TY - INPR ID - discovery10125186 N2 - 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 behaviour 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. AVAILABILITY: The tool is available at GitHub, https://github.com/drlaguna/GMSCA as open-source software. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. AV - public A1 - Sánchez, JA A1 - Gil-Martinez, AL A1 - Cisterna, A A1 - García-Ruíz, S A1 - Gómez-Pascual, A A1 - Reynolds, RH A1 - Nalls, M A1 - Hardy, J A1 - Ryten, M A1 - Botía, JA Y1 - 2021/03/17/ N1 - © The Author(s) 2021. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Supplementa UR - https://doi.org/10.1093/bioinformatics/btab175 TI - Modeling multifunctionality of genes with secondary gene co-expression networks in human brain provides novel disease insights. JF - Bioinformatics ER -