Dataset Information

Clustering microbiome data using mixtures of logistic normal multinomial models.

ABSTRACT: Discrete data such as counts of microbiome taxa resulting from next-generation sequencing are routinely encountered in bioinformatics. Taxa count data in microbiome studies are typically high-dimensional, over-dispersed, and can only reveal relative abundance therefore being treated as compositional. Analyzing compositional data presents many challenges because they are restricted to a simplex. In a logistic normal multinomial model, the relative abundance is mapped from a simplex to a latent variable that exists on the real Euclidean space using the additive log-ratio transformation. While a logistic normal multinomial approach brings flexibility for modeling the data, it comes with a heavy computational cost as the parameter estimation typically relies on Bayesian techniques. In this paper, we develop a novel mixture of logistic normal multinomial models for clustering microbiome data. Additionally, we utilize an efficient framework for parameter estimation using variational Gaussian approximations (VGA). Adopting a variational Gaussian approximation for the posterior of the latent variable reduces the computational overhead substantially. The proposed method is illustrated on simulated and real datasets.

SUBMITTER: Fang Y

PROVIDER: S-EPMC10484970 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Clustering microbiome data using mixtures of logistic normal multinomial models.

Fang Yuan Y Subedi Sanjeena S

Scientific reports 20230907 1

Discrete data such as counts of microbiome taxa resulting from next-generation sequencing are routinely encountered in bioinformatics. Taxa count data in microbiome studies are typically high-dimensional, over-dispersed, and can only reveal relative abundance therefore being treated as compositional. Analyzing compositional data presents many challenges because they are restricted to a simplex. In a logistic normal multinomial model, the relative abundance is mapped from a simplex to a latent va ...[more]

PMID: 37679485

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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.

Dataset Information

Clustering microbiome data using mixtures of logistic normal multinomial models.

Publications

Clustering microbiome data using mixtures of logistic normal multinomial models.

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