Streamlined Genotyping for HIV-1 Recombinants

 描述（由申请人提供）：本提案解决了HIV-1全球监测和流行病学研究中的一个关键问题：我们如何确保病毒基因分型信息的有效性和可靠性？这些信息经常被证明是不一致的，甚至是错误的，来自公共基因组库（如GenBank）。由于测序和监测工作的增加，以及缺乏可靠的基因分型参考序列，这种情况将继续恶化，因为已确定的艾滋病毒序列越来越多。因此，制定策略，以确保病毒基因分型质量应被视为高度优先的艾滋病毒研究，特别是考虑到基因分型信息的重要性，在流行病学监测，基因组研究和基因组保健。该项目的总体目标是开发一个可靠的HIV-1基因分型平台，特别是对于重组病例，由于重组事件的复杂性，重组病例比纯亚型更难进行基因分型。此外，我们的目标是开发一个高通量和系统化的平台，以满足先进基因组测序时代的当前研究需求。我们计划在这样一个平台中实现以下要素：1）用于可靠的HIV-1基因分型的高效计算管道; 2）可靠的HIV-1重组序列集合和可用作有效和可靠基因分型参考的重组体列表。通过首次对所有已发表的HIV序列的基因分型质量进行系统调查，我们的研究结果将为HIV基因组研究奠定坚实的基础，以帮助改善目前对不同流行病学背景下HIV进化模式的认识。更广泛地说，这一拟议的研究战略也将有助于其他生物体的研究，这些生物体同样需要可靠的分类来进行病例定义和治疗方案。

 DESCRIPTION (provided by applicant): This proposal addresses a critical issue in HIV-1 global surveillance and epidemiology study: how do we ensure the validity and reliability of virus genotyping information? Such information has frequently proven inconsistent, even erroneous, from public genome repositories (such as, GenBank). This situation will continue to deteriorate with the growing list of identified HIV sequences, as a result of increased sequencing and surveillance efforts, and in the face of lack of reliable genotyping reference sequences. Hence, developing strategies to ensure viral genotyping quality should be considered high priority in HIV research, particularly given the importance of genotyping information in regards to epidemiological surveillance, genomic research, and genomic health care. The overall goal of this project is to develop a platform for reliable HIV-1 genotyping, in particular for recombinant cases, which are more difficult than pure subtypes to be genotyped due to the complexity of recombination events. Additionally, we aim to develop a high-throughput and systematic platform that meets current research needs in the era of advanced genome sequencing. We plan to implement the following elements within such a platform: 1) an efficient computational pipeline for reliable HIV-1 genotyping; and 2) a reliable collection of HIV-1 recombinant sequences and a list of recombinants that can be used as valid and reliable genotyping references. Through this first of its kind, systematic investigation of genotyping quality of all published HIV sequences, our results will lay a robust foundation for HIV genomic research to help improve current knowledge of HIV evolutionary patterns under different epidemiological settings. More broadly, this proposed research strategy would also contribute to research in other organisms that similarly require reliable classifications for case definition and treatment options.