Mechanistic Modeling of Cellular Systems

蜂窝系统的机械建模

• 批准号: 10224267
• 负责人: LESLIE M LOEW
• 金额: $ 115.24万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10224267
• 关键词: 3-Dimensional; Aging; Algorithmic Software; Algorithms; Benchmarking; Biochemical Reaction; Biophysical Process; Cardiology; Cell model; Cell physiology; Cells; Cellular biology; Characteristics; Cloud Computing; Communities; Complex; Complex Analysis; Computer Models; Computer software; Connecticut; Databases; Diabetes Mellitus; Differential Equation; Diffusion; Disease; Documentation; Education and Outreach; Educational workshop; Electronic Mail; Electrophysiology (science); Equation; Geometry; Goals; High Performance Computing; Hybrids; Image; Infrastructure; Institutes; International; Joints; Kidney Diseases; Kinetics; Lateral; Maintenance; Malignant Neoplasms; Mathematics; Membrane; Metabolic Control; Modeling; Modernization; Online Systems; Operating System; Paper; Pathway interactions; Reaction; Reproducibility; Resources; Services; Shapes; Software Engineering; Software Tools; Supporting Cell; System; Systems Biology; Technology; Testing; Time; Training; Transmembrane Transport; Universities; Validation; Work; base; biophysical model; cell community; computerized tools; experience; experimental study; improved; insight; mathematical model; medical schools; meetings; models and simulation; nervous system disorder; open source; organizational structure; particle; portability; repository; simulation; software systems; tool; usability; user-friendly; virtual; web site

Project Summary This proposal aims to establish a National Resource for Mechanistic Modeling of Cellular Systems to serve the large community of cell and systems biologists. The Resource will encompass COPASI and Virtual Cell (VCell) software platforms, which are arguably the most comprehensive and widely used tools for computational modeling of the biophysical mechanisms controlling cell function. VCell supports a number of key biophysical mechanisms, including reaction kinetics, diffusion, flow, membrane transport, lateral membrane diffusion, electrophysiology and rule-based models of multi-state/multimolecular interactions. Simulations can be based on 0D, 1D, 2D or 3D analytical or experimental image-based geometries. Users may choose among multiple available simulation approaches: ordinary differential equations, partial differential equations, stochastic reaction kinetics, network-free simulations, spatial particle-based simulations and spatial hybrid stochastic/deterministic simulations. COPASI enables the simulation and analysis of complex biochemical reaction networks either deterministically or stochastically. It offers a broad range of analysis tools including parameter estimation/optimization, steady state analysis, stoichiometric analysis, sensitivity analysis and metabolic control analysis. VCell and COPASI each boast thousands of active users. Collectively, their users produce >100 papers per year relying on these software systems. Both VCell and COPASI will be hosted at the University of Connecticut School of Medicine. Thus, the Resource will benefit from: (1) the common institutional organization under which it will operate; (2) a joint website; (3) a common high performance computing facility that will serve the computationally intensive needs of users; (4) coordinated training and outreach to the user community in the form of web-based documentation and tutorials, a yearly Computational Cell Biology Workshop and numerous roadshows at national and international meetings. Additionally, VCell and COPASI will be leveraged by external systems biology software developers as user-friendly platforms for the wide dissemination of their third party algorithms, software and databases. Finally, the Resource will actively engage with the software standards community to assure the reproducibility and reusability of both the software and the models it generates.

项目摘要 该提案旨在建立一个国家的机械模型，以供蜂窝 为大型细胞和系统生物学家提供服务的系统。资源将 包含Copasi和虚拟单元格（VCELL）软件平台，可以说是最多的 用于生物物理的计算建模的全面且广泛使用的工具 控制细胞功能的机制。 VCELL支持许多关键的生物物理机制， 包括反应动力学，扩散，流动，膜转运，外侧膜扩散， 多状态/多分子相互作用的电生理学和规则模型。模拟 可以基于0D，1D，2D或3D分析或基于图像的几何形状。用户 可以在多种可用的模拟方法中选择：普通微分方程， 部分微分方程，随机反应动力学，无网络模拟，空间 基于粒子的模拟和空间混合随机/确定性模拟。科萨 可以启用复杂生化反应网络的模拟和分析 决定性或随机性。它提供了广泛的分析工具，包括参数 估计/优化，稳态分析，化学计量分析，灵敏度分析和 代谢控制分析。 VCELL和COPASI每个拥有数千名活跃用户。 总体而言，他们的用户每年依靠这些软件系统生产> 100篇论文。两个都 VCELL和COPASI将在康涅狄格大学医学院主持。因此， 资源将从：（1）其运营的共同机构组织中受益； （2）联合网站； （3）一个将服务的常见高性能计算设施 用户的计算密集需求； （4）协调培训和向用户推广 基于网络的文档和教程的形式的社区，年度计算单元格 在国家和国际会议上，生物学研讨会和众多路演。 此外，VCELL和COPASI将由外部系统生物学软件利用 开发人员是用户友好的平台，以广泛传播其第三方算法， 软件和数据库。最后，资源将积极参与软件标准 社区确保软件和模型的可重复性和可重复性 生成。