The mouse atlas database project

Lead Research Organisation: MRC Human Genetics Unit

Abstract

In the Edinburgh Mouse Atlas Project at the MRC Human Genetics Unit we have developed an on-line digital atlas describing how the mouse embryo develops from the single fertilized egg through to the fully developed embryo. The purpose is to support research into the mechanisms by which the genes control the development process and to provide a better understanding of congenital abnormalities and some cancers. The system provides a database that can be used by biomedical research to enable better use of data, more refined hypotheses and avoid repetition of lab experiments.||The emphasis for this project is the use of this resource for more extensive biomedical research on specific systems, in particular the development of the kidney and links to human development. In addition this cross-disciplinary programme involves novel work in image processing, databases and computing.

Technical Summary

The Edinburgh Mouse Atlas Project (EMAP) has developed a digital space and time framework to support the study of the genetic control of embryo development. This framework is now the de facto standard for mouse embryo and forms the basis of a number of gene-expression databases including the Edinburgh Mouse Atlas Gene Expression (EMAGE) database in the MRC Human Genetics Unit. This is an active and rapidly growing database of in situ gene-expression patterns at all stages of development in the mouse and allows researchers to submit, query and analyse data from many sources. In the first instance it acts as an index for gene-expression data and includes original data that would otherwise not be accessible. This means that data can be more easily be located and shared which will reduce experimental repetition. This resource is now in place, freely accessible and in regular use for research and teaching.||The programme we propose extends the existing framework with special emphasis on using the resource for translational research and studies. In particular we have established a series of collaborations to study all aspects of uro-genital development and to link the mouse-atlas databases to human data. This will mean that the data generated throughout the world on mouse embryogenesis can be used to support studies of clinical importance. The uro-genital programme of research is part of two large funded projects to capture, analyse and provide a database of data relevant to a deep understanding of the development process and the cause of mutations and abnormalities. The interoperability with human is through studies of the normal development at The Centre For Life, Newcastle, and on abnormal development here in the Human Genetics Unit.||To support this research we are formalising and extending the existing framework to enable more sophisticated and complex query, interoperability and automated workflow. For this we are using the emerging semantic web and grid infrastructures to allow secure interoperability, data management and virtual organisations. In addition we undertake original research on the image processing and data mapping aspects of the problem.||Finally, with the new computational techniques we will extend the atlas framework to higher resolution in space and time with better understanding of biological space in the context of the database.

Publications

10 25 50

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Armit C (2012) eMouseAtlas, EMAGE, and the spatial dimension of the transcriptome. in Mammalian genome : official journal of the International Mammalian Genome Society

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Baldock R (2005) Anatomical ontologies: names and places in biology. in Genome biology

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Baldock R (2001) The Edinburgh Mouse Atlas: using the CD. in Briefings in bioinformatics

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Baldock RA (2012) Biomedical atlases: systematics, informatics and analysis. in Advances in experimental medicine and biology

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Baldock RA (1997) 3-D Reconstructions for graphical databases of gene expression in Seminars in cell & developmental biology

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Baldock RA (1993) Video camera calibration for optical densitometry. in Journal of microscopy

 
Description High Performance Computing (HPC)
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
 
Description High Throughput sequencing provision for the UK
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
 
Description BBSRC Longer and Larger (LoLa) Grant (A three-dimensional atlas of gene expression during chick development with cross comparisons to the mouse)
Amount £364,900 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2008 
End 01/2012
 
Description FP7 Health - EUCOMMTOOLS
Amount £20,000 (GBP)
Funding ID 261492 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start  
 
Description FP7 Health - I-DCC (The International Data Coordination Centre)
Amount £80,000 (GBP)
Funding ID 223592 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 01/2009 
 
Description FP7 VPH - RICORDO
Amount £170,000 (GBP)
Funding ID 248502 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 10/2010 
End 09/2012
 
Description GUDMAP
Amount £450,000 (GBP)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 09/2010 
End 08/2011
 
