Fraser 2000

Metzker 2010

Metzker 2010

Boller and Felix 2009

Jones and Dangl 2006

Jones and Dangl 2006

Problems in pathogenic microbiology in pre-genomics era: Genes associated with deployment of virulence factors have strong but pleiotropic phenotypes Genes interacting with host and its immune system are typically redundant and have weak phenotypes Raskin et al. 2006 Lindeberg et al. 2006

Medini et al. 2008

Brown et al. 2001

Harris et al. 2010

Medini et al. 2008

Hacker and Kaper 2000

Hacker and Kaper 2000

Fraser 2000

Bumann 2009

Falkow 2004

Pallen and Wren 2007

Torto-Alalibo et al. 2009

Falkow 2004

Schneider and Collmer 2010

Biology is an Informational Science   "The Human Genome Project has propelled us toward the view that biological systems are fundamentally composed of two types of information: genes, encoding the molecular machines that execute the functions of life, and networks of regulatory interactions, specifying how genes are expressed. All of this information is hierarchical in nature: DNA  mRNA  protein  protein interactions  informational pathways  informational networks  cells  tissues or networks of cells  an organism  populations  ecologies. Of course, other macro-moleculesand small molecules also participate in these information hierarchies, but the process is driven by genes and interactions between genes and their environments. The central task of systems biology is (a) to comprehensively gather information from each of these distinct levels for individual biological systems and (b) to integrate these data to generate predictive mathematical models of the system". Biological information has several important features: It operates on multiple hierarchical levels of organization. It is processed in complex networks. These information networks are typically robust, such that many single perturbations will not greatly effect them. There are key nodes in the network where perturbations may have profound effects; these offer powerful targets for the understanding and manipulation of the system." From: Ideker, T., T. Galitski, and L. Hood. 2001. A new approach to decoding life: systems biology. Annu Rev Genomics Hum Genet 2:343-72.

Pathogenomics research overview Steps Limitations Genome sequencing and annotation (Conserved) hypotheticals, misannotation, next-gen sequencing problems with “mobilome” Comprehensive identification of virulence gene candidates by various means Bioinformatic prioritization of virulence gene candidates and generation of hypotheses regarding functions of encoded factors Protein structure/function prediction Experimental determination of functions of individual virulence factors “Characterization bottleneck” Integrate knowledge of factors for use in: -eco-evo-systems biology study of pathogen -comparative genomics Ongoing curation