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NeuroSCORE is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system

To identify candidate disease genes of central nervous system (CNS) phenotypes, we created the Neurogenetic Systematic Correlation of Omics-Related Evidence (NeuroSCORE). We identified five genome-wide metrics highly associated with CNS phenotypes to score 19,601 protein-coding genes. Genes scored o...

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Autores principales: Davis, Kyle W., Bilancia, Colleen G., Martin, Megan, Vanzo, Rena, Rimmasch, Megan, Hom, Yolanda, Uddin, Mohammed, Serrano, Moises A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971396/
https://www.ncbi.nlm.nih.gov/pubmed/35361823
http://dx.doi.org/10.1038/s41598-022-08938-y
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author Davis, Kyle W.
Bilancia, Colleen G.
Martin, Megan
Vanzo, Rena
Rimmasch, Megan
Hom, Yolanda
Uddin, Mohammed
Serrano, Moises A.
author_facet Davis, Kyle W.
Bilancia, Colleen G.
Martin, Megan
Vanzo, Rena
Rimmasch, Megan
Hom, Yolanda
Uddin, Mohammed
Serrano, Moises A.
author_sort Davis, Kyle W.
collection PubMed
description To identify candidate disease genes of central nervous system (CNS) phenotypes, we created the Neurogenetic Systematic Correlation of Omics-Related Evidence (NeuroSCORE). We identified five genome-wide metrics highly associated with CNS phenotypes to score 19,601 protein-coding genes. Genes scored one point per metric (range: 0–5), identifying 8298 scored genes (scores ≥ 1) and 1601 “high scoring” genes (scores ≥ 3). Using logistic regression, we determined the odds ratio that genes with a NeuroSCORE from 1 to 5 would be associated with known CNS-related phenotypes compared to genes that scored zero. We tested NeuroSCORE using microarray copy number variants (CNVs) in case–control cohorts and aggregate mouse model data. High scoring genes are associated with CNS phenotypes (OR = 5.5, p < 2e(-16)), enriched in case CNVs, and mouse ortholog genes that cause behavioral and nervous system abnormalities. We identified 1058 high scoring genes with no disease association in OMIM. Transforming the logistic regression results indicates high scoring genes have an 84–92% chance of being associated with a CNS phenotype. Top scoring genes include GRIA1, MAP4K4, SF1, TNPO2, and ZSWIM8. Finally, we interrogated CNVs in the Clinical Genome Resource, finding the majority of clinically significant CNVs contain high scoring genes. These findings can direct future research and improve molecular diagnostics.
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spelling pubmed-89713962022-04-01 NeuroSCORE is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system Davis, Kyle W. Bilancia, Colleen G. Martin, Megan Vanzo, Rena Rimmasch, Megan Hom, Yolanda Uddin, Mohammed Serrano, Moises A. Sci Rep Article To identify candidate disease genes of central nervous system (CNS) phenotypes, we created the Neurogenetic Systematic Correlation of Omics-Related Evidence (NeuroSCORE). We identified five genome-wide metrics highly associated with CNS phenotypes to score 19,601 protein-coding genes. Genes scored one point per metric (range: 0–5), identifying 8298 scored genes (scores ≥ 1) and 1601 “high scoring” genes (scores ≥ 3). Using logistic regression, we determined the odds ratio that genes with a NeuroSCORE from 1 to 5 would be associated with known CNS-related phenotypes compared to genes that scored zero. We tested NeuroSCORE using microarray copy number variants (CNVs) in case–control cohorts and aggregate mouse model data. High scoring genes are associated with CNS phenotypes (OR = 5.5, p < 2e(-16)), enriched in case CNVs, and mouse ortholog genes that cause behavioral and nervous system abnormalities. We identified 1058 high scoring genes with no disease association in OMIM. Transforming the logistic regression results indicates high scoring genes have an 84–92% chance of being associated with a CNS phenotype. Top scoring genes include GRIA1, MAP4K4, SF1, TNPO2, and ZSWIM8. Finally, we interrogated CNVs in the Clinical Genome Resource, finding the majority of clinically significant CNVs contain high scoring genes. These findings can direct future research and improve molecular diagnostics. Nature Publishing Group UK 2022-03-31 /pmc/articles/PMC8971396/ /pubmed/35361823 http://dx.doi.org/10.1038/s41598-022-08938-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Davis, Kyle W.
Bilancia, Colleen G.
Martin, Megan
Vanzo, Rena
Rimmasch, Megan
Hom, Yolanda
Uddin, Mohammed
Serrano, Moises A.
NeuroSCORE is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system
title NeuroSCORE is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system
title_full NeuroSCORE is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system
title_fullStr NeuroSCORE is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system
title_full_unstemmed NeuroSCORE is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system
title_short NeuroSCORE is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system
title_sort neuroscore is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971396/
https://www.ncbi.nlm.nih.gov/pubmed/35361823
http://dx.doi.org/10.1038/s41598-022-08938-y
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