Bioinformatic Approaches to Small Molecule Profiling of Cardiometabolic Disease

描述(由申请人提供)：本提案描述了Rahul Deo作为心脏代谢(CM)疾病计算生物学研究人员实现独立的五年发展计划。迪奥博士是马萨诸塞州综合医院(MGH)的心脏病研究员。本文描述的途径将使他能够利用哈佛医学院(HMS)的生物信息学研究和培训机会以及MGH的临床优势，在分子生物物理学和复杂疾病遗传学方面的背景基础上再接再厉。Deo博士将由HMS生物化学和分子药理学系副教授Frederick‘Fritz’Roth和哈佛医学院医学系副教授、哈佛和麻省理工学院博德研究所代谢组学平台主任Robert Gerszten共同指导。Roth博士是大型“基因组”数据集的计算生物学方面的公认专家，而Gerszten博士是代谢组学方面的专家，特别是在CM疾病上的应用。除了在过去五年中在众多代谢组学项目上密切合作外，Roth博士和Gerszten博士都有很好的指导记录。迪奥博士还将与马克·维达尔博士、约瑟夫·洛斯卡尔佐博士、艾萨克·科哈内博士和卡勒姆·麦克雷博士密切合作，他们将就拟议研究计划的执行提供职业指导和科学建议。该研究计划将强调使用生物信息学技术和代谢物图谱来推进CM疾病的特征和分类。越来越多的人认识到，我们目前的疾病分类方法不足以描述人类疾病的范围和异质性。代谢组学-分析生物体液样本中的代谢物水平-是一种非侵入性的方法，可以从患者那里获得定量的分子表型，以解决这一复杂性。这项研究计划旨在评估这样一种假设，即将以前为大型高通量生物“组学”数据开发的现代计算方法应用于代谢物图谱数据的分析将有助于我们改进疾病阐明。具体地说，该计划建议：1)使用数据集成和网络方法来表征对心脏代谢(CM)扰动的生物反应，以及2)使用相关的生物信息学分析技术来建立和测试区分CM患者和对照的代谢物分类器

DESCRIPTION (provided by applicant): This proposal describes a five-year development plan for Rahul Deo to achieve independence as an investigator in the computational biology of cardiometabolic (CM) disease. Dr. Deo is a Cardiology Fellow at the Massachusetts General Hospital (MGH). The path described herein will enable him to build upon his background in molecular biophysics and complex disease genetics by taking advantage of the bioinformatics research and training opportunities at Harvard Medical School (HMS) and the clinical strengths of MGH. Dr. Deo will be co-mentored by Frederick 'Fritz' Roth, an associate professor in the Department of Biological Chemistry and Molecular Pharmacology at HMS and Robert Gerszten, an associate professor in the Department of Medicine at Harvard Medical School, and Director of the Metabolomics Platform at the Broad Institute of Harvard and MIT. Dr. Roth is a recognized expert in the computational biology of large "omic" data sets while Dr. Gerszten is an expert in metabolomics, with particular application to CM disease. In addition to having worked closely together over the past five years on numerous metabolomics projects, Drs. Roth and Gerszten each have a strong record of mentorship. Dr. Deo will also work closely with Drs. Marc Vidal, Joseph Loscalzo, Isaac Kohane and Calum MacRae, who will provide career guidance and scientific advice on the execution of the proposed research plan. The research program will emphasize the use of bioinformatics techniques and metabolite profiling to advance the characterization and classification of CM disease. There is increasing recognition that our current disease categorization approaches are inadequate to describe the scope and heterogeneity of human disease. Metabolomics - the analysis of metabolite levels from biologic fluid samples - is one non-invasive way to obtain quantitative molecular phenotypes from patients to address this complexity. This research plan is designed to assess the hypothesis that the application of modern computational methods, previously developed for large high-throughput biological "omic" data, to the analysis of metabolite profiling data will help us improve disease elucidation. Specifically, this program proposes: 1) to use data integration and network approaches to characterize biologic responses to cardiometabolic (CM) perturbations and 2) to use related bioinformatic analytic techniques to build and test metabolite classifiers distinguishing CM disease patients from controls