Evolution of a single-cell predictive model for packaging and budding of
viruses based on TEM based measurements
Abstract
Although detailed experimental investigations would provide insight into
viral infections and vaccine production, building a computational
framework is necessary to identify the parameters that regulate the
budding and packaging of nucleocapsids. This study shows that a
predictive model for the complete infection cycle can be built using
nonlinear coupled ODEs and parameter estimation using a Genetic
algorithm. Specifically, we have used a dataset containing the occluded
virus information, budded virus in infected cells obtained by
transmission electron microscopy (TEM). A novel parameter estimation
strategy is proposed based on the k-medoid clustering of infected cells.
Firstly, we show that the parameter estimation framework can be used for
model evolution and selection of the feedback structure. Secondly, we
show that the model was capable of capturing the distribution of
packaged and unpackaged nucleocapsids in the nucleus, cytoplasm, and
plasma membrane, the number of packaged and unpackaged ODV, and
polyhedra in the nucleus. The proposed framework assumes importance in
generating data for achieving quality by design in the optimization of
vaccine/recombinant protein yield.