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

Virtual Tissues (VTs) are powerful computer simulations of cell behaviors within tissues and organs. They are a valuable resource and tool for researchers to delve into the mechanisms driving both normal and diseased tissue behaviors. Although VTs do not replace traditional wetlab experiments, they significantly contribute to the exploration and interpretation of existing data.

They enable researchers to conduct "virtual" experiments, offering guidance for additional laboratory and clinical investigations. The combination of VTs with experiments leads to a deeper comprehension of complex biological phenomena and bolsters the progress of scientific understanding. VTs play a crucial role in drug and therapy research, as well as in the creation of

Medical Digital Twins for Personalized Medicine. Currently, there is a lack of infrastructure for collaborative and progressive VT development. This limits their widespread adoption in biology and medicine. To address this limitation, this project aims to establish an active open-source community providing resources and tools—an ecosystem—that fosters collaboration among

researchers from diverse backgrounds. By facilitating the sharing and application of biomedical data and models, this project can transform VT development, accelerating biological and medical research and technological applications. Enhanced sharing and distribution of VTs will positively impact STEM education because VTs present an excellent opportunity to accelerate learning of

fundamental biological and medical principles in an accessible, appealing, and comprehensible manner. By incorporating VTs into educational curricula, the project can expand the reach of STEM education and inspire future generations of scientists and researchers. This work both expedites scientific discovery and understanding of complex biological systems and also

advances 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 will

initially unify and expand two existing widely used open-source platforms for building and running VT models, CompuCell3D, and PhysiCell. OpenVT will enable sharable, cross-platform modeling tools and shareable model specifications. OpenVT aims to accelerate the understanding of complex biological mechanisms related to tissue development, homeostasis, and disease. The

project will focus on agent-based modeling (ABM) approaches, where tissues and organs are constructed using discrete cells, coupled with subcellular network models of signaling, gene regulation and metabolism and partial differential equations that simulate the extracellular movement of oxygen, growth substrates, signaling factors, and therapeutic compounds. Specific

aims include: development of shared standards for specification of VT models between CompuCell3D and PhysiCell, creation of cell-type description libraries, standardization of initial conditions, and description of model outputs. These standards will then be used to define the needed APIs that allow the interconnection and reuse of models and software components across

the two platforms, while also providing a concrete technical roadmap to support the integration of additional open source ABM VT frameworks in the future. This approach allows for the integration of subcellular, cell-level, and tissue-level phenomena, providing explanatory power and enabling high-precision virtual experiments. The project will support the integration of other VT frameworks

and the creation of educational and distribution facilities to enable their widespread adoption and extension of OpenVT. The OpenVT ecosystem aligns with successful community-driven initiatives in scientific software development, such as the Systems Biology Markup Language (SBML) project. It aims to foster collaboration, establish standards for model inputs and outputs, and

provide user support and training. By transitioning to an open-source ecosystem, the project aims to reduce duplication of effort, promote software and modle sharing, and democratize access to modeling 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.