LINDSAY Virtual Human: Multi-scale, Agent-based, and Interactive

Jacob, Christian; Mammen, Sebastian von; Davison, Timothy; Sarraf-Shirazi, A.; Sarpe, Vladimir; Esmaeili, Afshin; Phillips, David J.; Yazdanbod, Iman; Novakowski, Scott; Steil, Scott; Gingras, Carey; Jamniczky, Heather A.; Hallgrímsson, Benedikt; Wright, Bruce

doi:10.1007/978-3-642-30154-4_14

Cited by 12 publications

(12 citation statements)

References 15 publications

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“…We will extend Prokaryo by including other pathways (such as chemotaxis) and embed Prokaryo into a colony of interacting cells. Prokaryo is part of the Lindsay Virtual Human ( LINDSAY ), a multi-scale computational physiology simulation environment [ 38 ], in which we can place E. coli cells inside the LINDSAY intestinal tract. Any cell can be selected, and one can navigate into its ‘cellular universe’, which is what we have described here as Prokaryo .…”

Section: Discussionmentioning

confidence: 99%

“…This hybrid modeling approach combines continuous mathematical models, to capture large scale changes in biomolecular concentrations, with discrete agent interactions among smaller numbers of entities (a few to thousands). In order to implement a cellular model that incorporates both mathematical and agent-based simulations of a bacterium, we use a physics enabled simulation platform called LINDSAY Composer , which we developed in our lab [ 38 ]. Composer combines high-end 3D graphics libraries [ 39 ] with a physics engine [ 14 ] and provides a (game) development environment for building visually appealing, semi-realistic agent-based models.…”

Section: Agent-based Model Of the Lac Operonmentioning

confidence: 99%

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PROKARYO: an illustrative and interactive computational model of the lactose operon in the bacterium Escherichia coli

Esmaeili

Davison

et al. 2015

BMC Bioinformatics

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BackgroundWe are creating software for agent-based simulation and visualization of bio-molecular processes in bacterial and eukaryotic cells. As a first example, we have built a 3-dimensional, interactive computer model of an Escherichia coli bacterium and its associated biomolecular processes. Our illustrative model focuses on the gene regulatory processes that control the expression of genes involved in the lactose operon. Prokaryo, our agent-based cell simulator, incorporates cellular structures, such as plasma membranes and cytoplasm, as well as elements of the molecular machinery, including RNA polymerase, messenger RNA, lactose permease, and ribosomes.ResultsThe dynamics of cellular ’agents’ are defined by their rules of interaction, implemented as finite state machines. The agents are embedded within a 3-dimensional virtual environment with simulated physical and electrochemical properties. The hybrid model is driven by a combination of (1) mathematical equations (DEQs) to capture higher-scale phenomena and (2) agent-based rules to implement localized interactions among a small number of molecular elements. Consequently, our model is able to capture phenomena across multiple spatial scales, from changing concentration gradients to one-on-one molecular interactions.We use the classic gene regulatory mechanism of the lactose operon to demonstrate our model’s resolution, visual presentation, and real-time interactivity. Our agent-based model expands on a sophisticated mathematical E. coli metabolism model, through which we highlight our model’s scientific validity.ConclusionWe believe that through illustration and interactive exploratory learning a model system like Prokaryo can enhance the general understanding and perception of biomolecular processes. Our agent-DEQ hybrid modeling approach can also be of value to conceptualize, illustrate, and—eventually—validate cell experiments in the wet lab.

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Section: Discussionmentioning

confidence: 99%

Section: Agent-based Model Of the Lac Operonmentioning

confidence: 99%

PROKARYO: an illustrative and interactive computational model of the lactose operon in the bacterium Escherichia coli

Esmaeili

Davison

et al. 2015

BMC Bioinformatics

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“…As part of the LINDSAY Virtual Human project [28], we are developing a 3-dimensional, interactive computer model of male and female anatomy and physiology to be used for medical education. One key characteristic of LINDSAY is the integration of computational models across scales in order to simulate physiological processes from the body level to the level of organs, tissues, cells, and sub-cellular structures.…”

Section: Methodsmentioning

confidence: 99%

Simulating the decentralized processes of the human immune system in a virtual anatomy model

