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Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles

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 parall...

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Autores principales: Jackson, Heather, Menikou, Stephanie, Hamilton, Shea, McArdle, Andrew, Shimizu, Chisato, Galassini, Rachel, Huang, Honglei, Kim, Jihoon, Tremoulet, Adriana, Thorne, Adam, Fischer, Roman, de Jonge, Marien I., Kuijpers, Taco, Wright, Victoria, Burns, Jane C., Casals-Pascual, Climent, Herberg, Jethro, Levin, Mike, Kaforou, Myrsini
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198135/
https://www.ncbi.nlm.nih.gov/pubmed/34073389
http://dx.doi.org/10.3390/ijms22115655
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author Jackson, Heather
Menikou, Stephanie
Hamilton, Shea
McArdle, Andrew
Shimizu, Chisato
Galassini, Rachel
Huang, Honglei
Kim, Jihoon
Tremoulet, Adriana
Thorne, Adam
Fischer, Roman
de Jonge, Marien I.
Kuijpers, Taco
Wright, Victoria
Burns, Jane C.
Casals-Pascual, Climent
Herberg, Jethro
Levin, Mike
Kaforou, Myrsini
author_facet Jackson, Heather
Menikou, Stephanie
Hamilton, Shea
McArdle, Andrew
Shimizu, Chisato
Galassini, Rachel
Huang, Honglei
Kim, Jihoon
Tremoulet, Adriana
Thorne, Adam
Fischer, Roman
de Jonge, Marien I.
Kuijpers, Taco
Wright, Victoria
Burns, Jane C.
Casals-Pascual, Climent
Herberg, Jethro
Levin, Mike
Kaforou, Myrsini
author_sort Jackson, Heather
collection PubMed
description 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 infections 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.
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spelling pubmed-81981352021-06-14 Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles Jackson, Heather Menikou, Stephanie Hamilton, Shea McArdle, Andrew Shimizu, Chisato Galassini, Rachel Huang, Honglei Kim, Jihoon Tremoulet, Adriana Thorne, Adam Fischer, Roman de Jonge, Marien I. Kuijpers, Taco Wright, Victoria Burns, Jane C. Casals-Pascual, Climent Herberg, Jethro Levin, Mike Kaforou, Myrsini Int J Mol Sci Article 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 infections 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. MDPI 2021-05-26 /pmc/articles/PMC8198135/ /pubmed/34073389 http://dx.doi.org/10.3390/ijms22115655 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
Jackson, Heather
Menikou, Stephanie
Hamilton, Shea
McArdle, Andrew
Shimizu, Chisato
Galassini, Rachel
Huang, Honglei
Kim, Jihoon
Tremoulet, Adriana
Thorne, Adam
Fischer, Roman
de Jonge, Marien I.
Kuijpers, Taco
Wright, Victoria
Burns, Jane C.
Casals-Pascual, Climent
Herberg, Jethro
Levin, Mike
Kaforou, Myrsini
Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
title Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
title_full Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
title_fullStr Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
title_full_unstemmed Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
title_short Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
title_sort kawasaki disease patient stratification and pathway analysis based on host transcriptomic and proteomic profiles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198135/
https://www.ncbi.nlm.nih.gov/pubmed/34073389
http://dx.doi.org/10.3390/ijms22115655
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