Calypso: a web software system supporting team-based, longitudinal genomic diagnostic care

Calypso：支持基于团队的纵向基因组诊断护理的网络软件系统

• 批准号: 10376642
• 负责人: Gabor T Marth
• 金额: $ 91.45万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10376642
• 关键词: Address; Adopted; Back; Bioinformatics; Caring; Clinic; Clinical; Collaborations; Communication; Communities; Complex; Computer software; Data; Data Analyses; Data Set; Diagnosis; Diagnostic; Discipline; Disease; Ensure; Environment; Evaluation; Felis catus; Funding; Genes; Genetic; Genetic Diseases; Genome; Genomics; Genotype; Goals; Hand; Individual; Infrastructure; Internet; Intuition; Joints; Knowledge; Literature; Medical; Medicine; Modernization; Molecular; National Human Genome Research Institute; Neonatal Intensive Care Units; Pathogenicity; Pathologist; Patients; Periodicity; Phenotype; Physicians; Process; Reporting; Research; Resources; Secure; Site; Software Tools; Support System; System; Testing; Time; United States National Institutes of Health; Universities; Update; Utah; Variant; Visual; adjudicate; base; clinical research site; clinically relevant; clinically significant; cloud based; cohort; computational pipelines; computer infrastructure; critically ill newborn; dashboard; data access; data infrastructure; design; diagnostic strategy; genetic counselor; genetic disorder diagnosis; genetic variant; genome sequencing; genomic data; implementation science; improved; insight; longitudinal analysis; member; molecular diagnostics; novel; phenotypic data; programs; rapid diagnosis; response; software development; software systems; support tools; tool; whole genome; Address; Adopted; Back; Bioinformatics; Caring; Clinic; Clinical; Collaborations; Communication; Communities; Complex; Computer software; Data; Data Analyses; Data Set; Diagnosis; Diagnostic; Discipline; Disease; Ensure; Environment; Evaluation; Felis catus; Funding; Genes; Genetic; Genetic Diseases; Genome; Genomics; Genotype; Goals; Hand; Individual; Infrastructure; Internet; Intuition; Joints; Knowledge; Literature; Medical; Medicine; Modernization; Molecular; National Human Genome Research Institute; Neonatal Intensive Care Units; Pathogenicity; Pathologist; Patients; Periodicity; Phenotype; Physicians; Process; Reporting; Research; Resources; Secure; Site; Software Tools; Support System; System; Testing; Time; United States National Institutes of Health; Universities; Update; Utah; Variant; Visual; adjudicate; base; clinical research site; clinically relevant; clinically significant; cloud based; cohort; computational pipelines; computer infrastructure; critically ill newborn; dashboard; data access; data infrastructure; design; diagnostic strategy; genetic counselor; genetic disorder diagnosis; genetic variant; genome sequencing; genomic data; implementation science; improved; insight; longitudinal analysis; member; molecular diagnostics; novel; phenotypic data; programs; rapid diagnosis; response; software development; software systems; support tools; tool; whole genome

PROJECT SUMMARY/ABSTRACT Some of the most challenging diagnostic cases involve patients who present with complex phenotypes that evolve over time and intersect multiple medical disciplines. The two primary clinical settings for diagnosing such patients are undiagnosed disease clinics and neonatal intensive care unit rapid genome sequencing programs. These clinics have adopted an approach where diagnostic analysis is based on comprehensive genomic sequencing data; and analysis is carried out by a large, collaborative clinical team. This team-based approach leverages the treating physician’s detailed understanding of the patient’s phenotype, the medical geneticist’s deep knowledge of genetic diseases, the bioinformatic analyst’s expertise in adjudicating a variant’s quality and predicted pathogenicity, as well as the diagnostic pathologist’s ability to synthesize all relevant information and reach a conclusion regarding a given variant’s clinical significance. Diagnostic analysis of patients in both of these environments is a long-term process that often continues for months or even years, until new phenotypes in the patient are observed or novel gene-disease associations are reported in the literature that provide the necessary insight for case solution. However, existing software tools typically only cater to the bioinformatician expert or the diagnostic molecular pathologist, but not the treating physician or the genetic counselor; focus on making a genetic diagnosis at a single timepoint, rather than following the patient over time during a lengthy diagnostic process, and are therefore unable to adequately support team-based, longitudinal genomic diagnostic care. Addressing this pressing need, here we propose to develop a comprehensive software system, Calypso, to address this pressing need. Calypso will support team-based diagnostics via intuitive and visual iobio web tools tailored for each team member’s specialized contribution to diagnostic analysis; and facilitate long-term genomic care by keeping patient genomic data up-to-date via a systematic variant re- annotation infrastructure. We will put Calypso into the hands of the clinical teams in our undiagnosed disease clinic and our neonatal intensive care unit, ideal testing grounds for evaluating our tool’s impact on long-term genome diagnostic care in the context of team-based medicine. We will also centrally deploy and evaluate our tool in NHGRI’s Undiagnosed Disease Network to help realize the collaborative diagnostic opportunities presented by a large, clinically focused research consortium.

项目摘要/摘要 一些最具挑战性的诊断病例​​涉及出现复杂表型的患者 随着时间的流逝而发展并与多个医学学科相交。诊断的两个主要临床环境 患者是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。 这些诊所采用了一种基于全面基因组的诊断分析的方法 测序数据；分析是由一个大型协作临床团队进行的。这个基于团队的 方法利用治疗身体对患者表型的详细理解，医疗 遗传学家对遗传疾病的深入了解，这是生物信息学分析师调整变体的专家 质量和预测的致病性，以及诊断病理学家合成所有相关的能力 有关给定变体的临床意义的信息并得出结论。诊断分析 这两个环境中的患者都是一个长期的过程，通常持续数月甚至数年， 在观察患者中的新表型或在文献中报道了新的基因疾病关联之前 这为案例解决方案提供了必要的见解。但是，现有的软件工具通常仅适合 生物信息学专家或诊断分子病理学家，但没有治疗物理或遗传 顾问;专注于在一个时间点上进行遗传诊断，而不是随着时间的流逝跟随患者 在漫长的诊断过程中，因此无法充分支持基于团队的纵向 基因组诊断护理。解决这种紧迫的需求，我们在这里建议开发一个全面的软件 系统，Calypso，以满足这种紧迫的需求。 Calypso将通过直觉和 为每个团队成员对诊断分析的专门贡献量身定制的Visual Iobio Web工具；和 通过将患者基因组数据通过系统变体保持最新的患者基因组数据来促进长期基因组护理 注释基础架构。我们将在未诊断的疾病中将Calypso交到临床团队的手中 诊所和我们的新生儿重症监护病房，理想的测试场所，以评估我们的工具对长期的影响 基因组诊断护理在基于团队的医学背景下。我们还将集中部署和评估我们的 NHGRI未经诊断的疾病网络中的工具，以帮助实现协作诊断机会 由大型临床研究联盟提出。