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

GeneMatcher、VariantMatcher 和 PhenoDB，新功能和连接的实现

• 批准号: 10332123
• 负责人: Nara Sobreira
• 金额: $ 63.89万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-07 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10332123
• 关键词: Affect; Animal Model; Back; Bioinformatics; Code; Collaborations; Communities; Consent; Country; DNA Sequence Analysis; Data; Data Analyses; Databases; Development; Disease; Docking; Education; Educational workshop; Electronic Mail; Ensure; Family; Frequencies; Genes; Genetics and Medicine; Genome; Genomic medicine; Genomics; Genotype; Human; Individual; Internet; Java; Learning Module; Link; Maps; Metadata; Methods; Mitochondrial DNA; Molecular; Orthologous Gene; Patients; Phenotype; Proteins; Publications; Pythons; Rare Diseases; Research Personnel; Resources; Single Nucleotide Polymorphism; Source Code; Stream; Students; Variant; Visualization; Work; analysis pipeline; base; data integration; data sharing; exome sequencing; gene discovery; genetic variant; genome sequencing; genomic data; improved; insertion/deletion mutation; interest; lectures; member; novel; online resource; phenome; phenotypic data; programs; public database; search engine; sharing platform; therapy development; tool; tool development; user-friendly; web-based tool

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.

项目概要/摘要 对全外显子组和基因组测序中发现的数千至数百万个变异的解释 （WES/WGS）分别是一项具有挑战性的任务，需要变异频率和表型 大多数公共数据库中没有提供的信息。开发支持数据共享的工具 基因组数据与表型特征的结合对于罕见病基因的发现至关重要。 2013年我们 创建了 GeneMatcher（93 个国家/地区的 10,574 位用户，在超过 380 种出版物中引用），这是第一个也是最常用的网络 基于工具来连接全球各地对以下领域感兴趣的个人（研究人员、临床医生、患者等） 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 查询的变体，61 个匹配的变体），共享来自 WES/WGS 的变体水平和表型数据。启用 为世界各地的研究人员提供变体优先级排序，我们开发了 PhenoDB（> 143 个独特的下载 源代码，来自 65 个国家的 1,828 位用户）。这个免费的、基于网络的工具允许用户天真地 用于存储、共享、分析和解释来自 WES/WGS 的患者表型和序列变异的生物信息学。 用户目前在 PhenoDB 的一个实例中存储了大量的表型数据（用 3,646 个术语描述） 映射到 HPO）来自 9,711 个家庭的 37,712 个人，平均每个受影响的个人有 6.8 个特征， 描述 > 2,282 种疾病。带注释的 WES/WGS 变体适用于 4,446 人中的 7,724 人 家庭。 PhenoDB 促进全球数据共享和分析访问。截至 2020 年 12 月 1 日，6,151 PhenoDB 中的测序个体已获得同意并提交用于表型和基因型匹配 通过 VariantMatcher。然而，新的测序方法、分析流程的不断开发 数据共享平台需要在我们高度利用的资源和数据中开发新颖的功能 与其他新创建的平台集成，以确保数千名调查人员能够执行状态 对基因组和表型数据进行艺术分析，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。为了满足这个需求，我们 将利用 PhenoDB、GeneMatcher 和 VariantMatcher 用户的输入，与创建者合作 功能互补的工具和平台，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，我们将： 1. 在 GeneMatcher、VariantMatcher 和 PhenoDB 中实现新功能，以启用更多类型 查询、变体过滤和优先级管道。 2. 将 GeneMatcher 和 VariantMatcher 与其他社区范围的数据共享工具连接起来 将 PhenoDB 与其他工作流程平台集成。 3. 扩大我们的 PhenoDB 基因组教育计划。