A state-of-the-art web platform for collaborative, longitudinal genome diagnostics

用于协作、纵向基因组诊断的最先进的网络平台

• 批准号: 10602647
• 负责人: Alistair Ward
• 金额: $ 100.09万
• 依托单位: FRAMESHIFT LABS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10602647
• 关键词: Address; Adopted; Algorithms; Bioinformatics; Caring; Clinic; Collaborations; Communication Tools; Communities; Community Hospitals; Complex; Computer software; Custom; Data; Diagnosis; Diagnostic; Disease; Ensure; Environment; Evaluation; Family; Feedback; Foundations; Funding; Genes; Genetic Diseases; Genetic Services; Genome; Genomics; Goals; Individual; Institution; Intuition; Investigation; Knowledge; Manuals; Marketing; Medical; Metadata; Modeling; National Human Genome Research Institute; Neonatal Intensive Care Units; Notification; Online Systems; Pain; Patients; Pharmacologic Substance; Phenotype; Physicians; Privacy; Process; Quality Control; Rare Diseases; Recording of previous events; Research; Role; Scientist; Secure; Security; Services; Source; Specialist; Standardization; Suggestion; Technology; Time; Universities; Update; Utah; Variant; Visual; Visualization; analysis pipeline; bioinformatics pipeline; citizen science; clinical research site; cloud based; cohort; computational pipelines; computer infrastructure; critically ill newborn; data management; data portal; data sharing; design; drug development; effectiveness evaluation; experience; genetic counselor; genetic testing; genetic variant; genome sequencing; genomic data; interest; member; mosaic; portability; programs; restraint; scale up; software systems; support tools; tool; user-friendly; web app; web platform; whole genome

Summary/Abstract Undiagnosed diseases clinics and newborn intensive care unit rapid genome sequencing programs have emerged as the primary settings for diagnosing patients with complex phenotypes. Subspecialty clinics, pharmaceutical companies, and direct-to-consumer genetic testing companies are increasingly adopting these technologies for diagnosing patients, or studying disease with the goal of developing treatments. In all cases, a diagnostic, or research analysis approach based on comprehensive genomic sequencing data, and, crucially, collaborative analysis by expert teams has been adopted. The team-based approach leverages the expertize of a wide array of specialists, for example, the physician's knowledge of the patient's phenotypes and family history; the medical geneticist's knowledge of genetic diseases; the bioinformatician's and variant scientist's expertise in interpreting the potential diagnostic role of individual genetic variants; the genetic counselors expertize in synthesizing all available data, and coordinating with patients, families and treating physicians. A patient's phenotypes, and more frequently, the myriad sources of evidence used to support the diagnostic role of variants, genes, and their associations with disease evolve over time, and consequently research and diagnostic analysis is a long-term process. Existing tools focus on analysis at a single point in time, and require over-burdened genetic counselors to manually evaluate cases for changes, or miss the opportunity for diagnosis due to a lack of evidence at the time of evaluation. Here, we propose to build a commercial software system to address two pressing needs faced by consumers of genomic sequencing data. First, a complete end-to-end bioinformatic pipeline to process raw sequencing data to lists of prioritized genetic variants, and structural variant calls, which explicitly includes an automated (or manually triggered) data re-analysis pipeline to support long-term genomic care. Second, a comprehensive, versatile, and yet easy-to-use visualization platform will seamlessly display all genomic data and metadata to the analysis teams in web applications custom designed to address the needs of the diverse experts collaborating on these projects. We will evaluate and refine this product in our undiagnosed diseases clinic and our newborn intensive care unit, ideal settings to garner critical feedback and suggestions from teams representative of the initial target market for this tool.

摘要/摘要 未确诊疾病诊所和新生儿重症监护室快速基因组测序计划， 成为诊断具有复杂表型的患者的主要设置。专科诊所， 制药公司和直接面向消费者的基因检测公司越来越多地采用这些技术。 用于诊断病人的技术，或以开发治疗方法为目标的疾病研究。在所有情况下， 基于全面基因组测序数据的诊断或研究分析方法，而且，至关重要的是， 采用了专家小组协作分析的办法。基于团队的方法利用了 例如，医生对患者表型和家族的了解 历史;医学遗传学家对遗传疾病的知识;生物信息学家和变异科学家的 解释个体遗传变异的潜在诊断作用的专业知识;遗传咨询师 擅长综合所有可用数据，并与患者，家属和治疗医生协调。一 患者的表型，更常见的是，用于支持诊断作用的无数证据来源 变异、基因及其与疾病的关系随着时间的推移而演变，因此研究和 诊断分析是一个长期的过程。现有的工具侧重于在单个时间点进行分析，并且需要 负担过重的遗传咨询师手动评估病例的变化，或错过机会， 由于评估时缺乏证据而导致诊断。在这里，我们建议建立一个商业软件， 该系统旨在解决基因组测序数据消费者面临的两个迫切需求。首先，一个完整的 - 端到端生物信息学管道，用于将原始测序数据处理为优先遗传变体列表，以及 结构变量调用，其中明确包括自动（或手动触发）数据重新分析管道 来支持长期的基因组护理。第二，全面、通用且易于使用的可视化 该平台将在网络应用程序中向分析团队无缝显示所有基因组数据和元数据 定制设计，以满足在这些项目上合作的不同专家的需求。我们将评估 并在我们的未确诊疾病诊所和新生儿重症监护室中完善该产品， 从代表此工具最初目标市场的团队中收集关键反馈和建议。