Multi-scale genome-based modeling of human metabolism for diagnostic and therapeutic applications

自从人类基因组序列完成以来，人们一直期待这样的序列信息可以映射到细胞功能上。最初的测序工作得到了几项进展的补充，包括大规模地绘制个体之间的序列和拷贝数变异图，以及开发快速测序技术来解码个体基因组。结合生物系统模型的发展，这些进展为“个性化营养和药物”提供了耐人寻味的机会。在许多情况下，包括癌症、糖尿病和肥胖症，新陈代谢发生了巨大的变化，促使人们进一步研究新陈代谢，以了解这种变化的机制以及设计诊断和治疗策略。作为该计划的一部分，我们将开发代谢的多尺度模型，并使用多尺度建模框架来分析在癌症和糖尿病期间观察到的代谢扰动，以确定新的治疗和诊断策略。

Ever since the human genome sequence was completed, it has been anticipated that such sequence information could be mapped to cellular functions. The initial sequencing effort has been complemented by several advances including large-scale efforts to map sequence and copy number variation among individuals along with the development of rapid sequencing technologies to decode individual genomes. Taken together with developments in the biological system modeling, these advances offer the intriguing opportunity for "personalized nutrition as well as medicine". In many instances, including cancer¸ diabetes, and obesity, metabolism is drastically altered motivating further investigation of metabolism to understand the mechanisms underlying such changes as well as for designing diagnostic and therapeutic strategies. As a part of this program, we will develop multi-scale models of metabolism, and use the multi-scale modeling framework to analyze metabolic perturbations observed during cancer and diabetes to identify novel therapeutic and diagnostic strategies.