OME: An Open Image Informatics Solution for Biological Microscopy Jason Swedlow

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OME:

An Open Image Informatics Solution for Biological Microscopy

Jason Swedlow

Wellcome Trust Biocentre

University of Dundee

Dundee, Scotland j.swedlow@dundee.ac.uk

Jigna

Patel

Ana

Amores

Paul

Andrews

Elena

Knatko

Markus

Posch

Guennadi

Khoudoli

Iain

Porter

Andrea

Falconi

Jean-Marie

Burel

Chris

Allan

Arwen

Wilcock

Mairead

Murnion

Melpi

Platani

Karen

Duncan

An Informatics Continuum

GAATTCCCAAATCAAGGAGAGATACTTAGACCTAGCTAATAGCGACAGGATGAGGTTCAAAACTCTCCTTTTTAAATGATGACTAAAATAAAGACAATCGAAAGAAAAAATACATAGACAACAAAACCACAA

GAAGATGAAGATGGAGGAGGAAGGCAAAAAAGTGCCAGCAAGCTGGGTGTGGTGGTAAACAGTAATGCTAGAACTTGGGTGAAGGATCAAGTTGTCTAGGCCATTCATTGCAGGAAAAGTTATTTTCCTATT

TTCAGTCACAAAGTGAGCTCACATCCCCTTCACCTGTGCTCTCAAACTGTCACTGCTTCACCCCAAAATTGTAGCAGCTTTCCTCAATCTGCCTACACTGGCCAATCACATTAACAAAAATCAGACTACAGG

AAGCTATTCCAAGAACACCCCTGCCTTTACCAACCTTGGCCACGGGGTGAAGCTGTAAAGGGGGTCATGAAATGGAAGCTACTATACTTACACGGCATTAGAGTTCTCAAATACAATGCCATTTATCTTAGT

TGTGTAATCACCATGTTAAGACATGAATCCGCTGGGACTCTGCCTGTTCTGAGAAAGAGAAACAAAACAAAACAAAAAACAATTTTTGCCATTGCATTGTTGGCAAAAAGGCCACATCTCAGGGCAAATGGT

TGAGAATTATGAGGAATGTTTAGTTCTGCCTTACATGGACTTTACTTGAACCCCGCCCGGACTTACAGACGTTTTTAATGTGGTTAGATGAGAACCATGCTTAACTGCTTTCCTATCCCTCACTCAGGCTTT

CCTCAAGGAACAGAGTTTAGCTGCGCACACTTAATAAGGCAGTATTTCTTTTCCAAGAAAATGGTGCAAACTTGACCTTACAATTCTCCAAAGGCACTCAAGGTTTATTTACTCAATTTCTCTATATTCTCT

GAGATGCCCAAGCTGTTAAGTGGTTCAGTATTACAGCGCTTTTTCAGGGAATGTGGGCGGCCCTGAGAAGGGCCTTTGGTTAGAAAATACAAATTAAAAAAGTCTTAGCCGCCGAATCCGTAGAGGGTGCGG

CCCTGGCGCTTGAGCGCGTAGACCACGTCCATGGCGGTGACGGTCTTGCGCTTGGCGTGCTCCGTGTAGGTGACGGCGTCGCGGATCACGTTCTCCAGGAACACCTTCAGCACACCGCGGGTCTCCTCGTAG

ATGAGGCCGGAGATGCGCTTCACTCCCCCGCGCCGGGCCAGGCGGCGGATGGCGGGCTTGGTGATGCCCTGGATGTTATCGCGGAGAACCTTACGGTGGCGCTTAGCGCCGCCTTTGCCCAGGCCTTTTCCT

CCCTTGCCGCGACCCGACATGTCTTAGGAAGAATGGAAAATGGAGTCAGAGCTGAGAGTCGGTCCTTTATATAGCTGCTTGGCCTTGATCTCCCACCCCCAACAGAATCACACAAACGAAAACCCGCCCGCC

GGACGGTGACGTCATAAACCCCGCCAATAAGACCTGGCGGGAAAGAACCGAAAGCGCCCGGGCGGGAAAGTGACGTCACAAATCCCTCCCATCAACCATGCCCCGAAAGCGCGCCGGCGGGAAAATGACATC

ACAAACCCCGCCCCTCAGCCAAGACCCGAAAGCGCGCCGGCGGGAAAGCGACATCAGTGATCCCTCCTCTCAGCCATGCCGGGAAAGACGCAAAAGCCCGCCGGCGGGAAAGTGACTTCACAAATTCCGCCC

