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群参与了中枢髓鞘形成和小胶质细胞(CNS免疫细胞)的成熟和功能，这是自闭症谱系障碍的核心缺陷。因此，研究肠道微生物分布及其代谢产物对于寻找多种疾病的新治疗靶点具有重要意义。然而，与对人类细胞的大量医学研究相比，我们对微生物生态系统的了解非常有限：对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了解。该方法具有快速、高效、高精度的特点。它们可广泛应用于任何元基因组和代谢组学研究。研究团队将包括博士后研究人员。该项目的主要目标是通过开发新的定量方法来检测、鉴定和定量各种疾病中的微生物种类及其代谢物，从而扩大我们对肠道微生物生态系统的了解。我们方法的敏感性和特异性使我们能够在非常低的覆盖率水平下准确检测微生物物种。这是一种翻译技术，应该会在生物医学研究和药物开发中得到实质性的使用。更具体地说，PIS应开发方法来识别微生物物种，特别是未知物种，减少代谢组分析中的错误，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，将元基因组和代谢物分析结合在一起研究微生物生态系统，建立分析模型，将代谢物图谱与物种图谱联系起来，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，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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. The research team will include post doctoral researchers. 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.