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Talk 2 Baldock Atlas

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    Atlas-Based Bioinformatics

    Richard BaldockMRC Human Genetics Unit Institute of Genetics and Molecular MedicineEdinburgh, UK 

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    R A Baldock Dundee 2012 2

    eMouseAtlas - Development and Gene-Expression

    GENE EXPRESSION

    Carol Wicking, University of Queensland

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    eMouseAtlas - Development and Gene-Expression

    GENE EXPRESSION

    Carol Wicking, University of Queensland

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    eMouseAtlas - Development and Gene-Expression

    TRANSGENICS

    cre induced-LacZ expression

    W. Hsu, University of RochesterAcridine OrangeJ. Burns

    University of Bristol

    APOPTOSIS

    Sigolène MeilhacInstitut Pasteur

    CELL LINEAGE

    anti-BrdU staining J. McDearmid

      McGill University

    CELL DIVISION

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    R A Baldock Dundee 2012 2

    eMouseAtlas - Development and Gene-Expression

    TRANSGENICS

    cre induced-LacZ expression

    W. Hsu, University of RochesterAcridine OrangeJ. Burns

    University of Bristol

    APOPTOSIS

    Sigolène MeilhacInstitut Pasteur

    CELL LINEAGE

    anti-BrdU staining J. McDearmid

      McGill University

    CELL DIVISION

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    eMouseAtlas Framework 

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    eMouseAtlas Framework 

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    VPH

    Atlas-Based Infrastructures

    emage

    Population

    Organism

    Tissue

    Cell

    Organelle

    Molecule

    Basic research   Clinical practice

    Hudsen  Virtual

    Patient

    Personal

    Atlas

    Visible

    Human

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    eMouseAtlas

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    eMouseAtlas

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    eMouseAtlas

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    eMouseAtlas

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    EMAGE - current status

    ~22K submissions

    Range Theiler 7-25

    ! MGI/GXD (~1,300)! Direct submission (~300)

    ! Large scale screens (~16K)

    Repository DB: 38.4K entries

    submissionsThursday, 16 February 2012

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    EMAGE - current status

    ~22K submissions

    Range Theiler 7-25

    ! MGI/GXD (~1,300)! Direct submission (~300)

    ! Large scale screens (~16K)

    Repository DB: 38.4K entries

    submissionsThursday, 16 February 2012

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    EMAGE Embryo Space

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    EMAGE Embryo Space

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    EMAGE Embryo Space

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    BioAtlas - data mapping

    • image collection - no mapping all spatialinterpretation left to user

    • implicit mapping - data interpreted andannotated with controlled vocabulary or

    ontology, image requires interpretation butsome query and pattern analysis possible -

     “simple” 

    • explicit mapping, full spatial delineation ofinformation e.g. expression pattern.

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    BioAtlas - data mapping

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    BioAtlas - data mapping

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    BioAtlas - data mapping

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    Spatial Data Mapping

    • Manual tie-point alignment (WlzWarp)! mesh-based constrained distance transform

    ! interactive

    ! arbitrary complexity

    • Automated fine tuning (ITK/ANTS)

    • Editor review

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    3D Data Mapping - WlzWarp

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    3D Data Mapping - WlzWarp

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    3D Data Mapping - WlzWarp

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    3D Mapping - Wnt signalling pathway

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    3D Mapping - Wnt signalling pathway

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    3D Visualisation

    • Applications:! SectionBrowser, JAtlasViewer

    ! Format conversion -> a.n.other

    • Browser-Based! canned views & movies

    ! Tiled zoom-viewer

    ! Extended to 3D protocol (IIP3D)

    ! Multi-layer

    ! Interactive overlays

    ! WebGL

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    OME Project Objectives

    To use and extend OMERO to meet mouse atlas andIGMM requirements:

    •Embed woolz images

    •Sparse reconstruction & mapping•large image data

    •Annotation overlay and visualisation

    •3D mapping - e.g. OPT images

    •IGMM imaging - archiving and analysis

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    Woolz images

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    Woolz images

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    Woolz images

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    Woolz images

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    Woolz images

    • 330K lines Ansi C code

    • 184K lines application code

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    Woolz Images

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    Woolz Images

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    Woolz Images

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    Woolz Images

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    Woolz Images

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    Woolz Images

    • Arbitrary bounding box

    • Interval coding - compact• Fast binary & morphological operations

    • Separation of domain from values enables valuedata sharing

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    Woolz Images

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    Woolz Images

    • value types: ubyte, short, int, float,double, rgba, bitmap• Value table can be shared by manyobjects

