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Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants
Victor L Jong1,2, Inge M L Ahout3, Henk-Jan van den Ham2
1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Researchers identified an 84-gene signature in hospitalized infants that accurately predicts the severity of respiratory syncytial virus (RSV) infection. This genomic signature, combined with age and sex, can aid in early clinical management of RSV patients.
Area of Science:
- Virology
- Genomics
- Pediatric Medicine
Background:
- Respiratory syncytial virus (RSV) infections present a wide spectrum of illness, from mild colds to severe lower respiratory tract infections.
- Predicting disease progression in infants upon initial presentation is clinically challenging, as RSV can rapidly escalate to critical illness.
Purpose of the Study:
- To investigate the existence of a genomic signature capable of accurately predicting the clinical course and severity of respiratory syncytial virus infections in hospitalized infants.
- To develop a potential prognostic tool to support early clinical decision-making for RSV patients.
Main Methods:
- Utilized early blood microarray transcriptome profiles from 39 hospitalized infants, retrospectively assessing disease severity.
- Applied support vector machine learning to age- and sex-standardized transcriptomic data to identify a predictive gene signature.
- Validated the identified signature on an independent cohort of 53 infants.
Main Results:
- An 84-gene signature was identified that effectively discriminated between infants with less severe and those with the most severe RSV infections.
- The gene signature achieved an area under the receiver operating characteristic curve (AUC) of 0.966 (cross-validation) and 0.858 (independent validation).
- Combining the gene signature with infant age and sex improved prediction accuracy to an AUC of 0.971.
Conclusions:
- The identified 84-gene signature demonstrates high accuracy in predicting RSV disease severity in hospitalized infants.
- This genomic signature holds promise as a basis for developing a novel prognostic test to enhance clinical management strategies for RSV.
- Integrating this signature with clinical factors like age and sex offers a robust approach for predicting RSV outcomes.
Abstract:
Respiratory syncytial virus (RSV) causes infections that range from common cold to severe lower respiratory tract infection requiring high-level medical care. Prediction of the course of disease in individual patients remains challenging at the first visit to the pediatric wards and RSV infections may rapidly progress to severe disease. In this study we investigate whether there exists a genomic signature that can accurately predict the course of RSV. We used early blood microarray transcriptome profiles from 39 hospitalized infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease. This signature yielded an area under the receiver operating characteristic curve (AUC) of 0.966 using leave-one-out cross-validation on the experimental data and an AUC of 0.858 on an independent validation cohort consisting of 53 infants. A combination of the gene signature with age and sex yielded an AUC of 0.971. Thus, the presented signature may serve as the basis to develop a prognostic test to support clinical management of RSV patients.
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