基于免疫系统和解毒基因信号分子基因多态性预测儿童支气管哮喘不可控病程

E. Suprun
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摘要

的目标。研究利用学习神经网络的统计方法,在考虑toll样受体、细胞因子和解毒系统基因遗传多态性的基础上,预测疾病发展各阶段哮喘控制的可能性。材料和方法。我们检查了167名患有支气管哮喘的儿童。测定哮喘控制程度,检测到以下突变:TLR2-Arg753Glu、TLR4-Asp299Gly、TLR4-Ghr399Ile、TLR9-T1237C、TLR9-A2848G;IL4-C589T、IL6- C174G、IL10-G1082A、IL10-C592A、IL10-C819T、IL12B-A1188C、TNFa-G308AGSTM, GSTT, GSTM/GSTT, GSTP1 Ile105Val, GSTP1 Ala114Val,通过PCR。使用STATISTICA自动化神经网络软件包对神经网络进行建模。该模型基于MLP(15-9-3)多层感知器架构,其中一层有15个输入神经元(由被分析变量的数量决定),一个隐藏的中间层有9个神经元,一个输出层有3个神经元(由分类变量的值决定)。BFGS选择了最适合分类任务的训练算法。传统上选择误差函数为偏差平方和。输出神经元的激活函数为Softmax。中间层的激活函数是双曲的。训练样本的体积为88组。该模型用于检测和质量控制的样本量为36套。所建立的模型预测目标变量(哮喘控制程度)的正确率为79.01%。开发的程序的应用使得在疾病的任何阶段预测不受控制或部分控制的哮喘的可能性成为可能,包括对哮喘高风险群体的临床前和疾病前。这使您可以在个性化治疗方法中单独调整哮喘的二级甚至一级预防措施。
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Prediction of uncontrolled course of bronchial asthma in children based on polymorphisms of genes of signaling molecules of the immune system and detoxification genes
Aim. To study the possibility of predicting the asthma control at various stages of the development of the disease, possibly on the basis of taking into account the genetic polymorphisms of Toll-like receptors, cytokines and detoxification system genes using the statistical method of learning neural networks.Materials and methods. We ex­amined 167 children with bronchial asthma. The degree of asthma control was determined, the following mutations were detected: TLR2-Arg753Glu, TLR4-Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G; IL4-C589T, IL6- C174G, IL10-G1082A, IL10-C592A, IL10-C819T, IL12B-A1188C, TNFa-G308A; GSTM, GSTT, GSTM/GSTT, GSTP1 Ile105Val, GSTP1 Ala114Val, by PCR. The STATISTICA Automated Neural Networks package was used to model neural networks.Results. The model is based on the MLP (15-9-3) multilayer perceptron architecture with a layer of 15 input neurons (by the number of analyzed variables), a hidden intermediate layer of 9 neurons and an output layer of 3 neurons by the number of values of the classified variable (control). The training algorithm was chosen by BFGS as the most adequate to the classification task. The error function is traditionally chosen as the sum of squared deviations. The activation function of output neurons is Softmax. The activation function of the intermediate layer is hyperbolic. The volume of the training sample was 88 sets. The volume of samples for testing and quality control of the model was 36 sets. The resulting model was able to predict 79.01% of the correct values of the target variable (the degree of asthma control).Conclusion. The application of the developed program makes it possible to predict the possibility of uncontrolled or partially controlled asthma at any stage of the disease, including preclinical and pre-nosological for groups with a high risk of asthma. This allows you to individually adjust the measures of secondary and even primary prevention of asthma within the personal­ization of therapeutic approaches.
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