    • Compact coding without compression• Iterators to navigate data• Tiled data can be memory mappedfor very fast access - minimal coding

    change

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    Woolz Images

    • value types: ubyte, short, int, float,double, rgba, bitmap• Value table can be shared by manyobjects

    • Compact coding without compression• Iterators to navigate data• Tiled data can be memory mappedfor very fast access - minimal coding

    change

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    Woolz image objects

    • Polylines, boundary lists• histograms

    • meshes - 2D & 3D

    • transforms! affine

    ! basis function

    ! mesh

    ! conforming mesh

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    Woolz image objects

    • Polylines, boundary lists• histograms

    • meshes - 2D & 3D

    • transforms! affine

    ! basis function

    ! mesh

    ! conforming mesh

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    Woolz image objects

    • Polylines, boundary lists• histograms

    • meshes - 2D & 3D

    • transforms! affine

    ! basis function

    ! mesh

    ! conforming mesh

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    Woolz image objects

    • Polylines, boundary lists• histograms

    • meshes - 2D & 3D

    • transforms! affine

    ! basis function

    ! mesh

    ! conforming mesh

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    Woolz image objects

    • Polylines, boundary lists• histograms

    • meshes - 2D & 3D

    • transforms! affine

    ! basis function

    ! mesh

    ! conforming mesh

    Thursday, 16 February 2012

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    Sparse Image Reconstruction & Mapping

    •EurExpress project

    ! 19.5K in situ probes, 350K images

    ! ~24 images per in situ probe

    ! ~0.5 micron resolution in plane

    ! 150 micron plane separation

    • EmbryoExpress - 20K images

    • Allen Brain Atlas - 200K images

    • Require automation - Advanced Normalisation Tool (ANTs)! sparse image, matching mask

    ! Full 3D affine then non-linear warping.

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    • Semi-automatic reconstruction

    • Automated segmentation

    •Manual mapping

    • 2D pseudo wholemount

    • full 3D in progress

    Pseudo Wholemount Mapping to Emap - done

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    P d Wh l M E d

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    • Semi-automatic reconstruction

    • Automated segmentation

    •Manual mapping

    • 2D pseudo wholemount

    • full 3D in progress

    Pseudo Wholemount Mapping to Emap - done

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    P d Wh l M i E d

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    • Semi-automatic reconstruction

    • Automated segmentation

    •Manual mapping

    • 2D pseudo wholemount

    • full 3D in progress

    Pseudo Wholemount Mapping to Emap - done

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    P d Wh l M i E d

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    • Semi-automatic reconstruction

    • Automated segmentation

    •Manual mapping

    • 2D pseudo wholemount

    • full 3D in progress

    Pseudo Wholemount Mapping to Emap - done

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    3D M i

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    3D Mapping to emap

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    3D M i

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    3D Mapping to emap

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    3D M i t

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    3D Mapping to emap

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    3D M i t

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    3D Mapping to emap

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    3D M i t

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    3D Mapping to emap

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    Large Image Data

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    Large Image Data

    • Single reconstructions already 30+GB• New EM embryo data ~0.5TB

    • OPT data - small (200MB) but many - 5K

    • Typical requirement to browse as sections• Require arbitrary angle re-sectioning

    • BLB - want to browse online using no more thata web-browser

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    Tiled Image Servers

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    Tiled Image Servers

    [maps.google.com]

    [Shawn Mikula, Issac Trotts, James M. Stone, and Edward G. Jones,Internet-Enabled High-

    Resolution Brain Mapping and Virtual Microscopy, Neuroimage, vol 35(1), p. 11, 2007]

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    Sectioning Parameters

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    Sectioning Parameters

    • Angles:

    ! Pitch, Yaw, Roll

    • Position:

    ! Fixed point (f) &distance

    • Scale

    • Tiling depends onorientation & scale

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    IIP3D Extensions

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    IIP3D - Extensions

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    IIP3D

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    IIP3D

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    IIP3DWeb App Architecture

