Mouse Atlas Project Research Articles

Emergence of structure in mouse embryos: Structural Entropy morphometry applied to digital models of embryonic anatomy.

We apply an information‐theoretic measure to anatomical models of the Edinburgh Mouse Atlas Project. Our goal is to quantify the anatomical complexity of the embryo and to understand how this quantity changes as the organism develops through time. Our measure, Structural Entropy, takes into account the geometrical character of the intermingling of tissue types in the embryo. It does this by a mathematical process that effectively imagines a point‐like explorer that starts at an arbitrary place in the 3D structure of the embryo and takes a random path through the embryo, recording the sequence of tissues through which it passes. Consideration of a large number of such paths yields a probability distribution of paths making connections between specific tissue types, and Structural Entropy is calculated from this (mathematical details are given in the main text). We find that Structural Entropy generally decreases (order increases) almost linearly throughout developmental time (4–18 days). There is one `blip’ of increased Structural Entropy across days 7–8: this corresponds to gastrulation. Our results highlight the potential for mathematical techniques to provide insight into the development of anatomical structure, and also the need for further sources of accurate 3D anatomical data to support analyses of this kind.

Towards Ontology-Based Integration of Biomedical Atlases

Medical imaging in clinical analysis has been the subject of significant research for many years. In many cases scan images like CT scan and MRI scan may compliment physical examinations. Linking these scan images to biomedical atlases is fundamental to facilitate analysis. Biomedical atlas provides mapping between the graphical model and the ontology. Mapping from one atlas to another corresponding atlas is complex when it involves atlases from different model organisms. For example, having a general accepted nomenclature for the components of mouse embryo which is in parallel with the human atlas nomenclature provide an efficient means for analysis and modeling in biomedicine. However, this lead to interoperability issue. Therefore, taking the advantage of Semantic Web, Intelligent Agents and Ontology, this project starts with research linking imaging data of mouse embryo MRI to a standard canonical mouse atlas as designed in Edinburgh Mouse Atlas Project and also research on spatial rules to identify matching regions in atlases and images.

Cyberinfrastructure for the digital brain: spatial standards for integrating rodent brain atlases.

Biomedical research entails capture and analysis of massive data volumes and new discoveries arise from data-integration and mining. This is only possible if data can be mapped onto a common framework such as the genome for genomic data. In neuroscience, the framework is intrinsically spatial and based on a number of paper atlases. This cannot meet today's data-intensive analysis and integration challenges. A scalable and extensible software infrastructure that is standards based but open for novel data and resources, is required for integrating information such as signal distributions, gene-expression, neuronal connectivity, electrophysiology, anatomy, and developmental processes. Therefore, the International Neuroinformatics Coordinating Facility (INCF) initiated the development of a spatial framework for neuroscience data integration with an associated Digital Atlasing Infrastructure (DAI). A prototype implementation of this infrastructure for the rodent brain is reported here. The infrastructure is based on a collection of reference spaces to which data is mapped at the required resolution, such as the Waxholm Space (WHS), a 3D reconstruction of the brain generated using high-resolution, multi-channel microMRI. The core standards of the digital atlasing service-oriented infrastructure include Waxholm Markup Language (WaxML): XML schema expressing a uniform information model for key elements such as coordinate systems, transformations, points of interest (POI)s, labels, and annotations; and Atlas Web Services: interfaces for querying and updating atlas data. The services return WaxML-encoded documents with information about capabilities, spatial reference systems (SRSs) and structures, and execute coordinate transformations and POI-based requests. Key elements of INCF-DAI cyberinfrastructure have been prototyped for both mouse and rat brain atlas sources, including the Allen Mouse Brain Atlas, UCSD Cell-Centered Database, and Edinburgh Mouse Atlas Project.

EMAP/EMAPA ontology of mouse developmental anatomy: 2013 update

BackgroundThe Edinburgh Mouse Atlas Project (EMAP) ontology of mouse developmental anatomy provides a standard nomenclature for describing normal and mutant mouse embryo anatomy. The ontology forms the core of the EMAP atlas and is used for annotating gene expression data by the mouse Gene Expression Database (GXD), Edinburgh Mouse Atlas of Gene Expression (EMAGE) and other database resources.FindingsThe original EMAP ontology listed anatomical entities for each developmental stage separately, presented as uniparental graphs organized as a strict partonomy. An "abstract" (i.e. non-stage-specific) representation of mouse developmental anatomy has since been developed. In this version (EMAPA) all instances for a given anatomical entity are presented as a single term, together with the first and last stage at which it is considered to be present. Timed-component anatomies are now derived using staging information in the "primary" non-timed version. Anatomical entities are presented as a directed acyclic graph enabling multiple parental relationships. Subsumption classification as well as partonomic and other types of relationships can now be represented. Most concept names are unique, with compound names constructed using standardized nomenclature conventions, and alternative names associated as synonyms.ConclusionsThe ontology has been extended and refined in a collaborative effort between EMAP and GXD, with additional input from others. Efforts are also underway to improve the revision process with regards to updating and editorial control. The revised EMAPA ontology is freely available from the OBO Foundry resource, with descriptive information and other documentation presented in associated Wiki pages (http://www.obofoundry.org/wiki/index.php/EMAPA:Main_Page).

