Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants.
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.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Victor L
VL
Jong
Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Inge M L
IM
Ahout
Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Henk-Jan
HJ
van den Ham
Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Jop
J
Jans
Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Fatiha
F
Zaaraoui-Boutahar
Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Aldert
A
Zomer
Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Elles
E
Simonetti
Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Maarten A
MA
Bijl
Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
H Kim
HK
Brand
Center for Biomics, Erasmus Medical Center, Rotterdam, The Netherlands.
Wilfred F J
WF
van IJcken
Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Marien I
MI
de Jonge
Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.
Pieter L
PL
Fraaij
Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Ronald
R
de Groot
Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.|Research Institute for Infectious Diseases and Zoonoses, Veterinary University Hannover, Germany.
Albert D M E
AD
Osterhaus
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Marinus J
MJ
Eijkemans
Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Gerben
G
Ferwerda
Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Arno C
AC
Andeweg
D001990:Bronchiolitis, Viral / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011379:Prognosis; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000378:metabolism*; D012720:Severity of Illness Index; D060388:Support Vector Machine; D059467:Transcriptome