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Published on: January 16, 2019
Distinguishing Kawasaki Disease from Febrile Infectious Disease Using Gene Pair Signatures
Jiayong Zhong1, Qingsheng Huang1, Yanfei Wang2
1Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Guangzhou, 510623 Guangdong, China.
Insights
This study identifies gene pair signatures as robust biomarkers to differentiate Kawasaki disease (KD) from febrile infectious (FI) diseases. These molecular markers offer a potential for faster, more accurate KD diagnosis in children.
Area of Science:
- Pediatric Rheumatology
- Molecular Diagnostics
- Bioinformatics
Background:
- Kawasaki disease (KD) is a childhood vasculitis often misdiagnosed due to reliance on clinical criteria.
- Current diagnostic methods lack specific molecular markers, leading to potential delays and misdiagnosis.
- Distinguishing KD from other febrile infectious (FI) diseases remains a clinical challenge.
Purpose of the Study:
- To identify robust gene pair signatures for differentiating KD from bacterial and viral FI diseases.
- To develop and validate a molecular classifier for improved KD diagnosis.
- To establish objective biomarkers for KD detection.
Main Methods:
- Utilized a relative-expression-based method (k-TSP) and resampling framework on a cohort of 808 childhood patients.
- Data was divided into discovery (n=224), validation-1 (n=197), and validation-2 (n=387) sets.
- Developed a top-ranked gene pair classifier (TRGP) using the top seven gene pair signatures.
Main Results:
- Identified 60 biologically relevant gene pairs distinguishing KD from FI.
- The TRGP classifier demonstrated high performance: Discovery set AUROC 0.947, Validation-1 AUROC 0.955.
- Validation-2 showed promising predictive performance with an AUROC of 0.796, indicating robustness across diverse datasets.
Conclusions:
- Gene pair signatures serve as reliable biomarkers for distinguishing KD from FI.
- The developed TRGP classifier offers a fast, simple, and effective molecular approach to enhance KD diagnosis.
- Objective molecular markers are crucial for improving the accuracy and timeliness of KD diagnosis in children.
Abstract:
Kawasaki disease (KD) is an acute systemic vasculitis of childhood with prolonged fever, and the diagnosis of KD is mainly based on clinical criteria, which is prone to misdiagnosis with other febrile infectious (FI) diseases. Currently, there remain no effective molecular markers for KD diagnosis. In this study, we aimed to use a relative-expression-based method k-TSP and resampling framework to identify robust gene pair signatures to distinguish KD from bacterial and virus febrile infectious diseases. Our study pool consisted of 808 childhood patients from several studies and assigned to three groups, namely, the discovery set (n = 224), validation set-1 (n = 197), and validation set-2 (n = 387). We had identified 60 biologically relevant gene pairs and developed a top-ranked gene pair classifier (TRGP) using the first seven signatures, with the area under the receiver-operating characteristic curves (AUROC) of 0.947 (95% CI, 0.918-0.976), a sensitivity of 0.936 (95% CI, 0.872-0.987), and a specificity of 0.774 (95% CI, 0.705-0.836) in the discovery set. In the validation set-1, the TRGP classifier distinguished KD from FI with AUROC of 0.955 (95% CI, 0.919-0.991), a sensitivity of 0.959 (95% CI, 0.925-0.986), and a specificity of 0.863 (95% CI, 0.764-0.961). In the validation set-2, the predictive performance of classification was with an AUROC of 0.796 (95% CI, 0.747-0.845), a sensitivity of 0.797 (95% CI, 0.720-0.864), and a specificity of 0.661 (95% CI, 0.606-0.717). Our study reveals that gene pair signatures are robust across diverse studies and can be utilized as objective biomarkers to distinguish KD from FI, helping to develop a fast, simple, and effective molecular approach to improve the diagnosis of KD.
