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Title: ProRata: A quantitative proteomics program for accurate protein abundance ratio estimation with confidence interval evaluation

Abstract

A profile likelihood algorithm is proposed for quantitative shotgun proteomics to infer the abundance ratios of proteins from the abundance ratios of isotopically labeled peptides derived from proteolysis. Previously, we have shown that the estimation variability and bias of peptide abundance ratios can be predicted from their profile signal-to-noise ratios. Given multiple quantified peptides for a protein, the profile likelihood algorithm probabilistically weighs the peptide abundance ratios by their inferred estimation variability, accounts for their expected estimation bias, and suppresses contribution from outliers. This algorithm yields maximum likelihood point estimation and profile likelihood confidence interval estimation of protein abundance ratios. This point estimator is more accurate than an estimator based on the average of peptide abundance ratios. The confidence interval estimation provides an "error bar" for each protein abundance ratio that reflects its estimation precision and statistical uncertainty. The accuracy of the point estimation and the precision and confidence level of the interval estimation were benchmarked with standard mixtures of isotopically labeled proteomes. The profile likelihood algorithm was integrated into a quantitative proteomics program, called ProRata, freely available at www.MSProRata.org.

Authors:
 [1];  [1];  [1];  [1];  [1];  [2];  [1];  [1];  [3]
  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:
930742
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; ABUNDANCE; ACCURACY; ALGORITHMS; EVALUATION; MIXTURES; PEPTIDES; PROTEINS; PROTEOLYSIS; SIGNAL-TO-NOISE RATIO

Citation Formats

Pan, Chongle, Kora, Guruprasad H, McDonald, W Hayes, Tabb, Dave L, Verberkmoes, Nathan C, Hurst, Gregory, Pelletier, Dale A, Samatova, Nagiza F, and Hettich, Robert. ProRata: A quantitative proteomics program for accurate protein abundance ratio estimation with confidence interval evaluation. United States: N. p., 2006. Web. doi:10.1021/ac060654b.
Pan, Chongle, Kora, Guruprasad H, McDonald, W Hayes, Tabb, Dave L, Verberkmoes, Nathan C, Hurst, Gregory, Pelletier, Dale A, Samatova, Nagiza F, & Hettich, Robert. ProRata: A quantitative proteomics program for accurate protein abundance ratio estimation with confidence interval evaluation. United States. doi:10.1021/ac060654b.
Pan, Chongle, Kora, Guruprasad H, McDonald, W Hayes, Tabb, Dave L, Verberkmoes, Nathan C, Hurst, Gregory, Pelletier, Dale A, Samatova, Nagiza F, and Hettich, Robert. Sun . "ProRata: A quantitative proteomics program for accurate protein abundance ratio estimation with confidence interval evaluation". United States. doi:10.1021/ac060654b.
@article{osti_930742,
title = {ProRata: A quantitative proteomics program for accurate protein abundance ratio estimation with confidence interval evaluation},
author = {Pan, Chongle and Kora, Guruprasad H and McDonald, W Hayes and Tabb, Dave L and Verberkmoes, Nathan C and Hurst, Gregory and Pelletier, Dale A and Samatova, Nagiza F and Hettich, Robert},
abstractNote = {A profile likelihood algorithm is proposed for quantitative shotgun proteomics to infer the abundance ratios of proteins from the abundance ratios of isotopically labeled peptides derived from proteolysis. Previously, we have shown that the estimation variability and bias of peptide abundance ratios can be predicted from their profile signal-to-noise ratios. Given multiple quantified peptides for a protein, the profile likelihood algorithm probabilistically weighs the peptide abundance ratios by their inferred estimation variability, accounts for their expected estimation bias, and suppresses contribution from outliers. This algorithm yields maximum likelihood point estimation and profile likelihood confidence interval estimation of protein abundance ratios. This point estimator is more accurate than an estimator based on the average of peptide abundance ratios. The confidence interval estimation provides an "error bar" for each protein abundance ratio that reflects its estimation precision and statistical uncertainty. The accuracy of the point estimation and the precision and confidence level of the interval estimation were benchmarked with standard mixtures of isotopically labeled proteomes. The profile likelihood algorithm was integrated into a quantitative proteomics program, called ProRata, freely available at www.MSProRata.org.},
doi = {10.1021/ac060654b},
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}
}