POSE: PHASE II: Open VT - A Standardized Ecosystem for Virtual Tissue Simulation

虚拟组织（Virtual Tissues，VT）是对组织和器官中细胞行为的强大计算机模拟。它们是研究人员深入研究驱动正常和病变组织行为的机制的宝贵资源和工具。尽管VT不能取代传统的湿实验室实验，但它们对现有数据的探索和解释做出了重大贡献。它们使研究人员能够进行“虚拟”实验，为其他实验室和临床研究提供指导。VT与实验的结合导致了对复杂生物现象的更深入理解，并促进了科学认识的进步。VT在药物和治疗研究以及创建个性化医疗的医疗数字孪生中发挥着至关重要的作用。目前，缺乏协作和渐进式VT开发的基础设施。这限制了它们在生物学和医学中的广泛应用。为了解决这一问题，本项目旨在建立一个积极的开放源代码社区，提供资源和工具-一个生态系统，促进来自不同背景的研究人员的合作。通过促进生物医学数据和模型的共享和应用，该项目可以改变VT的发展，加速生物和医学研究和技术应用。加强VT的共享和分发将对STEM教育产生积极影响，因为VT提供了一个极好的机会，可以以一种可访问的，吸引人的和全面的方式加速学习基础生物学和医学原理。通过将虚拟技术纳入教育课程，该项目可以扩大STEM教育的范围，并激励未来的科学家和研究人员。这项工作既加速了科学发现和对复杂生物系统的理解，也促进了美国生物技术和医学的发展。该项目将创建OpenVT，这是一个开源的，社区驱动的资源，标准和工具集合，用于扩大正常和患病生物组织的多细胞虚拟组织（VT）计算机模拟的使用和采用。OpenVT生态系统将基本上统一和扩展两个现有的广泛使用的开源平台，用于构建和运行VT模型，CompuCell 3D和PhysiCell。OpenVT将支持可共享的跨平台建模工具和可共享的模型规范。OpenVT旨在加速理解与组织发育、稳态和疾病相关的复杂生物学机制。该项目将侧重于基于代理的建模（ABM）方法，其中组织和器官是使用离散细胞，加上信号，基因调控和代谢的亚细胞网络模型和偏微分方程，模拟氧气，生长底物，信号因子和治疗化合物的细胞外运动。具体目标包括：开发CompuCell 3D和PhysiCell之间VT模型规范的共享标准，创建细胞类型描述库，初始条件的标准化以及模型输出的描述。这些标准将用于定义可扩展API，允许跨两个平台的模型和软件组件的互连和重用，同时还提供具体的技术路线图，以支持未来其他开源ABM VT框架的集成。这种方法允许整合亚细胞，细胞水平和组织水平的现象，提供解释能力，并实现高精度的虚拟实验。该项目将支持其他VT框架的整合，并创建教育和分发设施，以使其广泛采用和扩展OpenVT。OpenVT生态系统与科学软件开发中成功的社区驱动计划保持一致，例如系统生物学标记语言（SBML）项目。它旨在促进合作，建立模型输入和输出的标准，并提供用户支持和培训。通过过渡到开源生态系统，该项目旨在减少重复工作，促进软件和模型共享，并使建模能力的访问民主化。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

Virtual Tissues (VTs) are powerful computer simulations of cell behaviors within tissues andorgans. They are a valuable resource and tool for researchers to delve into the mechanismsdriving both normal and diseased tissue behaviors. Although VTs do not replace traditional wetlabexperiments, they significantly contribute to the exploration and interpretation of existing data.They enable researchers to conduct "virtual" experiments, offering guidance for additionallaboratory and clinical investigations. The combination of VTs with experiments leads to a deepercomprehension of complex biological phenomena and bolsters the progress of scientificunderstanding. VTs play a crucial role in drug and therapy research, as well as in the creation ofMedical Digital Twins for Personalized Medicine. Currently, there is a lack of infrastructure forcollaborative and progressive VT development. This limits their widespread adoption in biologyand medicine. To address this limitation, this project aims to establish an active open-sourcecommunity providing resources and tools—an ecosystem—that fosters collaboration amongresearchers from diverse backgrounds. By facilitating the sharing and application of biomedicaldata and models, this project can transform VT development, accelerating biological and medicalresearch and technological applications. Enhanced sharing and distribution of VTs will positivelyimpact STEM education because VTs present an excellent opportunity to accelerate learning offundamental biological and medical principles in an accessible, appealing, and comprehensiblemanner. By incorporating VTs into educational curricula, the project can expand the reach ofSTEM education and inspire future generations of scientists and researchers. This work bothexpedites scientific discovery and understanding of complex biological systems and alsoadvances American biotechnology and medicine. This project will create OpenVT, an open-source, community-driven collection of resources,standards and tools for expanding the use and adoption of multicellular virtual-tissue (VT)computer simulations of normal and diseased biological tissues. The OpenVT ecosystem willinitially unify and expand two existing widely used open-source platforms for building and runningVT models, CompuCell3D, and PhysiCell. OpenVT will enable sharable, cross-platform modelingtools and shareable model specifications. OpenVT aims to accelerate the understanding ofcomplex biological mechanisms related to tissue development, homeostasis, and disease. Theproject will focus on agent-based modeling (ABM) approaches, where tissues and organs areconstructed using discrete cells, coupled with subcellular network models of signaling, generegulation and metabolism and partial differential equations that simulate the extracellularmovement of oxygen, growth substrates, signaling factors, and therapeutic compounds. Specificaims include: development of shared standards for specification of VT models betweenCompuCell3D and PhysiCell, creation of cell-type description libraries, standardization of initialconditions, and description of model outputs. These standards will then be used to define theneeded APIs that allow the interconnection and reuse of models and software components acrossthe two platforms, while also providing a concrete technical roadmap to support the integration ofadditional open source ABM VT frameworks in the future. This approach allows for the integrationof subcellular, cell-level, and tissue-level phenomena, providing explanatory power and enablinghigh-precision virtual experiments. The project will support the integration of other VT frameworksand the creation of educational and distribution facilities to enable their widespread adoption andextension of OpenVT. The OpenVT ecosystem aligns with successful community-driven initiativesin scientific software development, such as the Systems Biology Markup Language (SBML)project. It aims to foster collaboration, establish standards for model inputs and outputs, andprovide user support and training. By transitioning to an open-source ecosystem, the project aimsto reduce duplication of effort, promote software and modle sharing, and democratize access tomodeling capabilities. Project outcomes will be available at OpenVT.org.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.