Kawasaki Disease patient stratification and pathway analysis based on host transcriptomic and proteomic profiles
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The aetiology of Kawasaki Disease (KD), an acute inflammatory disorder of childhood, remains unknown despite various triggers of KD having been proposed. Host ‘omic profiles offer insights into the host response to infection and inflammation, with the interrogation of multiple ‘omic levels in parallel providing a more comprehensive picture. We used differential abundance analysis, pathway analysis, clustering and classification techniques to explore whether the host response in KD is more similar to the response to bacterial or viral infection at the transcriptomic and proteomic levels through comparison of ‘omic profiles from children with KD to those with bacterial and viral infections. Pathways activated in patients with KD included those involved in anti-viral and anti-bacterial responses. Unsupervised clustering showed that the majority of KD patients clustered with bacterial patients on both ‘omic levels, whilst application of diagnostic signatures specific for bacterial and viral infections revealed that many transcriptomic KD samples had low probabilities of having bacterial or viral infections, suggesting that KD may be triggered by a different process not typical of either common bacterial or viral infections. Clustering based on the transcriptomic and proteomic responses during KD revealed three clusters of KD patients on both ‘omic levels, suggesting heterogeneity within the inflammatory response during KD. The observed heterogeneity may reflect differences in the host response to a common trigger, or variation dependent on different triggers of the condition.
Date Issued
2021-05-26
Date Acceptance
2021-05-04
Citation
International Journal of Molecular Sciences, 2021, 11 (11), pp.1-24
ISSN
1422-0067
Publisher
MDPI AG
Start Page
1
End Page
24
Journal / Book Title
International Journal of Molecular Sciences
Volume
11
Issue
11
Copyright Statement
© 2021 by the authors.
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/).
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/).
License URL
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Wellcome Trust
COSMIC (Children of St.Mary's Intensive Care)
Commission of the European Communities
Identifier
https://www.mdpi.com/1422-0067/22/11/5655
Grant Number
RD501 79560
206508/Z/17/Z
PC2230
848196
Subjects
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
Chemistry
infectious diseases
paediatrics
transcriptomics
proteomics
Kawasaki disease
host 'omics
systems biology
pathway analysis
clustering
classification
INFECTIONS
EXPRESSION
CRITERION
PACKAGE
Kawasaki disease
classification
clustering
host ‘omics
infectious diseases
paediatrics
pathway analysis
proteomics
systems biology
transcriptomics
Adolescent
Bacterial Infections
Child
Child, Preschool
Computational Biology
Female
Gene Expression Profiling
Humans
Male
Mucocutaneous Lymph Node Syndrome
Proteomics
Virus Diseases
Humans
Bacterial Infections
Virus Diseases
Mucocutaneous Lymph Node Syndrome
Gene Expression Profiling
Proteomics
Computational Biology
Adolescent
Child
Child, Preschool
Female
Male
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Chemical Physics
Publication Status
Published
Date Publish Online
2021-05-26