Close
Help





JOURNAL

Bioinformatics and Biology Insights

S2M: A Stochastic Simulation Model of Poliovirus Genetic State Transition

Submit a Paper


Bioinformatics and Biology Insights 2016:10 81-95

Methodology

Published on 27 Jun 2016

DOI: 10.4137/BBI.S38194


Further metadata provided in PDF



Sign up for email alerts to receive notifications of new articles published in Bioinformatics and Biology Insights

Abstract

Modeling the molecular mechanisms that govern genetic variation can be useful in understanding the dynamics that drive genetic state transition in quasispecies viruses. For example, there is considerable interest in understanding how the relatively benign vaccine strains of poliovirus eventually revert to forms that confer neurovirulence and cause disease (ie, vaccine-derived poliovirus). This report describes a stochastic simulation model, S2M, which can be used to generate hypothetical outcomes based on known mechanisms of genetic diversity. S2M begins with predefined genotypes based on the Sabin-1 and Mahoney wild-type sequences, constructs a set of independent cell-based populations, and performs in-cell replication and cell-to-cell infection cycles while quantifying genetic changes that track the transition from Sabin-1 toward Mahoney. Realism is incorporated into the model by assigning defaults for variables that constrain mechanisms of genetic variability based roughly on metrics reported in the literature, yet these values can be modified at the command line in order to generate hypothetical outcomes driven by these parameters. To demonstrate the utility of S2M, simulations were performed to examine the effects of the rates of replication error and recombination and the presence or absence of defective interfering particles, upon reaching the end states of Mahoney resemblance (semblance of a vaccine-derived state), neurovirulence, genome fitness, and cloud diversity. Simulations provide insight into how modeled biological features may drive hypothetical outcomes, independently or in combination, in ways that are not always intuitively obvious.



Downloads

PDF  (2.24 MB PDF FORMAT)

RIS citation   (ENDNOTE, REFERENCE MANAGER, PROCITE, REFWORKS)

Supplementary Files 1   (202.79 KB ZIP FORMAT)

BibTex citation   (BIBDESK, LATEX)

XML





Quick Links


New article and journal news notification services