Collaborative Research: Novel Statistical Tools for Metagenomics and Metabolomics Data

越来越多的证据表明，肠道微生物生态系统的破坏可以导致许多严重的疾病，包括慢性疾病如冠心病（CHD）、神经行为疾病如自闭症、炎症性疾病如炎症性肠病（IBD）等。例如，发育中的婴儿肠道微生物组与中央髓鞘形成和小胶质细胞的成熟和功能有关（中枢神经系统免疫细胞），自闭症谱系障碍的核心缺陷。因此，研究肠道微生物的分布及其代谢产物对于寻找治疗多种疾病的新靶点具有重要意义。然而，与大量的人体细胞医学研究相比，我们对微生物生态系统的了解非常有限：它们的生物多样性几乎没有研究，更不用说它们与人类宿主的相互作用了。该项目将开发一套统计理论和方法以及计算工具，以促进对肠道微生物生态系统的理解。所提出的方法是快速，高效，高精度。它们可以广泛应用于任何宏基因组学和代谢组学研究。研究生将通过参加研究活动进行培训。 该项目的主要目标是通过开发用于各种疾病中微生物物种及其代谢物检测、鉴定和定量的新的定量方法来扩展我们对肠道微生物生态系统的了解。 我们的方法的灵敏度和特异性允许在非常低的覆盖水平下准确检测微生物物种。这是一种转化技术，应该在生物医学研究和药物开发中找到大量用途。更具体地说，PI应开发用于识别微生物物种特别是未知物种的方法，减少代谢组学分析中的错误，估计微生物和代谢物分布，量化与疾病相关的微生物或代谢物分布差异，将宏基因组学和代谢组学分析结合起来研究微生物生态系统，建立分析模型，将代谢物谱与物种谱联系起来，以了解代谢物如何与遗传内容相互作用，并最终影响细胞代谢。该奖项反映了NSF的法定使命，并被认为值得支持通过使用基金会的知识价值和更广泛的影响审查标准进行评估。

Accumulating evidence suggests that disrupting intestinal microbial ecosystems can cause many serious diseases including chronic diseases such as coronary heart disease (CHD), neurobehavioral diseases such as autism, inflammatory diseases such as inflammatory bowel disease (IBD) and etc. For example, the developing infant intestinal microbiome has been implicated in central myelination and the maturation and function of microglia (CNS immune cells), a core deficiency in Autism Spectrum Disorders. Thus, the study of the gut microbial distributions and their metabolites are very important to find new therapeutic targets for many diseases. However, compared to the huge amounts of medical research on human cells, our understanding of the microbial ecosystem is very limited: the biodiversity of them is barely studied, not to mention their interactions with the human host. This project will develop a suite of statistical theory and methods as well as computational tools to facilitate the understanding of the intestinal microbial ecosystem. The proposed methods are fast, efficient, and highly accurate. They can be widely applied to any metagenomic and metabolomic investigations. Graduate students will be trained by participating in research activities. The main goal of this project is to extend our knowledge of intestinal microbial ecosystem by developing novel quantitative methods for microbial species and their metabolites detection, identification, and quantification in various diseases. The sensitivity and specificity of our methods permit accurate detection of microbial species at very low coverage levels. This is a translational technology that should find substantial use in biomedical researches and drug developments. More specifically, the PIs shall develop methods for identifying microbial species especially unknown species, reducing error in metabolomic analysis, estimating microbial and metabolite distributions, quantifying microbial or metabolites distributional differences that are associated with diseases, integrating metagenomic and metabolomic analysis together to study the microbial ecosystem, building analytical models to link metabolite profiling with species profiling to understand how metabolites interact with genetic contents and eventually affect cell metabolism.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.