论文标题

组成图形套索解决了寄生虫感染对斑马鱼模型中肠道微生物相互作用网络的影响

Compositional Graphical Lasso Resolves the Impact of Parasitic Infection on Gut Microbial Interaction Networks in a Zebrafish Model

论文作者

Tian, Chuan, Jiang, Duo, Hammer, Austin, Sharpton, Thomas, Jiang, Yuan

论文摘要

了解微生物如何彼此相互作用是揭示微生物在宿主或环境中发挥的潜在作用的关键,并将微生物识别为可能改变宿主或环境的代理。例如,了解微生物相互作用如何与寄生虫感染相关,可以帮助解决潜在的药物或寄生虫感染的诊断测试。为了解开微生物相互作用,现有工具通常依靠图形模型来推断微生物丰度的条件依赖性以表示其相互作用。但是,当前方法不能同时考虑微生物组数据固有的离散性,组成性和异质性。因此,我们通过将上述特征明确地纳入图形模型,在现有工具上构建一种称为“组成图形拉索”的新方法。我们说明了在各种模拟方案和基准研究Tara Oceans项目中,构图图形拉索的优势比当前方法的优点。此外,我们从斑马鱼寄生虫感染研究中对数据集的分析中介绍了结果。我们的方法确定了三个分类单元,光细菌,gemmobacter和paucibacter的感染和未感染个体之间的相互作用变化,这些分类群,gemmobacter和paucibacter被其他方法呈负预测。对这些特定方法的分类单元相互作用变化的进一步研究揭示了它们的生物学合理性。特别是,我们推测斑马鱼肠中光细菌和宝石杆菌的潜在病原体作用,以及paucibibacter的潜在益生菌作用。总体而言,我们的分析表明,组成图形套索提供了一种有力的方法,可以准确解决微生物群之间的相互作用,从而可以推动新颖的生物学发现。

Understanding how microbes interact with each other is key to revealing the underlying role that microorganisms play in the host or environment and to identifying microorganisms as an agent that can potentially alter the host or environment. For example, understanding how the microbial interactions associate with parasitic infection can help resolve potential drug or diagnostic test for parasitic infection. To unravel the microbial interactions, existing tools often rely on graphical models to infer the conditional dependence of microbial abundances to represent their interactions. However, current methods do not simultaneously account for the discreteness, compositionality, and heterogeneity inherent to microbiome data. Thus, we build a new approach called "compositional graphical lasso" upon existing tools by incorporating the above characteristics into the graphical model explicitly. We illustrate the advantage of compositional graphical lasso over current methods under a variety of simulation scenarios and on a benchmark study, the Tara Oceans Project. Moreover, we present our results from the analysis of a dataset from the Zebrafish Parasite Infection Study. Our approach identifies changes in interaction degree between infected and uninfected individuals for three taxa, Photobacterium, Gemmobacter, and Paucibacter, which are inversely predicted by other methods. Further investigation of these method-specific taxa interaction changes reveals their biological plausibility. In particular, we speculate on the potential pathobiotic roles of Photobacterium and Gemmobacter in the zebrafish gut, and the potential probiotic role of Paucibacter. Collectively, our analyses demonstrate that compositional graphical lasso provides a powerful means of accurately resolving interactions between microbiota and can thus drive novel biological discovery.

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