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Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow

Proteogenomics enable the discovery of novel peptides (from unannotated genomic protein-coding loci) and single amino acid variant peptides (derived from single-nucleotide polymorphisms and mutations). Increasing the reliability of these identifications is crucial to ensure their usefulness for geno...

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Autores principales: Zhu, Yafeng, Orre, Lukas M., Johansson, Henrik J., Huss, Mikael, Boekel, Jorrit, Vesterlund, Mattias, Fernandez-Woodbridge, Alejandro, Branca, Rui M. M., Lehtiö, Janne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834625/
https://www.ncbi.nlm.nih.gov/pubmed/29500430
http://dx.doi.org/10.1038/s41467-018-03311-y
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author Zhu, Yafeng
Orre, Lukas M.
Johansson, Henrik J.
Huss, Mikael
Boekel, Jorrit
Vesterlund, Mattias
Fernandez-Woodbridge, Alejandro
Branca, Rui M. M.
Lehtiö, Janne
author_facet Zhu, Yafeng
Orre, Lukas M.
Johansson, Henrik J.
Huss, Mikael
Boekel, Jorrit
Vesterlund, Mattias
Fernandez-Woodbridge, Alejandro
Branca, Rui M. M.
Lehtiö, Janne
author_sort Zhu, Yafeng
collection PubMed
description Proteogenomics enable the discovery of novel peptides (from unannotated genomic protein-coding loci) and single amino acid variant peptides (derived from single-nucleotide polymorphisms and mutations). Increasing the reliability of these identifications is crucial to ensure their usefulness for genome annotation and potential application as neoantigens in cancer immunotherapy. We here present integrated proteogenomics analysis workflow (IPAW), which combines peptide discovery, curation, and validation. IPAW includes the SpectrumAI tool for automated inspection of MS/MS spectra, eliminating false identifications of single-residue substitution peptides. We employ IPAW to analyze two proteomics data sets acquired from A431 cells and five normal human tissues using extended (pH range, 3–10) high-resolution isoelectric focusing (HiRIEF) pre-fractionation and TMT-based peptide quantitation. The IPAW results provide evidence for the translation of pseudogenes, lncRNAs, short ORFs, alternative ORFs, N-terminal extensions, and intronic sequences. Moreover, our quantitative analysis indicates that protein production from certain pseudogenes and lncRNAs is tissue specific.
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spelling pubmed-58346252018-03-06 Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow Zhu, Yafeng Orre, Lukas M. Johansson, Henrik J. Huss, Mikael Boekel, Jorrit Vesterlund, Mattias Fernandez-Woodbridge, Alejandro Branca, Rui M. M. Lehtiö, Janne Nat Commun Article Proteogenomics enable the discovery of novel peptides (from unannotated genomic protein-coding loci) and single amino acid variant peptides (derived from single-nucleotide polymorphisms and mutations). Increasing the reliability of these identifications is crucial to ensure their usefulness for genome annotation and potential application as neoantigens in cancer immunotherapy. We here present integrated proteogenomics analysis workflow (IPAW), which combines peptide discovery, curation, and validation. IPAW includes the SpectrumAI tool for automated inspection of MS/MS spectra, eliminating false identifications of single-residue substitution peptides. We employ IPAW to analyze two proteomics data sets acquired from A431 cells and five normal human tissues using extended (pH range, 3–10) high-resolution isoelectric focusing (HiRIEF) pre-fractionation and TMT-based peptide quantitation. The IPAW results provide evidence for the translation of pseudogenes, lncRNAs, short ORFs, alternative ORFs, N-terminal extensions, and intronic sequences. Moreover, our quantitative analysis indicates that protein production from certain pseudogenes and lncRNAs is tissue specific. Nature Publishing Group UK 2018-03-02 /pmc/articles/PMC5834625/ /pubmed/29500430 http://dx.doi.org/10.1038/s41467-018-03311-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhu, Yafeng
Orre, Lukas M.
Johansson, Henrik J.
Huss, Mikael
Boekel, Jorrit
Vesterlund, Mattias
Fernandez-Woodbridge, Alejandro
Branca, Rui M. M.
Lehtiö, Janne
Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow
title Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow
title_full Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow
title_fullStr Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow
title_full_unstemmed Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow
title_short Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow
title_sort discovery of coding regions in the human genome by integrated proteogenomics analysis workflow
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834625/
https://www.ncbi.nlm.nih.gov/pubmed/29500430
http://dx.doi.org/10.1038/s41467-018-03311-y
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