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SHIVA - a web application for drug resistance and tropism testing in HIV

机译:SHIVA-用于HIV耐药性和向性性测试的Web应用程序

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Background Drug resistance testing is mandatory in antiretroviral therapy in human immunodeficiency virus (HIV) infected patients for successful treatment. The emergence of resistances against antiretroviral agents remains the major obstacle in inhibition of viral replication and thus to control infection. Due to the high mutation rate the virus is able to adapt rapidly under drug pressure leading to the evolution of resistant variants and finally to therapy failure. Results We developed a web service for drug resistance prediction of commonly used drugs in antiretroviral therapy, i.e., protease inhibitors (PIs), reverse transcriptase inhibitors (NRTIs and NNRTIs), and integrase inhibitors (INIs), but also for the novel drug class of maturation inhibitors. Furthermore, co-receptor tropism (CCR5 or CXCR4) can be predicted as well, which is essential for treatment with entry inhibitors, such as Maraviroc. Currently, SHIVA provides 24 prediction models for several drug classes. SHIVA can be used with single RNA/DNA or amino acid sequences, but also with large amounts of next-generation sequencing data and allows prediction of a user specified selection of drugs simultaneously. Prediction results are provided as clinical reports which are sent via email to the user. Conclusions SHIVA represents a novel high performing alternative for hitherto developed drug resistance testing approaches able to process data derived from next-generation sequencing technologies. SHIVA is publicly available via a user-friendly web interface.
机译:背景技术为了成功治疗,在人类免疫缺陷病毒(HIV)感染患者的抗逆转录病毒疗法中必须进行耐药性测试。抗逆转录病毒药物耐药性的出现仍然是抑制病毒复制从而控制感染的主要障碍。由于高突变率,病毒能够在药物压力下快速适应,从而导致耐药变体的进化并最终导致治疗失败。结果我们开发了一个网络服务,用于预测抗逆转录病毒疗法中常用药物的耐药性,即蛋白酶抑制剂(PIs),逆转录酶抑制剂(NRTIs和NNRTIs)和整合酶抑制剂(INIs),而且还用于成熟抑制剂。此外,还可以预测共受体向性(CCR5或CXCR4),这对于使用进入抑制剂(例如Maraviroc)进行治疗至关重要。目前,SHIVA为几种药物类别提供24种预测模型。 SHIVA可以用于单个RNA / DNA或氨基酸序列,也可以用于大量的下一代测序数据,并且可以同时预测用户指定的药物选择。预测结果以临床报告的形式提供,并通过电子邮件发送给用户。结论SHIVA代表了迄今为止开发的耐药性测试方法的一种新型高性能替代方法,该方法能够处理来自下一代测序技术的数据。 SHIVA可通过用户友好的Web界面公开获得。

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