article: The cellular Potts model (CPM) is a powerful in silico method for simulating biological processes at tissue scale. Their inherently graphical nature makes CPMs very accessible in theory, but in practice, they are mostly implemented in specialised frameworks users need to master before they can run simulations. We here present Artistoo (Artificial Tissue Toolbox), a JavaScript library for building ‘explorable’ CPM simulations where viewers can change parameters interactively, exploring their effects in real time. Simulations run directly in the web browser and do not require third-party software, plugins, or back-end servers. The JavaScript implementation imposes no major performance loss compared to frameworks written in C++; Artistoo remains sufficiently fast for interactive, real-time simulations. Artistoo provides an opportunity to unlock CPM models for a broader audience: interactive simulations can be shared via a URL in a zero-install setting. We discuss applications in CPM research, science dissemination, open science, and education.
  A growing community of computational biologists uses simulation models to reason about complex processes in biological systems. The cellular Potts model (CPM, Box 1) is a well-established framework for simulating interacting cells. Originally proposed as a model for cell sorting (Graner and Glazier, 1992), the CPM has since been extended with a plethora of biological processes such as proliferation, apoptosis, cell motion, and chemotaxis – allowing CPM users to model diverse phenomena ranging from slime mould formation to blood vessel development, tumour growth, and cell migration (Marée et al. , 2007; Szabó and Merks, 2013; Hirashima et al. , 2017). Nowadays, several mature modelling frameworks with CPM implementations exist, such as CompuCell3D (Swat et al. , 2012), Morpheus (Starruß et al. , 2014), Tissue Simulation Toolkit (Daub and Merks, 2015), and CHASTE (Mirams et al. , 2013). Although CPMs are relatively efficient models, tissue-scale simulations still require substantial computational resources. For this reason, all of the abovementioned frameworks rely on the C++ programming language for computation steps, which requires them to be built for and installed on the user’s native operating system. Here, we present ‘Artistoo’ (Artificial Tissue Toolbox), a CPM framework built entirely in JavaScript. Although interpreted languages like JavaScript have classically been deemed too inefficient for running simulations, we found that this no longer holds: investments by major tech companies have tremendously improved JavaScript engines over the past years, to the point that our CPM now has no major performance disadvantage compared to existing C++ frameworks. The JavaScript implementation of Artistoo opens up new possibilities for rapid and low-barrier sharing of CPM simulations with students, collaborators, and readers or reviewers of a paper. Unlike existing frameworks, Artistoo allows building simulations that run in the web browser without the need to install any software: Artistoo models run on any platform providing a standards-compliant web browser – be it a desktop computer, a tablet, or a mobile phone. These simulations can be published on any web server or saved locally and do not rely on any back-end servers being available. They can be made explorable, enabling viewers to interact with the simulation and see the effect of changing model parameters in real time. In this paper, we will first briefly explain the key design principles behind Artistoo. We will then highlight applications in teaching, research, science dissemination, and open science where we envision that the zero-install, web-based architecture of our framework could be particularly useful.
  Artistoo is a JavaScript library implemented as an ECMAScript 6 module, which can be loaded into an HTML page or accessed from within a Node. js command line application. Artistoo is an open-source library released under the MIT license and is freely available on GitHub at https: //github. com/ingewortel/artistoo (copy archived at swh: 1: rev: 551ee76c3a972e86ac72ed7e977356a75d091763; Wortel and Textor, 2020). We here highlight a number of settings where Artistoo might complement other available modelling frameworks, focusing on the unique feature of Artistoo: it allows users to build and share explorable simulations in a zero-install setting. We discuss how this opens up novel opportunities of sharing CPM-based research and provide examples from our own work.
  The recent rise of the open science movement has changed the way research outputs are being shared and communicated. This may be especially important for computational models, which have classically been difficult to share because of the required software and coding skills. Transparent model sharing calls for new strategies to make models accessible for broader audiences. Indeed, several such efforts have been made in recent years. The CPM framework CompuCell3D now hosts an online version on NanoHub, which users can access without installing software locally (Gianlupi and Sego, 2021). Beyond the CPM field, modelling frameworks like Tellurium (Choi et al. , 2018) and PhysiCell (Ghaffarizadeh et al. , 2018) have also created online access through NanoHub; these frameworks have also shown how such online models can be made interactive by using (variations of) Jupyter notebooks (see, e. g. , Macklin and Heiland, 2020; Medley et al. , 2018; Somogyi, 2019). The potential of explorable online web pages in communication and teaching is also demonstrated by the emerging practice to share R models in the form of Shiny apps (Schönbrodt, 2014; Zehetleitner and Schönbrodt, 2015; Granjon, 2019). And finally, the online collection of ‘complexity explorables’ (Brockmann, 2020) is a fantastic example of how to combine interactive online simulations with explanatory text to communicate modelling research. With Artistoo, we now hope to open up this powerful avenue of model sharing for CPM research, allowing users to build online web pages and ‘explorables’ that combine interactive simulations with model explanations. We here show that the framework’s performance (similar to that of existing frameworks in C++) is sufficient to allow for interactive CPM simulations. We have been developing the library for more than 5 years, also using it for robust simulation work in our research; see, for example, Wortel et al. , 2020. We are continuing to develop the library for our own work and welcome suggestions and code contributions from the community. We do not envision Artistoo to replace existing modelling software; rather, it can complement software directed at computational biologists and developers by letting users build explorable and sharable versions of a simulation. To facilitate this process, we have built a (prototype) tool to help users convert models between different frameworks (currently: Artistoo and Morpheus). Although Artistoo already offers a wide range of methods, it does not (yet) support all features of existing frameworks (Morpheus, CHASTE, CompuCell3D, Tissue Simulation Toolkit), such as solvers for reaction–diffusion equations or SBML-encoded intracellular signalling, or writing output in formats like VTK and HDF5. Nevertheless, Artistoo simulations are highly customisable, and a wide range of CPM models can already be constructed using the framework in its current state. The software’s modular structure also makes it easy for future developers to extend it with custom code. In summary, to the best of our knowledge, Artistoo is the first CPM simulation framework supporting interactive simulations in the web browser that can be shared via a simple URL, without requiring installed software or back-end servers. We hope that this will unlock avenues of sharing and communicating (CPM) simulations to much larger audiences.
