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

PERFORM Consortium, Heather Jackson, Stephanie Menikou, Shea Hamilton, Andrew McArdle, Chisato Shimizu, Rachel Galassini, Honglei Huang, Jihoon Kim, Adriana Tremoulet, Adam Thorne, Roman Fischer, Marien I. de Jonge, Taco Kuijpers, Victoria Wright, Jane C. Burns, Climent Casals-Pascual, Jethro Herberg, Mike Levin, Myrsini Kaforou*

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

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    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.

    Originele taal-2English
    Artikelnummer5655
    Aantal pagina's24
    TijdschriftInternational Journal of Molecular Sciences
    Volume22
    Nummer van het tijdschrift11
    Vroegere onlinedatum26-mei-2021
    DOI's
    StatusPublished - jun-2021

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