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New Glycoproteomics Software, GlycoPep Evaluator, Generates Decoy Glycopeptides de Novo and Enables Accurate False Discovery Rate Analysis for Small Data Sets

[Image: see text] Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass...

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Autores principales: Zhu, Zhikai, Su, Xiaomeng, Go, Eden P., Desaire, Heather
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165450/
https://www.ncbi.nlm.nih.gov/pubmed/25137014
http://dx.doi.org/10.1021/ac502176n
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author Zhu, Zhikai
Su, Xiaomeng
Go, Eden P.
Desaire, Heather
author_facet Zhu, Zhikai
Su, Xiaomeng
Go, Eden P.
Desaire, Heather
author_sort Zhu, Zhikai
collection PubMed
description [Image: see text] Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. The software is provided at https://desairegroup.ku.edu/research.
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spelling pubmed-41654502015-08-19 New Glycoproteomics Software, GlycoPep Evaluator, Generates Decoy Glycopeptides de Novo and Enables Accurate False Discovery Rate Analysis for Small Data Sets Zhu, Zhikai Su, Xiaomeng Go, Eden P. Desaire, Heather Anal Chem [Image: see text] Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. The software is provided at https://desairegroup.ku.edu/research. American Chemical Society 2014-08-19 2014-09-16 /pmc/articles/PMC4165450/ /pubmed/25137014 http://dx.doi.org/10.1021/ac502176n Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Zhu, Zhikai
Su, Xiaomeng
Go, Eden P.
Desaire, Heather
New Glycoproteomics Software, GlycoPep Evaluator, Generates Decoy Glycopeptides de Novo and Enables Accurate False Discovery Rate Analysis for Small Data Sets
title New Glycoproteomics Software, GlycoPep Evaluator, Generates Decoy Glycopeptides de Novo and Enables Accurate False Discovery Rate Analysis for Small Data Sets
title_full New Glycoproteomics Software, GlycoPep Evaluator, Generates Decoy Glycopeptides de Novo and Enables Accurate False Discovery Rate Analysis for Small Data Sets
title_fullStr New Glycoproteomics Software, GlycoPep Evaluator, Generates Decoy Glycopeptides de Novo and Enables Accurate False Discovery Rate Analysis for Small Data Sets
title_full_unstemmed New Glycoproteomics Software, GlycoPep Evaluator, Generates Decoy Glycopeptides de Novo and Enables Accurate False Discovery Rate Analysis for Small Data Sets
title_short New Glycoproteomics Software, GlycoPep Evaluator, Generates Decoy Glycopeptides de Novo and Enables Accurate False Discovery Rate Analysis for Small Data Sets
title_sort new glycoproteomics software, glycopep evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165450/
https://www.ncbi.nlm.nih.gov/pubmed/25137014
http://dx.doi.org/10.1021/ac502176n
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