Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis

Detalhes bibliográficos
Autor(a) principal: Vilela, Joana
Data de Publicação: 2023
Outros Autores: Martiniano, Hugo, Marques, Ana Rita, Santos, João Xavier, Asif, Muhammad, Rasga, Célia, Oliveira, Guiomar, Vicente, Astrid Moura
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/8814
Resumo: (This article belongs to the Special Issue Neurodevelopmental Disabilities)
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spelling Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection AnalysisAutism Spectrum DisorderUltra-rare VariantsProtein–protein Interaction AnalysisSynaptic and Neurotransmitter GenesCommunity Detection AnalysisPerturbações do Desenvolvimento Infantil e Saúde MentalAutism(This article belongs to the Special Issue Neurodevelopmental Disabilities)Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by communication deficits and repetitive behavioral patterns. Hundreds of candidate genes have been implicated in ASD, including neurotransmission and synaptic (NS) genes; however, the genetic architecture of this disease is far from clear. In this study, we seek to clarify the biological processes affected by NS gene variants identified in individuals with ASD and the global networks that link those processes together. For a curated list of 1216 NS candidate genes, identified in multiple databases and the literature, we searched for ultra-rare (UR) loss-of-function (LoF) variants in the whole-exome sequencing dataset from the Autism Sequencing Consortium (N = 3938 cases). Filtering for population frequency was carried out using gnomAD (N = 60,146 controls). NS genes with UR LoF variants were used to construct a network of protein–protein interactions, and the etwork’s biological communities were identified by applying the Leiden algorithm. We further explored the expression enrichment of network genes in specific brain regions. We identified 356 variants in 208 genes, with a preponderance of UR LoF variants in the PDE11A and SYTL3 genes. Expression enrichment analysis highlighted several subcortical structures, particularly the basal ganglia. The interaction network defined seven network communities, clustering synaptic and neurotransmitter pathways with several ubiquitous processes that occur in multiple organs and systems. This approach also uncovered biological pathways that are not usually associated with ASD, such as brain cytochromes P450 and brain mitochondrial metabolism. Overall, the community analysis suggests that ASD involves the disruption of synaptic and neurotransmitter pathways but also ubiquitous, but less frequently implicated, biological processes.This research was funded by Fundação para a Ciência e a Tecnologia (UIDB/04046/2020 and UIDP/04046/2020 Center grants to BioISI), PAC-POCI-01-0145-FEDER-016428 MEDPERSYST, DeePer—Deep graph learning approaches to personalized medicine (EXPL/CCI-BIO/0126/2021) and the National Institute of Health Doutor Ricardo Jorge. J.V., A.R.M. and J.X.S. are recipients of a fellowship from the BioSys PhD program PD65-2012 (J.V. Ref: PD/BD/131390/2017; A.R.M. Ref: PD/BD/113773/2015; and J.X.S. Ref: PD/BD/114386/2016) from Fundação para a Ciência e a Tecnologia (Portugal)MDPIRepositório Científico do Instituto Nacional de SaúdeVilela, JoanaMartiniano, HugoMarques, Ana RitaSantos, João XavierAsif, MuhammadRasga, CéliaOliveira, GuiomarVicente, Astrid Moura2024-01-03T13:34:42Z2023-11-042023-11-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/8814engBiomedicines. 2023 Nov 4;11(11):2971. doi: 10.3390/biomedicines111129712227-905910.3390/biomedicines11112971info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-06T01:34:11Zoai:repositorio.insa.pt:10400.18/8814Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:30:30.516569Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis
title Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis
spellingShingle Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis
Vilela, Joana
Autism Spectrum Disorder
Ultra-rare Variants
Protein–protein Interaction Analysis
Synaptic and Neurotransmitter Genes
Community Detection Analysis
Perturbações do Desenvolvimento Infantil e Saúde Mental
Autism
title_short Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis
title_full Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis
title_fullStr Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis
title_full_unstemmed Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis
title_sort Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis
author Vilela, Joana
author_facet Vilela, Joana
Martiniano, Hugo
Marques, Ana Rita
Santos, João Xavier
Asif, Muhammad
Rasga, Célia
Oliveira, Guiomar
Vicente, Astrid Moura
author_role author
author2 Martiniano, Hugo
Marques, Ana Rita
Santos, João Xavier
Asif, Muhammad
Rasga, Célia
Oliveira, Guiomar
Vicente, Astrid Moura
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Vilela, Joana
Martiniano, Hugo
Marques, Ana Rita
Santos, João Xavier
Asif, Muhammad
Rasga, Célia
Oliveira, Guiomar
Vicente, Astrid Moura
dc.subject.por.fl_str_mv Autism Spectrum Disorder
Ultra-rare Variants
Protein–protein Interaction Analysis
Synaptic and Neurotransmitter Genes
Community Detection Analysis
Perturbações do Desenvolvimento Infantil e Saúde Mental
Autism
topic Autism Spectrum Disorder
Ultra-rare Variants
Protein–protein Interaction Analysis
Synaptic and Neurotransmitter Genes
Community Detection Analysis
Perturbações do Desenvolvimento Infantil e Saúde Mental
Autism
description (This article belongs to the Special Issue Neurodevelopmental Disabilities)
publishDate 2023
dc.date.none.fl_str_mv 2023-11-04
2023-11-04T00:00:00Z
2024-01-03T13:34:42Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/8814
url http://hdl.handle.net/10400.18/8814
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biomedicines. 2023 Nov 4;11(11):2971. doi: 10.3390/biomedicines11112971
2227-9059
10.3390/biomedicines11112971
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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