  To compare performance of Artistoo versus that of Morpheus (v2. 1. 0), we performed four different simulations in both frameworks. For this, we used the default examples provided with Morpheus and rebuilt similar simulations in Artistoo. This model of a migrating cell implements an actin-inspired migration model (Niculescu et al. , 2015) (see also Interactive Simulation 4 in Appendix 1). A single cell was seeded in the middle of a 200 × 200 pixel grid. Two obstacles of radius 10 were placed at a distance of 50 pixels to the left and right of the cell, respectively. Simulations were run for 15,000 MCS, logging the cell’s centroid every 10 MCS and saving a PNG every 250 MCS. This simulation is the Morpheus example CPM/Protrusion_2D. xml (version 4). This simulation implements the classical CPM model published by Graner and Glazier, 1992 (see also Interactive Simulation 5 in Appendix 1). Fifty cells each of two cell types were seeded on a 200 × 200 pixel grid within a circle of radius 67 from the grid midpoint. Simulations were run for 2000 MCS, logging statistics every 10 MCS and saving a PNG every 100 MCS. This simulation is the Morpheus example CPM/CellSorting_2D. xml (version 4), where the StopTime field was changed from 2. 5e4 to 2000. A CPM linked to cell division (see also Interactive Simulation 6 in Appendix 1) was simulated on a 500 × 500 pixel grid. The grid was initialised with 20 cells in a circle of radius 35 surrounding the grid midpoint. Simulations were run for 40,000 MCS, logging the number of cells every 100 MCS and saving a PNG every 1000 MCS. This simulation is the Morpheus example CPM/Proliferation_2D. xml (version 4). For the scalability simulations, simulations were run without outputting images. This allowed us to investigate the simulation speed separately from the time it takes to draw the entire grid. Note that if the drawing step becomes a limiting factor for running the simulation, it is always possible to speed up the process by drawing only once every few steps, or by choosing a more efficient drawing method (e. g. drawing only cell borders rather than entire cells). Simulations contained 1,5, 10,50,100,500, or 1000 cells per cell type. The grid dimensions were adaptively scaled such that x=y=1. 5⁢Ptot, with Ptot the total number of pixels of all the cells. Cells were seeded within a radius 0. 8⁢Ptot/π from the grid midpoint. Other settings were the same as in the cell sorting simulation described under Framework comparisons.
summary: Understanding complex systems, such as the weather or the spread of a pandemic, often relies on computational models that can simulate what is happening and what will happen next. Models like these can also be used to investigate biological processes. For example, cellular Potts models (or CPMs for short) are regularly used to simulate how cells move, self-organise to form tissues and respond to their surroundings. Computational biologists use a range of specialist skills and software to create these models. However, this can make it difficult for people who do not have programming experience to interact with these simulations and incorporate them in to their own research. If more people could engage with these models, this could help foster closer collaborations and ultimately lead to better models of biological systems. To make CPMs more accessible, Wortel and Textor created a toolbox called Artistoo that allows users to view and interact with simulations using just an internet browser. These simulations are very easy to interact with, and do not require any prior programming knowledge or specialised software. Viewers can input different parameters in to the simulation and watch in real time to see how this affects the biological system being modelled. Wortel and Textor showed that this toolbox can be used to build a range of different biological models and works just as fast as other, more complex programming tools. Artistoo has many potential applications and is a valuable education, learning, and collaboration tool. It may also encourage more open science, as having more accessible computational models could help with peer review and make it easier to collaborate across different research fields. A similar approach could be used to provide access to many other types of models in biology and beyond.
keywords: computational and systems biology
  cell biology
  tools and resources
title: Artistoo, a library to build, share, and explore simulations of cells and tissues in the web browser