bioinformatics resources for the systemslevel analysis of innate immunity: the innatedb interaction

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bioinformatics resources for the systems-level
analysis of innate immunity the innatedb
interaction database and a novel method for the
pathway-like layout of biological networks
dr. jennifer gardy centre for microbial diseases
immunity research the university of british
columbia, vancouver, bc, canada
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connect the dots
innate immunity style
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immunity
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adaptive immunity
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specific
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slow
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adaptive
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innate
adaptive
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effective against a
range of pathogens
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fast
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the bodys firewall
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recognition
Y
II
U
Y
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recognition
Y
II
U
Y
signaling cascades
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recognition
Y
II
U
Y
signaling cascades
effectors
cytokines
IC killing
chemokines
adaptive
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but
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effectors lead to
infection resolution
inflammation
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however
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infection resolution
inflammation
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thou shalt not kill. but you can defend your turf.
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tweak immunomodulation
LL-37
Mookherjee et al. J. Imm. 2006
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project goal 1
understand the innate immune response to -
pathogens - immunomodulators
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project goal 2
bring immunomodulators to the pre-clinical stage
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systems biology
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large-scale experimentation
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network context
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systems-level analysis needs

• a network
• parts list
• interactions
• an intuitive display
• hypothesis discovery

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our solutions

• InnateDB biomolecular interaction database
• CeReBRAL an intuitive network display tool

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InnateDB
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what?
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InnateDB is the first
comprehensive publicly-available innate
immunity-specific
biomolecular interaction database
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why?
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existing databases just dont do it for us.
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low coverage
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little ortholog information
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quantity over quality
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what does it look like?
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Interaction-specific Interaction
type Evidence Biosource Pathways Complexes Regulat
ory modules
Molecule-specific Multiple accession
numbers Gene, protein sequences Sequence
features Gene ontologies Innate immune
annotation Ortholog/paralog predictions
Ensembl backbone, HUPO PSI-MI, BioPax standards
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Automatic Extraction
Manual Submission
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front-end
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functions like
basic search advanced search hierarchical browsing
make exploring InnateDB easy
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with your data, you can
view an HTML table customize results
display download results view a network diagram
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systems-level analysis needs

• a network
• parts list
• interactions
• an intuitive display
• hypothesis discovery

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www.cytoscape.org
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L.A.J. ONeill. Nat. Rev. Imm.
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how do we go from this
to this?
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CeReBRAL
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Cell Region Based Rendering And Layout
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from hairball to pathway in a few seconds flat.
depends on network size
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1. a network
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2. localizations
MAPK11 nucleus MYD88 cytoplasm IKBKB
cytoplasm ATF2 nucleus TLR4 membrane NFKBIB
cytoplasm NFKBIA cytoplasm
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• select attribute file
• order localization layers

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3. downstream nodes 4. clustering attribute
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more tricks up our sleeve
pathway selection experiment comparison
stay tuned
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take-home points

• modulation of innate immunity is promising new
  therapeutic strategy
• InnateDB high-quantity/high-quality,
  user-friendly interaction database for innate
  immunity biomolecules
• CeReBRAL a Cytoscape plugin for generating
  pathway-like layouts of a network, given
  localization information

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acknowledgments
innatedb fiona roche, tim chan, matt laird, mike
acab, fiona brinkman bob hancock cerebral
aaron barsky, tamara munzner bob hancock
genome canada, bill melinda gates foundation,
michael smith foundation for health research,
canadian institutes of health research images
stock.xchng, uglydolls.com
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release info
CeReBRAL dec. 2006 majordomo_at_interchange.ubc.ca
subscribe cerebral-news InnateDB spring
2006 maillist_at_sfu.ca subscribe innatedb-update
slides www.cmdr.ubc.ca/jennifer