skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Robust Estimation of Peptide Abundance Ratios and Rigorous Scoring of Their Variability and Bias in Quantitative Shotgun Proteomics

Abstract

The abundance ratio between the light and heavy iso-topologues of an isotopically labeled peptide can be estimated from their selected ion chromatograms. How-ever, quantitative shotgun proteomics measurements yield selected ion chromatograms at highly variable signal-to-noise ratios for tens of thousands of peptides. This challenge calls for algorithms that not only robustly estimate the abundance ratios of different peptides but also rigorously score each abundance ratio for the expected estimation bias and variability. Scoring of the abundance ratios, much like scoring of sequence assignment for tandem mass spectra by peptide identification algorithms, enables filtering of unreliable peptide quantification and use of formal statistical inference in the subsequent protein abundance ratio estimation. In this study, aparallel paired covariance algorithm is used for robust peak detection in selected ion chromatograms. A peak profile is generated for each peptide, which is a scatter plot of ion intensities measured for the two isotopologues with in their chromatographic peaks. Principal component analysis of the peak profile is proposed to estimate the peptide abundance ratio and to score the estimation with the signal-to-noise ratio of the peak profile (profile signal-to-noise ratio). We demonstrate that the profile signal-to-noise ratio is inversely correlated with the variability and bias ofmore » peptide abundance ratio estimation.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [2];  [3];  [1]
  1. ORNL
  2. {Greg} B [ORNL
  3. {Bob} L [ORNL
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC)
OSTI Identifier:
1003641
DOE Contract Number:  
DE-AC05-00OR22725
Resource Type:
Journal Article
Resource Relation:
Journal Name: Analytical Chemistry; Journal Volume: 78; Journal Issue: 20
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; ABUNDANCE; ALGORITHMS; DETECTION; MASS SPECTRA; PEPTIDES; PROTEINS; SIGNAL-TO-NOISE RATIO

Citation Formats

Pan, Chongle, Kora, Guruprasad H, Tabb, Dave L, Pelletier, Dale A, McDonald, W Hayes, Hurst, Gregory, Hettich, Robert, and Samatova, Nagiza F. Robust Estimation of Peptide Abundance Ratios and Rigorous Scoring of Their Variability and Bias in Quantitative Shotgun Proteomics. United States: N. p., 2006. Web. doi:10.1021/ac0606554.
Pan, Chongle, Kora, Guruprasad H, Tabb, Dave L, Pelletier, Dale A, McDonald, W Hayes, Hurst, Gregory, Hettich, Robert, & Samatova, Nagiza F. Robust Estimation of Peptide Abundance Ratios and Rigorous Scoring of Their Variability and Bias in Quantitative Shotgun Proteomics. United States. doi:10.1021/ac0606554.
Pan, Chongle, Kora, Guruprasad H, Tabb, Dave L, Pelletier, Dale A, McDonald, W Hayes, Hurst, Gregory, Hettich, Robert, and Samatova, Nagiza F. Sun . "Robust Estimation of Peptide Abundance Ratios and Rigorous Scoring of Their Variability and Bias in Quantitative Shotgun Proteomics". United States. doi:10.1021/ac0606554.
@article{osti_1003641,
title = {Robust Estimation of Peptide Abundance Ratios and Rigorous Scoring of Their Variability and Bias in Quantitative Shotgun Proteomics},
author = {Pan, Chongle and Kora, Guruprasad H and Tabb, Dave L and Pelletier, Dale A and McDonald, W Hayes and Hurst, Gregory and Hettich, Robert and Samatova, Nagiza F},
abstractNote = {The abundance ratio between the light and heavy iso-topologues of an isotopically labeled peptide can be estimated from their selected ion chromatograms. How-ever, quantitative shotgun proteomics measurements yield selected ion chromatograms at highly variable signal-to-noise ratios for tens of thousands of peptides. This challenge calls for algorithms that not only robustly estimate the abundance ratios of different peptides but also rigorously score each abundance ratio for the expected estimation bias and variability. Scoring of the abundance ratios, much like scoring of sequence assignment for tandem mass spectra by peptide identification algorithms, enables filtering of unreliable peptide quantification and use of formal statistical inference in the subsequent protein abundance ratio estimation. In this study, aparallel paired covariance algorithm is used for robust peak detection in selected ion chromatograms. A peak profile is generated for each peptide, which is a scatter plot of ion intensities measured for the two isotopologues with in their chromatographic peaks. Principal component analysis of the peak profile is proposed to estimate the peptide abundance ratio and to score the estimation with the signal-to-noise ratio of the peak profile (profile signal-to-noise ratio). We demonstrate that the profile signal-to-noise ratio is inversely correlated with the variability and bias of peptide abundance ratio estimation.},
doi = {10.1021/ac0606554},
journal = {Analytical Chemistry},
number = 20,
volume = 78,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}