Identification of miRNA-mRNA Network in Autism Spectrum Disorder Using a Bioinformatics Method
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Identification of miRNA-mRNA Network in Autism Spectrum Disorder Using a Bioinformatics Method Rezvan Noroozi 1 & Marcel E. Dinger 2 & Razieh Fatehi 3 & Mohammad Taheri 4
&
Soudeh Ghafouri-Fard 5
Received: 10 July 2020 / Accepted: 28 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Autism spectrum disorder (ASD) includes a heterogeneous group of disorders with different contributing genetics and epigenetics factors. Aberrant expression of miRNAs has been detected in ASD children compared with normally developed children. Due to the heterogeneity of this disorder, there is no consensus on ASD-associated miRNAs; thus, it is necessary to develop a model for comprehensive assessment of the role of miRNAs in ASD. We interrogated the PubMed, Google Scholar, and Web of Science databases until the end of 2019 to identify ASD-associated miRNAs. In addition, mRNA-coding genes that contribute to the pathogenesis of ASD were downloaded from the SFARI GENE (https://gene.sfari.org/). The obtained 201 miRNAs and 478 target mRNAs were imported into the Cytoscape software suite to construct a miRNA-mRNA network. A protein-protein interaction network was constructed for target mRNAs using the CluPedia program in Cytoscape. Using this approach, we detected five modules that were associated with neurexins and neuroligins, glutamatergic synapse, cell adhesion molecules, NOTCH, MECP2 and circadian clock pathways, L1CAM interactions, and neurotransmitter release cycle. Taken together, functional analysis of these genes led to determination of critical pathways related to CNS disorders. Thus, the suggested approach in the current study resulted in the identification of the most relevant pathways in the pathogenesis of ASD that can be used as biomarkers or therapeutic targets. Keywords Autism spectrum disorder . miRNA . Bioinformatics
Introduction Rezvan Noroozi and Marcel E. Dinger contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12031-020-01695-5) contains supplementary material, which is available to authorized users. * Mohammad Taheri [email protected] * Soudeh Ghafouri-Fard [email protected] 1
Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland
2
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
3
Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
4
Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Autism spectrum disorder (ASD) is a neurodevelopmental condition that is diagnosed in children through detection of difficulties with communication and social interaction, atypical limited interests, and repetitive actions (McPartland et al. 2012). It is estimated that ASD affects 1 in 59 children, with a three-fold bias toward
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