论文标题

具有亚复合预测因子的多元对数对比回归:测试早产儿的肠道微生物组与神经行为结局之间的关联

Multivariate Log-Contrast Regression with Sub-Compositional Predictors: Testing the Association Between Preterm Infants' Gut Microbiome and Neurobehavioral Outcomes

论文作者

Liu, Xiaokang, Cong, Xiaomei, Li, Gen, Maas, Kendra, Chen, Kun

论文摘要

所谓的肠脑轴已激发了对微生物组的广泛研究。一个重点是评估某些临床结果与肠道微生物的相对丰度之间的关联,这些临床微生物可以作为符合细菌分类学层次结构的亚组分数据表示。由一项研究鉴定在早产儿的肠道微生物组中影响其后来神经行为结果的研究的动机,我们制定了一个约束的整合性多视觉回归,其中神经be虫得分形成了多变量反应,在其中,多元组成组形式的属于近观测组的属于局部构图,并构成了对应量的局部构图。确保符合单纯形几何形状。为了实现子组合/视图的联合选择和推断,我们假设所有子级矩阵可能都是低级别的,即,结果与微生物组相关联,通过不同的潜在亚组分因子来自不同的分类群。我们提出了一种模型估计的缩放综合核规范惩罚方法,并通过消除偏见来评估不同观点的重要性,制定假设检验程序。仿真研究证实了所提出的程序的有效性。在早产婴儿研究中,确定的微生物主要与现有的研究和生物学理解一致。我们的方法支持强调早期生活经历通过调节肠道轴的构成肠道微生物组。

The so-called gut-brain axis has stimulated extensive research on microbiomes. One focus is to assess the association between certain clinical outcomes and the relative abundances of gut microbes, which can be presented as sub-compositional data in conformity with the taxonomic hierarchy of bacteria. Motivated by a study for identifying the microbes in the gut microbiome of preterm infants that impact their later neurobehavioral outcomes, we formulate a constrained integrative multi-view regression, where the neurobehavioral scores form multivariate response, the sub-compositional microbiome data form multi-view feature matrices, and a set of linear constraints on their corresponding sub-coefficient matrices ensures the conformity to the simplex geometry. To enable joint selection and inference of sub-compositions/views, we assume all the sub-coefficient matrices are possibly of low-rank, i.e., the outcomes are associated with the microbiome through different sets of latent sub-compositional factors from different taxa. We propose a scaled composite nuclear norm penalization approach for model estimation and develop a hypothesis testing procedure through de-biasing to assess the significance of different views. Simulation studies confirm the effectiveness of the proposed procedure. In the preterm infant study, the identified microbes are mostly consistent with existing studies and biological understandings. Our approach supports that stressful early life experiences imprint gut microbiome through the regulation of the gut-brain axis.

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