Identification and In Silico Characterization of Novel lncRNAs Associated with Dengue Infection

Abstract Background Long noncoding RNAs (lncRNAs) are essential regulators of various biological processes in viral infections. In our previous study, we described the association of known lncRNAs with dengue disease progression. However, little is known about novel lncRNAs in the context of dengue infection. In this study, we aimed to identify novel lncRNAs and characterize their interaction with mRNAs during different stages of dengue infection using RNA sequencing (RNA-seq) technology to better understand their role in dengue pathogenesis. Methods We analyzed RNA-seq data (GSE94892) obtained from peripheral blood mononuclear cells (PBMCs) of 39 dengue-infected patients. RNA-seq data analysis was performed using the Tuxedo protocol, and the coding potential of novel transcripts was examined using CPC and CPAT tools. LncRNAs and cis-regulated mRNAs were identified through location-expression analysis within a 20 kbp genomic region surrounding the identified lncRNAs. Results We identified and characterized a total of 65 novel lncRNAs differentially expressed during dengue disease progression. These included 34 long intergenic lncRNAs, 2 antisense lncRNAs, and 25 alternatively spliced lncRNAs classified based on their localization. Bioinformatics analysis predicted potential cis-regulated target genes. Co-expression analysis revealed a strong correlation between lncRNAs and genes enriched in pathways related to megakaryocyte development and platelet production, suggesting a potential role in dengue pathogenesis. Furthermore, comparison with miRBase-21 indicated that some of the identified lncRNAs could act as miRNA precursors, highlighting a novel function of lncRNAs in gene regulation. Conclusion We developed an analytical pipeline to identify novel lncRNAs from RNA-seq data. Our analyses led to the identification of novel lncRNAs and their associated genes involved in dengue disease progression. These findings provide insights into the functional role of lncRNAs in dengue pathogenesis.