Creation of a knowledgebase of high quality assertions of the clinical actionability of somatic variants in cancer

创建癌症体细胞变异临床可行性的高质量断言知识库

• 批准号: 10555024
• 负责人: Malachi Griffith
• 金额: $ 64.21万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10555024
• 关键词: Acceleration; Address; Adopted; American Society of Clinical Oncology; Cancer Patient; Case Study; Classification; ClinVar; Clinical; Clinical Trials; Communities; Community Clinical Oncology Program; Consumption; DNA Sequence Alteration; Data; Databases; Dedications; Development; Diagnosis; Diagnostic; Disease; Ethics; FAIR principles; Gene Fusion; Genes; Genomics; Germ-Line Mutation; Goals; Growth; Guidelines; Health; Heritability; Human; Information Resources; Infrastructure; Knowledge; Knowledge Extraction; Leadership; Level of Evidence; Malignant Neoplasms; Modeling; Mutation; Natural Language Processing; Oncogenic; Outcome; Paper; Phenotype; Prediction of Response to Therapy; Procedures; Process; Prognosis; Protocols documentation; Publications; Research; Resources; Role; Science; Secure; Sister; Source; Specific qualifier value; Stream; System; Technology; Text; Time; Variant; Work; cancer diagnosis; cancer therapy; clinical translation; clinically actionable; clinically relevant; clinically significant; data interoperability; data resource; data sharing; editorial; experimental study; genome resource; genomic data; genomic variation; human disease; improved; individual patient; interoperability; knowledge curation; knowledgebase; member; neoplasm resource; online resource; organizational structure; pre-clinical; precision oncology; prognostic; recruit; tool; treatment response; working group

Project Summary Interpretation of the clinical significance of somatic variants in cancer remains a major challenge in cancer diagnosis, prognosis and treatment prediction. The Clinical Genome Resource (ClinGen) has established extensive infrastructure including tools, web resources, procedures, and expert panel templates to help communities of experts establish the clinical relevance of genes and variants. However, ClinGen’s effort is almost exclusively focused on the interpretation of germline variants and their role in heritable phenotypes, leaving a significant gap in clinical interpretation of somatic variants in cancer. Concurrently the Global Alliance for Genomics in Health (GA4GH) has begun to develop standards for genomic data interoperability. The Clinical Interpretation of Variants in Cancer (CIViC) resource provides a sophisticated variant knowledge curation interface. In this application, we propose to create a knowledgebase of high quality assertions of the clinical significance of somatic variants in cancer that utilizes the CIViC platform, adapts the procedures of ClinGen to somatic variant interpretation and implements the interoperability standards of the GA4GH. This effort is needed to broadly enable research and clinical translation involving the use of somatic cancer variant knowledge as it relates to oncogenicity, diagnosis, prognosis and therapeutic response. By adapting the ClinGen germline model, we will establish processes to engage the expert community and facilitate the creation of Somatic Cancer Variant Curation Expert Panels (SC-VCEPs). Formation of these SC-VCEPs will support creation of a ClinGen Somatic Knowledgebase of clinical cancer variant assertions curated and approved by experts. SC-VCEPs will be the primary drivers of curation and domain specific guideline creation. We will adopt and guide ongoing development of several emerging standards that enable the Findable, Accessible, Interoperable, and Reusable (FAIR) principles for genomic knowledge sharing. Specifically, we will adopt the GA4GH Variation Representation Specification (VRS) and associated genomic knowledge framework of the GA4GH Genomic Knowledge Standards (GKS) Work Stream. We will also use our expert-driven curation activities to inform and develop curation and minimal information standards. Finally, we will use natural language processing (NLP) to accelerate a set of defined human knowledge curation tasks that currently limit the rate of human curation. Specifically, NLP will be used to (1) streamline curator activities through integration of text-mined data directly into CIViC; (2) prioritize papers based on their likely evidence level such as clinical trials or case reports; (3) identify and match a larger variety of cancer variant types through a variant hierarchy system; and (4) automate simple but time-consuming tasks such as enforcing consistent synonym usage. Our ultimate goal is to support a large community of domain-specific expert panels working together to create a public knowledgebase of cancer variants and their clinical relevance.

项目摘要 对癌症体细胞变异的临床意义的解释仍然是癌症的主要挑战 诊断，预后和治疗预测。临床基因组资源（Clingen）已建立 广泛的基础架构，包括工具，网络资源，程序和专家小组模板，以帮助 专家社区建立了基因和变体的临床相关性。但是，克林根的努力是 几乎完全专注于对种系变体的解释及其在可遗传表型中的作用， 在癌症中体细胞变异的临床解释中留下了很大的差距。同时全球联盟 对于健康中的基因组学（GA4GH）已开始制定基因组数据互操作性的标准。这 癌症变体（CIVIC）资源的临床解释提供了复杂的变体知识 策展接口。在此应用程序中，我们建议创建一个知识库 利用公民平台的癌症中体细胞变异的临床意义，适应了 克林根（Clingen）对躯体变体解释并实现了GA4GH的互操作性标准。这 需要努力以广泛的研究和临床翻译涉及体细胞癌变体的使用 与致癌性，诊断，预后和治疗反应有关的知识。通过适应 克林根种系模型，我们将建立流程以吸引专家社区并促进 创建体癌变体策展专家小组（SC-VCEP）。这些SC-VCEP的形成将 支持创建一个临床癌变体的临床癌变异性主张的细胞知识基础，并 被专家批准。 SC-VCEP将是策展和域特定指南创建的主要驱动力。 我们将采用并指导几种新兴标准的持续发展，这些标准使可发现的标准可以 基因组知识共享的可访问，可互操作和可重复使用的（公平）原则。具体来说，我们会的 采用GA4GH变异表示规范（VRS）和相关的基因组知识 GA4GH基因组知识标准（GKS）工作流的框架。我们还将使用我们的 专家驱动的策展活动，以告知和开发策划和最小信息标准。最后，我们 将使用自然语言处理（NLP）加速一组定义的人类知识策展任务 目前限制人类策划的速度。具体而言，NLP将用于（1）简化策展人活动 通过将文本开采数据直接集成到CIVIC中； （2）根据可能的证据确定论文的优先级 临床试验或病例报告等级别； （3）识别并匹配更多的癌症变体类型 通过变体层次结构系统； （4）自动化简单但耗时的任务，例如执行 一致的同义词用法。我们的最终目标是支持大型特定领域的专家小组 共同创建一个癌症变体及其临床相关性的公共知识基础。