Open Access Highly Accessed Methodology article

Evading the annotation bottleneck: using sequence similarity to search non-sequence gene data

Michael J Gilchrist1*, Mikkel B Christensen1, Richard Harland2, Nicolas Pollet3, James C Smith1, Naoto Ueno4 and Nancy Papalopulu5

Author Affiliations

1 The Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge University, Cambridge, CB2 1QN, UK

2 University of California, Berkeley, Department of Molecular & Cell Biology, Life Sciences Addition #3200, Berkeley, CA 94720-3200, USA

3 Epigenomics Project, Genopole, CNRS, Univ Evry, Tour Evry2 10eme 523 Terrasses de l'Agora, F-91034 Evry, France; CNRS UMR 8080, F-91405 Orsay, France

4 Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Aichi 444-8585, Japan

5 Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

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BMC Bioinformatics 2008, 9:442  doi:10.1186/1471-2105-9-442

Published: 17 October 2008



Non-sequence gene data (images, literature, etc.) can be found in many different public databases. Access to these data is mostly by text based methods using gene names; however, gene annotation is neither complete, nor fully systematic between organisms, and is also not generally stable over time. This provides some challenges for text based access, especially for cross-species searches. We propose a method for non-sequence data retrieval based on sequence similarity, which removes dependence on annotation and text searches. This work was motivated by the need to provide better access to large numbers of in situ images, and the observation that such image data were usually associated with a specific gene sequence. Sequence similarity searches are found in existing gene oriented databases, but mostly give indirect access to non-sequence data via navigational links.


Three applications were built to explore the proposed method: accessing image data, literature and gene names. Searches are initiated with the sequence of the user's gene of interest, which is searched against a database of sequences associated with the target data. The matching (non-sequence) target data are returned directly to the user's browser, organised by sequence similarity. The method worked well for the intended application in image data management. Comparison with text based searches of the image data set showed the accuracy of the method. Applied to literature searches it facilitated retrieval of mostly high relevance references. Applied to gene name data it provided a useful analysis of name variation of related genes within and between species.


This method makes a powerful and useful addition to existing methods for searching gene data based on text retrieval or curated gene lists. In particular the method facilitates cross-species comparisons, and enables the handling of novel or otherwise un-annotated genes. Applications using the method are quick and easy to build, and the data require little maintenance. This approach largely circumvents the need for annotation, which can be a major obstacle to the development of genomic scale data resources.