Abstract

The field of computer modeling and simulation of biological systems is rapidly advancing, backed by significant progress in the fields of experimentation techniques, computer hardware, and programming software. The result of a simulation may be delivered in several ways, from numerical results, through graphs of the simulated run, to a visualization of the simulation. The vision of an in-silico experiment mimicking an in-vitro or in-vivo experiment as it is viewed under a microscope is appealing but technically demanding and computationally intensive. Here, we report “Cell Studio,” a generic, hybrid platform to simulate an immune microenvironment with biological and biophysical rules. We use game engines—generic programs for game creation which offer ready-made assets and tools—to create a visualized, interactive 3D simulation. We also utilize a scalable architecture that delegates the computational load to a server. The user may view the simulation, move the “camera” around, stop, fast-forward, and rewind it and inject soluble molecules into the extracellular medium at any point in time. During simulation, graphs are created in real time for a broad view of system-wide processes. The model is parametrized using a user-friendly Graphical User Interface (GUI). We show a simple validation simulation and compare its results with those from a “classical” simulation, validated against a “wet” experiment. We believe that interactive, real-time 3D visualization may aid in generating insights from the model and encourage intuition about the immunological scenario.

Highlights

  • Computer modeling is fueled by both advance in biological experimentation techniques5—which significantly increase the amount of data acquired in a given experiment—and advance in computer hardware technology—which boosts the resources available to the modeler

  • Once a T-cell expresses the CD4 receptor, it is by definition regarded as a helper T-cell, but properties dictated by this phenotype must still be explicitly defined

  • We have developed a hybrid, cellular-level, general-purpose platform for modeling and simulation of immunological processes

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Summary

Introduction

Computer modeling is fueled by both advance in biological experimentation techniques (the socalled “-omics”)5—which significantly increase the amount of data acquired in a given experiment—and advance in computer hardware technology—which boosts the resources available to the modeler. Several teams have built general purpose simulation systems, software frameworks that offer basic tools that should serve as building blocks to allow researchers to create an ad-hoc simulation for a particular biological case These simulation systems can be classified, apart from their aforementioned modeling paradigm, by their modelled biological scale: from the intracellular level to the complete organism level. Using ABM facilitates both the development of the modeling system—since Object Oriented Programming, the software architecture equivalent to agent-based modeling, is a prominent software engineering pattern—and the researcher’s work of creating the model—since assigning properties and abilities to each cell population separately emulates the biological study process more closely This modeling method may alleviate the need for advanced mathematical or algorithmic knowledge required to create a model.

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