Jyl Boline, PhD

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2006 Spring Brain ConferenceScience of the
Mouse BIRN

• Jyl Boline, PhD
• Laboratory of Neuro Imaging, UCLA

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Goals
Tools to share and mine multi-scale structural
and functional mouse brain data

• Digital Atlases
• Integrate Gene Expression Efforts
• Automated Image Processing
• Integrated Interface Applications
• Focus on
• Neurodegenerative Diseases

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Participants
UCLA LONI
Informatics Center for Mouse Neurogenetics
(UTHSC, Drexel)
Duke (CIVM)
Caltech (Beckman)
UCSD (NCMIR)
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Why the Mouse?

• Mouse closely related to humans
• Most human genes have mouse counterparts

Human genome sequenced and published in Nature,
April 2003 Mouse genome sequenced and published
in Nature, December 2002
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Mouse Models of Neurological Disease

• Disease causing mutations in humans often cause
  similar diseases in mice
• Targeted gene replacement
• mouse models of disease

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Other Advantages of the Mouse

• Single Strain Models
• Strain is its own control
• Multiple imaging modalities
• Study progression
• Different therapies
• Statistical significance
• Multiple strains genetics and environment

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Explosion of Data
Financial Anatomy
Research projects and programs supported by
Department of Health and Human Services for mouse
genetics 2001-2006

• Mouse Genetics Initiatives
• NIH Knockout Mouse Project
• NIH Plan for Mouse Genomics Genetics Resources
• NIMH Molecular, Cellular Genomic Neuroscience
  Research Branch
• NINDS Program Area NINDS

GENSAT 2146 genes
Mouse Genome Informatics 1466 genes
Knockout mouse project projected per year 20
million 18 K for microarray analysis of each
line.
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How to Face the Challenge?
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Paradigm Digital Atlases

• Highlight Anatomy
• Nomenclature
• Coordinate System
• Informatics Framework
• Multimodal
• Multiscale
• Integrative
• Scaleable
• Atlas as a Database

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Focus on Neurodegenerative Diseases

• Alzheimers Disease Test Bed
• Beta Amyloid Precursor Protein (APP) Transgenic
  Mouse
• Multiple Sclerosis Test Bed
• Experimental Autoimmune Encephalomyelitis (EAE)
• Parkinsons Disease Test Bed
• Alpha Synuclein (a-syn) Transgenic Mouse

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a-synuclein Mouse Model of Parkinsons Disease
Assessment of cognitive and motor function
Genetic analyses
Correlation of large-scale mapping of
immunolabeling and MRI studies
Ultrastructural studies using EM
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Images into 3D Anatomic Structures
Maryann Martone, UCSD
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Probabilistic Atlas
T2-weighted MRM scans of 25 adult C57/Bl/6J mice
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Mapping Phenotype to Genotype to Behavior
submission
disappointment
optimism
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Mouse BIRN Data Integration Framework
1. Create multimodal databases
4. Use mediator to navigate and query across
data sources
2. Create conceptual links to a shared ontology
3. Situate the data in a common spatial framework
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Data in a Common Spatial Framework
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Designing this Framework
Spatially Coregistered Images in Database
Ontologies
MOUSE BIRN ATLASING TOOLKIT
Coregistered Atlas Modules
Web Based Resources
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Mouse BIRN Atlasing Toolkit (MBAT)
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Delineations
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Intuitive Link to Databases
GeneNetwork allows access to many kinds of data,
but several steps (shown here) are needed to
find the gene expression level in a single
structure
With MBAT, gene expression levels are quickly
returned and displayed for multiple
areas Comparisons are quick and easy
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Time for an MBAT Demo?
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Where to Find Us (nbirn.net)
Jyl Boline jboline_at_loni.ucla.edu
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Where to Find Us (nbirn.net)
jboline_at_loni.ucla.edu