临床变异解释中变异效应的多重分析

IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY
Abbye E. McEwen, Malvika Tejura, Shawn Fayer, Lea M. Starita, Douglas M. Fowler
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引用次数: 0

摘要

临床基因检测的迅速发展显著提高了基因变异的检测水平。然而,大多数变异缺乏将其分类为致病性或良性所需的证据,导致意义不确定的变异积累,无法用于诊断或指导疾病的治疗。此外,癌症治疗的靶向治疗越来越依赖于正确识别致癌驱动突变,但在肿瘤中发现的许多变异的致癌性仍不清楚。为了应对这些挑战,对变异进行分类的努力越来越多地使用变异效应的多路分析(MAVEs),这是一种大规模的实验,可以同时生成数千种变异的功能数据。MAVE的兴起伴随着使用MAVE数据对种系变异进行分类以帮助临床实施的更好指导。在这里,我们概述了MAVE技术从开始到临床应用的增加,包括它们在揭示变异致病性机制和指导靶向治疗和药物开发方面的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Multiplexed assays of variant effect for clinical variant interpretation

Multiplexed assays of variant effect for clinical variant interpretation

The rapid expansion of clinical genetic testing has markedly improved the detection of genetic variants. However, most variants lack the evidence needed to classify them as pathogenic or benign, resulting in the accumulation of variants of uncertain significance that cannot be used to diagnose or guide treatment of disease. Moreover, targeted therapy for cancer treatment increasingly depends on correctly identifying oncogenic driver mutations, but the oncogenicity of many variants identified in tumours remains unclear. To address these challenges, efforts to classify variants are increasingly using multiplexed assays of variant effect (MAVEs), which are massively scaled experiments that can generate functional data for thousands of variants simultaneously. The rise of MAVEs is accompanied by better guidance on the use of MAVE data for classifying germline variants to aid their clinical implementation. Here, we overview MAVE technologies from their inception to their increased use in the clinic, including their roles in uncovering mechanisms for variant pathogenicity and guiding targeted therapy and drug development.

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来源期刊
Nature Reviews Genetics
Nature Reviews Genetics 生物-遗传学
CiteScore
57.40
自引率
0.50%
发文量
113
审稿时长
6-12 weeks
期刊介绍: At Nature Reviews Genetics, our goal is to be the leading source of reviews and commentaries for the scientific communities we serve. We are dedicated to publishing authoritative articles that are easily accessible to our readers. We believe in enhancing our articles with clear and understandable figures, tables, and other display items. Our aim is to provide an unparalleled service to authors, referees, and readers, and we are committed to maximizing the usefulness and impact of each article we publish. Within our journal, we publish a range of content including Research Highlights, Comments, Reviews, and Perspectives that are relevant to geneticists and genomicists. With our broad scope, we ensure that the articles we publish reach the widest possible audience. As part of the Nature Reviews portfolio of journals, we strive to uphold the high standards and reputation associated with this esteemed collection of publications.
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