Paola Rampelotto Ziani, Marco Antônio de Bastiani, Ellen Scotton, Pedro Henrique da Rosa, Tainá Schons, Giovana Mezzomo, Quênia de Carvalho, Flávio Kapczinski, Adriane R Rosa
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引用次数: 0
Abstract
Objective: The present study combined transcriptomic data and computational techniques based on gene expression signatures to identify novel bioactive compounds or FDA-approved drugs for the management of Bipolar Disorder (BD).
Methods: Five transcriptomic datasets, comprising a total of 165 blood samples from BD case-control, were selected from the Gene Expression Omnibus repository (GEO). The number of subjects varied from 6 to 60, with a mean age ranging from 35 to 48, with a gender variation between them. Most of the patients were on pharmacological treatment. Master Regulator Analysis (MRA) and Gene Set Enrichment Analysis (GSEA) were performed to identify statistically significant genes between BD and HC and their association with the mood states of BD. Additionally, existing molecules with the potential to reverse the transcriptomic profiles of disease-altered regulons in BD were identified using the LINCS and cMap databases.
Results: MRA identified 59 potential MRs candidates modulating the regulatory units enriched with genes altered in BD, while the GSEA identified 134 enriched genes, and a total of 982 regulons had their activation state determined. Both analyses showed genes exclusively associated with mania, depression, or euthymia, and some genes were common between the three mood states. We identified bioactive compounds and licensed drug candidates, including antihypertensives and antineoplastics, as promising candidates for treating BD. Nevertheless, experimental validation is essential to authenticate these findings in subsequent studies.
Conclusion: Although preliminary, our data provides some insights regarding the biological patterns of BD into distinct mood states and potential therapeutic targets. The combined transcriptomic and bioinformatics strategy offers a route to advance drug discovery and personalized medicine by tapping into gene expression information.
期刊介绍:
The Revista Brasileira de Psiquiatria (RBP) is the official organ of the Associação Brasileira de Psiquiatria (ABP - Brazilian Association of Psychiatry).
The Brazilian Journal of Psychiatry is a bimonthly publication that aims to publish original manuscripts in all areas of psychiatry, including public health, clinical epidemiology, basic science, and mental health problems. The journal is fully open access, and there are no article processing or publication fees. Articles must be written in English.