CXCL1: A new diagnostic biomarker for human tuberculosis discovered using Diversity Outbred mice
نویسندگان
چکیده
More humans have died of tuberculosis (TB) than any other infectious disease and millions still die each year. Experts advocate for blood-based, serum protein biomarkers to help diagnose TB, which afflicts people in high-burden countries. However, the biomarker pipeline is small. Here, we used Diversity Outbred (DO) mouse population address this gap, identifying five candidates. One biomarker, CXCL1, met World Health Organization’s Targeted Product Profile a triage test active TB from latent M . tb infection (LTBI), non-TB lung disease, normal sera HIV-negative, adults South Africa Vietnam. To find candidates, quantified seven immune cytokines four inflammatory proteins corresponding highly expressed genes unique progressor DO mice. Next, applied statistical machine learning methods data, i.e., 11 lungs 453 infected 29 non-infected After searching all combinations algorithms 239 subsets, validating, testing findings on independent two accurately diagnosed mice: Logistic Regression using MMP8; Gradient Tree Boosting panel 4: CXCL2, TNF, IL-10. Of those (MMP8 CXCL1) were crucial classifying mice; above limit detection most human samples; had not been widely assessed diagnostic performance before. In patient sera, CXCL1 exceeded criteria (>90% sensitivity; >70% specificity), while MMP8 did not. Using Area Under Curve analyses, averaged 94.5% sensitivity 88.8% specificity pulmonary (ATB) vs LTBI; 90.9% 71.4% ATB non-TB; 100.0% 98.4% sera. Our overall show that can discover diagnostic-quality, TB.
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ژورنال
عنوان ژورنال: PLOS Pathogens
سال: 2021
ISSN: ['1553-7366', '1553-7374']
DOI: https://doi.org/10.1371/journal.ppat.1009773