Coupling Existing Client and Server Software for Integrating Waxholm Space

Event Abstract Back to Event Coupling Existing Client and Server Software for Integrating Waxholm Space Richard Baldock1*, Daren Lee2, Seth Ruffins2 and Arthur Toga2 1 MRC, Western General Hospital, Human Genetic Unit and IGMM, United Kingdom 2 University of California Los Angeles, Laboratory of Neuro Imaging, United States The INCF Digital Atlasing Infrastructure (DAI) task force is developing a canonical three-dimensional representation of the mouse brain called Waxholm Space or WHS. The WHS model is based on high resolution (21µm3 isotropic voxels) T1, T2 and T2* MRI scans and 3D registered Nissl stained serial sections of a single C57Bl/6 male adult mouse brain. In addition to these image volumes, an indexed label image of segmented brain regions has also been generated to sub-divide the model brain. This data set acts as common space for mapping features, properties and the distribution of molecules in the brain. Such mappings results allow WHS to be a common spatial framework for accessing multiple mouse brain resources. Software for accessing and delivering online image databases have been developed independently of the INCF DAI. Rather than construct new tools de novo, straight forward extensions to the WoolzIIP server and MBAT have been written to accommodate WHS. The MouseBIRN project at LONI-UCLA and EMAP (Edinburgh Mouse Atlas Project) at the MRC-Human Genetics Unit, have brought together MBAT (MouseBIRN Atlasing Toolkit) and Woolz IIP server (a modified version of the Internet Imaging Protocol server) to deliver the the five image volumes comprising WHS mouse brain model. The Woolz IIP server allows rapid navigation and interaction with the model brain image within MBAT without the user having to download the entire set of image volumes to their local computer. MBAT’s viewer permits the user to display the model data concurrently with images from the local file system and/or other online resources. MBAT also allows registration of 2D images to the WHS model allowing the user to explore their data in the context of other resources mapped to WHS. Conference: Neuroinformatics 2010 , Kobe, Japan, 30 Aug - 1 Sep, 2010. Presentation Type: Poster Presentation Topic: Digital atlasing Citation: Baldock R, Lee D, Ruffins S and Toga A (2010). Coupling Existing Client and Server Software for Integrating Waxholm Space. Front. Neurosci. Conference Abstract: Neuroinformatics 2010 . doi: 10.3389/conf.fnins.2010.13.00133 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 18 Jun 2010; Published Online: 18 Jun 2010. * Correspondence: Richard Baldock, MRC, Western General Hospital, Human Genetic Unit and IGMM, Edinburgh, United Kingdom, sruffins@loni.ucla.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Richard Baldock Daren Lee Seth Ruffins Arthur Toga Google Richard Baldock Daren Lee Seth Ruffins Arthur Toga Google Scholar Richard Baldock Daren Lee Seth Ruffins Arthur Toga PubMed Richard Baldock Daren Lee Seth Ruffins Arthur Toga Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Representation of coordinate reference systems for the rodent brain in the INCF Digital Atlasing Infrastructure

Representation of coordinate reference systems for the rodent brain in the INCF Digital Atlasing Infrastructure

The Edinburgh Mouse Atlas Project: Data Mapping and Spatial Organisation

The Edinburgh Mouse Atlas Project: Data Mapping and Spatial Organisation

A high-resolution anatomical ontology of the developing murine genitourinary tract

Cataloguing gene expression during development of the genitourinary tract will increase our understanding not only of this process but also of congenital defects and disease affecting this organ system. We have developed a high-resolution ontology with which to describe the subcompartments of the developing murine genitourinary tract. This ontology incorporates what can be defined histologically and begins to encompass other structures and cell types already identified at the molecular level. The ontology is being used to annotate in situ hybridisation data generated as part of the Genitourinary Development Molecular Anatomy Project (GUDMAP), a publicly available data resource on gene and protein expression during genitourinary development. The GUDMAP ontology encompasses Theiler stage (TS) 17–27 of development as well as the sexually mature adult. It has been written as a partonomic, text-based, hierarchical ontology that, for the embryological stages, has been developed as a high-resolution expansion of the existing Edinburgh Mouse Atlas Project (EMAP) ontology. It also includes group terms for well-characterised structural and/or functional units comprising several sub-structures, such as the nephron and juxtaglomerular complex. Each term has been assigned a unique identification number. Synonyms have been used to improve the success of query searching and maintain wherever possible existing EMAP terms relating to this organ system. We describe here the principles and structure of the ontology and provide representative diagrammatic, histological, and whole mount and section RNA in situ hybridisation images to clarify the terms used within the ontology. Visual examples of how terms appear in different specimen types are also provided.

