Study design and experimental workflow. A two-phased strategy was employed to identify and characterize candidate protein biomarkers of ARV infection from NPL samples collected from participants in four experimental ARV challenge cohorts. For phase 1 discovery analysis, four NPL pools were prepared from H3N2 #1 cohort and analyzed using unbiased 2D-LC-MS/MS. The numbers of subject (N) with samples included in each pool are shown (Uninf = uninfected individuals; Inf = infected individuals; BL = baseline; T = time of maximal symptoms). For phase 2, the original and three additional independent challenge cohorts were assayed by targeted MRM. Quantitative peptide expression data from 80 individuals and 156 total samples were used in the derivation of an NPL ARV classifier, and classification performance was assessed in independent challenge cohorts using LOOCV.
Duke Health scientists have identified a group of proteins that, when detected in specific quantities in the mucous, are 86% accurate in confirming the infection is from a cold or flu virus, according to a small, proof-of-concept trial published online in the journal EBioMedicine. The researchers hope their initial work identifying the protein signature could aid the development of a quick, noninvasive doctor’s office test to determine the cause of upper respiratory illness and appropriate treatment.
“Every day, people are taking time off from work, going to emergency rooms, urgent care or their primary care doctors with symptoms of an upper respiratory infection,” said Geoffrey S. Ginsburg, M.D., Ph.D. and director of the Duke Center for Applied Genomics & Precision Medicine (DCAGPM), which led the study. “Looking for these proteins could be a relatively easy and inexpensive way of learning if a person has a viral infection, and if not, whether the use of antibiotics is appropriate.” Widespread use of antibiotics for upper respiratory infections don’t benefit patients with viral illness and can contribute to antibiotic-resistant superbugs.
For the trial, researchers infected 88 healthy adult volunteers with a common strain of cold or flu virus. Some participants didn’t get sick. Among those who developed infections, researchers found a distinct set of 25 proteins in fluid samples they gathered by flushing about 2 teaspoons of saline through the participant’s nasal passages.
“In the past, science has focused on identifying the pathogen someone is infected with in the blood or other sample,” said Thomas Burke, Ph.D., director of technology advancement and diagnostics at the DCAGPM. “Our approach flips the paradigm of how we look for infection. Instead of looking for the pathogen, we study the individual’s response to that pathogen and signature patterns in their genes, proteins, metabolites and other biomarkers.”
The Duke team has previously explored blood tests to examine a patient’s RNA for gene signatures to distinguish bacterial and viral infections in the upper respiratory tract and is working with a private company to develop potential diagnostics. Analyzing proteins in mucous is a less invasive approach and requires less processing than blood samples. The researchers hope additional studies verify the initial results and lead to the development of a paper-based test that could be used in doctor’s offices or even at home to determine whether a doctor’s visit is necessary, said Christopher Woods, M.D..
“The protein targets offer a faster, more cost-effective model for rapid screening and diagnoses of viral infections,” Woods said. “If the data are verified, the model could be valuable in many circumstances, such as rural settings or developing countries with less convenient access to health care, or even as an airport screening tool during an outbreak of a particularly threatening strain of flu.”
https://bme.duke.edu/about/news/61462
http://www.ebiomedicine.com/article/S2352-3964(17)30074-9/abstract
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