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

虚拟组织（VTs）是对组织和器官内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。虽然VTs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，为进一步的实验室和临床研究提供指导。视频与实验的结合可以使我们对复杂的生物现象有更深的理解，并促进科学认识的进步。VTs在药物和治疗研究以及为个性化医疗创建医疗数字双胞胎方面发挥着至关重要的作用。目前，缺乏协作式和渐进式VT开发的基础设施。这限制了它们在生物学和医学领域的广泛应用。为了解决这一限制，该项目旨在建立一个活跃的开源社区，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之间的合作。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。增强视频的共享和分布将对STEM教育产生积极影响，因为视频提供了一个极好的机会，以一种易于理解、吸引人且易于理解的方式加速学习基础生物学和医学原理。通过将视频教学纳入教育课程，该项目可以扩大stem教育的范围，并激励未来几代科学家和研究人员。这项工作既加速了科学发现和对复杂生物系统的理解，也推动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，用于扩大使用和采用多细胞虚拟组织（VT）计算机模拟正常和病变生物组织。OpenVT生态系统最初将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，CompuCell3D和PhysiCell。OpenVT将使共享的、跨平台的建模工具和共享的模型规范成为可能。OpenVT旨在加速对与组织发育、体内平衡和疾病相关的复杂生物学机制的理解。该项目将专注于基于主体的建模（ABM）方法，其中组织和器官使用离散细胞构建，结合信号传导、生成调节和代谢的亚细胞网络模型，以及模拟氧气、生长基质、信号传导因子和治疗化合物的细胞外运动的偏微分方程。具体目标包括：在encompass ucell3d和PhysiCell之间开发VT模型规范的共享标准，创建单元类型描述库，初始条件的标准化，以及模型输出的描述。然后，这些标准将用于定义所需的api，这些api允许跨两个平台的模型和软件组件的互连和重用，同时还提供了一个具体的技术路线图，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，提供解释力并实现高精度的虚拟实验。该项目将支持其他VT框架的集成，并创建教育和分发设施，以使它们能够广泛采用和扩展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。它旨在促进协作，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，并使建模功能的访问民主化。该奖项反映了美国国家科学基金会的法定使命，并通过基金会的知识价值和更广泛的影响审查标准进行评估，认为值得支持。

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.