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Title: Application of Peptide LC Retention Time Information in a Discriminant Function for Peptide Identification by Tandem Mass Spectrometry

Abstract

We describe the application of a peptide retention time reversed phase liquid chromatography (RPLC) prediction model previously reported (Petritis et al. Anal. Chem. 99, 2002, 11049) for improved peptide identification. The model uses peptide sequence information to generate a theoretical (predicted) elution time that can be compared with the observed elution time. Using data from a set of known proteins, the retention time parameter was incorporated into a discriminant function for use with tandem mass spectrometry (MS/MS) data analyzed with the peptide/protein identification program SEQUEST. For singly charged ions, the number of identifications increased by 12% when the elution time metric is included compared to when mass spectral data is the sole source of information in the context of a Drosophila melanogaster database. A 3-4% improvement was obtained for doubly and triply charged ions for the same biological system. Application to the larger Rattus norvegicus (rat) and human proteome databases resulted in an 8-9% overall increase in the number of identifications, when both the discriminant function and elution time are used. The effect of adding “runner-up” hits (peptide matches that are not the highest scoring for a spectra) from SEQUEST is also explored, and we find that the number ofmore » confident identifications is further increased when these hits are also considered. Finally, application of the discriminant functions derived in this work with ~2.2 million spectra from 330 LC-MS/MS analyses of peptides from human plasma protein resulted in a 19% increase in confident peptide identifications (9551 vs 8049) using elution time information. Further improvements from the use of elution time information can be expected as both the experimental control of elution time reproducibility and the predictive capability are improved.« less

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
15020860
Report Number(s):
PNNL-SA-40693
KP1501021; TRN: US200521%%399
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Journal of Proteome Research, 3(4):760-769
Additional Journal Information:
Journal Volume: 3; Journal Issue: 4
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CHROMATOGRAPHY; DROSOPHILA; FORECASTING; MASS SPECTROSCOPY; METRICS; PEPTIDES; PLASMA; PROTEINS; RETENTION; SPECTRA

Citation Formats

Strittmatter, Eric F, Kangas, Lars J, Petritis, Konstantinos, Mottaz, Heather M, Anderson, Gordon A, Shen, Yufeng, Jacobs, Jon M, Camp, David G, and Smith, Richard D. Application of Peptide LC Retention Time Information in a Discriminant Function for Peptide Identification by Tandem Mass Spectrometry. United States: N. p., 2004. Web. doi:10.1021/pr049965y.
Strittmatter, Eric F, Kangas, Lars J, Petritis, Konstantinos, Mottaz, Heather M, Anderson, Gordon A, Shen, Yufeng, Jacobs, Jon M, Camp, David G, & Smith, Richard D. Application of Peptide LC Retention Time Information in a Discriminant Function for Peptide Identification by Tandem Mass Spectrometry. United States. https://doi.org/10.1021/pr049965y
Strittmatter, Eric F, Kangas, Lars J, Petritis, Konstantinos, Mottaz, Heather M, Anderson, Gordon A, Shen, Yufeng, Jacobs, Jon M, Camp, David G, and Smith, Richard D. Fri . "Application of Peptide LC Retention Time Information in a Discriminant Function for Peptide Identification by Tandem Mass Spectrometry". United States. https://doi.org/10.1021/pr049965y.
@article{osti_15020860,
title = {Application of Peptide LC Retention Time Information in a Discriminant Function for Peptide Identification by Tandem Mass Spectrometry},
author = {Strittmatter, Eric F and Kangas, Lars J and Petritis, Konstantinos and Mottaz, Heather M and Anderson, Gordon A and Shen, Yufeng and Jacobs, Jon M and Camp, David G and Smith, Richard D},
abstractNote = {We describe the application of a peptide retention time reversed phase liquid chromatography (RPLC) prediction model previously reported (Petritis et al. Anal. Chem. 99, 2002, 11049) for improved peptide identification. The model uses peptide sequence information to generate a theoretical (predicted) elution time that can be compared with the observed elution time. Using data from a set of known proteins, the retention time parameter was incorporated into a discriminant function for use with tandem mass spectrometry (MS/MS) data analyzed with the peptide/protein identification program SEQUEST. For singly charged ions, the number of identifications increased by 12% when the elution time metric is included compared to when mass spectral data is the sole source of information in the context of a Drosophila melanogaster database. A 3-4% improvement was obtained for doubly and triply charged ions for the same biological system. Application to the larger Rattus norvegicus (rat) and human proteome databases resulted in an 8-9% overall increase in the number of identifications, when both the discriminant function and elution time are used. The effect of adding “runner-up” hits (peptide matches that are not the highest scoring for a spectra) from SEQUEST is also explored, and we find that the number of confident identifications is further increased when these hits are also considered. Finally, application of the discriminant functions derived in this work with ~2.2 million spectra from 330 LC-MS/MS analyses of peptides from human plasma protein resulted in a 19% increase in confident peptide identifications (9551 vs 8049) using elution time information. Further improvements from the use of elution time information can be expected as both the experimental control of elution time reproducibility and the predictive capability are improved.},
doi = {10.1021/pr049965y},
url = {https://www.osti.gov/biblio/15020860}, journal = {Journal of Proteome Research, 3(4):760-769},
number = 4,
volume = 3,
place = {United States},
year = {2004},
month = {7}
}