scholarly journals Structural landscape of the complete genomes of dengue virus serotypes and other viral hemorrhagic fevers

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Riccardo Delli Ponti ◽  
Marek Mutwil
Keyword(s):  
Secondary Structure ◽  
Dengue Virus ◽  
Rna Secondary Structure ◽  
High Throughput Sequencing ◽  
Denv Serotypes ◽  
Hemorrhagic Fevers ◽  
Interaction Sites ◽  
Significant Difference ◽  
Viral Hemorrhagic Fevers ◽  
Human Proteins

Abstract Background With more than 300 million potentially infected people every year, and with the expanded habitat of mosquitoes due to climate change, Dengue virus (DENV) cannot be considered anymore only a tropical disease. The RNA secondary structure is a functional characteristic of RNA viruses, and together with the accumulated high-throughput sequencing data could provide general insights towards understanding virus biology. Here, we profiled the RNA secondary structure of > 7000 complete viral genomes from 11 different species focusing on viral hemorrhagic fevers, including DENV serotypes, EBOV, and YFV. Results In our work we demonstrated that the secondary structure and presence of protein-binding domains in the genomes can be used as intrinsic signature to further classify the viruses. With our predictive approach, we achieved high prediction scores of the secondary structure (AUC up to 0.85 with experimental data), and computed consensus secondary structure profiles using hundreds of in silico models. We observed that viruses show different structural patterns, where e.g., DENV-2 and Ebola virus tend to be less structured than the other viruses. Furthermore, we observed virus-specific correlations between secondary structure and the number of interaction sites with human proteins, reaching a correlation of 0.89 in the case of Zika virus. We also identified that helicases-encoding regions are more structured in several flaviviruses, while the regions encoding for the contact proteins exhibit virus-specific clusters in terms of RNA structure and potential protein-RNA interactions. We also used structural data to study the geographical distribution of DENV, finding a significant difference between DENV-3 from Asia and South-America, where the structure is also driving the clustering more than sequence identity, which could imply different evolutionary routes of this subtype. Conclusions Our massive computational analysis provided novel results regarding the secondary structure and the interaction with human proteins, not only for DENV serotypes, but also for other flaviviruses and viral hemorrhagic fevers-associated viruses. We showed how the RNA secondary structure can be used to categorise viruses, and even to further classify them based on the interaction with proteins. We envision that these approaches can be used to further classify and characterise these complex viruses.

scholarly journals Structural landscape of the complete genomes of Dengue serotypes and other viral hemorrhagic fevers

2020 ◽  
Author(s):  
Riccardo Delli-Ponti ◽  
Marek Mutwil
Keyword(s):  
Secondary Structure ◽  
Rna Secondary Structure ◽  
High Throughput Sequencing ◽  
Sequencing Data ◽  
Infected People ◽  
Hemorrhagic Fevers ◽  
Interaction Sites ◽  
Significant Difference ◽  
Viral Hemorrhagic Fevers ◽  
Human Proteins

ABSTRACTBackgroundWith more than 300 million potentially infected people every year, and with the expanded habitat of mosquitoes due to climate change, dengue cannot be considered anymore only a tropical disease. The RNA secondary structure is a functional characteristic of RNA viruses, and together with the accumulated high-throughput sequencing data could provide general insights towards understanding virus biology. Here, we profiled the RNA secondary structure of >7500 complete viral genomes from 11 different species of viral hemorrhagic fevers, including dengue serotypes, ebola, and yellow fever.ResultsWe achieved hig prediction scores (AUC up to 0.85 with experimental data), and computed consensus secondary structure profiles using hundreds of structural in silico models. We observed that virulent viruses such as DENV-2 and ebola tend to be less structured than the other viruses. Furthermore, we observed virus-specific correlations between secondary structure and the number of interaction sites with human proteins, reaching a correlation of 0.89 in the case of zika. We demonstrate that the secondary structure and presence of protein-binding domains in the genomes can be used as intrinsic signature to further classify the viruses. We also used structural data to study the geographical distribution of dengue, finding a significant difference between DENV-3 from Asia and South-America, which could imply different evolutionary routes of this subtype.ConclusionsOur massive computational analysis provided novel results regarding the secondary structure and the interaction with human proteins, not only for Dengue serotypes, but also for other viral hemorrhagic fevers. We also provided a new approach to classify viruses according ot their structure, which could be useful for future cassifications. We envision that these approaches can be used by the scientific community to further classify and characterise these complex viruses.

