VB10, a new blood biomarker for differential diagnosis and recovery monitoring of acute viral and bacterial infections

Autor: Dipshikha Chakravortty, Gayathri Devi Dr, Chandrani Thakur, Kithiganahalli Narayanaswamy Balaji, Rooparani Kandukuru, Nagasuma Chandra, Sathyabaarathi Ravichandran, Amit Singh, U.C. Banerjee
Rok vydání: 2021
Předmět:
Adult
Male
0301 basic medicine
Medicine (General)
medicine.medical_specialty
Databases
Factual
medicine.drug_class
Antibiotics
India
Antimicrobial resistance
Classifier
Clinical decision support system
General Biochemistry
Genetics and Molecular Biology
Diagnosis
Differential
03 medical and health sciences
R5-920
0302 clinical medicine
Antibiotic resistance
Diagnostic score
Predictive Value of Tests
Internal medicine
medicine
Humans
Protein Interaction Maps
Gene Expression Profiling
Computational Biology
Biomarker
Bacterial Infections
General Medicine
Middle Aged
Decision Support Systems
Clinical
Molecular diagnostics
Observational Studies as Topic
Blood
030104 developmental biology
Virus Diseases
030220 oncology & carcinogenesis
Predictive value of tests
Cohort
Medicine
Biomarker (medicine)
Female
Differential diagnosis
Transcriptome
Systems biology
Biomarkers
Research Paper
Acute infections
Zdroj: EBioMedicine
EBioMedicine, Vol 67, Iss, Pp 103352-(2021)
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2021.103352
Popis: Background: Precise differential diagnosis between acute viral and bacterial infections is important to enable appropriate therapy, avoid unnecessary antibiotic prescriptions and optimize the use of hospital resources. A systems view of host response to infections provides opportunities for discovering sensitive and robust molecular diagnostics. Methods: We combine blood transcriptomes from six independent datasets (n = 756) with a knowledge-based human protein-protein interaction network, identifies subnetworks capturing host response to each infection class, and derives common response cores separately for viral and bacterial infections. We subject the subnetworks to a series of computational filters to identify a parsimonious gene panel and a standalone diagnostic score that can be applied to individual samples. We rigorously validate the panel and the diagnostic score in a wide range of publicly available datasets and in a newly developed Bangalore-Viral Bacterial (BL-VB) cohort. Finding: We discover a 10-gene blood-based biomarker panel (Panel-VB) that demonstrates high predictive performance to distinguish viral from bacterial infections, with a weighted mean AUROC of 0.97 (95% CI: 0.96–0.99) in eleven independent datasets (n = 898). We devise a new stand-alone patient-wise score (VB10) based on the panel, which shows high diagnostic accuracy with a weighted mean AUROC of 0.94 (95% CI 0.91–0.98) in 2996 patient samples from 56 public datasets from 19 different countries. Further, we evaluate VB10 in a newly generated South Indian (BL-VB, n = 56) cohort and find 97% accuracy in the confirmed cases of viral and bacterial infections. We find that VB10 is (a) capable of accurately identifying the infection class in culture-negative indeterminate cases, (b) reflects recovery status, and (c) is applicable across different age groups, covering a wide spectrum of acute bacterial and viral infections, including uncharacterized pathogens. We tested our VB10 score on publicly available COVID-19 data and find that our score detected viral infection in patient samples. Interpretation: Our results point to the promise of VB10 as a diagnostic test for precise diagnosis of acute infections and monitoring recovery status. We expect that it will provide clinical decision support for antibiotic prescriptions and thereby aid in antibiotic stewardship efforts. Funding: Grand Challenges India, Biotechnology Industry Research Assistance Council (BIRAC), Department of Biotechnology, Govt. of India.
Databáze: OpenAIRE
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