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Journal of Bacteriology, October 2009, p. 6262-6272, Vol. 191, No. 20
0021-9193/09/$08.00+0     doi:10.1128/JB.00475-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Comparative Genomics, Network-Based Approach to Understanding Virulence in Vibrio cholerae{triangledown} ,{dagger}

Jianying Gu,1,{ddagger}* Yufeng Wang,2,3,{ddagger} and Timothy Lilburn4*

Department of Biology, City University of New York, Staten Island, New York 10314,1 Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249,2 South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, Texas 78249,3 Department of Bacteriology, American Type Culture Collection, Manassas, Virginia 201104

Received 7 April 2009/ Accepted 31 July 2009

Our views of the genes that drive phenotypes have generally been built up one locus or operon at a time. However, a given phenotype, such as virulence, is a multilocus phenomenon. To gain a more comprehensive view of the genes and interactions underlying a phenotype, we propose an approach that incorporates information from comparative genomics and network biology and illustrate it by examining the virulence phenotype of Vibrio cholerae O1 El Tor N16961. We assessed the associations among the virulence-associated proteins from Vibrio cholerae and all the other proteins from this bacterium using a functional-association network map. In the context of this map, we were able to identify 262 proteins that are functionally linked to the virulence-associated genes more closely than is typical of the proteins in this strain and 240 proteins that are functionally linked to the virulence-associated proteins with a confidence score greater than 0.9. The roles of these genes were investigated using functional information from online data sources, comparative genomics, and the relationships shown by the protein association map. We also incorporated core proteome data from the family Vibrionaceae; 35% of the virulence-associated proteins have orthologs among the 1,822 orthologous groups of proteins in the core proteome, indicating that they may be dual-role virulence genes or encode functions that have value outside the human host. This approach is a valuable tool in searching for novel functional associations and in investigating the relationship between genotype and phenotype.

* Corresponding author. Mailing address for Jianying Gu: Biology Department, 65-126, 2800 Victory Blvd., College of Staten Island/CUNY, Staten Island, NY. Phone: (718) 982-4123. E-mail: guj{at}mail.csi.cuny.edu. Mailing address for Timothy Lilburn: Bacteriology, ATCC, 10801 University Boulevard, Manassas, VA. Phone: (703) 365-2700. Fax: (703) 334-2931. E-mail: tlilburn{at}atcc.org

{triangledown} Published ahead of print on 7 August 2009.

{dagger} Supplemental material for this article may be found at http://jb.asm.org.

{ddagger} J.G. and Y.W. contributed equally to this work.

Journal of Bacteriology, October 2009, p. 6262-6272, Vol. 191, No. 20
0021-9193/09/$08.00+0     doi:10.1128/JB.00475-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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