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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=745682
• 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databases were key in the identification and analysis of ERV sequences in the human genome all these resources are now outdated or have left the internet.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.

在人类基因组中存在着数以千计的内源性逆转录病毒（erv）。超过30个erv家族已经进入人类种系。由于突变的积累，大多数erv现在保持无活性，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和依赖于当前不可用资源的项目来扩展我的研究计划的生物信息学部分，即人类基因组中erv的交互式数据库。几个在线数据库是鉴定和分析人类基因组中ERV序列的关键，所有这些资源现在都过时或离开了互联网。显然，有必要建立一个现代的、功能性的ERV数据库，为研究人员提供一个研究这些病毒的平台。我的研究小组开发一个在线ERV数据库是及时的，因为：1)目前没有其他在线资源存在，2)NCBI刚刚发布了一个主要的人类基因组构建GRCh38, 3)对ERV研究的兴趣越来越大，因为它们越来越多地与生物学结果相关联。我的团队非常适合启动这项任务，因为我们已经开发了人类基因组中许多ERVK序列的内部生物信息学注释。在未来五年内，我们将分两个阶段推出该计划：第一阶段（1-2年）：使用新发布的人类基因组构建GRCh38对人类基因组中的ERV序列进行注释，并初步发布支持网络的RetroExplorer数据库。我们将注释和可视化地表示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，并提供与NCBI相关数据库的链接。我们还将列出可能受逆转录病毒LTRs及其NCBI基因链调控的侧翼人类基因。所有信息将被安置在一个核心数据库框架和托管在一个互动网站。阶段2（3-5年）：增强RetroExplorer数据库特性。一旦核心平台启用网络，我们将努力包括以前的ERV数据库所没有的功能，如ERV插入多态性和单核苷酸多态性，基于分子生物学筛选测定的病毒蛋白功能，病毒酶活性位点和保守基序的注释，ERV ltr中的转录因子结合位点，以及ERV家族共识序列比对。另一个重要特征将包括每个ERV的相关原始文献链接。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命名法、人类基因组中的位置和对这些基因组寄生虫固有功能的欣赏方面有一个坚实的基础。其他研究人员将从开放获取的数据库中受益；它将提供一个共享平台，在逆转录病毒学这一研究不足的领域开展合作和促进研究。