Rapid, Sample-to-Answer Host Gene Expression Test to Diagnose Viral Infection
| Autor: | Ephraim L. Tsalik, Micah T. McClain, Thomas W. Burke, Tino Alavie, Geoffrey S. Ginsburg, Ayeaye Khine, Ricardo Henao, Alaleh Samiei, Christopher W. Woods, Vilcy Parmar, A. Talebpour |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
business.industry medicine.disease Reverse transcriptase Procalcitonin law.invention Major Articles Gene expression profiling 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Infectious Diseases Real-time polymerase chain reaction Oncology Community-acquired pneumonia law Immunology Gene expression Medicine 030212 general & internal medicine business Polymerase chain reaction Whole blood |
| Zdroj: | Open Forum Infect Dis |
| Popis: | Objective Distinguishing bacterial, viral, or other etiologies of acute illness is diagnostically challenging with significant implications for appropriate antimicrobial use. Host gene expression offers a promising approach, although no clinically useful test has been developed yet to accomplish this. Here, Qvella’s FAST HR (Richmond Hill, Ontario, Canada) process was developed to quantify previously identified host gene expression signatures in whole blood in Method Whole blood was collected from 128 human subjects (mean age 47, range 18–88) with clinically adjudicated, microbiologically confirmed viral infection, bacterial infection, noninfectious illness, or healthy controls. Stabilized mRNA was released from cleaned and stabilized RNA-surfactant complexes using e-lysis, an electrical process providing a quantitative real-time reverse transcription polymerase chain reaction-ready sample. Threshold cycle values (CT) for 10 host response targets were normalized to hypoxanthine phosphoribosyltransferase 1 expression, a control mRNA. The transcripts in the signature were specifically chosen to discriminate viral from nonviral infection (bacterial, noninfectious illness, or healthy). Classification accuracy was determined using cross-validated sparse logistic regression. Results Reproducibility of mRNA quantification was within 1 cycle as compared to the difference seen between subjects with viral versus nonviral infection (up to 5.0 normalized CT difference). Classification of 128 subjects into viral or nonviral etiologies demonstrated 90.6% overall accuracy compared to 82.0% for procalcitonin (P = .06). FAST HR achieved rapid and accurate measurement of the host response to viral infection in less than 45 minutes. Conclusions These results demonstrate the ability to translate host gene expression signatures to clinical platforms for use in patients with suspected infection. Clinical Trials Registration NCT00258869. |
| Databáze: | OpenAIRE |
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