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转化平台在心血管疾病致病基因发现中的整合。

Integration of Transformative Platforms for the Discovery of Causative Genes in Cardiovascular Diseases.

机构信息

Department of Internal Medicine, University of Michigan Medical Center, 2800 Plymouth Rd, Ann Arbor, MI, 48109-2800, USA.

Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.

出版信息

Cardiovasc Drugs Ther. 2021 Jun;35(3):637-654. doi: 10.1007/s10557-021-07175-1. Epub 2021 Apr 15.

Abstract

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Genome-wide association studies (GWAS) are powerful epidemiological tools to find genes and variants associated with cardiovascular diseases while follow-up biological studies allow to better understand the etiology and mechanisms of disease and assign causality. Improved methodologies and reduced costs have allowed wider use of bulk and single-cell RNA sequencing, human-induced pluripotent stem cells, organoids, metabolomics, epigenomics, and novel animal models in conjunction with GWAS. In this review, we feature recent advancements relevant to cardiovascular diseases arising from the integration of genetic findings with multiple enabling technologies within multidisciplinary teams to highlight the solidifying transformative potential of this approach. Well-designed workflows integrating different platforms are greatly improving and accelerating the unraveling and understanding of complex disease processes while promoting an effective way to find better drug targets, improve drug design and repurposing, and provide insight towards a more personalized clinical practice.

摘要

心血管疾病是全球发病率和死亡率的主要原因。全基因组关联研究(GWAS)是一种强大的流行病学工具,可用于寻找与心血管疾病相关的基因和变异,而后续的生物学研究有助于更好地了解疾病的病因和机制,并确定因果关系。改进的方法和降低的成本允许更广泛地使用批量和单细胞 RNA 测序、人类诱导多能干细胞、类器官、代谢组学、表观基因组学和新型动物模型与 GWAS 结合使用。在这篇综述中,我们重点介绍了多学科团队将遗传发现与多种使能技术相结合所带来的与心血管疾病相关的最新进展,以强调这种方法具有坚实的变革潜力。整合不同平台的精心设计的工作流程极大地提高和加速了复杂疾病过程的揭示和理解,同时为寻找更好的药物靶点、改进药物设计和重新利用以及为更个性化的临床实践提供了有价值的见解提供了有效的途径。

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