Fraser 2000

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Fraser 2000
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Metzker 2010
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Metzker 2010
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Boller and Felix 2009
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Jones and Dangl 2006
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Jones and Dangl 2006
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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
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Medini et al. 2008
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Brown et al. 2001
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Harris et al. 2010
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Medini et al. 2008
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Hacker and Kaper 2000
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Hacker and Kaper 2000
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Fraser 2000
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Bumann 2009
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Falkow 2004
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Pallen and Wren 2007
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Torto-Alalibo et al. 2009
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Falkow 2004
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Schneider and Collmer 2010
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• 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".
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• 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 2343-72.

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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