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Nucleic Acids Research 2005 33(8):2521-2530; doi:10.1093/nar/gki545
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Published online 2 May 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

Nebulon: a system for the inference of functional relationships of gene products from the rearrangement of predicted operons

Sarath Chandra Janga, Julio Collado-Vides and Gabriel Moreno-Hagelsieb1,*

Program of Computational Genomics, CCG-UNAM Apdo Postal 565-A, Cuernavaca, Morelos, 62100 Mexico 1Department of Biology, Wilfrid Laurier University 75 University Avenue West, Waterloo, ON, N2L 3C5 Canada

*To whom correspondence should be addressed. Tel: (519) 884-0710 ext 2364; Fax: (519) 746-0677; Email: gmoreno{at}wlu.ca

Received March 2, 2005. Revised March 23, 2005. Accepted April 13, 2005.

Since operons are unstable across Prokaryotes, it has been suggested that perhaps they re-combine in a conservative manner. Thus, genes belonging to a given operon in one genome might re-associate in other genomes revealing functional relationships among gene products. We developed a system to build networks of functional relationships of gene products based on their organization into operons in any available genome. The operon predictions are based on inter-genic distances. Our system can use different kinds of thresholds to accept a functional relationship, either related to the prediction of operons, or to the number of non-redundant genomes that support the associations. We also work by shells, meaning that we decide on the number of linking iterations to allow for the complementation of related gene sets. The method shows high reliability benchmarked against knowledge-bases of functional interactions. We also illustrate the use of Nebulon in finding new members of regulons, and of other functional groups of genes. Operon rearrangements produce thousands of high-quality new interactions per prokaryotic genome, and thousands of confirmations per genome to other predictions, making it another important tool for the inference of functional interactions from genomic context.


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