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Personal Network Inference Unveils Heterogeneous Immune Response Patterns to Viral Infection in Children with Acute Wheezing

Human rhinovirus (RV)-induced exacerbations of asthma and wheeze are a major cause of emergency room presentations and hospital admissions among children. Previous studies have shown that immune response patterns during these exacerbations are heterogeneous and are characterized by the presence or a...

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Autores principales: Coleman, Laura A., Khoo, Siew-Kim, Franks, Kimberley, Prastanti, Franciska, Le Souëf, Peter, Karpievitch, Yuliya V., Laing, Ingrid A., Bosco, Anthony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706513/
https://www.ncbi.nlm.nih.gov/pubmed/34945765
http://dx.doi.org/10.3390/jpm11121293
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author Coleman, Laura A.
Khoo, Siew-Kim
Franks, Kimberley
Prastanti, Franciska
Le Souëf, Peter
Karpievitch, Yuliya V.
Laing, Ingrid A.
Bosco, Anthony
author_facet Coleman, Laura A.
Khoo, Siew-Kim
Franks, Kimberley
Prastanti, Franciska
Le Souëf, Peter
Karpievitch, Yuliya V.
Laing, Ingrid A.
Bosco, Anthony
author_sort Coleman, Laura A.
collection PubMed
description Human rhinovirus (RV)-induced exacerbations of asthma and wheeze are a major cause of emergency room presentations and hospital admissions among children. Previous studies have shown that immune response patterns during these exacerbations are heterogeneous and are characterized by the presence or absence of robust interferon responses. Molecular phenotypes of asthma are usually identified by cluster analysis of gene expression levels. This approach however is limited, since genes do not exist in isolation, but rather work together in networks. Here, we employed personal network inference to characterize exacerbation response patterns and unveil molecular phenotypes based on variations in network structure. We found that personal gene network patterns were dominated by two major network structures, consisting of interferon-response versus FCER1G-associated networks. Cluster analysis of these structures divided children into subgroups, differing in the prevalence of atopy but not RV species. These network structures were also observed in an independent cohort of children with virus-induced asthma exacerbations sampled over a time course, where we showed that the FCER1G-associated networks were mainly observed at late time points (days four–six) during the acute illness. The ratio of interferon- and FCER1G-associated gene network responses was able to predict recurrence, with low interferon being associated with increased risk of readmission. These findings demonstrate the applicability of personal network inference for biomarker discovery and therapeutic target identification in the context of acute asthma which focuses on variations in network structure.
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spelling pubmed-87065132021-12-25 Personal Network Inference Unveils Heterogeneous Immune Response Patterns to Viral Infection in Children with Acute Wheezing Coleman, Laura A. Khoo, Siew-Kim Franks, Kimberley Prastanti, Franciska Le Souëf, Peter Karpievitch, Yuliya V. Laing, Ingrid A. Bosco, Anthony J Pers Med Article Human rhinovirus (RV)-induced exacerbations of asthma and wheeze are a major cause of emergency room presentations and hospital admissions among children. Previous studies have shown that immune response patterns during these exacerbations are heterogeneous and are characterized by the presence or absence of robust interferon responses. Molecular phenotypes of asthma are usually identified by cluster analysis of gene expression levels. This approach however is limited, since genes do not exist in isolation, but rather work together in networks. Here, we employed personal network inference to characterize exacerbation response patterns and unveil molecular phenotypes based on variations in network structure. We found that personal gene network patterns were dominated by two major network structures, consisting of interferon-response versus FCER1G-associated networks. Cluster analysis of these structures divided children into subgroups, differing in the prevalence of atopy but not RV species. These network structures were also observed in an independent cohort of children with virus-induced asthma exacerbations sampled over a time course, where we showed that the FCER1G-associated networks were mainly observed at late time points (days four–six) during the acute illness. The ratio of interferon- and FCER1G-associated gene network responses was able to predict recurrence, with low interferon being associated with increased risk of readmission. These findings demonstrate the applicability of personal network inference for biomarker discovery and therapeutic target identification in the context of acute asthma which focuses on variations in network structure. MDPI 2021-12-03 /pmc/articles/PMC8706513/ /pubmed/34945765 http://dx.doi.org/10.3390/jpm11121293 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Coleman, Laura A.
Khoo, Siew-Kim
Franks, Kimberley
Prastanti, Franciska
Le Souëf, Peter
Karpievitch, Yuliya V.
Laing, Ingrid A.
Bosco, Anthony
Personal Network Inference Unveils Heterogeneous Immune Response Patterns to Viral Infection in Children with Acute Wheezing
title Personal Network Inference Unveils Heterogeneous Immune Response Patterns to Viral Infection in Children with Acute Wheezing
title_full Personal Network Inference Unveils Heterogeneous Immune Response Patterns to Viral Infection in Children with Acute Wheezing
title_fullStr Personal Network Inference Unveils Heterogeneous Immune Response Patterns to Viral Infection in Children with Acute Wheezing
title_full_unstemmed Personal Network Inference Unveils Heterogeneous Immune Response Patterns to Viral Infection in Children with Acute Wheezing
title_short Personal Network Inference Unveils Heterogeneous Immune Response Patterns to Viral Infection in Children with Acute Wheezing
title_sort personal network inference unveils heterogeneous immune response patterns to viral infection in children with acute wheezing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706513/
https://www.ncbi.nlm.nih.gov/pubmed/34945765
http://dx.doi.org/10.3390/jpm11121293
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