Mechanistic Modeling of Cellular Systems

蜂窝系统的机械建模

• 批准号: 10663862
• 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/10663862
• 关键词: 3-Dimensional; Aging; Algorithmic Software; Algorithms; Benchmarking; Binding; 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; Institution; International; Joints; Kidney Diseases; Kinetics; Lateral; Maintenance; Malignant Neoplasms; Mathematics; Membrane; Metabolic Control; Modeling; Modernization; Online Systems; Operating System; Paper; Parameter Estimation; 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; migration; models and simulation; nervous system disorder; open source; organizational structure; particle; portability; repository; simulation; skills; software systems; technology platform; 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.

项目概要 该提案旨在建立细胞机械建模国家资源 为细胞和系统生物学家的大型社区服务的系统。该资源将 涵盖 COPASI 和 Virtual Cell (VCell) 软件平台，这可以说是最 用于生物物理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、膜传输、横向膜扩散、 电生理学和基于规则的多状态/多分子相互作用模型。模拟 可以基于 0D、1D、2D 或 3D 分析或实验基于图像的几何形状。用户 可以在多种可用的模拟方法中进行选择：常微分方程， 偏微分方程、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。科帕西 能够模拟和分析复杂的生化反应网络 确定性或随机性。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 均拥有数千名活跃用户。 总的来说，他们的用户每年依靠这些软件系统发表超过 100 篇论文。两个都 VCell 和 COPASI 将在康涅狄格大学医学院主办。因此， 资源将受益于： (1) 其运作的共同机构组织； （二）联合网站； (3) 通用的高性能计算设施，服务于 用户的计算密集型需求； (4) 对用户进行协调培训和推广 社区以基于网络的文档和教程的形式，每年一次的计算单元 生物学研讨会以及在国内和国际会议上的多次路演。 此外，外部系统生物学软件将利用 VCell 和 COPASI 开发人员作为用户友好的平台来广泛传播他们的第三方算法， 软件和数据库。最后，资源将积极参与软件标准 社区确保软件及其模型的可重复性和可重用性 生成。