Paul Macklin

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  From single models to community advances: open source codes and data standards
  Paul Macklin

  Problems in tissue engineering, developmental biology, cancer, and related areas require that we study 3-D multicellular systems, coupling dynamics at many scales such as protein signaling, cell phenotype "decisions," biotransport, and mechanics. Developing, calibrating, and validating models to study these systems requires not only sophisticated tools, but also a huge variety of data ranging from molecular to clinical scales. No one research team can develop all the necessary software and gather all the required data on their own, so we present our recent work to (1) contribute scalable open source software to simulate 3-D biotransport of many substrates (BioFVM), 3-D multicellular systems (PhysiCell), and extraction of cell phenotype from high-throughput experiments (CellPD), (2) help build a community for collaboration by creating a standard for multicellular data (MultiCellDS), and (3) work with this community to link biosimulation software and open data repositories through data standards.

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  New open source tools for simulating large 3-D multicellular systems on the desktop
  Paul Macklin
  In diverse fields spanning developmental biology, tissue engineering, and cancer, dynamical interactions between large multicellular populations and the microenvironment shape the emergent behaviors of the larger systems, often in surprising ways. While mathematical models can help to understand these systems, 3-D simulation studies often require solving for the dynamics of 105 or more cells, along with several diffusing growth substrates and signaling factors. Such simulations are challenging, generally requiring either complex parallelization on supercomputers, or restriction to smaller systems of 103 or 104 cells in 2-D or very small 3-D domains. Moreover, largely incompatible data formats have impeded the development of robust tools for 3-D visualization and data analysis, further slowing systematic investigations. We will discuss our work to address these problems with parallelized open source codes designed for desktop computers or single HPC compute nodes. We will introduce PhysiCell: an agent-based model that simulates cell cycling, apoptosis, necrosis, volume changes, and biomechanics-based movement in 3-D systems of 105 to 106 cells. We will introduce BioFVM: a finite volume solver for diffusive transport in large 3-D tissues (5+ diffusing substrates on 106 or more voxels: 5-10 mm3 at 20 �m resolution). We will discuss MultiCellDS: a draft data standard for cell phenotype and multicellular simulation data. And we will discuss our efforts to connect these tools to simulate breast cancer and colon cancer metastases in the liver. It is our hope that this work will help seed an ecosystem of compatible computational tools and experimental data. At the close of the talk, we will open the floor to discussion on how these tools can be adapted to meet the needs of the stem cell modeling community. See mbi2015.MathCancer.org for more information.