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Atlas-Based Bioinformatics
Richard BaldockMRC Human Genetics Unit Institute of Genetics and Molecular MedicineEdinburgh, UK
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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
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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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
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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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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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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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