RetroExplorer: An Interactive Database of Endogenous Retroviruses in the Human Genome

RetroExplorer：人类基因组内源性逆转录病毒的交互式数据库

• 批准号: RGPIN-2016-05761
• 负责人: Douville, Renée
• 金额: $ 2.26万
• 依托单位: University of Winnipeg
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=649527
• 关键词: RetroExplorer; Interactive; Database; Endogenous; Retroviruses

Within the human genome reside thousands of Endogenous Retroviruses (ERVs). Over 30 families of ERVs have entered the human germline. Most ERVs now remain inactive due to accumulation of mutations, but some ERVs retain the capacity to produce viral RNA, proteins and virions. My goal is to expand the bioinformatics arm of my research program by developing HQP and projects reliant on a currently unavailable resource – an interactive database of ERVs in the human genome.***Several online databases were key in the identification and analysis of ERV sequences in the human genome – all these resources are now outdated or have left the internet. Clearly, there is a need for a modern and functional ERV database to provide researchers a platform from which to study these viruses. It is timely that my research group develops an online ERV database because: 1) no other online resources exist at the moment, 2) NCBI has just released a major human genome build GRCh38, and 3) there is a growing interest in ERV research, as they are increasingly associated with biological outcomes. My team is well suited to initiate this task, as we have developed in-house bioinformatic annotation of many ERVK sequences in the human genome. *** ***Over the next five years, we will roll-out this program in two phases:***Phase 1 (Years 1-2): Annotation of ERV sequences within the human genome using the newly released human genome build GRCh38 and initial release of web-enabled RetroExplorer database. We will annotate and visually represent ERV sequences, linking to NCBI accession numbers, current nomenclature, as well as alternative names. The retroviral genes and functional elements will be labeled, and links to relevant NCBI databases provided. We will also list the flanking human genes that may be regulated by the retroviral LTRs and their NCBI Genes link. All information will be housed in a core database framework and hosted on an interactive website. ***Phase 2 (Years 3-5): Enhancement of RetroExplorer database features. Once the core platform is web-enabled, we will strive to include features absent from previous ERV databases, such as ERV insertional and single-nucleotide polymorphisms, viral protein functionality based on molecular biology screening assays, annotation of viral enzyme active sites and conserved motifs, transcription factor binding sites in ERV LTRs, and ERV family consensus sequence alignments. Another key feature will include links to relevant original literature for each ERV. ***This bioinformatics program will complement and extend my existing research, allowing future studies to have a solid basis in ERV nomenclature, position within the human genome and appreciation for the inherent functionality of these genomic parasites. Other researchers will benefit from the open-access database; it will provide a shared platform from which to initiate collaborations and promote research in this understudied area of retrovirology. **

人类基因组中存在数千种内源性逆转录病毒(ERV)。已有30多个家庭的ERV进入人类生殖系。由于突变的积累，大多数ERV现在仍然处于不活跃状态，但一些ERV保留了产生病毒RNA、蛋白质和病毒粒子的能力。我的目标是通过开发HQP和依赖于目前无法获得的资源-人类基因组中ERV的交互数据库-的项目来扩大我研究计划的生物信息学部门。*几个在线数据库在识别和分析人类基因组中的ERV序列方面发挥了关键作用--所有这些资源现在都过时了，或者已经离开了互联网。显然，需要一个现代化和功能强大的ERV数据库，为研究人员提供一个研究这些病毒的平台。我的研究小组开发在线ERV数据库是及时的，因为：1)目前没有其他在线资源，2)NCBI刚刚发布了一个主要的人类基因组构建GRCh38，以及3)人们对ERV研究越来越感兴趣，因为它们与生物学结果越来越相关。我的团队非常适合启动这项任务，因为我们已经开发了对人类基因组中许多ERVK序列的内部生物信息学注释。*未来五年，我们将分两个阶段推出这项计划：*第一阶段(1-2年)：使用最新发布的人类基因组构建GRCh38注释人类基因组中的ERV序列，并初步发布具有网络功能的RetroExplorer数据库。我们将注释和直观地表示ERV序列，链接到NCBI加入号、当前命名法以及替代名称。逆转录病毒基因和功能元件将被标记，并提供到相关NCBI数据库的链接。我们还将列出可能受逆转录病毒LTRS及其NCBI基因链接调控的侧翼人类基因。所有信息都将存放在一个核心数据库框架中，并托管在一个互动网站上。*第二阶段(第3-5年)：增强RetroExplorer数据库功能。一旦核心平台具备网络功能，我们将努力包括以前ERV数据库中没有的功能，例如ERV插入和单核苷酸多态、基于分子生物学筛选分析的病毒蛋白功能、病毒酶活性部位和保守基序的注释、ERV LTRS中的转录因子结合位点，以及ERV家族共识序列比对。另一个关键功能将包括指向每个ERV的相关原创文献的链接。*这个生物信息学项目将补充和扩展我现有的研究，使未来的研究在ERV命名、在人类基因组中的位置以及对这些基因组寄生虫固有功能的认识方面有一个坚实的基础。其他研究人员将受益于开放获取的数据库；它将提供一个共享平台，以启动合作并促进这一未被研究的逆转录病毒学领域的研究。**