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

Fuente: arXiv
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Main Authors: Saadat, Ali, Fellay, Jacques
Format: Preprint
Published: 2024
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author Saadat, Ali
Fellay, Jacques
author_facet Saadat, Ali
Fellay, Jacques
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2410_17708
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Proteome-wide prediction of mode of inheritance and molecular mechanism underlying genetic diseases using structural interactomics
Saadat, Ali
Fellay, Jacques
Quantitative Methods
Genomics
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.
title Proteome-wide prediction of mode of inheritance and molecular mechanism underlying genetic diseases using structural interactomics
topic Quantitative Methods
Genomics
url https://arxiv.org/abs/2410.17708