Description GUDMAP 2
Amount £1,890,634 (GBP)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 10/2011 
End 09/2016
 
Description GUDMAP programme supplement
Amount $192,700 (USD)
Funding ID 3U01DK092983-03S1 
Organisation National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
Sector Public
Country United States
Start 08/2013 
End 07/2014
 
Description Human Brain Project
Amount £300,000 (GBP)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 09/2006 
End 08/2011
 
Description MRC Capacity Building Studentship
Amount £500,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2008 
End 09/2013
 
Description Nociceptive GenitoUrinary Development Molecular Anatomy Projects (nGUDMAP) (U01)
Amount $230,000 (USD)
Funding ID 1U01DK101037-01 
Organisation National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
Sector Public
Country United States
Start 12/2013 
End 08/2015
 
Description Nociceptive GenitoUrinary Development Molecular Anatomy Projects (nGUDMAP) (U01)
Amount $280,000 (USD)
Funding ID 1U01DK101036-01 
Organisation National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
Sector Public
Country United States
Start 12/2013 
End 08/2015
 
Description OME Infrastructure
Amount £176,862 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2011 
End 03/2015
 
Description PhenoImageShare BBSRC Bioinformatics and Biological Resources
Amount £308,599 (GBP)
Funding ID BB/K020021/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 11/2013 
End 11/2016
 
Description Wellcome Trust Strategic Award
Amount £16,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Title OPT Scanning scrtipts 
Description Upgrade to scanning software for the original OPT research machines to provide Mac OSX support and higher resolution imaging. 
Type Of Material Improvements to research infrastructure 
Year Produced 2009 
Provided To Others? Yes  
Impact Better more efficient OPT scanning and reconstruction. 
 
Title Spatial Data Analysis 
Description Techniques and software for spatial data comparison. Available as software and as an online service to query the database and pre-canned analyses. 
Type Of Material Improvements to research infrastructure 
Year Produced 2007 
Provided To Others? Yes  
Impact Widely used by the biological community via the emage gene-expression database query interfaces. 
 
Title WlzIIP 
Description A novel extension of an existing open source software to deliver arbitrary section views through 3D data using Web 2.0 style interfaces. 
Type Of Material Improvements to research infrastructure 
Year Produced 2009 
Provided To Others? Yes  
Impact Significant number of collaborations - University Edinburgh, NIMR, Sanger and others. Now used in teaching at Edinburgh University. 
 
Title eMouseAtlas 
Description The research has resulted in a major international database of mouse embryo atlas models, ontologies and a large data set of spatially mapped in situ gene-expression patterns 
Type Of Material Biological samples 
Year Produced 2006 
Provided To Others? Yes  
Impact The e-MouseAtlas website and emage database are internationally recognised as key bioinformatics and biological data resource. 
URL http://www.emouseatlas.org
 
Title eMouseAtlas CD-ROM 
Description Digital 3D mouse atlas models and software 
Type Of Material Biological samples 
Year Produced 2006 
Provided To Others? Yes  
Impact Many CDs have been distributed (on request) and have been used for research and teaching purposes. 
 
Title Chick Atlas of Development 
Description A 3D atlas of chick development coupled with a gene-expression database. 
Type Of Material Database/Collection of data 
Year Produced 2011 
Provided To Others? Yes  
Impact Used very widely for analysing gene-expression data in the chick and provides a standard for the staging of chick embryos. 
URL http://www.echickatlas.org
 
Title Edinburgh Mouse Atlas Database 
Description The pioneer gene-expression database based on full 3D models of mouse anatomy with data spatially mapped onto each stage of development. The database provides the standard reference for the mouse developmental anatomy, has defined the mouse developmental ontology and holds a major collection of all the gene-expression data collected throughout the world. 
Type Of Material Database/Collection of data 
Provided To Others? Yes  
Impact Major impacts across mouse development research, define the standards for such database and the technical developments have led to many similar databases for other species including human, chick and zebrafish. 
URL http://www.emouseatlas.org
 
