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Bioinformatics Advance Access published online on November 11, 2004

Bioinformatics, doi:10.1093/bioinformatics/bti135
Bioinformatics © Oxford University Press 2004; all rights reserved
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Received December 19, 2003
Revised October 18, 2004
Accepted November 2, 2004

Article

Predicting fold novelty based on ProtoNet hierarchical classification

Ilona Kifer 1, Ori Sasson 2, and Michal Linial 3*

1 Department of Biological Chemistry, Institute of Life Sciences, Jerusalem 91904, Israel; School of Computer Science and Engineering, The Hebrew University, Jerusalem 91904, Israel
2 School of Computer Science and Engineering, The Hebrew University, Jerusalem 91904, Israel
3 Department of Biological Chemistry, Institute of Life Sciences, Jerusalem 91904, Israel

* To whom correspondence should be addressed.
Michal Linial, E-mail: michall{at}cc.huji.ac.il


   Abstract

Motivation: Structural genomics projects aim to solve a large number of protein structures with the ultimate objective of representing the entire protein space. The computational challenge is to identify and prioritise a small set of proteins with new, currently unknown superfamilies or folds.

Results: We develop a method that assigns each protein a likelihood of it belonging to a new, yet undetermined structural superfamily. The method relies on a variant of ProtoNet, an automatic hierarchical classification scheme of all protein sequences from SwissProt. Our results show that proteins that are remote from solved structures in the ProtoNet hierarchy are more likely to belong to new superfamilies. The results are validated against SCOP releases from recent years that account for about half of the solved structures known to date. We show that our new method and the representation of ProtoNet are superior in detecting new targets, compared to our previous method using ProtoMap classification. Furthermore, our method outperforms PSI-BLAST search in detecting potential new superfamilies.

Availability: An interactive tool implementing this method, named ProTarget is available at http://www.protarget.cs.huji.ac.il. It can be used interactively to retrieve a list of candidate proteins for Structural Genomics projects.

Supplement: Supplementary material is available at http://www.protarget.cs.huji.ac.il/supplement.


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