Inference of microbial covariation networks using copula models with mixture margins.

Inference of microbial covariation networks using copula models with mixture margins.
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使用带有混合边缘的Copula模型的微生物协方差网络的推断。

DOI:
10.1093/bioinformatics/btad413
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发表时间:
2023-07-01
期刊:
Bioinformatics (Oxford, England)
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从16S rRNA和宏基因组测序数据中定量微生物共变异是困难的,因为它们的稀疏性质。在这篇文章中,我们建议使用混合零- β边际的copula模型,利用归一化微生物相对丰度的数据来估计分类群-分类群共变。copula允许从边际、边际协变量调整和不确定性测量中对依赖结构进行单独建模。我们的方法表明,两阶段最大似然方法提供了准确的模型参数估计。推导了相关参数对应的两阶段似然比检验,并用于构建协变网络。模拟研究表明,该测试是有效的,稳健的,并且比基于Pearson和秩相关的测试更强大。此外,我们证明了我们的方法可以用于基于美国肠道项目的数据集构建具有生物学意义的微生物网络。R包的实现可以在https://github.com/rebeccadeek/CoMiCoN上获得。
Quantification of microbial covariations from 16S rRNA and metagenomic sequencing data is difficult due to their sparse nature. In this article, we propose using copula models with mixed zero-beta margins for the estimation of taxon–taxon covariations using data of normalized microbial relative abundances. Copulas allow for separate modeling of the dependence structure from the margins, marginal covariate adjustment, and uncertainty measurement. Our method shows that a two-stage maximum-likelihood approach provides accurate estimation of model parameters. A corresponding two-stage likelihood ratio test for the dependence parameter is derived and is used for constructing covariation networks. Simulation studies show that the test is valid, robust, and more powerful than tests based upon Pearson’s and rank correlations. Furthermore, we demonstrate that our method can be used to build biologically meaningful microbial networks based on a dataset from the American Gut Project. R package for implementation is available at https://github.com/rebeccadeek/CoMiCoN.
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