Methods for microbiome compositional data

项目摘要 该项目的广泛和长期目标涉及开发新的定量方法和 微生物组数据分析的生物统计学工具，以协助微生物组发现科学。这个 微生物组，也被称为人类第二基因组，在过去的几年里受到了极大的关注。 由于它在人类健康和疾病中的关键作用，人类微生物组现在被认为是一种 个体化医疗方法的组成部分，因为它不仅解释了个体间的可变性 在疾病的所有方面，但也代表了一个潜在的可修改因素，可以通过 治疗学。尽管微生物组研究取得了这些丰硕而有希望的发现，但在 当前的领域是如何适当地分析数据，更不用说 还没有得到解决。几个挑战构成了这一困境，包括复杂的实验 微生物组研究的设计，微生物组和宿主之间未知的相互作用，极其稀疏和 数据的高维性，微生物分类群的系统发育相关性，以及 微生物组。因此，虽然已经开发了相当多的分析方法和工具来 在微生物组数据分析方面，方法学工具箱中存在几个具体的空白，阻碍了 基于微生物组的生物医学科学。为了填补这些空白，这项提案旨在开发强大的 微生物组数据分析的定量方法和工具。具体地说，目标1侧重于开发健壮的 以及在复杂研究设计中进行差异丰度分析的强大方法。它将开发新的 处理微生物组数据中的零膨胀、成分效应和相关性的方法。目标2侧重于 提高微生物群系多重测试能力的策略。它提出了两个新的多重测试 程序，分别解决混杂因素和系统发育相关问题。目标3建议 开发将微生物组数据与其他组学相结合的成分典型相关分析方法 数据。具体地说，它将开发一个高效和灵活的框架，用于整合不同种类的组学数据 利用微生物组数据，解释了组成效应和系统发育相关性。目标4将会发展 用户友好和高效的软件包，使社区可以最大限度地从方法和 这一应用所带来的科学进步。建议的方法将使用模拟进行评估， 更重要的是，在个体化中心正在进行的几项微生物组研究中的应用 梅奥诊所的内科医生。拟议的量化方法和开放源码软件包将 有助于微生物组生物标记物的发现和基于微生物组的机制研究。所有方法和 根据这笔赠款开发的工具将免费提供给感兴趣的研究人员和公众。

Project Summary The broad and long-term objective of this project concerns the development of novel quantitative methods and biostatistical tools for microbiome data analytics to aid in microbiome-based discovery sciences. The microbiome, also called the second genome of the human, has received much attention in the past few years. Due to its critical roles in human health and disease, the human microbiome has now been recognized as an integral part of the individualized medicine approach because it not only accounts for inter-individual variability in all aspects of a disease but also represents a potentially modifiable factor that is amenable to targeting by therapeutics. Despite those fruitful and promising findings from microbiome studies, there is no consensus in the current field as how to appropriately analyze the data, let alone the optimality and efficiency issues that have yet to be addressed. Several challenges amount to this predicament, including complex experimental designs of microbiome studies, an unknown interplay between microbiome and host, extremely sparsity and high dimensionality of the data, phylogenetic relatedness of the microbial taxa, and compositional structure of microbiome. As a result, although quite a few analytical methods and tools have been developed for microbiome data analysis, several specific gaps exist in the methodological toolbox, hindering the advance of microbiome-based biomedical sciences. To fill these gaps, this proposal aims to develop robust and powerful quantitative methods and tools for microbiome data analysis. Specifically, Aim 1 focuses on developing robust and powerful methods for differential abundance analysis in complex study designs. It will develop new methods to address zero-inflation, compositional effects and correlations in microbiome data. Aim 2 focuses on strategies to increase the power of microbiome-wide multiple testing. It proposes two new multiple testing procedures, which address confounders and phylogenetic relatedness, respectively. Aim 3 proposes to develop compositional canonical correlation analysis methods for integrating microbiome data with other omics data. Specifically, it will develop an efficient and flexible framework for integrating heterogeneous omics data with microbiome data, accounting for compositional effects and phylogenetic relatedness. Aim 4 will develop user-friendly and efficient software packages so the community can benefit maximally from methodological and scientific advances resulting from this application. The proposed methods will be evaluated using simulations, and more importantly, applications to several ongoing microbiome studies in the Center of Individualized Medicine at Mayo Clinic. The proposed quantitative methods and open-source software packages will contribute to microbiome biomarker discovery and microbiome-based mechanistic studies. All methods and tools developed under this grant will be made available free of charge to interested researchers and the public.