CONSeQuence: prediction of reference peptides for absolute quantitative proteomics using consensus machine learning approaches

Mol Cell Proteomics. 2011 Nov;10(11):M110.003384. doi: 10.1074/mcp.M110.003384. Epub 2011 Aug 3.

Abstract

Mass spectrometric based methods for absolute quantification of proteins, such as QconCAT, rely on internal standards of stable-isotope labeled reference peptides, or "Q-peptides," to act as surrogates. Key to the success of this and related methods for absolute protein quantification (such as AQUA) is selection of the Q-peptide. Here we describe a novel method, CONSeQuence (consensus predictor for Q-peptide sequence), based on four different machine learning approaches for Q-peptide selection. CONSeQuence demonstrates improved performance over existing methods for optimal Q-peptide selection in the absence of prior experimental information, as validated using two independent test sets derived from yeast. Furthermore, we examine the physicochemical parameters associated with good peptide surrogates, and demonstrate that in addition to charge and hydrophobicity, peptide secondary structure plays a significant role in determining peptide "detectability" in liquid chromatography-electrospray ionization experiments. We relate peptide properties to protein tertiary structure, demonstrating a counterintuitive preference for buried status for frequently detected peptides. Finally, we demonstrate the improved efficacy of the general approach by applying a predictor trained on yeast data to sets of proteotypic peptides from two additional species taken from an existing peptide identification repository.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Artificial Intelligence
  • Caenorhabditis elegans Proteins / chemistry
  • Computer Simulation
  • Drosophila Proteins / chemistry
  • Mass Spectrometry / standards*
  • Models, Molecular
  • Neural Networks, Computer
  • Peptides / chemistry
  • Peptides / standards*
  • Proteome / chemistry
  • Proteomics
  • Reference Standards
  • Saccharomyces cerevisiae Proteins / chemistry
  • Support Vector Machine

Substances

  • Caenorhabditis elegans Proteins
  • Drosophila Proteins
  • Peptides
  • Proteome
  • Saccharomyces cerevisiae Proteins