Identification of novel salivary candidate protein biomarkers for tuberculosis diagnosis: A preliminary biomarker discovery study

Hygon Mutavhatsindi; Bridget Calder; Shirley McAnda; Stephanus T Malherbe; Kim Stanley; Martin Kidd; Gerhard Walzl; Novel N Chegou

doi:10.1016/j.tube.2021.102118

Identification of novel salivary candidate protein biomarkers for tuberculosis diagnosis: A preliminary biomarker discovery study

Tuberculosis (Edinb). 2021 Sep:130:102118. doi: 10.1016/j.tube.2021.102118. Epub 2021 Aug 5.

Authors

Hygon Mutavhatsindi¹, Bridget Calder², Shirley McAnda³, Stephanus T Malherbe³, Kim Stanley³, Martin Kidd⁴, Gerhard Walzl³, Novel N Chegou⁵

Affiliations

¹ DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town, 8000, South Africa. Electronic address: hygon.mutavhatsindi@uct.ac.za.
² Division of Chemical & Systems Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, South Africa.
³ DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town, 8000, South Africa.
⁴ Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, Stellenbosch University, Cape Town, South Africa.
⁵ DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town, 8000, South Africa. Electronic address: novel@sun.ac.za.

PMID: 34371310
DOI: 10.1016/j.tube.2021.102118

Abstract

Background: There is an urgent need for new, accurate, rapid, and affordable tuberculosis (TB) diagnostic tests. The aim of the present study was to use mass spectrometry to identify new preliminary candidate TB diagnostic protein biomarkers in saliva obtained from individuals with TB, and patients with other respiratory diseases (ORD).

Methods: Saliva samples were collected from 22 individuals who self-presented with symptoms suggestive of TB as part of a larger TB biomarker project. Purified salivary proteins were subjected to tryptic digestion peptides were analyzed using a QExactive Orbitrap Mass Spectrometer. Data are available via ProteomeXchange with identifier PXD027294. Identified proteins were subjected to gene ontology and ingenuity pathway analysis for functional enrichment analysis.

Results: 26 of the 652 identified proteins significantly discriminated individuals with TB from those with ORD after Benjamini Hochberg correction (5% FDR), with five of these proteins diagnosing TB with an AUC ≥ 0.80. A 5-protein biosignature comprising of P01011, Q8NCW5, P28072, A0A2Q2TTZ9, and Q99574 diagnosed TB with an AUC of 1.00 (95% CI, 1.00-1.00), sensitivity of 100% (95% CI, 76.2-100%) and specificity of 90.9% (95% CI, 58.7-99.8%) after leave-one-out cross validation.

Conclusions: We identified novel candidate salivary protein biomarkers and biosignatures with strong potential as TB diagnostic candidates. Our results are preliminary and require validation in larger studies.

Keywords: Biomarkers; Diagnosis; Proteomics; Saliva; Tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers / analysis
Female
Humans
Male
Middle Aged
Proteome
Salivary Proteins and Peptides / analysis*
Sensitivity and Specificity
South Africa
Tuberculosis / diagnosis*

Substances

Biomarkers
Proteome
Salivary Proteins and Peptides