Informatics and Systems Department, Division of Engineering Research, National Research Centre, Tahrir Street, Cairo, Egypt.
Virol J. 2010 Jun 15;7:130. doi: 10.1186/1743-422X-7-130.
Hepatitis C virus (HCV) is a worldwide health problem with no vaccine and the only approved therapy is Interferon-based plus Ribavarin. Response prediction to treatment has health and economic impacts, and is a multi-factorial problem including both host and viral factors (e.g: age, sex, ethnicity, pre-treatment viral load, and dynamics of the HCV non-structural protein NS5A quasispecies). We implement a novel approach for extracting features including informative markers from mutations in the non-structural 5A protein (NS5A), specifically its Interferon sensitivity determining region (ISDR) and V3 regions, and use a novel bioinformatics approach for pattern recognition on the NS5A protein and its motifs to find biomarkers for response prediction using class association rules and comparing the predictability of the different features.
A total of 58 sequences from sustained responders and 94 from non-responders were downloaded from the HCV LANL database. Site-specific signatures for response prediction from the NS5A protein were extracted from the alignments. Class association rules were generated (e.g.: sustained response is associated with position A2368T in subtype 1a (support 100% and confidence 52.19%); in subtype 1b, response is associated with E2356G/D/K (support 76.3% and confidence 67.3%).
The V3 region was a more accurate biomarker than the ISDR region. Subtype-specific class association rules gave better support and confidence than profile hidden Markov models HMMs scores, genetic distances or number of variable sites, and would thus aid in the prediction of prognostic biomarkers and improve the accuracy of prognosis. Sites-specific class association rules in the V3 region of the NS5A protein have given the best support and confidence.
丙型肝炎病毒（HCV）是一个全球性的健康问题，目前尚无疫苗，唯一批准的治疗方法是基于干扰素加利巴韦林。治疗反应的预测对健康和经济都有影响，是一个多因素问题，包括宿主和病毒因素（如年龄、性别、种族、治疗前病毒载量和 HCV 非结构蛋白 NS5A 准种动力学）。我们提出了一种从非结构 5A 蛋白（NS5A）中的突变中提取特征的新方法，特别是其干扰素敏感性决定区（ISDR）和 V3 区，并使用一种新的生物信息学方法对 NS5A 蛋白及其基序进行模式识别，以找到用于反应预测的生物标志物，使用类关联规则，并比较不同特征的可预测性。
从 HCV LANL 数据库中下载了 58 个持续应答者和 94 个无应答者的序列。从 NS5A 蛋白的比对中提取了用于反应预测的位点特异性特征。生成了类关联规则（例如：1a 亚型中持续应答与位置 A2368T 相关（支持 100%，置信度 52.19%）；在 1b 亚型中，反应与 E2356G/D/K 相关（支持 76.3%，置信度 67.3%））。
V3 区比 ISDR 区更准确的生物标志物。亚型特异性类关联规则比 HMM 评分、遗传距离或可变位点数量提供了更好的支持和置信度，因此有助于预测预后生物标志物并提高预后的准确性。在 NS5A 蛋白的 V3 区的特定位置的类关联规则提供了最佳的支持和置信度。
