학술논문

Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
Document Type
article
Source
International Journal of Molecular Sciences. 22(11)
Subject
Microbiology
Biological Sciences
Precision Medicine
Infectious Diseases
Autoimmune Disease
Emerging Infectious Diseases
2.1 Biological and endogenous factors
Inflammatory and immune system
Infection
Adolescent
Bacterial Infections
Child
Child
Preschool
Computational Biology
Female
Gene Expression Profiling
Humans
Male
Mucocutaneous Lymph Node Syndrome
Proteomics
Virus Diseases
infectious diseases
paediatrics
transcriptomics
proteomics
Kawasaki disease
host 'omics
systems biology
pathway analysis
clustering
classification
host ‘omics
Other Chemical Sciences
Genetics
Other Biological Sciences
Chemical Physics
Biochemistry and cell biology
Medicinal and biomolecular chemistry
Language
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 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.