Dataset Information

Proteomic Discovery and Validation of Diagnostic Plasma Biomarkers for Pulmonary Tuberculosis

ABSTRACT: Despite more than a century fighting against tuberculosis, the World Health Organisation has estimated that around 1.7 million people died of tuberculosis in 2016 and over a quarter of the world’s population is infected. One of the critical hurdles for stopping tuberculosis transmission is early and effective diagnosis of patients with the active pulmonary disease. Although important innovations in molecular diagnosis have been recently developed (e.g. Xpert MTB/RIF, Cepheid Inc., USA), there are no suitable tests for population screening at point-of-care. The current tuberculosis diagnosis pipeline presents a highly variable performance and requires access to reference laboratory facilities. A non-sputum based rapid test with high specificity and sensitivity could save ~400,000 lives per year. Therefore, new biomarkers for diagnosis are urgently required for identifying patients with early symptoms and to expedite treatment. Variable sensitivity and specificity can be overcome using a combination of multiple biomarkers (5). Proteins, as ultimate biological effectors, are ideal candidates for diagnostic biomarkers; consequently, proteomic studies are a crucial platform for biomarker discovery in tuberculosis. This work aims to develop a multi-marker panel for tuberculosis diagnosis with high performance capable of differentiating tuberculosis patients from relevant controls. Quantitative Multidimensional Protein Identification Technology (qMudPIT) is applied for biomarker discovery identifying candidates for early diagnosis of tuberculosis. The multidimensional method optimised in this work led to the identification of 5022 plasma proteins and 3577 quantified proteins using iTRAQ labelling. Known and completely novel markers for active tuberculosis in plasma were identified including a peptide derived from Mycobacterium tuberculosis. Complementary statistical and bioinformatic analysis were applied to prioritise candidates for validation in one or two independent cohorts. The plasma proteomic profile here described represents a power strategy for biomarker discovery and the panel proposed has the potential to be translated to a rapid test and which might contribute to tuberculosis control.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Pulmonary Tuberculosis

SUBMITTER: Diana Garay

LAB HEAD: Spiro Garbis

PROVIDER: PXD020212 | Pride | 2021-09-09

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	010916_TB_Set3_Seg4_3.msf	Msf
	010916_TB_Set3_Seg4_31-7_9-8.raw	Raw
	010916_TB_Set3_Seg4_32-3_10.raw	Raw
	010916_TB_Set3_Seg4_32-7_10-2.raw	Raw
	010916_TB_Set3_Seg4_33-8_10-4.raw	Raw

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Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis.

Garay-Baquero Diana J DJ White Cory H CH Walker Naomi F NF Tebruegge Marc M Schiff Hannah F HF Ugarte-Gil Cesar C Morris-Jones Stephen S Marshall Ben G BG Manousopoulou Antigoni A Adamson John J Vallejo Andres F AF Bielecka Magdalena K MK Wilkinson Robert J RJ Tezera Liku B LB Woelk Christopher H CH Garbis Spiros D SD Elkington Paul P

JCI insight 20200917 18

BACKGROUNDTuberculosis (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.METHODSWe 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 contro ...[more]

PMID: 32780727

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