GeneMatcher, VariantMatcher and PhenoDB, implementation of new features and connections

项目摘要/摘要 对在整个外显子组和基因组测序中识别的数千到数百万个变异的解释 (WES/WGS)是一项具有挑战性的任务，需要不同的频率和表型 大多数公共数据库中没有的信息。支持数据共享的工具的开发 基因组数据和表型特征的结合对于罕见疾病基因的发现是至关重要的。2013年，我们 创建了GeneMatcher(93个国家和地区的10,574名用户，在&gt；380出版物中被引用)，第一个也是使用最多的网站- 基于工具，可将全球各地的个人(研究人员、临床医生、患者等)与 相同的基因、变异或表型。2019年，我们开发了VariantMatcher(43个国家的625个用户，428个 查询的变异体，61个匹配的变异体)，共享来自WES/WGS的变异体水平和表型数据。要启用 为世界各地的调查人员制定不同的优先顺序，我们开发了PhenoDB(&gt；143个独特的 源代码，来自65个国家的1,828名用户)。这个免费提供的基于Web的工具允许用户天真地 生物信息学，用于存储、共享、分析和解释WES/WGS的患者表型和序列变异。 用户目前在PhenoDB的一个实例中存储大量表型数据(用3,646个术语描述 映射到HPO)来自9,711个家庭的37,712个个体，平均6.8个特征/受影响的个体， 描述2,282种疾病。带注释的WES/WGS变体可供4,446人中的7,724人使用 家人。PhenoDB促进了全球范围内的数据共享和分析访问。截至2020年12月1日，6,151 PhenoDB中测序的个体被同意并提交进行表型和基因匹配 通过VariantMatcher。然而，随着新的测序方法的不断发展，分析管道 数据共享平台需要在我们高度利用的资源中开发新的功能 与其他新创建的平台集成，确保数千名调查人员可以执行状态 对基因组和表型数据进行ART分析，以更好地解释候选变异。迫切需要 维护和改进允许基因组和表型数据集成和共享的工具。为了满足这一需求，我们 将利用PhenoDB、GeneMatcher和VariantMatcher用户的输入，与 具有互补功能的工具和平台，以及我们在测序分析和基因方面不断发展的专业知识 发现，以改善我们的社区资源。为此，我们会： 1.在GeneMatcher、VariantMatcher和PhenoDB中实现新函数，以支持其他类型的 查询、变量过滤和优先顺序管道。 2.将GeneMatcher和VariantMatcher与其他社区范围的数据共享工具和 将PhenoDB与其他工作流平台集成。 3.扩展我们的PhenoDB基因组教育计划。

Project Summary/Abstract The interpretation of thousands to millions of variants identified in whole exome and genome sequencing (WES/WGS), respectively, is a challenging task and requires variant frequency together with phenotype information that are not available in most public databases. The development of tools that enable data sharing of genomic data together with phenotypic features is essential for rare disease gene discovery. In 2013 we created GeneMatcher (10,574 users in 93 countries, cited in >380 publications), the first and most used web- based tool to connect individuals (researchers, clinicians, patients, etc) around the globe with interest in the same genes, variants or phenotypes. In 2019, we developed VariantMatcher (625 users in 43 countries, 428 queried variants, 61 matched variants), to share variant-level and phenotypic data from WES/WGS. To enable variant prioritization for investigators around the world, we developed PhenoDB (> 143 unique downloads of source code, 1,828 users from 65 countries). This freely available, web-based tool allows users naïve to bioinformatics to store, share, analyze and interpret patient phenotypes and sequence variants from WES/WGS. Users currently store in one instance of PhenoDB extensive phenotypic data (described with 3,646 terms mapped to HPO) from 37,712 individuals in 9,711 families with an average of 6.8 features/affected individual, describing > 2,282 diseases. Annotated WES/WGS variants are available for 7,724 individuals from 4,446 families. PhenoDB facilitates data sharing and analysis access world-wide. As of 1 December 2020, 6,151 sequenced individuals in PhenoDB were consented and submitted for phenotypic and genotypic matching through VariantMatcher. However, the ongoing development of new sequencing methods, analysis pipelines and data sharing platforms requires development of novel functions in our highly utilized resources and integration with other newly created platforms to ensure that thousands of investigators can perform state of the art analysis of genomic and phenotypic data to better interpret candidate variants. There is a critical need to maintain and improve tools that allow genomic and phenotypic data integration and sharing. To fill this need, we will leverage input from users of PhenoDB, GeneMatcher and VariantMatcher, collaborations with creators of tools and platforms with complementary functions, and our evolving expertise in sequencing analysis and gene discovery to improve our community resources. To this end, we will: 1. Implement new functions in GeneMatcher, VariantMatcher and PhenoDB to enable additional types of queries, variant filtering and prioritization pipelines. 2. Connect GeneMatcher and VariantMatcher with other, community-wide data sharing tools and integrate PhenoDB with other workflow platforms. 3. Expand our PhenoDB Genomic Education program.