基于血液与脑脊液细胞因子的婴儿细菌性脑膜炎和病毒性脑炎早期鉴别的机器学习模型

Machine learning model for early differentiation of bacterial meningitis and viral encephalitis in infants based on blood and cerebrospinal fluid cytokines

  • 摘要:
    目的  比较血液及脑脊液的细胞因子在婴儿细菌性脑膜炎(BM)与病毒性脑炎(VE)的差异性,构建早期鉴别诊断机器学习模型。
    方法  选择2022年1月-2024年11月疑似中枢神经系统感染在宁波大学附属妇女儿童医院神经内科住院部收治的婴儿120例为研究对象。所有患儿在入院后即刻采集静脉血及脑脊液样本,最终根据金标准分为BM组40例、VE组40例和非中枢神经系统感染组(NC)患儿40例。比较三组血液和脑脊液细胞因子的差异,使用8种机器学习训练模型,采用受试者工作特征曲线、校准曲线、决策曲线分析等指标选择最佳模型。采用SHAP方法对模型进行解释。
    结果 BM组血清白细胞介素-6(IL-6)水平105.85(25.19,192.46)pg/ml高于VE组40.85(12.68,69.81)pg/ml和NC组(P<0.05),VE组高于NC组(P<0.05),VE组血清干扰素γ(IFN-γ)为7.29(1.66,37.37)pg/ml高于BM组2.21(1.12,5.65)pg/ml和NC组(P<0.05)。BM组血清IL-17A为1.96(0.92,4.88)pg/ml高于NC组(P<0.05)。BM组脑脊液IL-6、IL-10分别为102.13(31.38,569.60)pg/ml、15.88(5.56,43.79)pg/ml均高于VE组21.70(9.64,40.00)pg/ml、8.50(4.10,15.05)pg/ml和NC组(P<0.05),VE组脑脊液IL-6、IL-10均高于NC组(P<0.05),VE组脑脊液IFN-γ为1.61(1.33,2.74)pg/ml高于BM组1.13(0.30,1.75)pg/ml和NC组(P<0.05)。基于上述指标构建的8种机器学习模型中,梯度提升机(GBM)模型表现最好(曲线下面积为0.938、准确度为0.917、灵敏度为0.917、特异度为0.917、精确度为0.917、F1值为0.917)。SHAP分析显示特征对模型的贡献从大到小排序为:脑脊液IL-6、血清IFN-γ、血清IL-6、脑脊液IL-10、脑脊液IFN-γ。
    结论  脑脊液IL-6、血清IL-6、脑脊液IL-10与婴儿BM存在相关性,血清IFN-γ、脑脊液IFN-γ与婴儿VE存在相关性,这些指标有望成为早期区分BM和VE的辅助指标。

     

    Abstract:
    OBJECTIVE  To compare the differences in cytokines in blood and cerebrospinal fluid between bacterial meningitis (BM) and viral encephalitis (VE) in infants, and to construct a machine learning model for early differentiation and diagnosis.
    METHODS  A total of 120 infants admitted to the neurology department of the Women and Children's Hospital of Ningbo University with suspected central nervous system infections from Jan. 2022 to Nov. 2024 were selected as the study subjects. Venous blood and cerebrospinal fluid samples were collected from all patients immediately at the admisson to the hospital. The patients were ultimately divided into three groups based on the gold standard: 40 in the BM group, 40 in the VE group and 40 in the non-central nervous system infection (NC) group. Differences in blood and cerebrospinal fluid cytokines among the three groups were compared. Eight machine learning training models were used, and the optimal model was selected based on indicators such as receiver operating characteristic (ROC) curves, calibration curves and decision curves. The SHAP method was employed to interpret the model.
    RESULTS  The serum Interleukin-6 (IL-6) level in the BM group was 105.85 (25.19, 192.46) pg/ml, which was higher than that in the VE group 40.85 (12.68, 69.81) pg/ml and the NC group (P<0.05). The VE group had a higher serum IL-6 level than the NC group (P<0.05). The serum Interferon γ (IFN-γ) level in the VE group was 7.29 (1.66, 37.37) pg/ml, which was higher than that in the BM group 2.21 (1.12, 5.65) pg/ml and the NC group (P<0.05). The serum IL-17A level in the BM group was 1.96 (0.92, 4.88) pg/ml, which was higher than that in the NC group (P<0.05). The cerebrospinal fluid IL-6 and IL-10 levels in the BM group were 102.13 (31.38, 569.60) pg/ml and 15.88 (5.56, 43.79) pg/ml, respectively, which were both higher than those in the VE group 21.70 (9.64, 40.00) pg/ml and 8.50 (4.10, 15.05) pg/ml and the NC group (P<0.05). The cerebrospinal fluid IL-6 and IL-10 levels in the VE group were both higher than those in the NC group (P<0.05), and the cerebrospinal fluid IFN-γ level in the VE group was 1.61 (1.33, 2.74) pg/ml, which was higher than that in the BM group 1.13 (0.30, 1.75) pg/ml and the NC group (P<0.05). Among the eight machine learning models constructed based on the above indicators, the Gradient Boosting Machine (GBM) model performed the best (area under the curve=0.938, accuracy=0.917, sensitivity=0.917, specificity=0.917, precision=0.917, F1 score=0.917). The SHAP analysis revealed that the features contributing to the model in descending order of importance were: cerebrospinal fluid IL-6, serum IFN-γ, serum IL-6, cerebrospinal fluid IL-10 and cerebrospinal fluid IFN-γ.
    CONCLUSIONS  There is a correlation between cerebrospinal fluid IL-6, serum IL-6, cerebrospinal fluid IL-10 and infant BM, as well as between serum IFN-γ, cerebrospinal fluid IFN-γ and infant VE. These indicators are expected to serve as auxiliary markers for early differentiation between BM and VE.

     

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