Title Genito-urinary developmental molecular atlas (GUDMAP) 
Description A major international project funded by NIH/NIDDK to build a molecular map of the development of the genito-urinary system. 
Type Of Material Database/Collection of data 
Year Produced 2007 
Provided To Others? Yes  
Impact The primary database focussed on genito-urinary development and a heavily used resource for the research and clinical research community. 
URL http://www.gudmap.org
 
Description Albert Burger 
Organisation Heriot-Watt University
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborative research, student supervision, publications, presentations.
Collaborator Contribution Computational research, MSc and PhD students, contributions to research project management and external funding, collaboration with EU funded and BBSRC funded projects.
Impact Publications, students, funded research programmes, funded studentship programmes. Projects: ARGUDAS (BBSRC Project) ARGUDAS - Argumentation-based Data Sharing Across Gene Expression Databases - October 2009 - February 2011; - MRC HGU is a collaborator; - work on argumentation systems to deal with inconsistenct data within and across databases; - EMAGE provides a central use case to this project; ----------------------------------------------------------------------------- Sealife (EU Project) Sealife - A Semantic Grid Browser for the Life Sciences Applied to the Study of Infectious Diseases - EU Project Reference: IST-2006-027269 - April 2006 - March 2009 - MRC HGU is a collaborator - working with HWU: semantic description of EMAP and EMAGE web services, AI planning for workflow using gene expression examples, argumentation systems for gene expression databases (incl. EMAGE); leads to follow-up project ARGUDAS; ----------------------------------------------------------------------------- REWERSE (EU Project) Reasoning on the Web with Rules and Semantics - EU funded Network of Excellence; - HWU partner, MRC HGU collaborator; - EMAP/EMAGE provide use cases for Bioinformatics Semantic Web studies; ============================================================================= - MRC HGU supported SWAT4LS 2008 and SWAT4LS 2009 workshops (www.swat4ls.org) - Dr. Burger co-chair for both workshops ============================================================================= PhD projects relating to Mouse Atlas research: - current PhD students: Kenneth McLeod - Argumentation in bioinformatics; Karen Sutherland - AI planning-based task composition for biologists Rosely Bin Kumoi - Multi-Agent Systems Planning and Distributed Query Processing in Bioinformatics. Nurzi Juana Binti Mohd Zaizi - Interoperability of Biomedical Atlases Negin Moghim - Interoperability of Digital Brain Atlases - past PhD students: Aba-Sah Dadzie: 2D and 3D visualisation of anatomy ontologies - graduated December 2007. Kostas Karasavvas: Adjustable Autonomy in Multi-Agent Systems in Bioinformatics - graduated December 2006;.
 
Description Chick Atlas 
Organisation University College London
Department Biosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Part of a multi-site project to develop a chick atlas database of gene-expression.
Collaborator Contribution Collaboration contributing to publications and analysis.Collaboration and co-fundingCollaboration and analysis
Impact For the first query (Chick Atlas collaboration): This funded collaboration has arisen from our earlier collaborations. Thus far, the outcomes of the project include 1. a publication describing standardized methods used for 3D gene expression assays (*pmid: 18355805*) and 2. an infrastructure for co-ordinating the generation of gene expression data relating to signalling centres in the chick embryo and submitting this data to a database with an Internet accessible submission interface based on the Mouse Atlas EMAGE DB. This is now in production mode. There is also a second manuscript recently submitted.
Start Year 2008
 
Description Chick Atlas 
Organisation University of Bath
Department Department of Biology and Biochemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Part of a multi-site project to develop a chick atlas database of gene-expression.
Collaborator Contribution Collaboration contributing to publications and analysis.Collaboration and co-fundingCollaboration and analysis
Impact For the first query (Chick Atlas collaboration): This funded collaboration has arisen from our earlier collaborations. Thus far, the outcomes of the project include 1. a publication describing standardized methods used for 3D gene expression assays (*pmid: 18355805*) and 2. an infrastructure for co-ordinating the generation of gene expression data relating to signalling centres in the chick embryo and submitting this data to a database with an Internet accessible submission interface based on the Mouse Atlas EMAGE DB. This is now in production mode. There is also a second manuscript recently submitted.
Start Year 2008
 
