Multi-Tissue Transcriptomic study in dengue severe disease: In silico analysis of possible drugs for its management
Keywords:
dengue, transcriptome, drugs repositioning, genes expressionAbstract
Introduction: Dengue is a serious and growing health problem worldwide, without a specific antiviral treatment that allows early control of the infection. There are few transcriptomic analyzes of dengue and none in tissues. Our objective was to identify effective drugs against dengue disease by applying in silico investigation from a transcriptomic study in blood cells of individuals with dengue hemorrhagic fever and in liver and spleen cells of individuals who died from dengue.
Methods: It was used Next Generation Sequencing for the transcriptome study. It was assessed differentiated gene expression using the R DESeq2 package. They were analyzed modified molecular pathways using the gene interaction pathway bases Gene Ontology and Kyoto Encyclopedia of Genes and Genome. For the in silico analysis of drug repositioning, it was used the CMap Touchstone database containing perturbation data of 2837 compounds evaluated in 9 human cell lines.
Results: The genes and biological pathways overexpressed in splenic and blood liver cells were those associated with inflammation, cell destruction, apoptosis and viral replication processes; they were underexpressed those associated with cellular metabolism, antiviral response, and response to pathogens. They were identified 203 compounds with potential impact on the effects of dengue infection, and 4 differently expressed mechanisms of action between cases and controls in the 3 tissues studied. Conclusions: the present work constitutes the first transcriptome study in tissues of deceased patients due to dengue and the first in silico analysis for drug repositioning; it also allowed the identification of an important number of known drugs that constitute possible candidates to be evaluated in the future in the treatment of dengue disease.Downloads
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