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Pharmacogenomics of drug efficacy in the interferon treatment of chronic hepatitis C using classification algorithms

机译:使用分类算法分析干扰素治疗慢性丙型肝炎药物疗效的药物基因组学

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摘要

Chronic hepatitis C (CHC) patients often stop pursuing interferon-alfa and ribavirin (IFN-alfa/RBV) treatment because of the high cost and associated adverse effects. It is highly desirable, both clinically and economically, to establish tools to distinguish responders from nonresponders and to predict possible outcomes of the IFN-alfa/RBV treatments. Single nucleotide polymorphisms (SNPs) can be used to understand the relationship between genetic inheritance and IFN-alfa/RBV therapeutic response. The aim in this study was to establish a predictive model based on a pharmacogenomic approach. Our study population comprised Taiwanese patients with CHC who were recruited from multiple sites in Taiwan. The genotyping data was generated in the high-throughput genomics lab of Vita Genomics, Inc. With the wrapper-based feature selection approach, we employed multilayer feedforward neural network (MFNN) and logistic regression as a basis for comparisons. Our data revealed that the MFNN models were superior to the logistic regression model. The MFNN approach provides an efficient way to develop a tool for distinguishing responders from nonresponders prior to treatments. Our preliminary results demonstrated that the MFNN algorithm is effective for deriving models for pharmacogenomics studies and for providing the link from clinical factors such as SNPs to the responsiveness of IFN-alfa/RBV in clinical association studies in pharmacogenomics.
机译:慢性丙型肝炎 (CHC) 患者经常停止接受干扰素-α 和利巴韦林 (IFN-alfa/RBV) 治疗,因为治疗费用高且相关不良反应。从临床和经济角度来看,非常需要建立工具来区分反应者和无反应者,并预测 IFN-alfa/RBV 治疗的可能结果。单核苷酸多态性 (SNP) 可用于了解基因遗传与 IFN-alfa/RBV 治疗反应之间的关系。本研究的目的是建立一个基于药物基因组学方法的预测模型。我们的研究人群包括从台湾多个地点招募的台湾 CHC 患者。基因分型数据在 Vita Genomics, Inc. 的高通量基因组学实验室中生成。通过基于包装器的特征选择方法,我们采用多层前馈神经网络 (MFNN) 和逻辑回归作为比较的基础。我们的数据显示 MFNN 模型优于 logistic 回归模型。MFNN 方法提供了一种有效的方法来开发一种工具,用于在治疗前区分反应者和无反应者。我们的初步结果表明,MFNN 算法可有效推导药物基因组学研究模型,并在药物基因组学的临床关联研究中提供从 SNP 等临床因素到 IFN-alfa/RBV 反应性的联系。

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