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Journal of Clinical Microbiology, April 2005, p. 1807-1817, Vol. 43, No. 4
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.4.1807-1817.2005

System To Assess Genome Sequencing Needs for Viral Protein Diagnostics and Therapeutics

Shea N. Gardner,^* Thomas A. Kuczmarski, Carol E. Zhou, Marisa W. Lam, and Tom R. Slezak

Lawrence Livermore National Laboratory, P.O. Box 808, L-174, Livermore, California 94551

Received 23 February 2004/ Returned for modification 8 May 2004/ Accepted 15 December 2004

Computational analyses of genome sequences may elucidate protein signatures unique to a target pathogen. We constructed a Protein Signature Pipeline to guide the selection of short peptide sequences to serve as targets for detection and therapeutics. In silico identification of good target peptides that are conserved among strains and unique compared to other species generates a list of peptides. These peptides may be developed in the laboratory as targets of antibody, peptide, and ligand binding for detection assays and therapeutics or as targets for vaccine development. In this paper, we assess how the amount of sequence data affects our ability to identify conserved, unique protein signature candidates. To determine the amount of sequence data required to select good protein signature candidates, we have built a computationally intensive system called the Sequencing Analysis Pipeline (SAP). The SAP performs thousands of Monte Carlo simulations, each calling the Protein Signature Pipeline, to assess how the amount of sequence data for a target organism affects the ability to predict peptide signature candidates. Viral species differ substantially in the number of genomes required to predict protein signature targets. Patterns do not appear based on genome structure. There are more protein than DNA signatures due to greater intraspecific conservation at the protein than at the nucleotide level. We conclude that it is necessary to use the SAP as a dynamic system to assess the need for continued sequencing for each species individually and to update predictions with each additional genome that is sequenced.

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* Corresponding author. Mailing address: Lawrence Livermore National Laboratory, P.O. Box 808, L-174, Livermore, CA 94551. Phone: (925) 422-4317. Fax: (925) 423-6437. E-mail: gardner26{at}llnl.gov.

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Journal of Clinical Microbiology, April 2005, p. 1807-1817, Vol. 43, No. 4
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.4.1807-1817.2005

This article has been cited by other articles:

• Gardner, S. N., Lam, M. W., Smith, J. R., Torres, C. L., Slezak, T. R. (2005). Draft versus finished sequence data for DNA and protein diagnostic signature development. Nucleic Acids Res 33: 5838-5850 [Abstract] [Full Text]