Multi-Cellular Metabolic Modeling

描述（由申请人提供）：在Genomatica，我们开发了一种名为SimPheny的新型技术平台，该平台能够使用基于约束的建模方法有效开发基因组规模的代谢模型及其模拟。在该SBIR计划的第一阶段，我们证明了将我们的建模方法从单细胞微生物网络扩展到多细胞人体代谢的科学和技术可行性，使用人体脂肪细胞（脂肪细胞）和肌细胞（肌细胞）的集成双细胞模型。使用重建的多细胞模型，我们计算了SimPheny中两种细胞类型的综合功能，并制定了可以通过实验验证的假设，并增加了我们对人体代谢和生理学的理解。基于我们在SimPheny中建模多细胞人体代谢的初步成功以及市场对计算机建模和数据集成平台不断增长的需求，我们已经启动了一个3-5年的计划，以开发用于建模高等真核生物的计算平台，并构建人体代谢的细胞，组织和疾病特异性模型。作为这个长期计划的一部分，我们寻求开发一个计算基础设施和生物内容，用于在这个第二阶段SBIR计划中重建和建模集成的多细胞人类网络。该第二阶段提案的总体目标是开发一个数据集成和计算软件平台以及一个用于人类代谢的综合数据库，该数据库解释了注释的人类基因，蛋白质和代谢途径。在成功完成第二阶段提案后，我们将拥有一个完整的基础设施，用于内容管理，数据分析和SimPheny软件平台内高通量数据的可视化，以及人类代谢网络信息的综合纲要，以及用于脂肪细胞-肌细胞代谢的基于扩展基因组的集成多细胞模型。该提案中开发的基础设施和内容将使我们能够在未来与学术，生物技术和制药研究小组合作开发组织和疾病特异性模型。

DESCRIPTION (provided by applicant): At Genomatica, we have developed a novel technology platform, called SimPheny that enables the efficient development of genome-scale models of metabolism and their simulation using a constraint-based modeling approach. In the Phase I of this SBIR program, we demonstrated the scientific and technical feasibility of extending our modeling approach from single-cell microbial networks to multi-cellular human metabolism using an integrated two-cell model of human adipocyte (fatty cell) and myocyte (muscle cell). Using the reconstructed multi-cellular model, we computed the integrated function of the two cell types in SimPheny and formulated hypotheses that may be verified experimentally and increase our understanding of human metabolism and physiology. Based on our initial success with modeling multi-cellular human metabolism in SimPheny and the growing market demand for in silico modeling and data integration platform, we have initiated a 3-5 year plan to develop a computational platform for modeling higher eukaryotes and to construct cell-, tissue-, and disease-specific models for human metabolism. As a part of this long-term plan, we seek to develop a computational infrastructure and biological content for reconstructing and modeling integrated multi-cellular human networks in this Phase II SBIR program. The overall goal of this Phase II proposal is to develop a data-integration and computational software platform and a comprehensive database for human metabolism that accounts for the annotated human genes, proteins, and metabolic pathways. Upon the successful completion of this Phase II proposal, we will have a complete infrastructure for content management, data analysis, and visualization of high throughput data within SimPheny software platform and a comprehensive compendium of network information for human metabolism, as well as an expanded genome based integrated multi-cellular model for adipocyte-myocyte metabolism. The infrastructure and content developed in this proposal will enable us to develop tissue- and disease-specific models in collaboration with academic, biotechnology, and pharmaceutical research groups in the future.