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基因组学 2 蛋白质门户:将遗传筛选结果与蛋白质序列和结构联系起来的资源和发现工具。

Genomics 2 Proteins portal: a resource and discovery tool for linking genetic screening outputs to protein sequences and structures.

机构信息

Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

PATTERN, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

出版信息

Nat Methods. 2024 Oct;21(10):1947-1957. doi: 10.1038/s41592-024-02409-0. Epub 2024 Sep 18.

Abstract

Recent advances in AI-based methods have revolutionized the field of structural biology. Concomitantly, high-throughput sequencing and functional genomics have generated genetic variants at an unprecedented scale. However, efficient tools and resources are needed to link disparate data types-to 'map' variants onto protein structures, to better understand how the variation causes disease, and thereby design therapeutics. Here we present the Genomics 2 Proteins portal ( https://g2p.broadinstitute.org/ ): a human proteome-wide resource that maps 20,076,998 genetic variants onto 42,413 protein sequences and 77,923 structures, with a comprehensive set of structural and functional features. Additionally, the Genomics 2 Proteins portal allows users to interactively upload protein residue-wise annotations (for example, variants and scores) as well as the protein structure beyond databases to establish the connection between genomics to proteins. The portal serves as an easy-to-use discovery tool for researchers and scientists to hypothesize the structure-function relationship between natural or synthetic variations and their molecular phenotypes.

摘要

基于人工智能的方法的最新进展彻底改变了结构生物学领域。与此同时,高通量测序和功能基因组学以前所未有的规模产生了遗传变异。然而,需要有效的工具和资源将不同的数据类型联系起来,将变体映射到蛋白质结构上,以更好地理解变异如何导致疾病,从而设计治疗方法。在这里,我们介绍基因组学 2 蛋白质门户 ( https://g2p.broadinstitute.org/ ):一个人类蛋白质组范围的资源,它将 20,076,998 个遗传变体映射到 42,413 个蛋白质序列和 77,923 个结构上,并具有全面的结构和功能特征。此外,基因组学 2 蛋白质门户允许用户交互式地上传蛋白质残基注释(例如变体和分数)以及数据库之外的蛋白质结构,以建立基因组学与蛋白质之间的联系。该门户作为一个易于使用的发现工具,供研究人员和科学家假设自然或合成变异与其分子表型之间的结构-功能关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe64/11466821/c52f39397439/41592_2024_2409_Fig1_HTML.jpg

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