NovoHMM:  A Hidden Markov Model for de Novo Peptide Sequencing

Bernd Fischer, Volker Roth, Franz Roos,§ Jonas Grossmann, Sacha Baginsky, Peter Widmayer,§ Wilhelm Gruissem, and Joachim M. Buhmann
Institute of Computational Science, Institute of Plant Sciences, and Institute of Theoretical Computer Science, ETH Zurich, Switzerland
Anal. Chem., 2005, 77 (22), pp 7265–7273
DOI: 10.1021/ac0508853
Publication Date (Web): October 11, 2005
Copyright © 2005 American Chemical Society

Abstract

De novo sequencing of peptides poses one of the most challenging tasks in data analysis for proteome research. In this paper, a generative hidden Markov model (HMM) of mass spectra for de novo peptide sequencing which constitutes a novel view on how to solve this problem in a Bayesian framework is proposed. Further extensions of the model structure to a graphical model and a factorial HMM to substantially improve the peptide identification results are demonstrated. Inference with the graphical model for de novo peptide sequencing estimates posterior probabilities for amino acids rather than scores for single symbols in the sequence. Our model outperforms state-of-the-art methods for de novo peptide sequencing on a large test set of spectra.

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This article has been cited by 10 ACS Journal articles (5 most recent appear below).

  • Cover Image

    De Novo Sequencing of Tryptic Peptides Derived from Deinococcus radiodurans Ribosomal Proteins Using 157 nm Photodissociation MALDI TOF/TOF Mass Spectrometry

    Liangyi Zhang and James P. Reilly
    Journal of Proteome Research2010 9 (6), 3025-3034
    • De Novo Sequencing of Tryptic Peptides Derived from Deinococcus radiodurans Ribosomal Proteins Using 157 nm Photodissociation MALDI TOF/TOF Mass Spectrometry

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      Journal of Proteome Research2010 9 (6), 3025-3034

      Vacuum ultraviolet photodissociation of peptide ions in a matrix assisted laser desorption ionization (MALDI) tandem time-of-flight (TOF) mass spectrometer is used to characterize peptide mixtures derived from Deinococcus radiodurans ribosomal proteins. ...

  • Cover Image

    pNovo: De novo Peptide Sequencing and Identification Using HCD Spectra

    Hao Chi, Rui-Xiang Sun, Bing Yang, Chun-Qing Song, Le-Heng Wang, Chao Liu, Yan Fu, Zuo-Fei Yuan, Hai-Peng Wang, Si-Min He and Meng-Qiu Dong
    Journal of Proteome Research2010 9 (5), 2713-2724
    • pNovo: De novo Peptide Sequencing and Identification Using HCD Spectra

      Hao Chi, Rui-Xiang Sun, Bing Yang, Chun-Qing Song, Le-Heng Wang, Chao Liu, Yan Fu, Zuo-Fei Yuan, Hai-Peng Wang, Si-Min He and Meng-Qiu Dong
      Journal of Proteome Research2010 9 (5), 2713-2724

      De novo peptide sequencing has improved remarkably in the past decade as a result of better instruments and computational algorithms. However, de novo sequencing can correctly interpret only 30% of high- and medium-quality spectra generated by collision-...

  • Cover Image

    Peptide de Novo Sequencing Using 157 nm Photodissociation in a Tandem Time-of-Flight Mass Spectrometer

    Liangyi Zhang and James P. Reilly
    Analytical Chemistry2010 82 (3), 898-908
    • Peptide de Novo Sequencing Using 157 nm Photodissociation in a Tandem Time-of-Flight Mass Spectrometer

      Liangyi Zhang and James P. Reilly
      Analytical Chemistry2010 82 (3), 898-908

      It has previously been shown that photodissociation of tryptic peptide ions with 157 nm light in a matrix-assisted laser desorption/ionization (MALDI) tandem time-of-flight (TOF) mass spectrometer generates an abundance of x-type ions. A peptide de novo ...

  • Cover Image

    A Ranking-Based Scoring Function for Peptide−Spectrum Matches

    Ari M. Frank
    Journal of Proteome Research2009 8 (5), 2241-2252
    • A Ranking-Based Scoring Function for Peptide−Spectrum Matches

      Ari M. Frank
      Journal of Proteome Research2009 8 (5), 2241-2252

      We present a novel approach to scoring of peptide−spectrum matches. We use discriminative boosting-based algorithms that are able to harnesses the large volume of MS/MS data presently available to train more accurate scoring models. Our new method ...

  • Cover Image

    DirecTag: Accurate Sequence Tags from Peptide MS/MS through Statistical Scoring

    David L. Tabb, Ze-Qiang Ma, Daniel B. Martin, Amy-Joan L. Ham and Matthew C. Chambers
    Journal of Proteome Research2008 7 (9), 3838-3846
    • DirecTag: Accurate Sequence Tags from Peptide MS/MS through Statistical Scoring

      David L. Tabb, Ze-Qiang Ma, Daniel B. Martin, Amy-Joan L. Ham and Matthew C. Chambers
      Journal of Proteome Research2008 7 (9), 3838-3846

      In shotgun proteomics, tandem mass spectra of peptides are typically identified through database search algorithms such as Sequest. We have developed DirecTag, an open-source algorithm to infer partial sequence tags directly from observed fragment ions. ...

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History

  • Published In Issue November 15, 2005
  • Received for review May 20, 2005. Accepted September 2, 2005.

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