Holmes, Ian, Harris, Keith and Quince, Christopher (2012) Dirichlet multinomial mixtures : generative models for microbial metagenomics. PLoS One, Volume 7 (Number 2). Article number e30126. doi:10.1371/journal.pone.0030126 ISSN 1932-6203.

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Abstract

We introduce Dirichlet multinomial mixtures (DMM) for the probabilistic modelling of microbial metagenomics data. This data can be represented as a frequency matrix giving the number of times each taxa is observed in each sample. The samples have different size, and the matrix is sparse, as communities are diverse and skewed to rare taxa. Most methods used previously to classify or cluster samples have ignored these features. We describe each community by a vector of taxa probabilities. These vectors are generated from one of a finite number of Dirichlet mixture components each with different hyperparameters. Observed samples are generated through multinomial sampling. The mixture components cluster communities into distinct ‘metacommunities’, and, hence, determine envirotypes or enterotypes, groups of communities with a similar composition. The model can also deduce the impact of a treatment and be used for classification. We wrote software for the fitting of DMM models using the ‘evidence framework’ (http://code.google.com/p/microbedmm/). This includes the Laplace approximation of the model evidence. We applied the DMM model to human gut microbe genera frequencies from Obese and Lean twins. From the model evidence four clusters fit this data best. Two clusters were dominated by Bacteroides and were homogenous; two had a more variable community composition. We could not find a significant impact of body mass on community structure. However, Obese twins were more likely to derive from the high variance clusters. We propose that obesity is not associated with a distinct microbiota but increases the chance that an individual derives from a disturbed enterotype. This is an example of the ‘Anna Karenina principle (AKP)’ applied to microbial communities: disturbed states having many more configurations than undisturbed. We verify this by showing that in a study of inflammatory bowel disease (IBD) phenotypes, ileal Crohn's disease (ICD) is associated with a more variable community.

Item Type:	Journal Article
Subjects:	Q Science > QA Mathematics Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Dirichlet problem, Population genetics, Bacterial diseases, Bacterial genomes
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	2012
Dates:	Date Event 2012 UNSPECIFIED
Volume:	Volume 7
Number:	Number 2
Article Number:	Article number e30126
DOI:	10.1371/journal.pone.0030126
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Funder:	Engineering and Physical Sciences Research Council (EPSRC), National Institutes of Health (U.S.) (NIH), National Institute of General Medical Sciences (U.S.) (NIGMS)
Grant number:	EP/H003851/1 (EPSRC), R01-GM076705 (NIH/NIGMS)

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