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Article

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

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Faculty of Medicine, Imperial College London, London SW7 2AZ, UK
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Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
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Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK
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Department of Biomedical Informatics, University of California San Diego, La Jolla, CA 92093, USA
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Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
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Discovery Proteomics Facility, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UK
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Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
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Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children’s Hospital, Amsterdam University Medical Center (AMC), 1105 AZ Amsterdam, The Netherlands
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Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK
*
Author to whom correspondence should be addressed.
Shared first author.
Shared final author.
§
Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management (PERFORM), London SW7 2AZ, UK.
Academic Editor: Sarath Janga Chandra
Int. J. Mol. Sci. 2021, 22(11), 5655; https://doi.org/10.3390/ijms22115655
Received: 9 April 2021 / Accepted: 4 May 2021 / Published: 26 May 2021
(This article belongs to the Special Issue Host Infectomics in the Childhood)
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. View Full-Text
Keywords: infectious diseases; paediatrics; transcriptomics; proteomics; Kawasaki disease; host ‘omics; systems biology; pathway analysis; clustering; classification infectious diseases; paediatrics; transcriptomics; proteomics; Kawasaki disease; host ‘omics; systems biology; pathway analysis; clustering; classification
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MDPI and ACS Style

Jackson, H.; Menikou, S.; Hamilton, S.; McArdle, A.; Shimizu, C.; Galassini, R.; Huang, H.; Kim, J.; Tremoulet, A.; Thorne, A.; Fischer, R.; de Jonge, M.I.; Kuijpers, T.; Wright, V.; Burns, J.C.; Casals-Pascual, C.; Herberg, J.; Levin, M.; Kaforou, M.; on behalf of the PERFORM Consortium. Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles. Int. J. Mol. Sci. 2021, 22, 5655. https://doi.org/10.3390/ijms22115655

AMA Style

Jackson H, Menikou S, Hamilton S, McArdle A, Shimizu C, Galassini R, Huang H, Kim J, Tremoulet A, Thorne A, Fischer R, de Jonge MI, Kuijpers T, Wright V, Burns JC, Casals-Pascual C, Herberg J, Levin M, Kaforou M, on behalf of the PERFORM Consortium. Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles. International Journal of Molecular Sciences. 2021; 22(11):5655. https://doi.org/10.3390/ijms22115655

Chicago/Turabian Style

Jackson, Heather, 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, and on behalf of the PERFORM Consortium. 2021. "Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles" International Journal of Molecular Sciences 22, no. 11: 5655. https://doi.org/10.3390/ijms22115655

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