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DeepGenePrior: A deep learning model for prioritizing genes affected by copy number variants

The genetic etiology of brain disorders is highly heterogeneous, characterized by abnormalities in the development of the central nervous system that lead to diminished physical or intellectual capabilities. The process of determining which gene drives disease, known as “gene prioritization,” is not...

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Autores principales: Rahaie, Zahra, Rabiee, Hamid R., Alinejad-Rokny, Hamid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399873/
https://www.ncbi.nlm.nih.gov/pubmed/37486921
http://dx.doi.org/10.1371/journal.pcbi.1011249
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author Rahaie, Zahra
Rabiee, Hamid R.
Alinejad-Rokny, Hamid
author_facet Rahaie, Zahra
Rabiee, Hamid R.
Alinejad-Rokny, Hamid
author_sort Rahaie, Zahra
collection PubMed
description The genetic etiology of brain disorders is highly heterogeneous, characterized by abnormalities in the development of the central nervous system that lead to diminished physical or intellectual capabilities. The process of determining which gene drives disease, known as “gene prioritization,” is not entirely understood. Genome-wide searches for gene-disease associations are still underdeveloped due to reliance on previous discoveries and evidence sources with false positive or negative relations. This paper introduces DeepGenePrior, a model based on deep neural networks that prioritizes candidate genes in genetic diseases. Using the well-studied Variational AutoEncoder (VAE), we developed a score to measure the impact of genes on target diseases. Unlike other methods that use prior data to select candidate genes, based on the "guilt by association" principle and auxiliary data sources like protein networks, our study exclusively employs copy number variants (CNVs) for gene prioritization. By analyzing CNVs from 74,811 individuals with autism, schizophrenia, and developmental delay, we identified genes that best distinguish cases from controls. Our findings indicate a 12% increase in fold enrichment in brain-expressed genes compared to previous studies and a 15% increase in genes associated with mouse nervous system phenotypes. Furthermore, we identified common deletions in ZDHHC8, DGCR5, and CATG00000022283 among the top genes related to all three disorders, suggesting a common etiology among these clinically distinct conditions. DeepGenePrior is publicly available online at http://git.dml.ir/z_rahaie/DGP to address obstacles in existing gene prioritization studies identifying candidate genes.
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spelling pubmed-103998732023-08-04 DeepGenePrior: A deep learning model for prioritizing genes affected by copy number variants Rahaie, Zahra Rabiee, Hamid R. Alinejad-Rokny, Hamid PLoS Comput Biol Research Article The genetic etiology of brain disorders is highly heterogeneous, characterized by abnormalities in the development of the central nervous system that lead to diminished physical or intellectual capabilities. The process of determining which gene drives disease, known as “gene prioritization,” is not entirely understood. Genome-wide searches for gene-disease associations are still underdeveloped due to reliance on previous discoveries and evidence sources with false positive or negative relations. This paper introduces DeepGenePrior, a model based on deep neural networks that prioritizes candidate genes in genetic diseases. Using the well-studied Variational AutoEncoder (VAE), we developed a score to measure the impact of genes on target diseases. Unlike other methods that use prior data to select candidate genes, based on the "guilt by association" principle and auxiliary data sources like protein networks, our study exclusively employs copy number variants (CNVs) for gene prioritization. By analyzing CNVs from 74,811 individuals with autism, schizophrenia, and developmental delay, we identified genes that best distinguish cases from controls. Our findings indicate a 12% increase in fold enrichment in brain-expressed genes compared to previous studies and a 15% increase in genes associated with mouse nervous system phenotypes. Furthermore, we identified common deletions in ZDHHC8, DGCR5, and CATG00000022283 among the top genes related to all three disorders, suggesting a common etiology among these clinically distinct conditions. DeepGenePrior is publicly available online at http://git.dml.ir/z_rahaie/DGP to address obstacles in existing gene prioritization studies identifying candidate genes. Public Library of Science 2023-07-24 /pmc/articles/PMC10399873/ /pubmed/37486921 http://dx.doi.org/10.1371/journal.pcbi.1011249 Text en © 2023 Rahaie et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rahaie, Zahra
Rabiee, Hamid R.
Alinejad-Rokny, Hamid
DeepGenePrior: A deep learning model for prioritizing genes affected by copy number variants
title DeepGenePrior: A deep learning model for prioritizing genes affected by copy number variants
title_full DeepGenePrior: A deep learning model for prioritizing genes affected by copy number variants
title_fullStr DeepGenePrior: A deep learning model for prioritizing genes affected by copy number variants
title_full_unstemmed DeepGenePrior: A deep learning model for prioritizing genes affected by copy number variants
title_short DeepGenePrior: A deep learning model for prioritizing genes affected by copy number variants
title_sort deepgeneprior: a deep learning model for prioritizing genes affected by copy number variants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399873/
https://www.ncbi.nlm.nih.gov/pubmed/37486921
http://dx.doi.org/10.1371/journal.pcbi.1011249
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