Informatics and simulation in a genomic approach to understanding virulence

The DNA sequences of several human pathogens are known. Using the DNA sequence and bioinformatics tools, it is possible to design a series of biological experiments to improve our understanding of virulence pathways. Computers are critical to managing the experimental data. New tools are needed to extract information from the large data sets and to integrate data. Sometimes the data are of the same type but from different organisms (comparative genomics). Sometimes dissimilar data, such as mRNA and protein structure, also need to be integrated. Using the bacterium Yersinia pestis, we are implementing a whole-genome study of virulence mechanisms. This paper describes informatic successes and limitations of this data-intensive approach. We also suggest improvements to genomic data collection with the potential to universalize transcript profiling for a broad class of bacteria. Finally, we examine the potential of computer simulation to integrate data and test hypotheses.