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7-Feb-0 2 Richard Baldock 1 MRC Human Genetics Unit www.hgu.mrc.ac.uk The Mouse Gene- Expression Information Resource Richard Baldock MRC Human Genetics Unit, Edinburgh http://genex.hgu.mrc.ac.uk/

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Page 1: MRC Human Genetics Unit  7-Feb-02Richard Baldock 1 The Mouse Gene-Expression Information Resource Richard Baldock MRC Human Genetics

7-Feb-02Richard Baldock

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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/

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

11.5-day old mouse embryo

How does

this embryo develop?

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

in situ hybridization data

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

Image capture

James Sharpe et al, Science 296(2002)541-545

Optical Projection Tomography

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

Flourescent Double Labelling

Blue - HNF3b

Green - neurofilament

Red - autoflourescence of heart

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

mouse E12.5 nasal region Msx1 mRNA, net

Words are not enough -

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

spatial indexing

gene expression database

Semi-automatic image mapping

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Bioinformatics frameworks

gene expressionmutant phenotype

cell behaviour

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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

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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

?

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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

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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

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Image - Model embryos

Time (E days)

Theiler Stage

Birth

1 2 12 13 14 26 27

1 8 8.5 9 18

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

Model embryos

images of serial, stained sections

stacked and aligned

….to produce a 3D block

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

Voxels building blocks of the 3D models

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Text - Anatomy

Time (E days)

Theiler Stage

Birth

1 2 12 13 14 26 27

1 8 8.5 9 18

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

Resolution of the vocabulary

Jonathan Bard, Matt Kaufman

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

Voxels Pigeon-holes in a spatial database

anatomical name

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

Mapping anatomy to the models

• comprehensive

• exclusive

• not detailed

Renske Brune

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MRC Human Genetics Unit www.hgu.mrc.ac.uk

EMAP: Spatio-Temporal Framework for Developmental Biology

Iconic SymbolicSpace

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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

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anatomical name

gene expression

mutant phenotype

cell behaviour

bibliographic references

Using the Atlas: gene-expression database

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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

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Staging and Other data

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MGI/GXD

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Mouse Atlas - EMAP & EMAGE

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Tools

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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