Research article

Probabilistic annotation of protein sequences based on functional classifications

Emmanuel D Levy^1,3 , Christos A Ouzounis¹ , Walter R Gilks² and Benjamin Audit^1,4

¹Computational Genomics Group, The European Bioinformatics Institute, EMBL Cambridge Outstation, Cambridge CB10 1SD, UK

²Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge CB2 2SR, UK

³Computational Genomics Group, MRC Laboratory of Molecular Biology, Hills Rd, Cambridge CB2 2QH, UK

⁴Laboratoire Joliot-Curie and Laboratoire de Physique, CNRS UMR5672, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cedex 07, France

author email corresponding author email

BMC Bioinformatics 2005, 6:302doi:10.1186/1471-2105-6-302

Published:	14 December 2005

Abstract

Background

One of the most evident achievements of bioinformatics is the development of methods that transfer biological knowledge from characterised proteins to uncharacterised sequences. This mode of protein function assignment is mostly based on the detection of sequence similarity and the premise that functional properties are conserved during evolution. Most automatic approaches developed to date rely on the identification of clusters of homologous proteins and the mapping of new proteins onto these clusters, which are expected to share functional characteristics.

Results

Here, we inverse the logic of this process, by considering the mapping of sequences directly to a functional classification instead of mapping functions to a sequence clustering. In this mode, the starting point is a database of labelled proteins according to a functional classification scheme, and the subsequent use of sequence similarity allows defining the membership of new proteins to these functional classes. In this framework, we define the Correspondence Indicators as measures of relationship between sequence and function and further formulate two Bayesian approaches to estimate the probability for a sequence of unknown function to belong to a functional class. This approach allows the parametrisation of different sequence search strategies and provides a direct measure of annotation error rates. We validate this approach with a database of enzymes labelled by their corresponding four-digit EC numbers and analyse specific cases.

Conclusion

The performance of this method is significantly higher than the simple strategy consisting in transferring the annotation from the highest scoring BLAST match and is expected to find applications in automated functional annotation pipelines.