Proteome-wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomics
Summary: 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 a...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225010739 |
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| author | Ali Saadat Jacques Fellay |
| author_facet | Ali Saadat Jacques Fellay |
| author_sort | Ali Saadat |
| collection | DOAJ |
| description | Summary: 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 | Article |
| id | doaj-art-c6de8b83d5cb45ea83708d947323a14f |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-c6de8b83d5cb45ea83708d947323a14f2025-08-20T02:07:30ZengElsevieriScience2589-00422025-07-0128711281210.1016/j.isci.2025.112812Proteome-wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomicsAli Saadat0Jacques Fellay1School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, SwitzerlandSchool of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland; Precision Medicine Unit, Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225010739molecular interactionmolecular networkneural networksquantitative genetics |
| spellingShingle | Ali Saadat Jacques Fellay Proteome-wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomics iScience molecular interaction molecular network neural networks quantitative genetics |
| title | Proteome-wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomics |
| title_full | Proteome-wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomics |
| title_fullStr | Proteome-wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomics |
| title_full_unstemmed | Proteome-wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomics |
| title_short | Proteome-wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomics |
| title_sort | proteome wide prediction of the mode of inheritance and molecular mechanisms underlying genetic diseases using structural interactomics |
| topic | molecular interaction molecular network neural networks quantitative genetics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225010739 |
| work_keys_str_mv | AT alisaadat proteomewidepredictionofthemodeofinheritanceandmolecularmechanismsunderlyinggeneticdiseasesusingstructuralinteractomics AT jacquesfellay proteomewidepredictionofthemodeofinheritanceandmolecularmechanismsunderlyinggeneticdiseasesusingstructuralinteractomics |