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.

中文翻译：

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鉴定用于结核病诊断的新型唾液候选蛋白生物标志物：初步生物标志物发现研究

背景

迫切需要新的、准确、快速和负担得起的结核病 (TB) 诊断测试。本研究的目的是使用质谱法在从结核病患者和其他呼吸系统疾病 (ORD) 患者获得的唾液中鉴定新的初步候选结核病诊断蛋白生物标志物。

方法

作为更大的 TB 生物标志物项目的一部分，从 22 名自我表现出提示 TB 症状的个体中收集唾液样本。对纯化的唾液蛋白进行胰蛋白酶消化，使用 QExactive Orbitrap 质谱仪分析肽。数据可通过 ProteomeXchange 获得，标识符为 PXD027294。对鉴定的蛋白质进行基因本体论和独创性途径分析，以进行功能富集分析。

结果

在 Benjamini Hochberg 校正 (5% FDR) 后，652 种已鉴定的蛋白质中有 26 种可显着区分结核病个体和 ORD 个体，其中 5 种蛋白质以 AUC ≥ 0.80 诊断结核病。由 P01011、Q8NCW5、P28072、A0A2Q2TTZ9 和 Q99574 组成的 5 种蛋白质生物印记以 1.00 (95% CI, 1.00–1.00) 的 AUC (95% CI, 1.00–1.00)、100% (95% CI, 76.2–100%) 的敏感性和特异性诊断为 TB留一交叉验证后的 90.9% (95% CI, 58.7–99.8%)。

结论

我们确定了新的候选唾液蛋白生物标志物和生物印记，它们具有作为结核病诊断候选物的强大潜力。我们的结果是初步的，需要在更大的研究中进行验证。