From genotype to phenotype: can systems biology be used to predict Staphylococcus aureus virulence?

Abstract

With the advent of high-throughput whole-genome sequencing, it is now possible to sequence a bacterial genome in a matter of hours. However, although the presence or absence of a particular gene can be determined, we do not yet have the tools to extract information about the true virulence potential of an organism from sequence data alone. Here, we focus on the important human pathogen Staphylococcus aureus and present a framework for the construction of a broad systems biology-based tool that could be used to predict virulence phenotypes from S. aureus genomic sequences using existing technology.

Figure 1. The known virulence-regulatory network in Staphylococcus aureus.

Inside the circle are all the regulatory genes shown to have an effect on each other and on virulence^{,,,,,,,,,,,,,,,,,,,,,,,,,,,,,}. Outside the circle are the known effects of each regulator on adhesiveness (A), toxicity (T) and evasiveness (E). Much of the data used to generate this image is qualitative. A question mark indicates that there is either no information regarding the direct activity of the regulator or the available information is conflicting.

Figure 2. Staphylococcus aureus sequence variability.

The sequence variability within virulence-regulatory genes across ten Staphylococcus aureus strains. Pi is the probability that nucleotides in a gene differ between individuals.