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Modeling multifunctionality of genes with secondary gene co-expression networks in human brain provides novel disease insights

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dc.contributor.authorSánchez Laguna, Juan Antonio
dc.contributor.authorGil Martínez, Ana Luisa
dc.contributor.authorCisterna, Alejandro
dc.contributor.authorGarcía Ruiz, Sonia
dc.contributor.authorGómez Pascual, Alicia
dc.contributor.authorReynolds, Regina H.
dc.contributor.authorBotía Blaya, Juan Antonio
dc.contributor.authorNalls, Mike
dc.contributor.authorHardy, John
dc.contributor.authorRyten, Mina
dc.contributor.departmentIngeniería de la Información y las Comunicaciones
dc.contributor.otherFacultades de la UMU::Facultad de Informática
dc.date.accessioned2026-03-02T09:32:22Z
dc.date.available2026-03-02T09:32:22Z
dc.date.copyright© The Author(s) 2021
dc.date.issued2021-03-18
dc.description.abstractMotivation Co-expression networks are a powerful gene expression analysis method to study how genes co-express together in clusters with functional coherence that usually resemble specific cell type behavior for the genes involved. They can be applied to bulk-tissue gene expression profiling and assign function, and usually cell type specificity, to a high percentage of the gene pool used to construct the network. One of the limitations of this method is that each gene is predicted to play a role in a specific set of coherent functions in a single cell type (i.e. at most we get a single <gene, function, cell type> for each gene). We present here GMSCA (Gene Multifunctionality Secondary Co-expression Analysis), a software tool that exploits the co-expression paradigm to increase the number of functions and cell types ascribed to a gene in bulk-tissue co-expression networks. Results We applied GMSCA to 27 co-expression networks derived from bulk-tissue gene expression profiling of a variety of brain tissues. Neurons and glial cells (microglia, astrocytes and oligodendrocytes) were considered the main cell types. Applying this approach, we increase the overall number of predicted triplets <gene, function, cell type> by 46.73%. Moreover, GMSCA predicts that the SNCA gene, traditionally associated to work mainly in neurons, also plays a relevant function in oligodendrocytes.
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dc.identifier.citationSánchez JA, Gil-Martinez AL, Cisterna A, García-Ruíz S, Gómez-Pascual A, Reynolds RH, Nalls M, Hardy J, Ryten M, Botía JA. Modeling multifunctionality of genes with secondary gene co-expression networks in human brain provides novel disease insights. Bioinformatics. 2021 Sep 29;37(18):2905-2911. doi: 10.1093/bioinformatics/btab175.
dc.identifier.doihttps://doi.org/10.1093/bioinformatics/btab175
dc.identifier.eissn1474-7596
dc.identifier.issn1367-4803
dc.identifier.urihttp://hdl.handle.net/10201/216901
dc.languagespa
dc.publisherOxford University Press
dc.relationFinanciado por el Medical Research Council (MRC, Reino Unido) y Wellcome Trust, en el marco de proyectos competitivos de investigación en genómica y neurociencia (según sección Funding del artículo). R.H.R. was supported through the award of a Leonard Wolfson Doctoral Training Fellowship in Neurodegeneration. J.H. and M.R. were supported by the UK Medical Research Council (MRC), with J.H. supported by a grant [MR/N026004/] and M.R and S.G.R. through the award of a Tenure Track Clinician Scientist Fellowship [MR/N008324/1]. J.H. was also supported by the UK Dementia Research Institute, The Wellcome Trust [202903/Z/16/Z], the Dolby Family Fund and the NIHR. A.C. was supported by Fundación Séneca—Science and Technology Agency of the Region of Murcia, [20762/FPI/18]. A.L.G.M. was funded by Fundación Séneca [21230/PD/19]. J.B. was supported by the same agency [00007/COVI/20].
dc.relation.publisherversionhttps://academic.oup.com/bioinformatics/article/37/18/2905/6178279
dc.rightsAttribution 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleModeling multifunctionality of genes with secondary gene co-expression networks in human brain provides novel disease insights
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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relation.isAuthorOfPublication848746a7-05ac-4d08-82cb-e6a80680c24f
relation.isAuthorOfPublicationee187cf4-aebe-4d10-bfe0-09dedbc8daaf
relation.isAuthorOfPublication.latestForDiscovery6af5f802-d58a-431a-be33-ca6ea7d73da5
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