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Computational genetics

Bioinformatics beyond sequence: mapping gene function in the embryo

Nature Reviews Genetics volume 2, pages 409–417 (2001)Cite this article

Key Points

  • The concept of a bioinformatic framework is exemplified by sequence databases. DNA sequences provide a one-dimensional framework to which additional information concerning structure and function can be added.

  • Additional frameworks are being developed, such as controlled vocabularies and ontologies, so that information about gene expression and function can be indexed and compared between experiments and between organisms.

  • Frameworks are being developed at many levels of biological organization, such as gene sequence, protein structure, metabolic pathway and organism.

  • Organism-level frameworks are essential for comparison of gene expression and function in development. Such frameworks can be textual or can be digital spatio-temporal models of development.

  • One such framework is being constructed by the Edinburgh Mouse Atlas Project (EMAP). Additional frameworks are being developed in other model systems, such as zebrafish.

  • EMAP at present provides a reference framework to identify and name parts of the embryo, and a framework to which gene expression data can be mapped. This allows comparisons to be made between gene expression patterns.

  • Future goals of this work will be to map other types of data, such as phenotypic data on mouse mutants, and to integrate data with similar frameworks in other model systems.

Abstract

The spatio-temporal expression pattern of a gene during development is a valuable piece of information. But there is no way to compare precisely the patterns of expression of different genes, or the way the patterns are changed in a mutant. One way to solve this problem is to construct digital reference images of development (a bioinformatics framework), to which expression patterns can be mapped and stored, then compared. Such frameworks are under active development in several model systems. They will form the basis of powerful and integrated gene expression databases, which facilitate comparisons between genes, tissues and species.

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Figure 1: Genomic sequence as a framework.
Figure 2: Textual anatomical frameworks.
Figure 3: EMAP model embryos.
Figure 4: Integrating anatomical names with development in time and space in an atlas framework.
Figure 5: The zebrafish atlas.
Figure 6: The deployment of framework data.
Figure 7: Mapping gene expression data to a framework.

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Acknowledgements

The Edinburgh Mouse Atlas Project (EMAP) is a collaboration between D.D. and R.B. at the MRC Human Genetics Unit and M. Kaufman and J. Bard at the Department of Biomedical Sciences, University of Edinburgh. EMAP has been advised by networks with grants from the European Science Foundation and the Wellcome Trust. We thank the FlyBase and the WormBase consortiums for permission to use material from these databases and V. Hartenstein, R. Jacobs, F. Verbeek and T. Strachan for sharing information about work in progress.

Author information

Authors and Affiliations

  1. MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK

    Duncan Davidson & Richard Baldock

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Supplementary information

Three-dimensional model of mouse stage 12 embryo.

Model embryos in the EMAP Atlas can be viewed in section or as three-dimensional movies that highlight particular anatomical structures to show their spatial relationships and developmental changes. This movie shows a Theiler stage 12 embryo (embryonic day (E)8.0). Two tissues have been highlighted; the remaining tissue domains and the underlying histological structure are hidden from view (orange, neural tissue; translucent, surface ectoderm).

Three-dimensional model of mouse stage 13 embryo.

Model embryos in the EMAP Atlas can be viewed in section or as three-dimensional movies that highlight particular anatomical structures to show their spatial relationships and developmental changes. This movie shows a Theiler stage 13 embryo (E8.5). Two tissues have been highlighted; the remaining tissue domains and the underlying histological structure are hidden from view (orange, neural tissue; translucent, surface ectoderm).

Related links

Related links

DATABASE LINKS

Wnt2

Msx2

Msx1

FURTHER INFORMATION

FlyBase

FlyBase vocabulary

Gene Ontology (GO) Consortium

Mouse Genome Informatics Database

Saccharomyces Genome Database

Mouse Genome Informatics Gene Expression Database

The Edinburgh Mouse Atlas Project

EMAP: anatomy

Jackson Laboratory

μMRI Mouse Atlas

Zebrafish development

The Multidimensional Human Embryo

FlyBrain

Multimodal brain atlases

Mouse Brain Library

Brain Molecular Anatomy Project

Mouse Brain Atlas

Rat Brain Atlas

Zebrafish Atlas

Two-dimensional images of parts of the fly

EMAP:GXD Query interface

OMIM

TBASE

Dysmorphic Human–Mouse Homology Database

The Mouse Gene Expression Information Resource

Window from FlyBase

WormBase

FlyBase: anatomy

GenBank

SWISS-PROT

CATH — Protein Structure Classification

KEGG — Kyoto Encyclopedia of Genes and Genomes

EcoCyc — Encyclopedia of E. coli Genes and Metabolism

The stages of Xenopus embryonic development

NCBI taxonomy

Chick development

MGI: anatomy

Human Developmental Anatomy Centre

Human developmental anatomy

Glossary

CONTROLLED VOCABULARY

A list of permitted terms that can be used to describe data: for example, radius, forelimb and bone.

ONTOLOGY

A collection of terms that describe concepts, entities and their relationships: for example, the 'radius' is part of the 'forelimb' or the 'radius' is an instance of 'bone'.

DIRECTED ACYCLIC GRAPH

A graph of relationships between objects in which any object can have more than one parent, each link is directional and cyclical relationships are prohibited.

THEILER STAGE

Stages of development of the mouse embryo determined by particular developmental events: for example, eye closure or appearance of digits.

XML FORMAT

The eXtensible Markup Language (XML) is related to HyperText Markup Language (HTML) and is an emerging standard for structuring documents.

OBJECT-ORIENTATED

The term used to describe a programming design in which all data are regarded as parts of objects that hold both the data and the procedures or methods that can be applied to that data. This encapsulation enforces good programming practice and makes code more portable.

CORBA

Common object request broker architecture is an industrial standard protocol for making objects, both data and methods, accessible over the Internet for remote access and invocation. If a database provides a CORBA interface then it is CORBA-compliant.

JAVA

An object-orientated language developed by Sun Microsystems that has become a standard for programs delivered as part of World Wide Web documents.

VOXEL

A digital image is represented as an array of image values, either as a grey-level or colour. A voxel is the term for one value in a three-dimensional array for a three-dimensional image.

MORPHOMETRIC

A measure of shape.

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Davidson, D., Baldock, R. Bioinformatics beyond sequence: mapping gene function in the embryo . Nat Rev Genet 2, 409–417 (2001). https://doi.org/10.1038/35076500

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