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

详细信息    查看全文

• 作者：Chongle Pan ; Guruprasad Kora ; David L. Tabb ; Dale A. Pelletier ; W. Hayes McDonald ; Gregory B. Hurst ; Robert L. Hettich ; Nagiza F. Samatova
• 刊名：Analytical Chemistry
• 出版年：2006
• 出版时间：October 15, 2006
• 年：2006
• 卷：78
• 期：20
• 页码：7110 - 7120
• 全文大小：513K
• 年卷期：v.78,no.20(October 15, 2006)
• ISSN：1520-6882

文摘

The abundance ratio between the light and heavy isotopologues of an isotopically labeled peptide can beestimated from their selected ion chromatograms. However, quantitative shotgun proteomics measurementsyield selected ion chromatograms at highly variable signal-to-noise ratios for tens of thousands of peptides. Thischallenge calls for algorithms that not only robustlyestimate the abundance ratios of different peptides butalso rigorously score each abundance ratio for the expected estimation bias and variability. Scoring of theabundance ratios, much like scoring of sequence assignment for tandem mass spectra by peptide identificationalgorithms, enables filtering of unreliable peptide quantification and use of formal statistical inference in thesubsequent protein abundance ratio estimation. In thisstudy, a parallel paired covariance algorithm is used forrobust peak detection in selected ion chromatograms. Apeak profile is generated for each peptide, which is ascatterplot of ion intensities measured for the two isotopologues within their chromatographic peaks. Principalcomponent analysis of the peak profile is proposed toestimate the peptide abundance ratio and to score theestimation with the signal-to-noise ratio of the peak profile(profile signal-to-noise ratio). We demonstrate that theprofile signal-to-noise ratio is inversely correlated with thevariability and bias of peptide abundance ratio estimation.