Providing visualisation support for the analysis of anatomy ontology data

BackgroundImprovements in technology have been accompanied by the generation of large amounts of complex data. This same technology must be harnessed effectively if the knowledge stored within the data is to be retrieved. Storing data in ontologies aids its management; ontologies serve as controlled vocabularies that promote data exchange and re-use, improving analysis.The Edinburgh Mouse Atlas Project stores the developmental stages of the mouse embryo in anatomy ontologies. This project is looking at the use of visual data overviews for intuitive analysis of the ontology data.ResultsA prototype has been developed that visualises the ontologies using directed acyclic graphs in two dimensions, with the ability to study detail in regions of interest in isolation or within the context of the overview. This is followed by the development of a technique that layers individual anatomy ontologies in three-dimensional space, so that relationships across multiple data sets may be mapped using physical links drawn along the third axis.ConclusionUsability evaluations of the applications confirmed advantages in visual analysis of complex data. This project will look next at data input from multiple sources, and continue to develop the techniques presented to provide intuitive identification of relationships that span multiple ontologies.

Integrating partonomic hierarchies in anatomy ontologies

BackgroundAnatomy ontologies play an increasingly important role in developing integrated bioinformatics applications. One of the primary relationships between anatomical tissues represented in such ontologies is part-of. As there are a number of ways to divide up the anatomical structure of an organism, each may be represented by more than one valid partonomic (part-of) hierarchy. This raises the issue of how to represent and integrate multiple such hierarchies.ResultsIn this paper we describe a solution that is based on our work on an anatomy ontology for mouse embryo development, which is part of the Edinburgh Mouse Atlas Project (EMAP). The paper describes the basic conceptual aspects of our approach and discusses strengths and limitations of the proposed solution. A prototype was implemented in Prolog for evaluation purposes.ConclusionWith the proposed name set approach, rather than having to standardise hierarchies, it is sufficient to agree on a suitable set of basic tissue terms and their meaning in order to facilitate the integration of multiple partonomic hierarchies.

The informatics of a C57BL/6J mouse brain atlas.

The Mouse Atlas Project (MAP) aims to produce a framework for organizing and analyzing the large volumes of neuroscientific data produced by the proliferation of genetically modified animals. Atlases provide an invaluable aid in understanding the impact of genetic manipulations by providing a standard for comparison. We use a digital atlas as the hub of an informatics network, correlating imaging data, such as structural imaging and histology, with text-based data, such as nomenclature, connections, and references. We generated brain volumes using magnetic resonance microscopy (MRM), classical histology, and immunohistochemistry, and registered them into a common and defined coordinate system. Specially designed viewers were developed in order to visualize multiple datasets simultaneously and to coordinate between textual and image data. Researchers can navigate through the brain interchangeably, in either a text-based or image-based representation that automatically updates information as they move. The atlas also allows the independent entry of other types of data, the facile retrieval of information, and the straight-forward display of images. In conjunction with centralized servers, image and text data can be kept current and can decrease the burden on individual researchers' computers. A comprehensive framework that encompasses many forms of information in the context of anatomic imaging holds tremendous promise for producing new insights. The atlas and associated tools can be found at http://www.loni.ucla.edu/MAP.

Symposium on Computer Modelling for Anatomists and Clinicians

The following review articles are based on presentations given at a Symposium on Computer Modelling for Anatomists and Clinicians held in July 1997 at the Department of Anatomy, University of Edinburgh. The Symposium formed part of the Summer Meeting of the Anatomical Society of Great Britain and Ireland. There were 6 invited speakers, and 4 of these have produced review articles which are published in this issue of the Journal. In 3 of the presentations, recent advances in the use of 3D methodology to analyse mouse and human developmental anatomy were described. The reviews by Kaufman et al. and Baldock et al. (the latter to be published in a forthcoming issue of the Journal) complement each other in that they describe different aspects of a collaborative project (the Mouse Atlas Project, or MAP) involving the preparation of a text database of mouse developmental anatomy and a digital Atlas of normal mouse development. In the first of these presentations the principles underlying the methodology employed to reconstruct a range of early post-implantation mouse embryos spanning the stages between the primitive streak and the early limb-bud that had previously been serially sectioned was briefly described. Because of the efficiency of the computer technology involved (termed the warping program), the grey level images of the embryo histology could be arbitrarily resectioned to view the embryo as if sectioned in any orientation. Furthermore, all anatomically-defined tissues could be individually delineated (or painted) and viewed either in isolation or in combination with other appropriately labelled tissues and organs.