CTCAGTCACGACCAGAAAGCGCGCCGGCGGGAAAGTGATGTCACATATCTCGCCCATCAGCCCCGCCCCGAAAGCCGGACGGCGGGAAAAGTGACATCACAGACCCCTCTCTGGATCGGAGCCCTTTAAGGA

CCGAAAGCCTGCGAGCAGGTCACGTCAGAGATCCGACCCGTACATTTTACGCATATTCCACGGGTAAAACCAGACACTCAGTTGACCTATTTTGTACTTGATATCAACTTTGGGCTGTTATAAACTCAAGTT

TTGGGGAATATCCACCGTTATAGACACTAGGGAACATATAGGTTCGTTTAAGGATGGAGTAAATTACAGCCATTTTACTTGAAATCGTGTGTGGCTCTGAAAAGAGCCTTTGGTTAATTCCGTAGAACTGTA

CGGAACTGTACAATTACGCCCTCTCCCCGCGGATGCGGCGGGCCAGTTGGATGTCCTTGGGCATGATGGTGACACGCTTGGCGTGGATGGCGCACAGGTTGGTGTCCTCAAACAGACCCACAAGGTAGGCCT

CACAGGCCTCCTGCAGAGCCATGACGGCCGAGCTCTGGAAGCGCAGGTCGGTCTTGAAGTCCTGCGCGATCTCGCGCACCAGGCGCTGGAACGGCAGCTTGCGGATCAGCAGCTCGGTCGACTTCTGGTAGC

GCCGGATCTCGCGCAGCGCCACGGTGCCGGGACGGTAGCGGTGAGGCTTCTTCACGCCGCCGGTGGCCGGGGCGCTCTTGCGGGCGGCCTTGGTAGCCAGCTGCTTACGCGGGGCCTTGCCACCGGTGGACT

TGCGAGCGGTCTGCTTAGTACGAGCCATAGCAAAAACTAGAAAGCAAGCGGGTGAGCACTTGGAGATGGTGAGTTCAGAACTACTATTTATAGTATGCAAAGGATAGTGATTGGATGAAAATACTGGTTATC

TGTGACGTTTAAGACTCTGATTGGTTTATGTTTAAGAACTGCAGTTGAGGCTAAGGTAGTCTGCCGCGGTACTTATTTTTGTATGTGTGTGTTTTAAAGTAAATGGAATAAAATTCCAGTGACTGTTATCTT

CTACAGCACATCTGCTTCCAAACACATTGCAGCTTGAACTTAGTGGCATTGAAGAATAGAGAACAATCTTGTTATCTTCATTATTGAAATGTAAGAATGTGACTTCTACATTGAAGGAGAGTAGGCCAGATT

CTACCTTTTGATTGGTTTACTGCCTTTCGTAAATAGCCACTAAAACAGCAGATTTAGAACTCTTCATTTGCGTGGAAAGTCTCCATTTTGTTGCAACCCACACTGTAAAGAAATGGAGAGAAACATGGGAGT

AAAAGTTACAGACGTCTGACTCGGGTTATTCTGAGCATTTCTTCATTAAATGGCTGTACTTGTATGGATGCTTTCAGTTCTTGCATTTGGAGCTTGAATTTTCAAAATACTTTCACGCATTTTTGGCCAGAT

ATCACTGATACGTTCGAAAACAATTTTTTAACTATAAACTATAGAAATCGTCATAGCATGTTAGGATTGCACTTTTAAATTCTTTTAAAAAAAAAAATGGGCAAGACTTTCCCAGAGCTATTGTGTACTTGC

ATATCCTGGGAAAAGTCGTGTCCTGCCTTTTCTCTTTTTATTTGAGCCACTACTGGCTCACAATATGAAATCACTGTCGCAAGCTGACACTCCTTAAAAGAACACTAAGCCTCTTGCATAACTAATATATAA

AGTAACGATACATTGCTCCCATTACTGCCAAGAATCAATACTGAAACCCGCAGAGAAGGCCCACAAGCTGGCTTTCTGGGTTTTAATTGACTAATTTACAGCCACCTTTCACTAGTTGAGCTCCTTTTTGAT

AGGCATCTACCACTTTCTGATGATAAAACAGGAGAGTACAAGGAGAATCTGCTGTGGTTGAAATTCCACCTCAAGCAGCCAGCCGGAGAAGTTTTGAGGCCGCCTCCTCTACCTGCAAAAACACGAAGCTAG

GTCGGTGGAATCGCAAAGGAGTTAGTTTCTGAAATCTTGCAGGCAGACAGGCGCACGGGAGGCGGGGCCTTAGGGTCCAGGGGGCGGGCGTTAGCATTCACCAATCACAGCACAGCACTGCTCTATAAATAC

