Multi-Cellular Metabolic Modeling

在Genomatica，我们开发了一个新的技术平台，称为SimPheny，它使高效的 基因组规模新陈代谢模型的建立及其基于约束的模拟 建模方法。在这个SBIR计划的第一阶段，我们展示了科学和技术 将我们的建模方法从单细胞微生物网络扩展到多细胞人类的可行性 使用人类脂肪细胞(脂肪细胞)和肌肉细胞(肌肉细胞)的综合两细胞模型进行代谢。 使用重建的多细胞模型，我们计算了两种细胞类型的积分函数 SimPheny和公式化的假说，这些假说可以在实验上得到验证，并增加我们对 人类的新陈代谢和生理学。基于我们对多细胞人体模型的初步成功 SimPheny的新陈代谢和日益增长的市场对In Silico建模和数据集成的需求 平台，我们已经启动了一个3-5年的计划，为更高的建模开发一个计算平台 并为人类新陈代谢构建细胞、组织和疾病特异性模型。作为…的一部分 这项长期计划，我们寻求开发一个计算基础设施和生物内容 在这个第二阶段的SBIR计划中，重建和建模集成的多细胞人类网络。这个 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 以及一个全面的人类新陈代谢数据库，它解释了注释的人类基因， 蛋白质和代谢途径。当这项第二阶段计划成功完成后，我们将会有一个 用于内容管理、数据分析和高吞吐量数据可视化的完整基础架构 在SimPheny软件平台内，为人类提供全面的网络信息纲要 新陈代谢以及基于扩展基因组的脂肪细胞-心肌细胞整合多细胞模型 新陈代谢。这项提案中开发的基础设施和内容将使我们能够开发组织和 与学术、生物技术和制药研究合作的疾病特定模型 未来的群体。

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.