Chen Gahao, Yang Ziwei
Department of pediatrics, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
PLoS One. 2025 Jul 9;20(7):e0327564. doi: 10.1371/journal.pone.0327564. eCollection 2025.
Intravenous immunoglobulin (IVIG) has been established as the first-line therapy for Kawasaki disease (KD). However, approximately 10%-20% of pediatric patients exhibit IVIG resistance. Current machine learning (ML) models demonstrate suboptimal predictive performance in KD treatment response prediction, primarily due to their limited ability to effectively process categorical variables and interpret tabular clinical data. This study aims to develop and interpretable transformer-based clinical prediction model for IVIG resistant KD and validate its clinical utility. This retrospective study analyzed clinical records of KD patients from the Affiliated Hospital of North Sichuan Medical College (Nanchong, China) between January 1, 2014 and December 31, 2024. A cohort of 1,578 pediatric KD cases was systematically divided into training and validation sets. Six machine learning algorithms - Random Forest (RF), AdaBoost, Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting (XGBoost), Categorical Boosting (CatBoost), and Tabular Prior-data Fitted Network version 2.0 (TabPFN-V2) - were implemented with five-fold cross-validation to optimize model hyperparameters. Model performance was rigorously evaluated using seven metrics: accuracy, precision, recall, F1-score, Matthews correlation coefficient (MCC), area under the receiver operating characteristic (ROC-AUC), and area under the precision-recall curve (PR-AUC). The top-performing model was subsequently subjected to interpretability analysis through Shapley Additive Explanations (SHAP) to elucidate feature contributions. The transformer-based TabPFN-V2 model demonstrated superior predictive performance in KD analysis, achieving an impressive validation set accuracy of 0.97. Comprehensive evaluation metrics confirmed its robust performance: precision 0.98, recall 0.97, F1-score 0.98, MCC 0.95, ROC-AUC 0.99, and PR-AUC 0.99. Global interpretability analysis through kernel SHAP methodology identified the ten most influential predictive features ranked by significance: Coronary artery lesions (CAL), Aspartate aminotransferase (AST), C-reactive protein (CRP), whether it was incomplete KD (KDtype), Neutrophil count (N), Platelet count (PLT), Albumin (ALB), age, White blood cell count (WBC) and Hemoglobin (Hb). Local interpretability analysis revealed distinct correlation patterns with IVIG resistance:AST, CRP, and N demonstrated significant positive correlations, where elevated values corresponded to increased IVIG resistance risk; PLT and ALB showed negative correlations, with higher levels associated with reduced resistance probability. Notably, age and WBC parameters demonstrated threshold effects, where optimal cutoff values enabled re-calibration of single-variable predictive scores. This threshold-dependent relationship suggests potential clinical utility in risk stratification protocols.The TabPFN-V2 model, leveraging an interpretable transformer architecture, demonstrates dual clinical utilities in KD management: (1) accurate prediction of IVIG resistance risk, and (2) data-driven support for personalized therapeutic decision-making. This framework enables probabilistic estimation of treatment resistance likelihood while providing transparent feature contribution analyses essential for developing patient-specific management protocols.
静脉注射免疫球蛋白(IVIG)已被确立为川崎病(KD)的一线治疗方法。然而,约10%-20%的儿科患者表现出IVIG抵抗。当前的机器学习(ML)模型在KD治疗反应预测中表现出次优的预测性能,主要是因为它们有效处理分类变量和解释表格临床数据的能力有限。本研究旨在开发一种基于可解释变压器的IVIG抵抗性KD临床预测模型,并验证其临床效用。这项回顾性研究分析了2014年1月1日至2024年12月31日期间川北医学院附属医院(中国南充)KD患者的临床记录。一组1578例儿科KD病例被系统地分为训练集和验证集。六种机器学习算法——随机森林(RF)、AdaBoost、轻梯度提升机(LightGBM)、极端梯度提升(XGBoost)、分类提升(CatBoost)和表格先验数据拟合网络版本2.0(TabPFN-V2)——通过五折交叉验证来优化模型超参数。使用七个指标对模型性能进行严格评估:准确率、精确率、召回率、F1分数、马修斯相关系数(MCC)、受试者操作特征曲线下面积(ROC-AUC)和精确率-召回率曲线下面积(PR-AUC)。随后,通过Shapley加法解释(SHAP)对表现最佳的模型进行可解释性分析,以阐明特征贡献。基于变压器的TabPFN-V2模型在KD分析中表现出卓越的预测性能,在验证集中取得了令人印象深刻的0.97准确率。综合评估指标证实了其稳健的性能:精确率0.98、召回率0.97、F1分数0.98、MCC 0.95、ROC-AUC 0.99和PR-AUC 0.99。通过核SHAP方法进行的全局可解释性分析确定了按重要性排序的十个最具影响力的预测特征:冠状动脉病变(CAL)、天冬氨酸转氨酶(AST)、C反应蛋白(CRP)、是否为不完全KD(KDtype)、中性粒细胞计数(N)、血小板计数(PLT)、白蛋白(ALB)、年龄、白细胞计数(WBC)和血红蛋白(Hb)。局部可解释性分析揭示了与IVIG抵抗的不同相关模式:AST、CRP和N呈现显著正相关,值升高对应IVIG抵抗风险增加;PLT和ALB呈负相关,水平越高与抵抗概率降低相关。值得注意的是,年龄和WBC参数表现出阈值效应,其中最佳临界值能够重新校准单变量预测分数。这种阈值依赖性关系表明在风险分层方案中具有潜在的临床效用。TabPFN-V2模型利用可解释的变压器架构,在KD管理中展示了双重临床效用:(1)准确预测IVIG抵抗风险,以及(2)为个性化治疗决策提供数据驱动的支持。该框架能够对治疗抵抗可能性进行概率估计,同时提供对制定患者特异性管理方案至关重要的透明特征贡献分析。