task in the analysis of these data is to cluster microbiome compositions into subtypes. This subdivision of samples into subgroups serves as an intermediary step in achieving personalized diagnosis and treatment. In applying existing clustering methods to modern microbiome studies including the American Gut Project (AGP) data, we found that this seemingly standard task, however, is very challenging in the microbiome composition context due to several key features of such data. Standard distance-based clustering algorithms generally do not produce reliable results as they do not take into account the heterogeneity of the cross-sample variability among the bacterial taxa, while existing model-based approaches do not allow sufficient flexibility for the identification of complex within-cluster variation from cross-cluster variation. Direct applications of such methods generally lead to overly dispersed clusters in the AGP data and such phenomenon is common for other microbiome data. To overcome these challenges, we introduce Dirichlet-tree multinomial mixtures (DTMM) as a Bayesian generative model for clustering amplicon sequencing data in microbiome studies. DTMM models the microbiome population with a mixture of Dirichlet-tree kernels that utilizes the phylogenetic tree to offer a more flexible covariance structure in characterizing within-cluster variation, and it provides a means for identifying a subset of signature taxa that distinguish the clusters. We perform extensive simulation studies to evaluate the performance of DTMM and compare it to state-of-the-art model-based and distance-based clustering methods in the microbiome context, and carry out a validation study on a publicly available longitudinal data set to confirm the biological relevance of the clusters. Finally, we report a case study on the fecal data from the AGP to identify compositional clusters among individuals with inflammatory bowel disease and diabetes. Among our most interesting findings is that enterotypes (i.e., gut microbiome clusters) are not always defined by the most dominant species as previous analyses had assumed, but can involve a number of less abundant OTUs, which cannot be identified with existing distance-based and method-based approaches.

Project description:Dysbiosis of microbial communities is associated with various human diseases, raising the possibility of using microbial compositions as biomarkers for disease diagnosis. We have developed a Bayes classifier by modeling microbial compositions with Dirichlet-multinomial distributions, which are widely used to model multicategorical count data with extra variation. The parameters of the Dirichlet-multinomial distributions are estimated from training microbiome data sets based on maximum likelihood. The posterior probability of a microbiome sample belonging to a disease or healthy category is calculated based on Bayes' theorem, using the likelihood values computed from the estimated Dirichlet-multinomial distribution, as well as a prior probability estimated from the training microbiome data set or previously published information on disease prevalence. When tested on real-world microbiome data sets, our method, called DMBC (for Dirichlet-multinomial Bayes classifier), shows better classification accuracy than the only existing Bayesian microbiome classifier based on a Dirichlet-multinomial mixture model and the popular random forest method. The advantage of DMBC is its built-in automatic feature selection, capable of identifying a subset of microbial taxa with the best classification accuracy between different classes of samples based on cross-validation. This unique ability enables DMBC to maintain and even improve its accuracy at modeling species-level taxa. The R package for DMBC is freely available at https://github.com/qunfengdong/DMBC. IMPORTANCE By incorporating prior information on disease prevalence, Bayes classifiers have the potential to estimate disease probability better than other common machine-learning methods. Thus, it is important to develop Bayes classifiers specifically tailored for microbiome data. Our method shows higher classification accuracy than the only existing Bayesian classifier and the popular random forest method, and thus provides an alternative option for using microbial compositions for disease diagnosis.

Dataset Information

A Dirichlet-tree multinomial regression model for associating dietary nutrients with gut microorganisms.

Publications

A Dirichlet-tree multinomial regression model for associating dietary nutrients with gut microorganisms.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets