Simbiotics: A Multiscale Integrative Platform for 3D Modeling of Bacterial Populations

Abstract

Simbiotics is a spatially explicit multiscale modeling platform for the design, simulation and analysis of bacterial populations. Systems ranging from planktonic cells and colonies, to biofilm formation and development may be modeled. Representation of biological systems in Simbiotics is flexible, and user-defined processes may be in a variety of forms depending on desired model abstraction. Simbiotics provides a library of modules such as cell geometries, physical force dynamics, genetic circuits, metabolic pathways, chemical diffusion and cell interactions. Model defined processes are integrated and scheduled for parallel multithread and multi-CPU execution. A virtual lab provides the modeler with analysis modules and some simulated lab equipment, enabling automation of sample interaction and data collection. An extendable and modular framework allows for the platform to be updated as novel models of bacteria are developed, coupled with an intuitive user interface to allow for model definitions with minimal programming experience. Simbiotics can integrate existing standards such as SBML, and process microscopy images to initialize the 3D spatial configuration of bacteria consortia. Two case studies, used to illustrate the platform flexibility, focus on the physical properties of the biosystems modeled. These pilot case studies demonstrate Simbiotics versatility in modeling and analysis of natural systems and as a CAD tool for synthetic biology.

Phage mobility is a core determinant of phage–bacteria coexistence in biofilms

“…Existing biofilm simulation frameworks are flexible and have excellent experimental support ( Hellweger and Bucci, 2009 ; Bucci et al , 2011 ; Lardon et al , 2011 ; Estrela et al , 2012 ; Estrela and Brown, 2013 ; Hellweger et al , 2016 ; Nadell et al , 2016 ; Naylor et al , 2017 ), but they become impractical when applied to the problem of phage infection. We therefore developed a new simulation framework to study phage–biofilm interactions.…”

Toward Engineering Biosystems With Emergent Collective Functions

“…Although computational frameworks have been available since the 1980s to support this process, it is only during the past decade that tools have been tailored for synthetic biology applications and reached sufficient performance ( Gorochowski et al, 2012 ; Oishi and Klavins, 2014 ; Goñi-Moreno and Amos, 2015 ). More recently, the effective use of highly parallel computing resources has expanded the complexity of biological models that can be simulated ( Rudge et al, 2012 ; Naylor et al, 2017 ; Li et al, 2019 ; Cooper et al, 2020 ). Automated coarse-graining of representations enable faster simulation without impacting on the accuracy of predictions ( Graham et al, 2017 ), while advanced tools allow verification, validation and uncertainty quantification for such simulations ( Richardson et al, 2020 ).…”

Population Dynamics of Autocatalytic Sets in a Compartmentalized Spatial World

“…Simulations were performed with the Simbiotics package [ 38 ]. Simbiotics is a multicellular simulator which represents cells as individual physical entities embedded in chemical gradients, where each cell can have defined dynamics and can interact with its environment as well as other cells.…”

“…The simulation toolkit provides a versatile set of data collection and analysis tools, and can be easily extended with user-defined modules and libraries. A more detailed description of Simbiotics is available elsewhere [ 38 ]. Here, we briefly describe the particular features used in this study.…”