Universidad Peruana Cayetano Heredia

Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

Mostrar el registro sencillo del ítem

dc.contributor.author Garay-Baquero, D.J.
dc.contributor.author White, C.H.
dc.contributor.author Walker, N.F.
dc.contributor.author Tebruegge, M.
dc.contributor.author Schiff, H.F.
dc.contributor.author Ugarte Gil, Cesar Augusto
dc.contributor.author Morris-Jones, S.
dc.contributor.author Marshall, B.G.
dc.contributor.author Manousopoulou, A.
dc.contributor.author Adamson, J.
dc.contributor.author Vallejo, A.F.
dc.contributor.author Bielecka, M.K.
dc.contributor.author Wilkinson, R.J.
dc.contributor.author Tezera, L.B.
dc.contributor.author Woelk, C.H.
dc.contributor.author Garbis, S.D.
dc.contributor.author Elkington, P.
dc.date.accessioned 2020-12-14T16:06:24Z
dc.date.available 2020-12-14T16:06:24Z
dc.date.issued 2020
dc.identifier.uri https://hdl.handle.net/20.500.12866/8712
dc.description.abstract BACKGROUND. Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma. METHODS. We applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203). RESULTS. We generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low-molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81). CONCLUSION. We report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test. FUNDING. Colciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research. en_US
dc.language.iso eng
dc.publisher American Society for Clinical Investigation
dc.relation.ispartofseries JCI Insight
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Plasma proteomic en_US
dc.subject Biomarkers en_US
dc.subject Tuberculosis en_US
dc.title Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1172/JCI.INSIGHT.137427
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00
dc.relation.issn 2379-3708


Ficheros en el ítem

Ficheros Tamaño Formato Ver

No hay ficheros asociados a este ítem.

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

info:eu-repo/semantics/restrictedAccess Excepto si se señala otra cosa, la licencia del ítem se describe como info:eu-repo/semantics/restrictedAccess

Buscar en el Repositorio


Listar

Panel de Control

Estadísticas