TCCGTGCAGGGGCCTTGTCTTTCTACTTCTTTTCTTCGTCTTGGGTATAGCTGTTGTTTATTCATCAGCGACCATGTCGGAGACGGCGCCAGTCGCTCAGGCTGCTTCTACTGCCACGGAGAAACCTGCTGC

TGCAAAGAAGACCAAGAAGCCGGCAAAAGCTGCCGCTCCTCGGAAGAAGCCCGCGGGACCTTCGGTGTCGGAGCTCATCGTGCAGGCAGTTTCTTCTTCCAAAGAGCGCAGTGGCGTGTCCTTGGCCGCGCT

CAAGAAGTCGCTGGCTGCGGCGGGATACGATGTGGAGAAGAACAACAGCCGCATCAAACTGGGGCTGAAAAGCCTGGTGAATAAAGGCACACTGGTGCAGACCAAGGGCACCGGCGCTGCTGGCTCTTTTAA

GCTGAACAAGAAGGCTGAGTCCAAGGCCATCACCACCAAGGTGTCAGTGAAGGCGAAAGCATCCGGGGCTGCTAAGAAACCTAAGAAGACTGCTGGGGCTGCAGCTAAGAAGACTGTCAAGACTCCGAAGAA

GCCCAAGAAGCCTGCAGTTTCCAAGAAGACTTCCAAGAGCCCCAAGAAGCCGAAGGTGGTGAAGGCCAAGAAGGTAGCCAAAAGCCCTGCCAAGGCGAAGGCAGTGAAGCCTAAGGCTTCCAAGGCGAAAGT

GACAAAGCCAAAGACCCCAGCTAAGCCCAAGAAGGCAGCGCCCAAGAAAAAGTGAACAGTTGGAGGCTTCTTCTATAACCCAACGGCTCTTTTCAGAGCCACCAACATAACTCAAAGAGCCTGACACTTGTT

TCACACTATAACAACTGCATTTGGGTACAAGCCTGGTGGGATTTAGGCATTATTAATTTCCCCCAGTAAACTGACAATTTGGGTCAGTCTAGTTTCTAGTTTTATTTCCCTGAGATTCTGGGAAAACAGCCT

TGTTAGCCCTGGGAGGCGCTACCCTCTCCAGGTGTGGTGGATAAGCTCTCTATGGTATGGTAGTGCAATGGCCTGGGTGCCTCAACCAGATAAGGTCCTATTTTGCCAATGAGGATGAGAACTCAGGTGCTT

GATCAGTAAGAGTGGGCTGCAGCAAGGGTTCACATGCAATAGAGTTTTTTTTGTTTGTTTTTTTAGGGGGGGGGGGGCCGAGACCGGTTTCTCAGTGTAGCCCTGACTGTCCTTGAACTCACTCTAGACCAG

GCTGGCCTTGAACTAAGAAATCCGCCTGCCTCTGCAGTGCTGGAATTAAAGGCGAACGCCACCACGCCCGGCTGCAATAGTTTTTTTAATTCAAGCCCACCAAGACTGTTCCTTACAGGAATGCTAGGTGCT

TGGAGGCTTGGTTTTGTGAGGAAGTGGTTATCTCCCATGTACTGCAATGTTCACAGGCAGCTCTTGAAGCCTTTATTGATTTTTGCTAAGTAGCCACTTTTGTCCCTGCATTGATCCTCCTTCCTCCAAAGA

GCTAGAGTTAACGCCCCACACCGTGATTTGCTGGGCTCCCTTATTCTGAGCTCAGTTTTTAAATTATTGGGGGTGGGGGGATTGTCTGGAAGTTGAGGGGCAACTTGAAATTGGTTCTCTTCCACTACTTGA

GTCCAGGAGACTAGTTAAAGTCATCAGGCTTGGCGGCAAGTTCCTCTTACTCTGAGTGTCTTCTGGCCCTGAATTTAACTTTGTTGTCCTCTTTCAACAAAAAATTAGAAAACCAAGTGTCTGAGGCGATTG

GCCTGTTATCTCAAGTACACAGGAGGCCAAAGTAGTTTGGACTTCCTGAATTC

An Informatics Continuum

Live HeLa Cell

GFP-coilin

YFP-histone H2B

Platani et al (2002) Nature Cell Biol. 4:502-508

An Informatics Continuum

25

20

15

10

5

0

-3 -2.6 -2.2 -1.8 -1.4

-1 -0.6 -0.2

0.2

0.6

1 1.4

1.8

2.2

log D

Log D

Control (N = 250)

Sodium Azide (N = 103)

Platani et al (2002) Nature Cell Biol. 4:502-508

Image Informatics-- The Dirty Laundry

Ctrl Sodium Azide

Towards Image Informatics

What to Save?