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    IIP3D Web-App Architecture

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    IIP3DWeb App Architecture

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    IIP3D Web-App Architecture

    DB image server

    Remote Object

    protocol

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    Performance

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    Performance

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    Performance

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    Performance

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    IIP3D Clients

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    IIP3D Clients

    • Javascript! Ajax

    ! MVC design, uses MooTools & Yahoo Widgets

    • Multi-section at high resolution

    • Volume overlays

    • Anatomy & gene-expression overlays

    • Controls! viewing angles - virtual sections

    ! zoom

    ! distance, fixed point

    ! section locator & view angle feedback

    ! distance measurement, query by image value

    ! ......

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    Annotation Overlay & Visualisation

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    Annotation Overlay & Visualisation

    • Atlas models include ontology and domains -image regions for anatomical terms. Typicallyexclusive

    • Gene-expression data, open ended, multipleoverlapping patterns

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    Layers Overlays & Indexed Objects

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    Layers, Overlays & Indexed Objects

    • Multiple layers via html image overlay including opacity! currently layers constrained to identical domains

    • Regional overlays using an indexed object! currently using “compound object” - regions can overlap

    ! TBD - standard indexed volume - regions spatially exclusive

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    Image Processing IIP3D extensions

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    Image Processing IIP3D extensions

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    IIP3D Examples

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    IIP3D Examples

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    IIP3D Examples

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    IIP3D Examples

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    IIP3D Examples

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    IIP3D Examples

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    IIP3D Examples

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    IIP3D Examples

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    WebGL

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    •IIP3D viewer extension to 3D visualisation

    ! Use X3Dom - Javascript binding to X3D

    • navigation feedback

    • Anatomy visualisation! see demo

    • Extend to 4D

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    3D mapping - WlzWarp

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    R A Baldock Toshiba Medical Visualisation Systems Europe 21/4/11

    3D mapping WlzWarp

    •Allows placement of landmarks (points of

    equivalence) on source and target on volume

    renders instead of isosurfaces

    • On-the-fly feedback of warping progress

    • Uses constrained distance transform (CDT) inwarping• Woolz, Qt, Coin3D(+SIMVoleon)• Linux, OS X, Windoes

    • Open Source (Free!)

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    3D mapping - WlzWarp

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    R A Baldock Toshiba Medical Visualisation Systems Europe 21/4/11

    3D mapping WlzWarp

    •Allows placement of landmarks (points of

    equivalence) on source and target on volume

    renders instead of isosurfaces

    • On-the-fly feedback of warping progress

    • Uses constrained distance transform (CDT) inwarping• Woolz, Qt, Coin3D(+SIMVoleon)• Linux, OS X, Windoes

    • Open Source (Free!)

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    Lineage & the Brain

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    g

    •Embryo development 7-5-8.5 dpc

    • 11-fold growth of ectoderm cell layer

    • complex folding

    • lineage clones via HRP cell labelling(iontophoresis)

    • pattern recognition very difficult

    • conformal transform of ectodermal surface to “flat-map” 

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    Lineage & the Brain

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    g

    A Camus, K Lawson, W Hill et al

    Development 2011

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    Lineage & the Brain

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    g

    A Camus, K Lawson, W Hill et al

    Development 2011

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    eMouseAtlas

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    MRC Human Genetics Unit, Edinburgh 

    EMAGE:Chris Armit

    Shanmugasundaram VenkataramanLorna RichardsonPeter Stevenson

    EMAP:Albert Burger

    Bill HillNick BurtonYiya YangJulie MossLiz Graham

    Allyson Ross

    Duncan DavidsonRichard Baldock

    Other 

    Jonathan BardMatt Kaufman

    NIH GUDMAP:Simon Harding

    Bernard HaggertyKoosum Roochum

    BBSRC:Mike Wicks

    FP7 RICORDO:Xu Gu

    Wellcome OME:Jianguo Rao

    University of Edinburgh 

    Douglas ArmstrongNestor Milyeav

    Institute of Human Genetics, Newcastle University 

    Susan LindsayJanet Kerwin

    Colin SemplePedro Coutinho

    Ian Overton

    Heriot Watt University 

    Albert Burger


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