RESUMEN
There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by influencing gene expression through a wide range of mechanisms. By mining whole-transcriptome shotgun sequencing (RNA-seq) data using machine learning approaches, we detected two lncRNAs (ENSG00000254680 and ENSG00000273149) that are downregulated in a wide range of viral infections and different cell types, including blood monocluclear cells, umbilical vein endothelial cells, and dermal fibroblasts. The efficiency of these two lncRNAs was positively validated in different viral phenotypic scenarios. These two lncRNAs showed a strong downregulation in virus-infected patients when compared to healthy control transcriptomes, indicating that these biomarkers are promising targets for infection diagnosis. To the best of our knowledge, this is the very first study using host lncRNAs biomarkers for the diagnosis of human viral infections.
Asunto(s)
Células Endoteliales/metabolismo , Fibroblastos/metabolismo , Monocitos/metabolismo , ARN Largo no Codificante/sangre , Virosis/metabolismo , Adulto , Pueblo Asiatico , Biomarcadores/sangre , Biomarcadores/metabolismo , Preescolar , Minería de Datos , Regulación hacia Abajo , Células Endoteliales/microbiología , Infecciones por Escherichia coli/genética , Infecciones por Escherichia coli/metabolismo , Fibroblastos/microbiología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Gripe Humana/genética , Gripe Humana/metabolismo , Aprendizaje Automático , México , Monocitos/microbiología , Monocitos/virología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , RNA-Seq , Infecciones por Rotavirus/genética , Infecciones por Rotavirus/metabolismo , Infección por el Virus de la Varicela-Zóster/genética , Infección por el Virus de la Varicela-Zóster/metabolismo , Virosis/genética , Población BlancaRESUMEN
BACKGROUND: Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations. OBJECTIVE: This study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children. METHODS: This was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS). RESULTS: Four SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44-3.21, pâ¯<â¯0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, pâ¯=â¯0.02, and for rs12603332, pâ¯=â¯0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus. CONCLUSIONS: We confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus.