Bioinformatics, Vol 15, 391-412, Copyright © 1999 by Oxford University Press
MA Andrade, NP Brown, C Leroy, S Hoersch, A de Daruvar, C Reich, A Franchini, J Tamames, A Valencia, C Ouzounis and C Sander
MOTIVATION: Large-scale genome projects generate a rapidly increasing
number of sequences, most of them biochemically uncharacterized. Research
in bioinformatics contributes to the development of methods for the
computational characterization of these sequences. However, the
installation and application of these methods require experience and are
time consuming. RESULTS: We present here an automatic system for
preliminary functional annotation of protein sequences that has been
applied to the analysis of sets of sequences from complete genomes, both to
refine overall performance and to make new discoveries comparable to those
made by human experts. The GeneQuiz system includes a Web-based browser
that allows examination of the evidence leading to an automatic annotation
and offers additional information, views of the results, and links to
biological databases that complement the automatic analysis. System
structure and operating principles concerning the use of multiple sequence
databases, underlying sequence analysis tools, lexical analyses of database
annotations and decision criteria for functional assignments are detailed.
The system makes automatic quality assessments of results based on prior
experience with the underlying sequence analysis tools; overall error rates
in functional assignment are estimated at 2.5-5% for cases annotated with
highest reliability ('clear' cases). Sources of over-interpretation of
results are discussed with proposals for improvement. A conservative
definition for reporting 'new findings' that takes account of database
maturity is presented along with examples of possible kinds of discoveries
(new function, family and superfamily) made by the system. System
performance in relation to sequence database coverage, database dynamics
and database search methods is analysed, demonstrating the inherent
advantages of an integrated automatic approach using multiple databases and
search methods applied in an objective and repeatable manner. AVAILABILITY:
The GeneQuiz system is publicly available for analysis of protein sequences
through a Web server at http://www.sander.ebi.ac. uk/gqsrv/submit
ARTICLES
Automated genome sequence analysis and annotation
European Bioinformatics Institute (EBI), Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK.
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