NSF Award
2303695
Virtual Tissues (VTs) are powerful computer simulations of cell behaviors within tissues and<br/>organs. They are a valuable resource and tool for researchers to delve into the mechanisms<br/>driving both normal and diseased tissue behaviors. Although VTs do not replace traditional wetlab<br/>experiments, they significantly contribute to the exploration and interpretation of existing data.<br/>They enable researchers to conduct "virtual" experiments, offering guidance for additional<br/>laboratory and clinical investigations. The combination of VTs with experiments leads to a deeper<br/>comprehension of complex biological phenomena and bolsters the progress of scientific<br/>understanding. VTs play a crucial role in drug and therapy research, as well as in the creation of<br/>Medical Digital Twins for Personalized Medicine. Currently, there is a lack of infrastructure for<br/>collaborative and progressive VT development. This limits their widespread adoption in biology<br/>and medicine. To address this limitation, this project aims to establish an active open-source<br/>community providing resources and tools—an ecosystem—that fosters collaboration among<br/>researchers from diverse backgrounds. By facilitating the sharing and application of biomedical<br/>data and models, this project can transform VT development, accelerating biological and medical<br/>research and technological applications. Enhanced sharing and distribution of VTs will positively<br/>impact STEM education because VTs present an excellent opportunity to accelerate learning of<br/>fundamental biological and medical principles in an accessible, appealing, and comprehensible<br/>manner. By incorporating VTs into educational curricula, the project can expand the reach of<br/>STEM education and inspire future generations of scientists and researchers. This work both<br/>expedites scientific discovery and understanding of complex biological systems and also<br/>advances American biotechnology and medicine. <br/><br/>This project will create OpenVT, an open-source, community-driven collection of resources,<br/>standards and tools for expanding the use and adoption of multicellular virtual-tissue (VT)<br/>computer simulations of normal and diseased biological tissues. The OpenVT ecosystem will<br/>initially unify and expand two existing widely used open-source platforms for building and running<br/>VT models, CompuCell3D, and PhysiCell. OpenVT will enable sharable, cross-platform modeling<br/>tools and shareable model specifications. OpenVT aims to accelerate the understanding of<br/>complex biological mechanisms related to tissue development, homeostasis, and disease. The<br/>project will focus on agent-based modeling (ABM) approaches, where tissues and organs are<br/>constructed using discrete cells, coupled with subcellular network models of signaling, gene<br/>regulation and metabolism and partial differential equations that simulate the extracellular<br/>movement of oxygen, growth substrates, signaling factors, and therapeutic compounds. Specific<br/>aims include: development of shared standards for specification of VT models between<br/>CompuCell3D and PhysiCell, creation of cell-type description libraries, standardization of initial<br/>conditions, and description of model outputs. These standards will then be used to define the<br/>needed APIs that allow the interconnection and reuse of models and software components across<br/>the two platforms, while also providing a concrete technical roadmap to support the integration of<br/>additional open source ABM VT frameworks in the future. This approach allows for the integration<br/>of subcellular, cell-level, and tissue-level phenomena, providing explanatory power and enabling<br/>high-precision virtual experiments. The project will support the integration of other VT frameworks<br/>and the creation of educational and distribution facilities to enable their widespread adoption and<br/>extension of OpenVT. The OpenVT ecosystem aligns with successful community-driven initiatives<br/>in scientific software development, such as the Systems Biology Markup Language (SBML)<br/>project. It aims to foster collaboration, establish standards for model inputs and outputs, and<br/>provide user support and training. By transitioning to an open-source ecosystem, the project aims<br/>to reduce duplication of effort, promote software and modle sharing, and democratize access to<br/>modeling capabilities. Project outcomes will be available at OpenVT.org.<br/><br/>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.
