Author:
Bannert C,Welfle A,aus dem Spring C,Schomburg D
Abstract
Abstract
Background
Models for the simulation of metabolic networks require the accurate prediction of enzyme function. Based on a genomic sequence, enzymatic functions of gene products are today mainly predicted by sequence database searching and operon analysis. Other methods can support these techniques: We have developed an automatic method "BrEPS" that creates highly specific sequence patterns for the functional annotation of enzymes.
Results
The enzymes in the UniprotKB are identified and their sequences compared against each other with BLAST. The enzymes are then clustered into a number of trees, where each tree node is associated with a set of EC-numbers. The enzyme sequences in the tree nodes are aligned with ClustalW. The conserved columns of the resulting multiple alignments are used to construct sequence patterns. In the last step, we verify the quality of the patterns by computing their specificity. Patterns with low specificity are omitted and recomputed further down in the tree. The final high-quality patterns can be used for functional annotation. We ran our protocol on a recent Swiss-Prot release and show statistics, as well as a comparison to PRIAM, a probabilistic method that is also specialized on the functional annotation of enzymes. We determine the amount of true positive annotations for five common microorganisms with data from BRENDA and AMENDA serving as standard of truth. BrEPS is almost on par with PRIAM, a fact which we discuss in the context of five manually investigated cases.
Conclusions
Our protocol computes highly specific sequence patterns that can be used to support the functional annotation of enzymes. The main advantages of our method are that it is automatic and unsupervised, and quite fast once the patterns are evaluated. The results show that BrEPS can be a valuable addition to the reconstruction of metabolic networks.
Publisher
Springer Science and Business Media LLC
Subject
Applied Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Structural Biology
Reference24 articles.
1. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol 1990, 215: 403–410.
2. Rost B: Enzyme function less conserved than anticipated. J Mol Biol 2002, 318: 595–608. 10.1016/S0022-2836(02)00016-5
3. Scheeff ED, Fink JL: Fundamentals of protein structure. In Structural Bioinformatics. Edited by: Bourne PE, Weissig H. Hoboken, Wiley-Liss Inc; 2003:15–39.
4. Bornberg-Bauer E, Beaussart F, Kummerfeld SK, Teichmann SA, Weiner J: The evolution of domain arangements in proteins and interaction networks. Cell Mol Life Sci 2005, 62: 435–445. 10.1007/s00018-004-4416-1
5. Attwood TK: The role of pattern databases in sequence analysis. Brief Bioinform 2000, 1(1):45–59. 10.1093/bib/1.1.45
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