Description Chick Atlas 
Organisation University of Edinburgh
Department The Roslin Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Part of a multi-site project to develop a chick atlas database of gene-expression.
Collaborator Contribution Collaboration contributing to publications and analysis.Collaboration and co-fundingCollaboration and analysis
Impact For the first query (Chick Atlas collaboration): This funded collaboration has arisen from our earlier collaborations. Thus far, the outcomes of the project include 1. a publication describing standardized methods used for 3D gene expression assays (*pmid: 18355805*) and 2. an infrastructure for co-ordinating the generation of gene expression data relating to signalling centres in the chick embryo and submitting this data to a database with an Internet accessible submission interface based on the Mouse Atlas EMAGE DB. This is now in production mode. There is also a second manuscript recently submitted.
Start Year 2008
 
Description Euregene 
Organisation European Commission
Department EC FP6 Collaborative Projects
Country European Union (EU) 
Sector Academic/University 
PI Contribution We designed, implemented and maintain the Kidney Atlas database which is the principal means by which the data from this project are integrated and presented, apart from conventional publications.
Collaborator Contribution PLEASE NOTE that this entry describes the Kidney Atlas Component of the Euregene Project and was supported by only a proportion of the financial contribution given above (see entry by Prof Hastie HGU). The collaboration has enabled us to develop a graphical, 3D Kidney Atlas, which will form a key part of our e-Mouse Atlas. The project also contributed gene expression data that will form part of our systems-level analysis of gene expression.
Impact The gene expression and mutant phenotype data from the consortium, presented and integrated of data by Kidney Atlas database, plays an important part in the discovery and application of mouse models of human kidney disease. Please see www.euregene.org.
 
Description GUDMAP 
Organisation Harvard University
Department Department of Molecular and Cellular Biology
Country United States 
Sector Academic/University 
PI Contribution We jointly built an extended anatomy ontology for the developing genitourinary system with Prof M. Little, University of Queensland, Australia Publication 17452023. We are responsible for the design, implementation and maintenance of the GUDMAP database which presents all data generated by consortium members on a public website to view, query, and download. The Edinburgh group of this consortium (see above) is also responsible for curating the gene expression data entered into this database.
Collaborator Contribution At the scientific level, this project, together with the EuReGene project, has provided detailed gene expression data for the kidney and other parts of the genitourinary system that will support our core interest in systems-level analysis of gene expression. The consortium helped us to develop the genitourinary part of the e-Mouse Atlas anatomy ontology, providing the most detailed developmental anatomy of the genitourinary tract yet published (publication 17452023). At the technical level, the substantial resources funded by GUDMAP allowed us to solve a number of database and interface problems (publication 18287559). The benefits have been carried through to the EMAGE database using the more limited resources available from core MRC funding (publication 19767607). WITHIN the GUDMAP consortium we lead the 'Edinburgh Group' which is itself a collaboration with Prof. Jamie Davies in the Department of Integrative Physiology at the University of Edinburgh. Prof Davies group curates the gene expression data coming from GUDMAP collaborators. The GUDMAP curators work closely with EMAGE curators so that we have jointly benefited by increasing curation expertise in EMAGE and more specifically by jointly articulating generic standard formats for gene expression metadata.
Impact The GUDMAP database is the leading source of gene expression data for the developing genitourinary system in the mouse. Please see www.gudmap.org. The data presented in this database will be important for our understanding of the molecular pathways involved in GU development and function. It will provide information crucial to the discovery and use of mouse models of human genitourinary diseases. This collaboration has now attracted further funding $600,000 to extend for one year and we have submitted a grant proposal ($3M) for a further five years.
 
