Publication: Modeling multifunctionality of genes with secondary gene co-expression networks in human brain provides novel disease insights
Authors
Sánchez Laguna, Juan Antonio ; Gil Martínez, Ana Luisa ; Cisterna, Alejandro ; García Ruiz, Sonia ; Gómez Pascual, Alicia ; Reynolds, Regina H. ; Botía Blaya, Juan Antonio ; Nalls, Mike ; Hardy, John ; Ryten, Mina
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Facultades de la UMU::Facultad de Informática
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Publisher
Oxford University Press
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DOI
https://doi.org/10.1093/bioinformatics/btab175
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info:eu-repo/semantics/article
Description
Abstract
Motivation
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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Citation
Sánchez 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.
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