Administrative Supplement: The Clinical Genome Resource - Advancing genomic medicine through biocuration and expert assessment of genes and variants at scale

行政补充：临床基因组资源 - 通过大规模基因和变异的生物管理和专家评估推进基因组医学

• 批准号: 10841906
• 负责人: JONATHAN S BERG
• 金额: $ 39.94万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10841906
• 关键词: Address; Administrative Supplement; American; Area; Clinical; Decision Making; Development; District of Columbia; Funding; Genes; Genetic; Genomic medicine; Genomics; Grant; Health; Health system; Hybrids; Individual; Intervention; Leadership; Medical Genetics; Mendelian disorder; Morbidity - disease rate; National Human Genome Research Institute; Outcome; Persons; Population; Procedures; Research; Science; Variant; Work; cost effectiveness; disorder risk; economic evaluation; ethical, legal, and social implication; evidence base; genome resource; improved; medical schools; meetings; member; mortality; polygenic risk score; poor health outcome; population health; screening; virtual; working group

PROJECT SUMMARY/ABSTRACT In this supplement, we propose two distinct activities focused on the use of genomics in population screening. We will establish a new ClinGen working group to develop an evidence framework to inform decision-making about which targets to include in population screening efforts in unselected populations. We will leverage the expertise and well-established procedures of the ClinGen Actionability Working Group, including recent efforts to develop a new framework for the polygenic risk score (PRS) context. Given that nascent population genomic screening efforts are already in underway in some centers and health systems, this framework development is timely and necessary to provide guidance on conditions that should be considered for screening based on key factors including actionability and cost effectiveness. Overall, this work will significantly contribute to the advancement of genomic medicine at the population scale and provide evidence-based assessments of population health impact for a broad range of end-users. This supplement also requests funds for the UNC team to host and oversee the 2023 annual meeting of the NHGRI Division of Genomic Medicine meeting (GM XV), planned and conducted by the Advisory Council’s Genomic Medicine Working Group. These meetings have historically addressed timely topics in genomic medicine to identify research directions for the field and for NHGRI. The focus of the 2023 meeting will be on genomics and population screening, with meeting objectives aligned with assessing the current state of the science, determining the key challenges and opportunities, and outlining a research agenda. The UNC ClinGen grant is well- suited to help plan this meeting given our close relationship and subcontract with the American College of Medical Genetics and Genomics (ACMG), through which we have coordinated dozens of in-person, virtual, and hybrid Steering Committee meetings and in-person meetings between members of ClinGen’s Clinical Domain Working Groups and Expert Panels.

项目概要/摘要 在本增刊中，我们提出了两项​​不同的活动，重点关注基因组学的应用 人群筛查。 我们将建立一个新的 ClinGen 工作组来开发证据框架来告知 决定将哪些目标纳入未选定的人群筛查工作中 我们将利用 ClinGen 的专业知识和完善的程序。 可行动性工作组，包括最近为制定新框架所做的努力 鉴于新生群体基因组筛查工作正在开展。 该框架的制定已经在一些中心和卫生系统取得进展，是及时的 并有必要就基于筛查应考虑的条件提供指导 总体而言，这项工作将显着影响可操作性和成本效益等关键因素。 为人口规模基因组医学的进步做出贡献，并提供 对广大最终用户的人口健康影响进行循证评估。 本补充文件还要求为北卡罗来纳大学团队提供资金，以主办和监督 2023 年年度会议 NHGRI 基因组医学部门会议（GM XV），计划并举行 这些会议具有历史意义。 及时讨论基因组医学主题，以确定该领域的研究方向和 NHGRI。2023 年会议的重点将是基因组学和群体筛查，其中 实现与评估科学现状相一致的目标，确定关键 挑战和机遇，并概述了北卡罗来纳大学 ClinGen 的研究议程。 鉴于我们与美国的密切关系和分包合同，适合帮助计划这次会议 医学遗传学与基因组学学院 (ACMG)，我们通过该学院协调 数十次面对面、虚拟和混合的指导委员会会议和面对面会议 ClinGen 临床领域工作组和专家小组成员之间的交流。

项目成果

Reappraisal of Reported Genes for Sudden Arrhythmic Death: Evidence-Based Evaluation of Gene Validity for Brugada Syndrome.

重新评估已报道的心律失常性死亡基因：布鲁格达综合征基因有效性的循证评估。

• 发表时间: 2018-09-18
• 影响因子: 37.8
• 作者: Hosseini, S Mohsen;Kim, Raymond;Udupa, Sharmila;Costain, Gregory;Jobling, Rebekah;Liston, Eriskay;Jamal, Seema M;Szybowska, Marta;Morel, Chantal F;Bowdin, Sarah;Garcia, John;Care, Melanie;Sturm, Amy C;Novelli, Valeria;Ackerman, Michael J;Wa
• 通讯作者: Wa

Establishing the Medical Actionability of Genomic Variants.

建立基因组变异的医学可行性。

• 发表时间: 2022-08-31
• 作者: Goddard, Katrina A B;Lee, Kristy;Buchanan, Adam H;Powell, Bradford C;Hunter, Jessica Ezzell
• 通讯作者: Hunter, Jessica Ezzell

Variant Classification for Pompe disease; ACMG/AMP specifications from the ClinGen Lysosomal Diseases Variant Curation Expert Panel.

庞贝病的变异分类；

• 发表时间: 2023
• 影响因子: 3.8
• 作者: Goldstein, Jennifer L;McGlaughon, Jennifer;Kanavy, Dona;Goomber, Shelly;Pan, Yinghong;Deml, Brett;Donti, Taraka;Kearns, Liz;Seifert, Bryce A;Schachter, Miriam;Son, Rachel G;Thaxton, Courtney;Udani, Rupa;Bali, Deeksha;Baudet, Heather;Caggana
• 通讯作者: Caggana

Predicting Genetic Variation Severity Using Machine Learning to Interpret Molecular Simulations.

使用机器学习解释分子模拟来预测遗传变异的严重程度。

• 发表时间: 2021-10-19
• 影响因子: 3.4
• 作者: McCoy, Matthew D;Hamre 3rd, John;Klimov, Dmitri K;Jafri, M Saleet
• 通讯作者: Jafri, M Saleet

Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death.

评估心律失常性猝死中 CPVT 和短 QT 综合征的基因有效性。

• 发表时间: 2022-04-14
• 影响因子: 39.3
• 作者: Walsh, Roddy;Adler, Arnon;Amin, Ahmad S;Abiusi, Emanuela;Care, Melanie;Bikker, Hennie;Amenta, Simona;Feilotter, Harriet;Nannenberg, Eline A;Mazzarotto, Francesco;Trevisan, Valentina;Garcia, John;Hershberger, Ray E;Perez, Marco V;Sturm, Amy C
• 通讯作者: Sturm, Amy C