High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression

ABSTRACT The circulating microRNA (miRNA) profile has been widely used for identifying potential biomarkers against viral infections. However, data on circulating microRNA expression patterns in dengue patients are scanty. Considering the impact of severity caused by dengue infection, circulating mi...

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Autores principales:	Jaya Saini, Bhaswati Bandyopadhyay, Abhay Deep Pandey, V. G. Ramachandran, Shukla Das, Vikas Sood, Arup Banerjee, Sudhanshu Vrati
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	dengue RNA sequencing circulating miRNA plasma microRNA Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3be4c808cb0d468eb918b617a11aeeed
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spelling	oai:doaj.org-article:3be4c808cb0d468eb918b617a11aeeed2021-12-02T19:47:33ZHigh-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression10.1128/mSystems.00724-202379-5077https://doaj.org/article/3be4c808cb0d468eb918b617a11aeeed2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00724-20https://doaj.org/toc/2379-5077ABSTRACT The circulating microRNA (miRNA) profile has been widely used for identifying potential biomarkers against viral infections. However, data on circulating microRNA expression patterns in dengue patients are scanty. Considering the impact of severity caused by dengue infection, circulating miRNA profiles in plasma of dengue patients may prove to be valuable for developing early prognostic markers for the disease severity. Here, we described an in-depth analytical study of small RNA sequencing data obtained from the plasma of 39 dengue patients. Integrating bioinformatics and in vitro studies, we identified differentially expressed miRNAs (DEMs) (log2 fold change ≥1.5, P < 0.05) associated with dengue disease progression. In comparing miRNA expression pattern with the follow-up samples, nine miRNAs were found to exhibit an altered expression that could distinguish between severe dengue and the convalescent patients. To understand the abundance and specificity of the DEMs in the context of dengue infection and disease progression, eight top-hit DEMs were further validated in the dengue virus-infected cell lines as well as in the patient’s plasma and peripheral blood mononuclear cells (PBMCs) using the quantitative reverse transcription-PCR (qRT‐PCR) method. Importantly, receiver operating curve analysis further confirmed that the plasma expression pattern of hsa-miR-122-5p could differentiate between different stages of dengue infection (area under the concentration-time curve [AUC] = 0.792), and dengue-negative patients with other febrile illnesses (AUC = 0.984). The in silico analysis of DEM target genes suggested an enrichment of the pathways associated with metabolism and inflammation. Our study gives a global view of miRNA expression in the plasma from dengue patients and provides a precious resource of candidate miRNAs involved in dengue infection and disease progression. IMPORTANCE Dengue virus (DENV) infection usually causes dengue fever (DF) with flu-like illness affecting infants, young children, and adults. The DF occasionally evolves into a potentially lethal complication called dengue severe (DS) leading to a rapid fall in platelet count along with plasma leakage, fluid accumulation, respiratory distress, and severe bleeding. The diverse clinical spectrum of dengue disease, as well as its significant similarity to other febrile viral illnesses, makes early identification more challenging in this high-risk group. microRNAs (miRNAs) are small (∼19 to 21 nucleotides [nt] in length), noncoding RNAs, extremely stable and easily detectable in the plasma; thus, they have potential as biomarkers for diagnosing and monitoring human diseases. This study provides a comprehensive analysis of miRNAs circulating in plasma of dengue virus-infected patients and identifies the miRNA signatures that have biomarker potential for dengue infection and disease progression.Jaya SainiBhaswati BandyopadhyayAbhay Deep PandeyV. G. RamachandranShukla DasVikas SoodArup BanerjeeSudhanshu VratiAmerican Society for MicrobiologyarticledengueRNA sequencingcirculating miRNAplasma microRNAMicrobiologyQR1-502ENmSystems, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	dengue RNA sequencing circulating miRNA plasma microRNA Microbiology QR1-502
spellingShingle	dengue RNA sequencing circulating miRNA plasma microRNA Microbiology QR1-502 Jaya Saini Bhaswati Bandyopadhyay Abhay Deep Pandey V. G. Ramachandran Shukla Das Vikas Sood Arup Banerjee Sudhanshu Vrati High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression
description	ABSTRACT The circulating microRNA (miRNA) profile has been widely used for identifying potential biomarkers against viral infections. However, data on circulating microRNA expression patterns in dengue patients are scanty. Considering the impact of severity caused by dengue infection, circulating miRNA profiles in plasma of dengue patients may prove to be valuable for developing early prognostic markers for the disease severity. Here, we described an in-depth analytical study of small RNA sequencing data obtained from the plasma of 39 dengue patients. Integrating bioinformatics and in vitro studies, we identified differentially expressed miRNAs (DEMs) (log2 fold change ≥1.5, P < 0.05) associated with dengue disease progression. In comparing miRNA expression pattern with the follow-up samples, nine miRNAs were found to exhibit an altered expression that could distinguish between severe dengue and the convalescent patients. To understand the abundance and specificity of the DEMs in the context of dengue infection and disease progression, eight top-hit DEMs were further validated in the dengue virus-infected cell lines as well as in the patient’s plasma and peripheral blood mononuclear cells (PBMCs) using the quantitative reverse transcription-PCR (qRT‐PCR) method. Importantly, receiver operating curve analysis further confirmed that the plasma expression pattern of hsa-miR-122-5p could differentiate between different stages of dengue infection (area under the concentration-time curve [AUC] = 0.792), and dengue-negative patients with other febrile illnesses (AUC = 0.984). The in silico analysis of DEM target genes suggested an enrichment of the pathways associated with metabolism and inflammation. Our study gives a global view of miRNA expression in the plasma from dengue patients and provides a precious resource of candidate miRNAs involved in dengue infection and disease progression. IMPORTANCE Dengue virus (DENV) infection usually causes dengue fever (DF) with flu-like illness affecting infants, young children, and adults. The DF occasionally evolves into a potentially lethal complication called dengue severe (DS) leading to a rapid fall in platelet count along with plasma leakage, fluid accumulation, respiratory distress, and severe bleeding. The diverse clinical spectrum of dengue disease, as well as its significant similarity to other febrile viral illnesses, makes early identification more challenging in this high-risk group. microRNAs (miRNAs) are small (∼19 to 21 nucleotides [nt] in length), noncoding RNAs, extremely stable and easily detectable in the plasma; thus, they have potential as biomarkers for diagnosing and monitoring human diseases. This study provides a comprehensive analysis of miRNAs circulating in plasma of dengue virus-infected patients and identifies the miRNA signatures that have biomarker potential for dengue infection and disease progression.
format	article
author	Jaya Saini Bhaswati Bandyopadhyay Abhay Deep Pandey V. G. Ramachandran Shukla Das Vikas Sood Arup Banerjee Sudhanshu Vrati
author_facet	Jaya Saini Bhaswati Bandyopadhyay Abhay Deep Pandey V. G. Ramachandran Shukla Das Vikas Sood Arup Banerjee Sudhanshu Vrati
author_sort	Jaya Saini
title	High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression
title_short	High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression
title_full	High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression
title_fullStr	High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression
title_full_unstemmed	High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression
title_sort	high-throughput rna sequencing analysis of plasma samples reveals circulating microrna signatures with biomarker potential in dengue disease progression
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/3be4c808cb0d468eb918b617a11aeeed
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High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression

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