Image File

Towards Image Informatics

What to Save?

Experiment-

Cells

Experiment-

Protocol

Acquisition

System

File-

Structure

File-

Image

File-

Display

Processing--

Images

Processing--

Results

Processing

History

Measurements Tracking ……

Proposal:

• Store images, metadata, and analytic results in a

single relational database

• Make an interface for easy access from desktop

for processing and analysis

• Apply query and mining tools on database for discovery

Applications:

• Discovery and analysis of cellular structure & dynamics

• Cell-based HTS of small molecule libraries

Open Microscopy Environment

• Relational database for digital microscope images &

informatics

• Open system that specifies database architecture

& interface

• Designed to promote platform & package

independent access to data

• Open source code (modeled after Linux; licensed

under LGPL)

• Allows database mining and querying

• Promotes IP for digital image screening and informatics http://www.openmicroscopy.org

OME Academic Collaborators:

Jason Swedlow, University of Dundee

Peter Sorger, MIT

Ilya Goldberg, NIH

Erik Brauner, Harvard Medical School, ICCB

Gaudenz Danuser, ETH Zurich

Commercial Partners

Applied Precision, Inc.

Universal Imaging, Corp.

Carl Zeiss Vision, Inc.

Olympus, Inc.

Improvision, Inc. Leica Microsystems

Chroma Technology Corp. Omega Optical

Intelligent Imaging SVision, LLC

Innovations, Inc.

http://www.openmicroscopy.org

OME-- An Image Informatics Solution!!!!

Visualisation

Querying

Open source

Wrapper

API

Acquisition

Transformation

OME

Storage

Analysis http://www.openmicroscopy.org

Cell based screening:

Nuclear Import Screen: Yan Feng, Harvard ICCB

Milestones Achieved in OME 1.0

• Successful integration of acquired image data,

analysis and relational database

• Use of querying tools for analysis of images from

time-lapses studies and cell-based screens

• Established use of relational database as interface

between proprietary files and legacy code http://www.openmicroscopy.org

What’s in OME 2.0

• XML File Schema:

http://www.openmicroscopy.org/docs.html

¸ Image data (pixels)

¸ Metadata (acquisition info, image stats, etc.)

¸ Complete transformation and analysis history

Swedlow et al (2003) Science 300:100-104

OME XML File Schema:

http://www.openmicroscopy.org/docs.html

Swedlow et al (2003) Science 300:100-104

What’s in OME 2.0

• XML File Schema:

http://www.openmicroscopy.org/docs.html

• An Updated SVG-based Image Viewer

Swedlow et al (2003) Science 300:100-104

What’s in OME 2.0

• XML File Schema:

http://www.openmicroscopy.org/docs.html

• An Updated SVG-based Image Viewer

• Use of Semantic Typing for Data Storage & Manipulation

¸ Support for analysis steps and paths

¸ Multiple levels of attributes

¸ Extensibility of database schema

Swedlow et al (2003) Science 300:100-104

An Informatics Continuum

Live HeLa Cell

GFP-coilin

YFP-histone H2B

Platani et al (2002) Nature Cell Biol. 4:502-508

Diffusion measurements by FRAP

CB

WF/CCD Microscope +

10 mW solid state laser @ 488 nm

Nucleoplasm

Operational record

• Each analysis result has an associated data-dependency tree

– Encodes exactly which modules and intermediate results were used to calculate a given piece of data.

– Provides the precise description of an analysis result

– In most cases, obviates the need for an external, agreed “standard”

Swedlow et al (2003) Science 300:100-104

Analysis chains

• Analysis modules perform small computations

• Modules linked together into analysis chains to perform larger, more useful computations

Swedlow et al (2003) Science 300:100-104

Analysis chains

• Inputs, outputs, and links are all strongly semantically typed

• Semantic types define the way in which modules can link together

Swedlow et al (2003) Science 300:100-104

Analysis chains

• Any directed acyclic graph (DAG) is a valid analysis chain

• Of course, a more complex graph is entirely possible

(and likely):

Swedlow et al (2003) Science 300:100-104

Extensibility in OME

• New semantic types and analysis modules can be added to OME

– Both are defined by an

XML specification

– Database tables used to store metadata are derived from XML spec

– New modules can refer to existing types, allowing them to link to existing modules

Swedlow et al (2003) Science 300:100-104

OME Design and Use

Open Microscopy Environment

Jason Swedlow (Dundee)

Andrea Falconi

Jean-Marie Burel

Chris Allan

Ilya Goldberg (NIH)

Josiah Johnson

Erik Brauner (Harvard Med)

Peter Sorger (MIT)

Brian Hughes

Doug Creager

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