Development of a cloud-based analytical tool for polygenic risk score and its implication in heart failure research.

开发基于云的多基因风险评分分析工具及其对心力衰竭研究的影响。

• 批准号: 10826562
• 负责人: Vasan S Ramachandran
• 金额: $ 25.23万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10826562
• 关键词: Administrative Supplement; Age; Award; Biological; Cardiac; Cardiovascular Diseases; Chronic Disease; Clinical; Cloud Computing; Collaborations; Computer software; Data; Data Set; Development; Disease susceptibility; Early Diagnosis; Echocardiography; Environment; Etiology; Event; Genetic; Genetic Databases; Genetic Predisposition to Disease; Genetic Risk; Heart failure; Heritability; Incidence; Institution; Intervention; Knowledge; Language; Measures; Mitochondria; Morbidity - disease rate; Parents; Pathway interactions; Performance; Polygenic Traits; Procedures; Research; Research Personnel; Research Support; Resources; Risk; Series; Structure; Testing; Trans-Omics for Precision Medicine; United States National Institutes of Health; Variant; analytical tool; catalyst; cloud based; cloud platform; cohort; computational platform; data harmonization; experience; genetic architecture; genetic variant; genome resource; genome sequencing; genome wide association study; genomic data; genomic locus; improved; insight; interest; mortality; parent project; performance tests; polygenic risk score; population based; prevent; programs; response; stem; tool; tool development; user-friendly; whole genome

ABSTRACT This application is an administrative supplement in response to NIH Notice of Special Interest (NOT-OD-23-070): Administrative Supplements to Support the Exploration of Cloud in NIH-supported Research. The parent project aims to elucidate the genetic architecture of cardiac structure and function and to improve heart failure (HF) prediction by using polygenic risk scores (PRS) constructed for cardiac structure and function. HF increases with age markedly and is associated with a 50% 5-year mortality. It is heritable; genome-wide association studies (GWAS) have identified scores of genetic loci for HF, suggesting polygenic inheritance. PRS quantifies chronic disease susceptibility stemming from multiple genetic variants, which has demonstrated the potential to tailor clinical intervention for cardiovascular disease. Few studies have explored PRS for HF. Although packages of PRS construction have been developed, the effort to transit resources to cloud platforms to facilitate cloud-based analyses, where large-scale genomic data are hosted, is limited. For this administrative supplement, we therefore aim to 1) develop a PRS construction and analyses tool on BioData Catalyst (BDC), a cloud computing platform designated by the TOPMed program, and 2) assess the use of PRS for predicting HF development, in a collaborative cloud environment. It is distinct from the parent award as the parent award focuses on PRS of cardiac structure and function, not HF, and the parent award doesn’t include effort to develop a cloud-based analytical tool. This supplement is also complementary to the parent award as the analytical tool built could facilitate the analyses of the parent award and the construction of HF PRS could advance of knowledge of HF etiology, in line with the parent award. The completion of this supplement will provide valuable experience for tools development on BDC, deliver a user-friendly tool for BDC users, and demonstrate the advantage of incorporating genetic susceptibility to early-detect and to prevent HF, an essential step in decreasing HF- associated morbidity and mortality.

摘要 本申请是对NIH特别关注通知（NOT-OD-23-070）的行政补充： 在NIH支持的研究中支持云探索的管理补充。父项目 旨在阐明心脏结构和功能的遗传结构，并改善心力衰竭（HF） 通过使用针对心脏结构和功能构建的多基因风险评分（PRS）进行预测。HF增加， 年龄显著，与50%的5年死亡率相关。它是可遗传的;全基因组关联研究 （GWAS）已经鉴定了HF的遗传位点的分数，表明多基因遗传。PRS量化慢性 疾病的易感性源于多种遗传变异，这已经证明了定制的潜力 心血管疾病的临床干预。很少有研究探索HF的PRS。虽然包装的 PRS建设已经开发完成，努力将资源中转到云平台，方便基于云 在托管大规模基因组数据的情况下进行的分析有限。对于这一行政补充，我们 目标是1）在云计算平台BioData Catalyst（BDC）上开发PRS构建和分析工具 由TOPMed计划指定，和2）评估PRS用于预测HF发展的使用， 协作云环境。它与母公司奖项不同，因为母公司奖项侧重于 心脏结构和功能，而不是HF，并且母公司奖项不包括开发基于云的 分析工具。这一补充也是对母公司奖的补充，因为建立的分析工具可以 方便对母奖的分析，构建HF PRS可以提高对HF的认识 病因学，符合父母奖。这一补充的完成将为以下方面提供宝贵的经验： BDC上的工具开发，为BDC用户提供一个用户友好的工具，并展示了 将遗传易感性纳入早期检测和预防HF，这是减少HF的重要步骤， 相关的发病率和死亡率。