Design considerations in building in silico equivalents of common experimental influenza virus assays

Abstract

Experimentation in vitro is a vital part of the process by which the clinical and epidemiological characteristics of a particular influenza virus strain are determined. We detail the considerations which must be made in designing appropriate theoretical/mathematical models of these experiments and show how modeling can increase the information output of such experiments. Starting from a traditional system of ordinary differential equations, common to infectious disease modeling, we broaden the approach by using an agent-based model, applicable to more general experimental geometries and assumptions about the biological properties of viruses, cell and their interaction. Within this framework, we explore the limits of the assumptions made by more traditional models and the conditions under which these assumptions begin to break down, requiring the use of more sophisticated models. We apply the agent-based model to experimental plaque growth of two influenza strains, one resistant to the antiviral oseltamivir, and extract the values of key infection parameters specific to each strain.

Keywords::

• Influenza
• mathematical modeling
• agent-based models
• viral plaque
• in vitro methods

Acknowledgements

The computational aspects of this work were made possible by the facilities of the Shared Hierarchical Academic Research Computing Network (SHARCNET: www.sharcnet.ca) and Compute/Calcul Canada.

Declaration of interest: This study was supported by the Canadian Institutes for Health Research [funding reference number 86937] (GB and CAAB) and by the Natural Sciences and Engineering Research Council of Canada (CAAB). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.