Modeling in the Time of COVID-19: Statistical and Rule-based Mesoscale Models.

Ngan Nguyen,Tobias Klein,Martina Maritan,Ivan Viola,David S Goodsell,Ondrej Strnad,Peter Mindek,Ludovic Autin,Peter Wonka,Ruwayda Alharbi,Deng Luo

doi:10.1109/tvcg.2020.3030415

Abstract

We present a new technique for the rapid modeling and construction of scientifically accurate mesoscale biological models. The resulting 3D models are based on a few 2D microscopy scans and the latest knowledge available about the biological entity, represented as a set of geometric relationships. Our new visual-programming technique is based on statistical and rule-based modeling approaches that are rapid to author, fast to construct, and easy to revise. From a few 2D microscopy scans, we determine the statistical properties of various structural aspects, such as the outer membrane shape, the spatial properties, and the distribution characteristics of the macromolecular elements on the membrane. This information is utilized in the construction of the 3D model. Once all the imaging evidence is incorporated into the model, additional information can be incorporated by interactively defining the rules that spatially characterize the rest of the biological entity, such as mutual interactions among macromolecules, and their distances and orientations relative to other structures. These rules are defined through an intuitive 3D interactive visualization as a visual-programming feedback loop. We demonstrate the applicability of our approach on a use case of the modeling procedure of the SARS-CoV-2 virion ultrastructure. This atomistic model, which we present here, can steer biological research to new promising directions in our efforts to fight the spread of the virus.

Highlights

All living organisms on Earth share a common complex, hierarchical structure
If structural evidence is available in the form of electron microscopy (EM) images, our system determines basic structural properties from these images while requiring few inputs from the user. We demonstrate this rapid modeling method for integrating data from electron microscopy with structural information for the novel coronavirus SARS-CoV-2
The benefit of rule-based modeling is the nature of templating, which is advantageous for its ability to reuse the assembly patterns for other highly similar biological models

Summary

Introduction

At the lowest level of the hierarchy, biomolecules such as proteins and DNA perform all of the basic nanoscale tasks of information management, energy transformation, directed motion, etc These biomolecules are assembled into cells, the basic units of life. Cells typically are surrounded by a lipid bilayer membrane, which encloses several thousand different types of biomolecules that choreograph the processes of finding resources, responding to environmental changes, and growing and reproducing. Most familiar organisms, such as plants and animals, add an additional level to this hierarchy, with multiple cells cooperating to form large, multi-cellular organisms. Some viruses include a surrounding envelope composed of a lipid bilayer membrane that is acquired as the virus buds from an infected cell

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