Description INCF 
Organisation International Neuroinformatics Coordinating Facility
Country Sweden 
Sector Multiple 
PI Contribution INCF - International Neuroinformatics Coordination Facility - actively involved in the standardisation of brain digital atlases; - Prof. Baldock member of the Oversight Committee of the Digital Atlasing Programme; - Dr. Burger member of Waxholm Space Task Force, Digital Atlasing Infrastructure Task Force, and the Representation and Deployment Task Force of the Program on Ontologies of Neural Structures; - first INCF Digital Atlas Infrastructure Hub developed for EMAP/EMAGE;
Collaborator Contribution Collaboration on standards for interoperable spatial frameworks such as atlases.
Impact Reports and standards recommendations. EMAP/EMAGE INCF Digital Atlas Hub providing the key interoperability layer. RA Baldock invited as a program committee member for the major international conference and as a speaker.
Start Year 2009
 
Description International Mouse Phenotype Consortium (IMPC) 
Organisation MRC Harwell
Country United Kingdom 
Sector Academic/University 
PI Contribution I am on the Scientific Advisory Panel for this project but also collaborate directly with the MRC Harwell group.
Collaborator Contribution MRC Harwell have provided access to specific atlas models in use within IMPC and examples data sets for developing the prototype ePhenotype interface.
Impact No outputs yet
Start Year 2016
 
Description Limb Atlas Project 
Organisation Medical Research Council (MRC)
Department MRC National Institute for Medical Research (NIMR)
Country United Kingdom 
Sector Public 
PI Contribution Delivered software resources, support and extended visualisation tools for user access to the atlas models.
Collaborator Contribution Developed special systems (limb) spatial atlases for the mouse embryo, helped extend the user interface software in terms of function and utility.
Impact http://www.nimr.mrc.ac.uk/3dlimb/ Pubmed: 17452023
Start Year 2006
 
Description NeSC and BIRN 
Organisation University of Edinburgh
Department School of Informatics Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Long standing collaboration with development of mouse atlas tools and resources, extension to other species, import and delivery of the UK BIRN node.
Collaborator Contribution Development of e-Science aspect of the mouse atlas databases, multiple collaborative projects, donation of the BIRN node equipment to HGU, provision of conferencing and meeting room facilities for medium scale meetings.
Impact This long-standing collaboration has resulted in a number of funded projects and software development. This include a number of publications.
 
Description Newcastle University, Institute Human Genetics. 
Organisation Newcastle University
Department Institute of Human Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution Long standing collaboration to develop and extend the atlases, team contributions via software development, resources, expertise, publications. This funded collaboration continues and will be extended by further joint funding.
Collaborator Contribution Long standing collaboration to develop a human embryo atlas and gene-expression database.
Impact Website, databases and publications.
 
Description Sanger Knock-out LacZ Project 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Preliminary work to capture LacZ expression patterns in mouse embryo.
Collaborator Contribution Collaboration to forge links between the gene-expression and mouse atlas databases and the knock-out mouse consortium databases and the mouse phenotype data. Sanger provides the embryo material for imaging at HGU.
Impact Output so far is a proof of principle and a proposed pilot project (Sanger funded) to investigate in more detail the capture of the reporter expression patterns. This may lead to a funded collaboration to capture medium-scale data that integrates emage with Knock-out Mouse Consortia Databases.
Start Year 2009
 
Title Optical Projection Tomography 
Description Development of a novel microscopy imaging technique 
IP Reference US2006093200 
Protection Patent granted
Year Protection Granted 2006
Licensed Commercial In Confidence
Impact OPT machines are currently being produced and marketed by MRCT.
 
Description Online video presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The mouse atlas programme funded a video and graphics student to prepare and deliver a number of videos showing aspects of the developmental process.

Online videos.
Year(s) Of Engagement Activity 2006,2007,2008,2009