Artistoo: build, share, and explore simulations of cells and tissues in the web browser

  1. Inge M. N. Wortel
  2. Johannes Textor

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Abstract

Summary

The Cellular Potts Model (CPM) is a powerful in silico method for simulating diverse biological processes at tissue scale. Because of its inherently graphical nature, this model should in theory be accessible to a large audience of biologists – without requiring extensive mathematical expertise. But in practice, CPMs are mostly implemented in specialized frameworks that users need to master before they can run and modify the simulation. We here present Artistoo (Artificial Tissue Toolbox), a JavaScript library for building “explorable” CPM simulations where users can change model parameters and see their effects in real time. Artistoo simulations run directly in the web browser and do not require any third-party software, plugins, or back-end servers. Although implemented in JavaScript, Artistoo does not suffer from a major performance loss compared to frameworks written in C++; it remains sufficiently fast to let users interact with simulations in real time. Artistoo provides an opportunity to unlock CPM models for a broader audience: interactive simulations can be shared through a simple URL in a zero-install setting. We discuss how such model sharing may benefit modelling research, science dissemination, open science, and education.

Availability and Implementation

Artistoo is an open-source library released under the MIT license, and is freely available on GitHub at https://github.com/ingewortel/artistoo .

Contact

Johannes.Textor@radboudumc.nl

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  1. eLife

    Reviewer #2:

    Overall, this is a very well written paper that presents software that fills an interesting niche: interactive, real-time simulations of complex multicellular systems that can run in a web browser, without any need for users to install or configure software. As the authors describe, this enables new modes of education, science communication, and multidisciplinary collaboration. The software itself is impressive, and the supplied examples are clean and beautifully fluid. It is eye-opening that Javascript can run these models so well. The authors also did a fantastic and complete job in sharing their full source code, from the overall software down to individual scripts used to generate figures.

    Some points that the authors should address in a revision:

    1. Suitability of the software for researchers:

      a. Artistoo simulations do not appear to have any method to save data for external manipulation and archival. This makes their use somewhat less applicable to robust simulation-driven investigations, particularly where postprocessing and further analyses are required.

      b. It is unclear if Artistoo-based models can be exported into other cellular Potts (CP) frameworks such as CC3D or Morpheus. This may leave researcher end users without a clear "upgrade path" after exploring model ideas in Artistoo and moving to larger simulations (e.g., larger or more complex domains), running simulations in high throughput on HPC resources, or adapting approximate Bayeseian techniques for parameter estimation that require automating many simulation runs. Without an upgrade path, such users may wish to immediately begin in research-focused platforms rather than start with Artistoo and re-implement in another framework later.

      c. Similarly, it is unclear if a model developed in Morpheus or CC3D can be directly imported into Artistoo. If such an import were possible rather than re-implementing models in Aristoo, research-focused users would be more likely to use Artistoo for scientific communication and outreach.

    2. Need for improved educational scaffolding: The examples provided in the paper are excellent. However, they lack context on what the parameters mean or do. (For example, what are max_act and lambda_act in the cell migration model?) This may limit the educational impact because users will be unclear on what to change, and how the parameters relate to cell biophysical processes.

      The authors should include more background information with each model, define parameters, and give end users some idea of what to expect when parameters are changed. We have also found it useful to help guide a new user's exploration of a model by suggesting parameter sets and describing what they should see. This can serve as an educational scaffolding to help learners build and grow.

      The authors' sample models should serve as a template to Artistoo users on best practices for communicating models to diverse audiences.

    3. New developments in online cellular Potts simulators: The authors should note that CompuCell3D has recently been ported to run interactively online in a web browser. See https://nanohub.org/resources/compucell3d. This recent development should be addressed in the paper.

    4. Narrow review of interactive, "zero install" simulation frameworks: The authors focus too narrowly by only comparing Artistoo with other cellular Potts frameworks, while the main use case for Artistoo is for interactively sharing and communicating complex simulation models online.

      The authors should discuss non-CP frameworks that worked towards this, such as CC3D on nanoHUB (see above), online Tellurium (https://nanohub.org/resources/tellurium), current practice to share R models online as Shiny apps, and recent work to use xml2jupyter to automatically convert research-focused (command line) PhysiCell models to interactive Jupyter notebooks that can be shared as interactive webapps on nanoHUB (e.g., https://nanohub.org/tools/pc4cancerimmune). All of these serve similar purposes of creating zero-install, interactive versions of models for science education and communication. The authors should briefly discuss these to further contextualize their work.

    5. While this is a more minor point, I would feel more comfortable if the supplementary information had convergence and accuracy testing. Are there limits on computational step sizes for numerically accurate simulations, particularly for large energies or when including diffusion processes?

    Overall, this is some fantastic work.

  2. eLife

    Reviewer #1:

    The authors present a novel framework for running CPM simulations in the web browser. The CPM framework is a well-established model methodology for cells and tissues. Several well established other simulation platforms exist, however they do not run in the web browser, and require varying amounts of setup. This often presents an insurmountable roadblock since many researchers do not have the required software packages or expertise to read, execute, and run models in different formats. Artistoo on the other hand promises a zero-install experience for end-users, and ease of model construction for modellers.

    The unique feature of Artistoo is that it runs in the web browser. This allows users to execute simulations in a zero-install setting. In the web browser users can change model parameters, and observe resulting effects instantly. Extending or modifying models requires the user to know JS. Artistoo implements core modern CPM features. Artistoo is successfully benchmarked against the existing software of Morpheus. The source code is available on github. A wiki with an apparent complete and extensive documentation is available.

    The authors argue for three main avenues of impact: (1) accelerated feedback loops on models with experimental collaborators, (2) science communication, and (3) in teaching.

    The authors' points have merit, point (1) in particular. Installation and execution of tissue modelling software by non-experts is a well known challenge. Artistoo elegantly avoids this issue, by allowing models to be shared via the web browser. The non-expert is able to gain insights into model dynamics, and can explore the model's parameter space at ease. This approach has the potential of stimulating more frequent feedback between experimentalists and modellers, and maybe even the adoption of such a model by experimentalists.

    There is no markup language support. The software package Morpheus describes simulations using a markup language, allowing non-expert users to assemble complex models without writing a single line of C++, while at the same time preserving exact details of each simulation run. Morpheus is (as far as I know) the only based on a markup language. It would be fantastic if Artistoo could read and execute Morpheus ML files. From a technical point of view this should be possible. This would mean, all `Morpheus' models become "Artistoo' models, meaning that Artistoo would become the standard for sharing CPM models with collaborators. Finally the markup language would allow novices to implement new models without being discouraged by the JS requirement. Adopting a common markup language between projects would be the first example of standardization across open-source CPM software packages.

    I can see Artistoo being adopted by ``CPM modellers', who want to share models with collaborators, a wider audience (science communication). It may also find adoption in teaching. At the same time, the adoption of Artistoo faces some challenges: (1) Among modellers existing platforms have more features, are familiar, and have similar computational efficiency; (2) existing models are to be rewritten in the Artistoo framework.

  3. Version published to 10.1101/2020.05.01.072975 on bioRxiv