Sarpe

Jacob

2013

BMC Bioinformatics

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BackgroundMany physiological processes within the human body can be perceived and modeled as large systems of interacting particles or swarming agents. The complex processes of the human immune system prove to be challenging to capture and illustrate without proper reference to the spacial distribution of immune-related organs and systems. Our work focuses on physical aspects of immune system processes, which we implement through swarms of agents. This is our first prototype for integrating different immune processes into one comprehensive virtual physiology simulation.ResultsUsing agent-based methodology and a 3-dimensional modeling and visualization environment (LINDSAY Composer), we present an agent-based simulation of the decentralized processes in the human immune system. The agents in our model - such as immune cells, viruses and cytokines - interact through simulated physics in two different, compartmentalized and decentralized 3-dimensional environments namely, (1) within the tissue and (2) inside a lymph node. While the two environments are separated and perform their computations asynchronously, an abstract form of communication is allowed in order to replicate the exchange, transportation and interaction of immune system agents between these sites. The distribution of simulated processes, that can communicate across multiple, local CPUs or through a network of machines, provides a starting point to build decentralized systems that replicate larger-scale processes within the human body, thus creating integrated simulations with other physiological systems, such as the circulatory, endocrine, or nervous system. Ultimately, this system integration across scales is our goal for the LINDSAY Virtual Human project.ConclusionsOur current immune system simulations extend our previous work on agent-based simulations by introducing advanced visualizations within the context of a virtual human anatomy model. We also demonstrate how to distribute a collection of connected simulations over a network of computers. As a future endeavour, we plan to use parameter tuning techniques on our model to further enhance its biological credibility. We consider these in silico experiments and their associated modeling and optimization techniques as essential components in further enhancing our capabilities of simulating a whole-body, decentralized immune system, to be used both for medical education and research as well as for virtual studies in immunoinformatics.

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“…This innovative program allows virtual dissection and traveling through the body visualizations. The physiology models within LINDSAY Virtual Human are mainly implemented using the agent-based approach [10].…”

Section: Introductionmentioning

confidence: 99%

Development of In-Browser Simulators for Medical Education: Introduction of a Novel Software Toolchain

Šilar¹,

Polák²,

Mládek³

et al. 2019

J Med Internet Res

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BackgroundSimulators used in teaching are interactive applications comprising a mathematical model of the system under study and a graphical user interface (GUI) that allows the user to control the model inputs and visualize the model results in an intuitive and educational way. Well-designed simulators promote active learning, enhance problem-solving skills, and encourage collaboration and small group discussion. However, creating simulators for teaching purposes is a challenging process that requires many contributors including educators, modelers, graphic designers, and programmers. The availability of a toolchain of user-friendly software tools for building simulators can facilitate this complex task.ObjectiveThis paper aimed to describe an open-source software toolchain termed Bodylight.js that facilitates the creation of browser-based client-side simulators for teaching purposes, which are platform independent, do not require any installation, and can work offline. The toolchain interconnects state-of-the-art modeling tools with current Web technologies and is designed to be resilient to future changes in the software ecosystem.MethodsWe used several open-source Web technologies, namely, WebAssembly and JavaScript, combined with the power of the Modelica modeling language and deployed them on the internet with interactive animations built using Adobe Animate.ResultsModels are implemented in the Modelica language using either OpenModelica or Dassault Systèmes Dymola and exported to a standardized Functional Mock-up Unit (FMU) to ensure future compatibility. The C code from the FMU is further compiled to WebAssembly using Emscripten. Industry-standard Adobe Animate is used to create interactive animations. A new tool called Bodylight.js Composer was developed for the toolchain that enables one to create the final simulator by composing the GUI using animations, plots, and control elements in a drag-and-drop style and binding them to the model variables. The resulting simulators are stand-alone HyperText Markup Language files including JavaScript and WebAssembly. Several simulators for physiology education were created using the Bodylight.js toolchain and have been received with general acclaim by teachers and students alike, thus validating our approach. The Nephron, Circulation, and Pressure-Volume Loop simulators are presented in this paper. Bodylight.js is licensed under General Public License 3.0 and is free for anyone to use.ConclusionsBodylight.js enables us to effectively develop teaching simulators. Armed with this technology, we intend to focus on the development of new simulators and interactive textbooks for medical education. Bodylight.js usage is not limited to developing simulators for medical education and can facilitate the development of simulators for teaching complex topics in a variety of different fields.

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LINDSAY Virtual Human: Multi-scale, Agent-based, and Interactive

Cited by 12 publications

References 15 publications

PROKARYO: an illustrative and interactive computational model of the lactose operon in the bacterium Escherichia coli

PROKARYO: an illustrative and interactive computational model of the lactose operon in the bacterium Escherichia coli

Simulating the decentralized processes of the human immune system in a virtual anatomy model

Development of In-Browser Simulators for Medical Education: Introduction of a Novel Software Toolchain

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