Multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism

Abstract It is well established that epilepsy and autism spectrum disorder (ASD) commonly co-occur; however, the underlying biological mechanisms of the co-occurence from their genetic susceptibility are not well understood. Our aim in this study is to characterize genetic modules of subgroups of ep...

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Autores principales:	Jacqueline Peng, Yunyun Zhou, Kai Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/538145d3e7294c148050618d6296d848
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spelling	oai:doaj.org-article:538145d3e7294c148050618d6296d8482021-12-02T15:23:03ZMultiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism10.1038/s41598-020-78654-y2045-2322https://doaj.org/article/538145d3e7294c148050618d6296d8482021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78654-yhttps://doaj.org/toc/2045-2322Abstract It is well established that epilepsy and autism spectrum disorder (ASD) commonly co-occur; however, the underlying biological mechanisms of the co-occurence from their genetic susceptibility are not well understood. Our aim in this study is to characterize genetic modules of subgroups of epilepsy and autism genes that have similar phenotypic manifestations and biological functions. We first integrate a large number of expert-compiled and well-established epilepsy- and ASD-associated genes in a multiplex network, where one layer is connected through protein–protein interaction (PPI) and the other layer through gene-phenotype associations. We identify two modules in the multiplex network, which are significantly enriched in genes associated with both epilepsy and autism as well as genes highly expressed in brain tissues. We find that the first module, which represents the Gene Ontology category of ion transmembrane transport, is more epilepsy-focused, while the second module, representing synaptic signaling, is more ASD-focused. However, because of their enrichment in common genes and association with both epilepsy and ASD phenotypes, these modules point to genetic etiologies and biological processes shared between specific subtypes of epilepsy and ASD. Finally, we use our analysis to prioritize new candidate genes for epilepsy (i.e. ANK2, CACNA1E, CACNA2D3, GRIA2, DLG4) for further validation. The analytical approaches in our study can be applied to similar studies in the future to investigate the genetic connections between different human diseases.Jacqueline PengYunyun ZhouKai WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jacqueline Peng Yunyun Zhou Kai Wang Multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism
description	Abstract It is well established that epilepsy and autism spectrum disorder (ASD) commonly co-occur; however, the underlying biological mechanisms of the co-occurence from their genetic susceptibility are not well understood. Our aim in this study is to characterize genetic modules of subgroups of epilepsy and autism genes that have similar phenotypic manifestations and biological functions. We first integrate a large number of expert-compiled and well-established epilepsy- and ASD-associated genes in a multiplex network, where one layer is connected through protein–protein interaction (PPI) and the other layer through gene-phenotype associations. We identify two modules in the multiplex network, which are significantly enriched in genes associated with both epilepsy and autism as well as genes highly expressed in brain tissues. We find that the first module, which represents the Gene Ontology category of ion transmembrane transport, is more epilepsy-focused, while the second module, representing synaptic signaling, is more ASD-focused. However, because of their enrichment in common genes and association with both epilepsy and ASD phenotypes, these modules point to genetic etiologies and biological processes shared between specific subtypes of epilepsy and ASD. Finally, we use our analysis to prioritize new candidate genes for epilepsy (i.e. ANK2, CACNA1E, CACNA2D3, GRIA2, DLG4) for further validation. The analytical approaches in our study can be applied to similar studies in the future to investigate the genetic connections between different human diseases.
format	article
author	Jacqueline Peng Yunyun Zhou Kai Wang
author_facet	Jacqueline Peng Yunyun Zhou Kai Wang
author_sort	Jacqueline Peng
title	Multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism
title_short	Multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism
title_full	Multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism
title_fullStr	Multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism
title_full_unstemmed	Multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism
title_sort	multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/538145d3e7294c148050618d6296d848
work_keys_str_mv	AT jacquelinepeng multiplexgeneandphenotypenetworktocharacterizesharedgeneticpathwaysofepilepsyandautism AT yunyunzhou multiplexgeneandphenotypenetworktocharacterizesharedgeneticpathwaysofepilepsyandautism AT kaiwang multiplexgeneandphenotypenetworktocharacterizesharedgeneticpathwaysofepilepsyandautism
_version_	1718387324399648768

Multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism

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