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的五年发展计划，以实现作为心脏代谢（CM）疾病计算生物学研究者的独立性。Deo博士是马萨诸塞州总医院（MGH）的心脏病学研究员。本文所述的路径将使他能够通过利用哈佛医学院（HMS）的生物信息学研究和培训机会以及MGH的临床优势来建立他在分子生物物理学和复杂疾病遗传学方面的背景。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兼哈佛和麻省理工学院布罗德研究所代谢组学平台主任Robert Gerszten共同指导。Roth博士是大型"组学"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，特别适用于CM疾病。除了在过去五年中在许多代谢组学项目上密切合作外，Roth和Gerszten博士都有很好的指导记录。Deo博士还将与Marc Vidal、Joseph Loscalzo、Isaac Kohane和Calum MacRae博士密切合作，他们将为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产物分析，以推进CM疾病的表征和分类。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-分析生物液体样本中的代谢物水平-是一种非侵入性的方法，可以从患者中获得定量分子表型，以解决这种复杂性。这项研究计划旨在评估的假设，即应用现代计算方法，以前开发的大型高通量生物“组学”数据，代谢物分析数据的分析，将有助于我们提高疾病的阐明。具体而言，该计划提出：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，2）使用相关的生物信息学分析技术来构建和测试区分CM疾病患者和对照组的代谢物分类器

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