Dirichlet multinomial mixtures: generative models for microbial metagenomics.

Dirichlet multinomial mixtures: generative models for microbial metagenomics.
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DIRICHLET多项式混合物:微生物宏基因组学的生成模型。

DOI:
10.1371/journal.pone.0030126
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Quince C
Quince C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Holmes I;Harris K;Quince C

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我们引入了Dirichlet多项式混合(DMM)来对微生物元基因组数据进行概率建模。该数据可以用频率矩阵表示,该频率矩阵给出了在每个样本中观察到每个分类群的次数。样本大小不同,基质稀疏,因为群落多样化,偏向稀有类群。以前用来对样本进行分类或分类的大多数方法都忽略了这些特征。我们用分类群概率向量来描述每个群落。这些向量是从有限数量的Dirichlet混合成分中的一个产生的,每个Dirichlet混合成分具有不同的超参数。观测样本是通过多项抽样产生的。混合成分将群落聚集成不同的“元群落”,从而确定环境类型或肠道类型,即具有相似组成的群落组。该模型还可以推断处理的影响,并用于分类。我们使用证据框架(http://code.google.com/p/microbedmm/).)编写了用于数字MM模型拟合的软件这包括模型证据的拉普拉斯近似。我们将DMM模型应用于肥胖双胞胎和瘦双胞胎的肠道微生物属频率。从模型证据来看,有四个集群最符合这一数据。两个群落以类杆菌为主,且同质性;两个群落组成变化较大。我们没有发现体重对群落结构的显著影响。然而,肥胖的双胞胎更有可能来自高方差聚类。我们认为,肥胖与不同的微生物区系无关,但会增加个体因肠型紊乱而产生的几率。这是‘安娜·卡列尼娜原理(AKP)’应用于微生物群落的一个例子:受干扰的状态比未受干扰的状态具有更多的构型。我们通过显示在炎症性肠病(IBD)表型的研究中,回肠克罗恩病(ICD)与一个更易变的社区相关来验证这一点。
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.
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