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 未诊断的疾病诊所和新生儿重症监护病房快速基因组测序计划具有 成为诊断患有复杂表型患者的主要环境。亚科诊所， 制药公司以及直接面向消费者的基因测试公司越来越多地采用这些 用于诊断患者或研究疾病的技术以发展治疗。在所有情况下， 基于全面的基因组测序数据，至关重要的是，诊断或研究分析方法 已经采用了专家团队的协作分析。基于团队的方法利用专家 例如，各种各样的专家，医生对患者表型和家庭的了解 历史;医学遗传学家对遗传疾病的了解；生物信息学家和变体科学家的 解释单个遗传变异的潜在诊断作用方面的专业知识；遗传顾问 在综合所有可用数据并与患者，家庭和治疗医师协调方面的专业化。一个 患者的表型，更频繁地，用于支持诊断角色的无数证据来源 随着时间的流逝，变体，基因及其与疾病的关联的发展，因此研究和研究 诊断分析是一个长期过程。现有工具专注于单个时间点的分析，并需要 过于负担的遗传咨询师可以手动评估案件的变化，或者错过了机会 评估时缺乏证据，诊断。在这里，我们建议建立一个商业软件 解决基因组测序数据消费者面临的两个压力需求的系统。首先，一个完整 端到端生物信息学管道将原始测序数据处理到优先级遗传变异的列表，并 结构变体调用，明确包括自动化（或手动触发）数据重新分析管道 支持长期基因组护理。其次，全面，多才多艺又易于使用的可视化 平台将无缝向Web应用程序中的分析团队无缝显示所有基因组数据和元数据 定制旨在满足各种专家在这些项目上合作的需求。我们将评估 并在我们未诊断的疾病诊所和我们的新生重症监护病房中完善该产品，理想的环境 获得了代表此工具最初目标市场的团队的重要反馈和建议。