Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection
| Autor: | Lobelia Samavati, Harvinder Talwar, Sorin Draghici, Samer Hanoudi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Tuberculosis Microarray T7 phage 030106 microbiology Protein Array Analysis lcsh:QR1-502 Enzyme-Linked Immunosorbent Assay immunoscreening Sensitivity and Specificity Article lcsh:Microbiology Mycobacterium tuberculosis 03 medical and health sciences Antigen Bacteriophage T7 Virology Immunoscreening Humans Medicine sarcoidosis Gene Library Immunoassay Antigens Bacterial biology medicine.diagnostic_test T7phage library business.industry Middle Aged medicine.disease biology.organism_classification 3. Good health 030104 developmental biology Infectious Diseases ROC Curve tuberculosis biology.protein Female Antibody Cell Surface Display Techniques business microarray Biomarkers |
| Zdroj: | Viruses Volume 10 Issue 7 Viruses, Vol 10, Iss 7, p 375 (2018) |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v10070375 |
| Popis: | Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB) and transmitted through inhalation of aerosolized droplets. Eighty-five percent of new TB cases occur in resource-limited countries in Asia and Africa and fewer than 40% of TB cases are diagnosed due to the lack of accurate and easy-to-use diagnostic assays. Currently, diagnosis relies on the demonstration of the bacterium in clinical specimens by serial sputum smear microscopy and culture. These methods lack sensitivity, are time consuming, expensive, and require trained personnel. An alternative approach is to develop an efficient immunoassay to detect antibodies reactive to MTB antigens in bodily fluids, such as serum. Sarcoidosis and TB have clinical and pathological similarities and sarcoidosis tissue has yielded MTB components. Using sarcoidosis tissue, we developed a T7 phage cDNA library and constructed a microarray platform. We immunoscreened our microarray platform with sera from healthy (n = 45), smear positive TB (n = 24), and sarcoidosis (n = 107) subjects. Using a student t-test, we identified 192 clones significantly differentially expressed between the three groups at a False Discovery Rate (FDR) < 0.01. Among those clones, we selected the top ten most significant clones and validated them on independent test set. The area under receiver operating characteristics (ROC) for the top 10 significant clones was 1 with a sensitivity of 1 and a specificity of 1. Sequence analyses of informative phage inserts recognized as antigens by active TB sera may identify immunogenic antigens that could be used to develop therapeutic or prophylactic vaccines, as well as identify molecular targets for therapy. |
| Databáze: | OpenAIRE |
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