Proteome-wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomics

IF 4.6 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Ali Saadat , Jacques Fellay
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引用次数: 0

Abstract

Genetic diseases can be classified according to their modes of inheritance and their underlying molecular mechanisms. Autosomal dominant disorders often result from DNA variants that cause loss-of-function, gain-of-function, or dominant-negative effects, while autosomal recessive diseases are primarily linked to loss-of-function variants. In this study, we introduce a graph-of-graphs approach that leverages protein-protein interaction networks and high-resolution protein structures to predict the mode of inheritance of diseases caused by variants in autosomal genes and to classify dominant-associated proteins based on their functional effect. Our approach integrates graph neural networks, structural interactomics, and topological network features to provide proteome-wide predictions, thus offering a scalable method for understanding genetic disease mechanisms.

Abstract Image

利用结构相互作用组学预测遗传模式和遗传疾病的分子机制
遗传病可根据其遗传方式及其潜在的分子机制进行分类。常染色体显性遗传病通常由DNA变异引起功能丧失、功能获得或显性负效应引起,而常染色体隐性遗传病主要与功能丧失变异有关。在这项研究中,我们引入了一种图的方法,利用蛋白质-蛋白质相互作用网络和高分辨率的蛋白质结构来预测由常染色体基因变异引起的疾病的遗传模式,并根据其功能效应对显性相关蛋白进行分类。我们的方法集成了图神经网络、结构相互作用组学和拓扑网络特征,以提供蛋白质组范围的预测,从而为理解遗传疾病机制提供了一种可扩展的方法。
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来源期刊
iScience
iScience Multidisciplinary-Multidisciplinary
CiteScore
7.20
自引率
1.70%
发文量
1972
审稿时长
6 weeks
期刊介绍: Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.
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