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Candidate prioritization for low-abundant differentially expressed proteins in 2D-DIGE datasets

BACKGROUND: Two-dimensional differential gel electrophoresis (2D-DIGE) provides a powerful technique to separate proteins on their isoelectric point and apparent molecular mass and quantify changes in protein expression. Abundantly available proteins in spots can be identified using mass spectrometr...

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Autores principales: Nandal, Umesh K, Vlietstra, Wytze J, Byrman, Carsten, Jeeninga, Rienk E, Ringrose, Jeffrey H, van Kampen, Antoine HC, Speijer, Dave, Moerland, Perry D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384356/
https://www.ncbi.nlm.nih.gov/pubmed/25627479
http://dx.doi.org/10.1186/s12859-015-0455-x
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author Nandal, Umesh K
Vlietstra, Wytze J
Byrman, Carsten
Jeeninga, Rienk E
Ringrose, Jeffrey H
van Kampen, Antoine HC
Speijer, Dave
Moerland, Perry D
author_facet Nandal, Umesh K
Vlietstra, Wytze J
Byrman, Carsten
Jeeninga, Rienk E
Ringrose, Jeffrey H
van Kampen, Antoine HC
Speijer, Dave
Moerland, Perry D
author_sort Nandal, Umesh K
collection PubMed
description BACKGROUND: Two-dimensional differential gel electrophoresis (2D-DIGE) provides a powerful technique to separate proteins on their isoelectric point and apparent molecular mass and quantify changes in protein expression. Abundantly available proteins in spots can be identified using mass spectrometry-based approaches. However, identification is often not possible for low-abundant proteins. RESULTS: We present a novel computational approach to prioritize candidate proteins for unidentified spots. Our approach exploits noisy information on the isoelectric point and apparent molecular mass of a protein spot in combination with functional similarities of candidate proteins to already identified proteins to select and rank candidates. We evaluated our method on a 2D-DIGE dataset comparing protein expression in uninfected and HIV-1 infected T-cells. Using leave-one-out cross-validation, we show that the true-positive rate for the top-5 ranked proteins is 43.8%. CONCLUSIONS: Our approach shows good performance on a 2D-DIGE dataset comparing protein expression in uninfected and HIV-1 infected T-cells. We expect our method to be highly useful in (re-)mining other 2D-DIGE experiments in which especially the low-abundant protein spots remain to be identified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0455-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-43843562015-04-04 Candidate prioritization for low-abundant differentially expressed proteins in 2D-DIGE datasets Nandal, Umesh K Vlietstra, Wytze J Byrman, Carsten Jeeninga, Rienk E Ringrose, Jeffrey H van Kampen, Antoine HC Speijer, Dave Moerland, Perry D BMC Bioinformatics Methodology Article BACKGROUND: Two-dimensional differential gel electrophoresis (2D-DIGE) provides a powerful technique to separate proteins on their isoelectric point and apparent molecular mass and quantify changes in protein expression. Abundantly available proteins in spots can be identified using mass spectrometry-based approaches. However, identification is often not possible for low-abundant proteins. RESULTS: We present a novel computational approach to prioritize candidate proteins for unidentified spots. Our approach exploits noisy information on the isoelectric point and apparent molecular mass of a protein spot in combination with functional similarities of candidate proteins to already identified proteins to select and rank candidates. We evaluated our method on a 2D-DIGE dataset comparing protein expression in uninfected and HIV-1 infected T-cells. Using leave-one-out cross-validation, we show that the true-positive rate for the top-5 ranked proteins is 43.8%. CONCLUSIONS: Our approach shows good performance on a 2D-DIGE dataset comparing protein expression in uninfected and HIV-1 infected T-cells. We expect our method to be highly useful in (re-)mining other 2D-DIGE experiments in which especially the low-abundant protein spots remain to be identified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0455-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-28 /pmc/articles/PMC4384356/ /pubmed/25627479 http://dx.doi.org/10.1186/s12859-015-0455-x Text en © Nandal et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology Article
Nandal, Umesh K
Vlietstra, Wytze J
Byrman, Carsten
Jeeninga, Rienk E
Ringrose, Jeffrey H
van Kampen, Antoine HC
Speijer, Dave
Moerland, Perry D
Candidate prioritization for low-abundant differentially expressed proteins in 2D-DIGE datasets
title Candidate prioritization for low-abundant differentially expressed proteins in 2D-DIGE datasets
title_full Candidate prioritization for low-abundant differentially expressed proteins in 2D-DIGE datasets
title_fullStr Candidate prioritization for low-abundant differentially expressed proteins in 2D-DIGE datasets
title_full_unstemmed Candidate prioritization for low-abundant differentially expressed proteins in 2D-DIGE datasets
title_short Candidate prioritization for low-abundant differentially expressed proteins in 2D-DIGE datasets
title_sort candidate prioritization for low-abundant differentially expressed proteins in 2d-dige datasets
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384356/
https://www.ncbi.nlm.nih.gov/pubmed/25627479
http://dx.doi.org/10.1186/s12859-015-0455-x
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