Research on cognitive disorders such as Alzheimer's disease (AD Bullido et al., 1998), intellectual disability (ID Kaufman et al., 2010), autism spectrum disorder (ASD Bailey et al., 1996 Voineagu et al., 2011 Berg and Geschwind, 2012 Ecker et al., 2012), schizophrenia (SZ Andreasen, 1995), circadian rhythm and bipolar disorder (BD Akula et al., 2014, 2016 Takahashi, 2015), Parkinson's disease (PD Polymeropoulos, 2000), and several syndromes or disorders associated with ID or cognitive impairment (SY Greydanus and Pratt, 2005) has thus already identified several candidate genes involved in cognition. For example, causative mutations point to the genes that should in their wild-type variants be important for providing for healthy cognitive abilities. However, the actual molecular mechanisms that underlie these morphological changes are still not well understood.Ĭandidate genes that are involved in the molecular mechanisms of cognition can be identified through biomedical studies on cognitive disorders. In humans, cognitive processes such as use of language, social behavior, and decision-making have been attributed to the frontal lobe ( Duncan et al., 1996 Chayer and Freedman, 2001). Their central role in the network suggests them as excellent new candidates for playing an essential role in the regulatory network of the human frontal lobe, which should be investigated in future studies.īroadly defined, cognition refers to the biological mechanisms through which animals perceive, learn and memorize information from the environment and decide to act upon them ( Shettleworth, 2009). Interestingly, several hubs of the consensus network encode for GRFs that have not yet been associated with brain functions. Within this network, we detected a strong central module that is enriched for 166 GRFs known to be involved in brain development and/or cognitive disorders. This consensus network revealed robust GRF interactions that are conserved across the frontal lobes of different healthy human individuals. To instead focus on the most confident information from these 10 networks we developed a method for integrating such independently derived networks into a consensus network. We observed a high level of variability among these 10 independently derived networks, pointing out that relying on results from a single study can only provide limited biological insights. Using genome wide human frontal lobe expression data from 10 independent data sets, we first derived 10 individual coexpression networks for all GRFs including their potential target genes. Because many of these genes are gene regulatory factors (GRFs) we aimed to provide insights into the gene regulatory networks active in the human frontal lobe. One approach for analyzing the genetic networks involved in cognitive functions is to study the coexpression networks of genes with known importance for proper cognitive functions, such as genes that have been associated with cognitive disorders like intellectual disability (ID) or autism spectrum disorders (ASD). Not much is known yet about the molecular basis of cognitive abilities, but it seems clear that cognitive abilities are determined by the interplay of many genes. 5Institute for Theoretical Chemistry, University of Vienna, Vienna, AustriaĬognitive abilities, such as memory, learning, language, problem solving, and planning, involve the frontal lobe and other brain areas.4Department of Mathematics and Computer Sciences, University of Southern Denmark, Odense, Denmark.3Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.2Paul-Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.1Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University Leipzig, Leipzig, Germany.Stefano Berto 1,2,3 * Alvaro Perdomo-Sabogal 1 Daniel Gerighausen 1 Jing Qin 4,5 Katja Nowick 1,2 *
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