Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10400.18/8549 |
Resumo: | This article belongs to the Special Issue Metabolomics in Health and Disease. |
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Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker SignatureTuberculosisDiagnosisBiomarkersBlood SerumMass SpectrometryMultiomicsInfecções RespiratóriasThis article belongs to the Special Issue Metabolomics in Health and Disease.Tuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which the discovery of effective diagnostic biomarkers is crucial. In this study, we aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Two independent cohorts comprising 29 and 34 subjects were assayed by proteomics, and 49 were included for metabolomic analysis. All subjects were arranged into three experimental groups-healthy controls (controls), latent TB infection (LTBI), and TB patients. LC-MS/MS blood serum protein and metabolite levels were submitted to univariate, multivariate, and ROC analysis. From the 149 proteins quantified in the discovery set, 25 were found to be differentially abundant between controls and TB patients. The AUC, specificity, and sensitivity, determined by ROC statistical analysis of the model composed of four of these proteins considering both proteomic sets, were 0.96, 93%, and 91%, respectively. The five metabolites (9-methyluric acid, indole-3-lactic acid, trans-3-indoleacrylic acid, hexanoylglycine, and N-acetyl-L-leucine) that better discriminate the control and TB patient groups (VIP > 1.75) from a total of 92 metabolites quantified in both ionization modes were submitted to ROC analysis. An AUC = 1 was determined, with all samples being correctly assigned to the respective experimental group. An integrated ROC analysis enrolling one protein and four metabolites was also performed for the common control and TB patients in the proteomic and metabolomic groups. This combined signature correctly assigned the 12 controls and 12 patients used only for prediction (AUC = 1, specificity = 100%, and sensitivity = 100%). This multiomics approach revealed a biomarker signature for tuberculosis diagnosis that could be potentially used for developing a point-of-care diagnosis clinical test.New INDIGO Programme on Biotechnology-Human Health (INDIGO-DBT2-062), ERA NET Project supported by FCT. Partially supported by project PTDC/CVT-CVT/29510/2017 funded by Fundação para a Ciência a Tecnologia; Projects LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) and UID/Multi/04378/2019) funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI); by ONEIDA project (LISBOA-01-0145-FEDER-016417) co-funded by FEEI-”Fundos Europeus Estruturais e de Investimento” from “Programa Operacional Regional Lisboa 2020” and by national funds from Fundação para a Ciência e a Tecnologia. European Regional Development Fund (ERDF), through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia, I.P., under projects: POCI-01-0145-FEDER-007440 (ref. UIDB/04539/2020 and UIDP/04539/2020), and by The Na tional Mass Spectrometry Network (RNEM) under the contract POCI-01-0145-FEDER-402-022125 (ref.: ROTEIRO/0028/2013). Luis G Gonçalves was financed by an FCT contract according to DL57/2016, [SFRH/BPD/111100/2015].MDPIRepositório Científico do Instituto Nacional de SaúdeFernandes, Ana FilipaGonçalves, Luís GafeiraBento, MariaAnjo, Sandra I.Manadas, BrunoBarroso, ClaraVillar, MiguelMacedo, RitaSimões, Maria JoãoCoelho, Ana Varela2023-03-08T15:08:37Z2022-11-082022-11-08T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/8549engInt J Mol Sci. 2022 Nov 8;23(22):13733. doi: 10.3390/ijms232213733.1661-659610.3390/ijms232213733info: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:RCAAP2023-07-20T15:42:38Zoai:repositorio.insa.pt:10400.18/8549Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:43:11.354776Repositório 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 |
Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature |
| title |
Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature |
| spellingShingle |
Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature Fernandes, Ana Filipa Tuberculosis Diagnosis Biomarkers Blood Serum Mass Spectrometry Multiomics Infecções Respiratórias |
| title_short |
Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature |
| title_full |
Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature |
| title_fullStr |
Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature |
| title_full_unstemmed |
Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature |
| title_sort |
Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature |
| author |
Fernandes, Ana Filipa |
| author_facet |
Fernandes, Ana Filipa Gonçalves, Luís Gafeira Bento, Maria Anjo, Sandra I. Manadas, Bruno Barroso, Clara Villar, Miguel Macedo, Rita Simões, Maria João Coelho, Ana Varela |
| author_role |
author |
| author2 |
Gonçalves, Luís Gafeira Bento, Maria Anjo, Sandra I. Manadas, Bruno Barroso, Clara Villar, Miguel Macedo, Rita Simões, Maria João Coelho, Ana Varela |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
| dc.contributor.author.fl_str_mv |
Fernandes, Ana Filipa Gonçalves, Luís Gafeira Bento, Maria Anjo, Sandra I. Manadas, Bruno Barroso, Clara Villar, Miguel Macedo, Rita Simões, Maria João Coelho, Ana Varela |
| dc.subject.por.fl_str_mv |
Tuberculosis Diagnosis Biomarkers Blood Serum Mass Spectrometry Multiomics Infecções Respiratórias |
| topic |
Tuberculosis Diagnosis Biomarkers Blood Serum Mass Spectrometry Multiomics Infecções Respiratórias |
| description |
This article belongs to the Special Issue Metabolomics in Health and Disease. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-11-08 2022-11-08T00:00:00Z 2023-03-08T15:08:37Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10400.18/8549 |
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http://hdl.handle.net/10400.18/8549 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Int J Mol Sci. 2022 Nov 8;23(22):13733. doi: 10.3390/ijms232213733. 1661-6596 10.3390/ijms232213733 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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