A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modifications

Detalhes bibliográficos
Autor(a) principal: Nunes, João
Data de Publicação: 2019
Outros Autores: Charneira, Catarina, Nunes, Carolina, Gouveia-Fernandes, Sofia, Serpa, Jacinta, Morello, Judit, Antunes, Alexandra M M
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/83739
Resumo: This work was supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal, through projects UID/QUI/00100/2019, IF/01091/2013/CP1163/CT0001 and PTDC/QUIQAN/32242/2017 as well as doctoral fellowships SFRH/BD/102846/2014 (to CC) and SFRH/BD/140157/2018 (to JN);joint funding from FCT and the COMPETE Program is also acknowledge through RNEM-LISBOA-01-0145-FEDER-022125-funded postdoctoral fellowship (to JM).
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spelling A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modificationsadductomicsmetabolomicsmass spectrometrychemometricstoxicologyacrylamideglycidamidehistonesThis work was supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal, through projects UID/QUI/00100/2019, IF/01091/2013/CP1163/CT0001 and PTDC/QUIQAN/32242/2017 as well as doctoral fellowships SFRH/BD/102846/2014 (to CC) and SFRH/BD/140157/2018 (to JN);joint funding from FCT and the COMPETE Program is also acknowledge through RNEM-LISBOA-01-0145-FEDER-022125-funded postdoctoral fellowship (to JM).Identification of protein covalent modifications (adducts) is a challenging task mainly due to the lack of data processing approaches for adductomics studies. Despite the huge technological advances in mass spectrometry (MS) instrumentation and bioinformatics tools for proteomics studies, these methodologies have very limited success on the identification of low abundant protein adducts. Herein we report a novel strategy inspired on the metabolomics workflows for the identification of covalently-modified peptides that consists on LC-MS data preprocessing followed by statistical analysis. The usefulness of this strategy was evaluated using experimental LC-MS data of histones isolated from HepG2 and THLE2 cells exposed to the chemical carcinogen glycidamide. LC-MS data was preprocessed using the open-source software MZmine and potential adducts were selected based on the m/z increments corresponding to glycidamide incorporation. Then, statistical analysis was applied to reveal the potential adducts as those ions are differently present in cells exposed and not exposed to glycidamide. The results were compared with the ones obtained upon the standard proteomics methodology, which relies on producing comprehensive MS/MS data by data dependent acquisition and analysis with proteomics data search engines. Our novel strategy was able to differentiate HepG2 and THLE2 and to identify adducts that were not detected by the standard methodology of adductomics. Thus, this metabolomics driven approach in adductomics will not only open new opportunities for the identification of protein epigenetic modifications, but also adducts formed by endogenous and exogenous exposure to chemical agents.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNNunes, JoãoCharneira, CatarinaNunes, CarolinaGouveia-Fernandes, SofiaSerpa, JacintaMorello, JuditAntunes, Alexandra M M2019-10-08T22:50:42Z2019-07-312019-07-31T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/83739eng2296-2646PURE: 14622967https://doi.org/10.3389/fchem.2019.00532info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:37:28Zoai:run.unl.pt:10362/83739Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:36:23.779235Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modifications
title A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modifications
spellingShingle A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modifications
Nunes, João
adductomics
metabolomics
mass spectrometry
chemometrics
toxicology
acrylamide
glycidamide
histones
title_short A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modifications
title_full A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modifications
title_fullStr A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modifications
title_full_unstemmed A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modifications
title_sort A Metabolomics-Inspired Strategy for the Identification of Protein Covalent Modifications
author Nunes, João
author_facet Nunes, João
Charneira, Catarina
Nunes, Carolina
Gouveia-Fernandes, Sofia
Serpa, Jacinta
Morello, Judit
Antunes, Alexandra M M
author_role author
author2 Charneira, Catarina
Nunes, Carolina
Gouveia-Fernandes, Sofia
Serpa, Jacinta
Morello, Judit
Antunes, Alexandra M M
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Nunes, João
Charneira, Catarina
Nunes, Carolina
Gouveia-Fernandes, Sofia
Serpa, Jacinta
Morello, Judit
Antunes, Alexandra M M
dc.subject.por.fl_str_mv adductomics
metabolomics
mass spectrometry
chemometrics
toxicology
acrylamide
glycidamide
histones
topic adductomics
metabolomics
mass spectrometry
chemometrics
toxicology
acrylamide
glycidamide
histones
description This work was supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal, through projects UID/QUI/00100/2019, IF/01091/2013/CP1163/CT0001 and PTDC/QUIQAN/32242/2017 as well as doctoral fellowships SFRH/BD/102846/2014 (to CC) and SFRH/BD/140157/2018 (to JN);joint funding from FCT and the COMPETE Program is also acknowledge through RNEM-LISBOA-01-0145-FEDER-022125-funded postdoctoral fellowship (to JM).
publishDate 2019
dc.date.none.fl_str_mv 2019-10-08T22:50:42Z
2019-07-31
2019-07-31T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/83739
url http://hdl.handle.net/10362/83739
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2296-2646
PURE: 14622967
https://doi.org/10.3389/fchem.2019.00532
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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