Competitive Renewal of Development, Improvement and Extension of the Tissue Simu

描述（由申请人提供）：在NIH GM077138、EPA的ComTox计划、邓迪计算肿瘤学研究以及越来越多的发育生物学家和组织工程师的两年半资助下，采用了CompuCell3D （CC3D）作为建模平台。CC3D已经成为最广泛接受的多尺度、多细胞（MSMC）发育现象和相关疾病模拟的标准，拥有100多名训练有素的用户，因为它的开源组合了Glazier-Graner-Hogeweg （GGH）模型的多细胞功能，兼容smml的亚细胞生化网络，以及组织水平现象的连续体和有限元建模。复杂的用户界面和脚本功能允许快速构建有用的生物医学模型，并具有可调的建模细节级别。在我们越来越多的翻译用户的要求的激励下，这一竞争更新将开发一个并行（图形处理单元（GPU），多核和集群）CC3D2，具有流体流动支持，比CC3D的速度提高了100倍，并且能够运行非常大规模的模拟（许多cm3, 107-109细胞，整个胚胎/器官），具有从笔记本电脑到各种并行架构的简单迁移路径（具体目标1）。这是非常重要的，因为CC3D2将改变MSMC建模的能力，允许开发未来临床研究应用所需的详细的、可验证的模型，实现由美国国立卫生研究院领导的跨机构建模和分析小组（IMAG）确定的目标：“开发开源的、多尺度的生物模拟环境，在单处理器和并行计算机上运行，并且……，（允许）用户选择模拟细节的级别，而无需进一步修改他们的模拟。”它是创新的，因为它结合了CC3D开发团队的现有专业知识和D'Souza集团广泛的GPU和并行化经验，提供了一个强大的并行MSMC环境和第一个基于GPU的GGH方法实现，允许以前无法实现的模拟。应临床和生物医学用户的要求，CC3D2将提供一种创新，快速和生物学直观的模型设计方法，具有新颖的细胞行为模型规范语言（CBMSL）（特定目标3）和第一个可用于MSMC的可共享图形模型定义（特定目标2）。CBMSL将允许研究人员专注于生物学而不是计算细节，并极大地促进模型交叉验证和共享，为未来的MSMC模型描述标准化工作提供重要的用例。图形化的工作流程控制和增强的用户支持和文档（具体目标4）将进一步改善CC3D2的可用性并增加用户的采用。

DESCRIPTION (provided by applicant): During two-and-a-half years of funding under NIH GM077138, the EPA's ComTox program, the Dundee computational oncology effort and an increasing number of developmental biologists and tissue engineers have adopted CompuCell3D (CC3D) as a modeling platform. CC3D has become the most widely accepted standard for multi-scale, multi-cell (MSMC) simulations of developmental phenomena and related diseases, with more than 100 trained users, because its open-source combination of the multi-cell capabilities of the Glazier-Graner-Hogeweg (GGH) model, the SBML-compatible subcellular biochemical networks, and continuum and finite-element modeling of tissue-level phenomena, sophisticated user interfaces and scripting capabilities allow rapid construction of useful biomedical models with tunable levels of modeling detail. Motivated by the requests of our increasing number of translational users, this competing renewal will develop a parallel (Graphical Processing Unit (GPU), multi-core and cluster) CC3D2 with fluid-flow support providing up to a hundred-fold increase in speed over CC3D plus the ability to run very large-scale simulations (many cm3, 107-109 cell, whole embryo/organ) with a simple migration path from laptop to diverse parallel architectures (Specific Aim 1). It is significant, because CC3D2 will transform the power of MSMC modeling to allow the development of the detailed, verifiable models required for future clinical-research applications, achieving the goal identified by the NIH-led Interagency Modeling and Analysis Group (IMAG) group: "the development of open source, multi-scale biological simulation environments which run both on single processors and parallel computers and which ..., [permit] users to select the level of simulation detail without further modifying their simulations." It is innovative because it combines the existing expertise of the CC3D development team and the extensive GPU and parallelization experience of the D'Souza group to provide a robust parallel MSMC environment and the first GPU-based implementation of the GGH methodology to allow simulations which were formerly unachievable. As requested by our clinical and biomedical users, CC3D2 will provide an innovative, fast and biologically- intuitive approach to model design, with a novel Cell Behavior Model Specification Language (CBMSL) (Specific Aim 3) and the first sharable graphical model definition available for MSMC (Specific Aim 2). CBMSL will allow researchers to focus on biology rather than computational details and greatly facilitate model cross-validation and sharing, providing an important use-case for future MSMC model-description standardization efforts. Graphical workflow control and enhanced user support and documentation (Specific Aim 4) will further improve CC3D2 usability and increase user adoption.