ArticlePLoS pathogens2021
CXCL1: A new diagnostic biomarker for human tuberculosis discovered using Diversity Outbred mice.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- The study of immunological markers in tuberculosis across animal models and its translation to human research.Lab animal · 2026Review
- Emerging insights into CC and CXC chemokines and their receptors in Mycobacterium tuberculosis infection.FEBS open bio · 2026Review
- Article
- Fifteen years of the Diversity Outbred mouse model: a review.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Article
- Transcriptomic insights intoThe veterinary quarterly · 2025Article
- Tuberculosis susceptibility in genetically diverse mice reveals functional diversity of neutrophils.eLife · 2025Article
- Cathepsin Z is a conserved susceptibility factor underlying tuberculosis severity.PLoS biology · 2025Article
- The Evolving Landscape of Host Biomarkers for Diagnosis and Monitoring of Tuberculosis.Biomedicines · 2025Review
- Backtranslation of human RNA biosignatures of tuberculosis disease risk into the preclinical pipeline is condition dependent.mSphere · 2025Article
- Immunological roads diverged: mapping tuberculosis outcomes in mice.Trends in microbiology · 2025Review
- Recent progress in tuberculosis diagnosis: insights into blood-based biomarkers and emerging technologies.Frontiers in cellular and infection microbiology · 2025Review
- Cellular and Molecular Network Characteristics ofInternational journal of molecular sciences · 2024Article
- B cells in perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell signatures identify asymptomaticInfection and immunity · 2024Article
- Preclinical murine models for the testing of antimicrobials against Mycobacterium abscessus pulmonary infections: Current practices and recommendations.Tuberculosis (Edinburgh, Scotland) · 2024Review
- Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice.PLoS pathogens · 2024Article
- ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6-specific nanobody restrictseLife · 2024Article
- ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6 specific nanobody restricts M. tuberculosis growth in macrophages.bioRxiv : the preprint server for biology · 2024Article
- Multiple genetic loci influence vaccine-induced protection against Mycobacterium tuberculosis in genetically diverse mice.PLoS pathogens · 2024Article
- Prediction of Tuberculosis From Lung Tissue Images of Diversity Outbred Mice Using Jump Knowledge Based Cell Graph Neural Network.IEEE access : practical innovations, open solutions · 2024Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
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 millions of people in high-burden countries. However, the protein biomarker pipeline is small. Here, we used the Diversity Outbred (DO) mouse population to address this gap, identifying five protein biomarker candidates. One protein biomarker, serum CXCL1, met the World Health Organization's Targeted Product Profile for a triage test to diagnose active TB from latent M.tb infection (LTBI), non-TB lung disease, and normal sera in HIV-negative, adults from South Africa and Vietnam. To find the biomarker candidates, we quantified seven immune cytokines and four inflammatory proteins corresponding to highly expressed genes unique to progressor DO mice. Next, we applied statistical and machine learning methods to the data, i.e., 11 proteins in lungs from 453 infected and 29 non-infected mice. After searching all combinations of five algorithms and 239 protein subsets, validating, and testing the findings on independent data, two combinations accurately diagnosed progressor DO mice: Logistic Regression using MMP8; and Gradient Tree Boosting using a panel of 4: CXCL1, CXCL2, TNF, IL-10. Of those five protein biomarker candidates, two (MMP8 and CXCL1) were crucial for classifying DO mice; were above the limit of detection in most human serum samples; and had not been widely assessed for diagnostic performance in humans before. In patient sera, CXCL1 exceeded the triage diagnostic test criteria (>90% sensitivity; >70% specificity), while MMP8 did not. Using Area Under the Curve analyses, CXCL1 averaged 94.5% sensitivity and 88.8% specificity for active pulmonary TB (ATB) vs LTBI; 90.9% sensitivity and 71.4% specificity for ATB vs non-TB; and 100.0% sensitivity and 98.4% specificity for ATB vs normal sera. Our findings overall show that the DO mouse population can discover diagnostic-quality, serum protein biomarkers of human TB.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.