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基于机器学习的丙型肝炎病毒全基因组变异治疗预测模型。

A machine learning-based treatment prediction model using whole genome variants of hepatitis C virus.

机构信息

Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.

Genome Informatics Unit, Institute for Promotion of Medical Science Research, Yamagata University, Yamagata, Japan.

出版信息

PLoS One. 2020 Nov 5;15(11):e0242028. doi: 10.1371/journal.pone.0242028. eCollection 2020.

Abstract

In recent years, the development of diagnostics using artificial intelligence (AI) has been remarkable. AI algorithms can go beyond human reasoning and build diagnostic models from a number of complex combinations. Using next-generation sequencing technology, we identified hepatitis C virus (HCV) variants resistant to directing-acting antivirals (DAA) by whole genome sequencing of full-length HCV genomes, and applied these variants to various machine-learning algorithms to evaluate a preliminary predictive model. HCV genomic RNA was extracted from serum from 173 patients (109 with subsequent sustained virological response [SVR] and 64 without) before DAA treatment. HCV genomes from the 109 SVR and 64 non-SVR patients were randomly divided into a training data set (57 SVR and 29 non-SVR) and a validation-data set (52 SVR and 35 non-SVR). The training data set was subject to nine machine-learning algorithms selected to identify the optimized combination of functional variants in relation to SVR status following DAA therapy. Subsequently, the prediction model was tested by the validation-data set. The most accurate learning method was the support vector machine (SVM) algorithm (validation accuracy, 0.95; kappa statistic, 0.90; F-value, 0.94). The second-most accurate learning algorithm was Multi-layer perceptron. Unfortunately, Decision Tree, and Naive Bayes algorithms could not be fitted with our data set due to low accuracy (< 0.8). Conclusively, with an accuracy rate of 95.4% in the generalization performance evaluation, SVM was identified as the best algorithm. Analytical methods based on genomic analysis and the construction of a predictive model by machine-learning may be applicable to the selection of the optimal treatment for other viral infections and cancer.

摘要

近年来,人工智能(AI)在诊断方面的发展引人注目。AI 算法可以超越人类的推理能力,从许多复杂的组合中构建诊断模型。我们通过对全长 HCV 基因组进行全基因组测序,利用下一代测序技术鉴定出对直接作用抗病毒药物(DAA)耐药的丙型肝炎病毒(HCV)变异体,并将这些变异体应用于各种机器学习算法,以评估初步预测模型。在 DAA 治疗前,从 173 例患者(109 例后续持续病毒学应答[SVR]和 64 例无)的血清中提取 HCV 基因组 RNA。109 例 SVR 和 64 例非 SVR 患者的 HCV 基因组随机分为训练数据集(57 例 SVR 和 29 例非 SVR)和验证数据集(52 例 SVR 和 35 例非 SVR)。将训练数据集应用于 9 种机器学习算法,以确定与 DAA 治疗后 SVR 状态相关的功能变异的最佳组合。随后,通过验证数据集测试预测模型。最准确的学习方法是支持向量机(SVM)算法(验证准确率为 0.95;kappa 统计量为 0.90;F 值为 0.94)。第二准确的学习算法是多层感知机。不幸的是,由于准确性较低(<0.8),决策树和朴素贝叶斯算法无法应用于我们的数据集。总的来说,在泛化性能评估中,SVM 的准确率为 95.4%,被确定为最佳算法。基于基因组分析的分析方法和机器学习构建预测模型可能适用于选择其他病毒感染和癌症的最佳治疗方法。

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