Draft versus finished sequence data for DNA and protein diagnostic signature development

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Sequencing pathogen genomes is costly, demanding careful allocation of limited sequencing resources. We built a computational Sequencing Analysis Pipeline (SAP) to guide decisions regarding the amount of genomic sequencing necessary to develop high-quality diagnostic DNA and protein signatures. SAP uses simulations to estimate the number of target genomes and close phylogenetic relatives (near neighbors, or NNs) to sequence. We use SAP to assess whether draft data is sufficient or finished sequencing is required using Marburg and variola virus sequences. Simulations indicate that intermediate to high quality draft with error rates of 10{sup -3}-10{sup -5} ({approx} 8x coverage) of target organisms ... continued below

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PDF-file: 33 pages; size: 0.4 Mbytes

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Gardner, S N; Lam, M W; Smith, J R; Torres, C L & Slezak, T R October 29, 2004.

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Sequencing pathogen genomes is costly, demanding careful allocation of limited sequencing resources. We built a computational Sequencing Analysis Pipeline (SAP) to guide decisions regarding the amount of genomic sequencing necessary to develop high-quality diagnostic DNA and protein signatures. SAP uses simulations to estimate the number of target genomes and close phylogenetic relatives (near neighbors, or NNs) to sequence. We use SAP to assess whether draft data is sufficient or finished sequencing is required using Marburg and variola virus sequences. Simulations indicate that intermediate to high quality draft with error rates of 10{sup -3}-10{sup -5} ({approx} 8x coverage) of target organisms is suitable for DNA signature prediction. Low quality draft with error rates of {approx} 1% (3x to 6x coverage) of target isolates is inadequate for DNA signature prediction, although low quality draft of NNs is sufficient, as long as the target genomes are of high quality. For protein signature prediction, sequencing errors in target genomes substantially reduce the detection of amino acid sequence conservation, even if the draft is of high quality. In summary, high quality draft of target and low quality draft of NNs appears to be a cost-effective investment for DNA signature prediction, but may lead to underestimation of predicted protein signatures.

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PDF-file: 33 pages; size: 0.4 Mbytes

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  • Journal Name: Nucleic Acids Research; Journal Volume: 33; Journal Issue: 18

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  • Report No.: UCRL-JRNL-208671
  • Grant Number: W-7405-ENG-48
  • Office of Scientific & Technical Information Report Number: 875660
  • Archival Resource Key: ark:/67531/metadc878971

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Office of Scientific & Technical Information Technical Reports

Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

Office of Scientific and Technical Information (OSTI) is the Department of Energy (DOE) office that collects, preserves, and disseminates DOE-sponsored research and development (R&D) results that are the outcomes of R&D projects or other funded activities at DOE labs and facilities nationwide and grantees at universities and other institutions.

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  • October 29, 2004

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  • Sept. 21, 2016, 2:29 a.m.

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  • Dec. 7, 2016, 10:55 a.m.

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Gardner, S N; Lam, M W; Smith, J R; Torres, C L & Slezak, T R. Draft versus finished sequence data for DNA and protein diagnostic signature development, article, October 29, 2004; Livermore, California. (digital.library.unt.edu/ark:/67531/metadc878971/: accessed December 12, 2017), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.