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7-Feb-02Richard Baldock
1
MRC Human Genetics Unit www.hgu.mrc.ac.uk
The Mouse Gene-Expression Information Resource
Richard BaldockMRC Human Genetics Unit, Edinburgh
http://genex.hgu.mrc.ac.uk/
7-Feb-02Richard Baldock
2
MRC Human Genetics Unit www.hgu.mrc.ac.uk
11.5-day old mouse embryo
How does
this embryo develop?
7-Feb-02Richard Baldock
3
MRC Human Genetics Unit www.hgu.mrc.ac.uk
in situ hybridization data
7-Feb-02Richard Baldock
4
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Image capture
James Sharpe et al, Science 296(2002)541-545
Optical Projection Tomography
7-Feb-02Richard Baldock
5
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Flourescent Double Labelling
Blue - HNF3b
Green - neurofilament
Red - autoflourescence of heart
7-Feb-02Richard Baldock
6
MRC Human Genetics Unit www.hgu.mrc.ac.uk
mouse E12.5 nasal region Msx1 mRNA, net
Words are not enough -
7-Feb-02Richard Baldock
7
MRC Human Genetics Unit www.hgu.mrc.ac.uk
spatial indexing
gene expression database
Semi-automatic image mapping
7-Feb-02Richard Baldock
8
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Bioinformatics frameworks
gene expressionmutant phenotype
cell behaviour
7-Feb-02Richard Baldock
9
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Gene expression patterns
Mutant phenotypes
Cell death, proliferation,migration.
Published results of manipulation experiments
Map to the same framework
Explore relationships between different data
7-Feb-02Richard Baldock
10
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Gene expression patterns
Mutant phenotypes
Cell death, proliferation,migration.
Published results of manipulation experiments
Map to the same framework
Explore relationships between different data
What kind of
framework
?
7-Feb-02Richard Baldock
11
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Gene expression patterns
Mutant phenotypes
Cell death, proliferation,migration.
Published results of manipulation experiments
Map to the same framework
Explore relationships between different data
7-Feb-02Richard Baldock
12
MRC Human Genetics Unit www.hgu.mrc.ac.uk
The structure of the Mouse Atlas
• Image
• Text
• Link
- controlled anatomical vocabulary
- volumetric digital model embryos
- named parts are delineated in the models
7-Feb-02Richard Baldock
13
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Image - Model embryos
Time (E days)
Theiler Stage
Birth
1 2 12 13 14 26 27
1 8 8.5 9 18
7-Feb-02Richard Baldock
14
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Model embryos
images of serial, stained sections
stacked and aligned
….to produce a 3D block
7-Feb-02Richard Baldock
15
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Voxels building blocks of the 3D models
7-Feb-02Richard Baldock
16
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Text - Anatomy
Time (E days)
Theiler Stage
Birth
1 2 12 13 14 26 27
1 8 8.5 9 18
7-Feb-02Richard Baldock
17
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Resolution of the vocabulary
Jonathan Bard, Matt Kaufman
7-Feb-02Richard Baldock
18
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Voxels Pigeon-holes in a spatial database
anatomical name
7-Feb-02Richard Baldock
19
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Mapping anatomy to the models
• comprehensive
• exclusive
• not detailed
Renske Brune
7-Feb-02Richard Baldock
20
MRC Human Genetics Unit www.hgu.mrc.ac.uk
EMAP: Spatio-Temporal Framework for Developmental Biology
Iconic SymbolicSpace
7-Feb-02Richard Baldock
21
MRC Human Genetics Unit www.hgu.mrc.ac.uk
EMAP: Time
Time (E days)
Theiler Stage
Birth
… 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
… 4.5 5 6 6.5 7 7.5 8 8.5 9 9.5 10 10.5 11 11.5 12 12.5 13 14 15 16 17 18
E0 E17.5Anatomy ontology: structure, development, lineage
7-Feb-02Richard Baldock
22
MRC Human Genetics Unit www.hgu.mrc.ac.uk
anatomical name
gene expression
mutant phenotype
cell behaviour
bibliographic references
Using the Atlas: gene-expression database
7-Feb-02Richard Baldock
23
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Mouse Gene-Expression Information Resource
• Staging criteria (html)• Spatially mapped data (EMAGE)• Anatomy Ontology mapped data (MGI/GXD)• Interfaces/software
7-Feb-02Richard Baldock
24
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Staging and Other data
7-Feb-02Richard Baldock
25
MRC Human Genetics Unit www.hgu.mrc.ac.uk
MGI/GXD
7-Feb-02Richard Baldock
26
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Mouse Atlas - EMAP & EMAGE
7-Feb-02Richard Baldock
27
MRC Human Genetics Unit www.hgu.mrc.ac.uk
Tools
7-Feb-02Richard Baldock
28
MRC Human Genetics Unit www.hgu.mrc.ac.uk
MRC Human Genetics Unit, EdinburghR A Baldock, N Burton, W Hill, D HoughtonK Opstad, A Ross, M Stark, A WaterHouse,Y Yang, D Davidson, G Feng, J Rao
M Ringwald
Biomedical Sciences, University of EdinburghJ B L Bard, R M Brune, M Kaufman, C Oram, L Richardson, D Smith
Hubrecht Laboratorium, UtrechtK Lawson
Computing and Electrical Engineering Heriot Watt UniversityA Burger
Informatics, Jackson Laboratory