scholarly journals A comprehensive database of high-throughput sequencing-based RNA secondary structure probing data (Structure Surfer)

2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Nathan D. Berkowitz ◽  
Ian M. Silverman ◽  
Daniel M. Childress ◽  
Hilal Kazan ◽  
Li-San Wang ◽  
...  
Keyword(s):  
Data Structure ◽  
Secondary Structure ◽  
High Throughput ◽  
Rna Secondary Structure ◽  
High Throughput Sequencing ◽  
Comprehensive Database ◽  
Structure Probing

scholarly journals Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Ashley L St John ◽  
Abhay PS Rathore ◽  
Bhuvanakantham Raghavan ◽  
Mah-Lee Ng ◽  
Soman N Abraham
Keyword(s):  
Mast Cells ◽  
Dengue Virus ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Vascular Leakage ◽  
Clinical Samples ◽  
Specific Product ◽  
Hemorrhagic Fevers ◽  
Viral Hemorrhagic Fevers

Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infection, and we show that this elevates systemic levels of their vasoactive products, including chymase, and promotes vascular leakage. Treatment of infected animals with MC-stabilizing drugs or a leukotriene receptor antagonist restores vascular integrity during experimental DENV infection. Validation of these findings using human clinical samples revealed a direct correlation between MC activation and DENV disease severity. In humans, the MC-specific product, chymase, is a predictive biomarker distinguishing dengue fever (DF) and dengue hemorrhagic fever (DHF). Additionally, our findings reveal MCs as potential therapeutic targets to prevent DENV-induced vasculopathy, suggesting MC-stabilizing drugs should be evaluated for their effectiveness in improving disease outcomes during viral hemorrhagic fevers.

scholarly journals Dynamic changes in RNA–protein interactions and RNA secondary structure in mammalian erythropoiesis

2021 ◽  
Vol 4 (9) ◽  
pp. e202000659
Author(s):  
Mengge Shan ◽  
Xinjun Ji ◽  
Kevin Janssen ◽  
Ian M Silverman ◽  
Jesse Humenik ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Protein Interactions ◽  
Rna Secondary Structure ◽  
Rna Binding ◽  
Developmental Process ◽  
Global Analysis ◽  
Sequence Motifs ◽  
Rna Molecules ◽  
Interaction Sites ◽  
Rna Interaction

Two features of eukaryotic RNA molecules that regulate their post-transcriptional fates are RNA secondary structure and RNA-binding protein (RBP) interaction sites. However, a comprehensive global overview of the dynamic nature of these sequence features during erythropoiesis has never been obtained. Here, we use our ribonuclease-mediated structure and RBP-binding site mapping approach to reveal the global landscape of RNA secondary structure and RBP–RNA interaction sites and the dynamics of these features during this important developmental process. We identify dynamic patterns of RNA secondary structure and RBP binding throughout the process and determine a set of corresponding protein-bound sequence motifs along with their dynamic structural and RBP-binding contexts. Finally, using these dynamically bound sequences, we identify a number of RBPs that have known and putative key functions in post-transcriptional regulation during mammalian erythropoiesis. In total, this global analysis reveals new post-transcriptional regulators of mammalian blood cell development.

DSARna: RNA Secondary Structure Alignment Based on Digital Sequence Representation

2020 ◽  
Vol 23 ◽  
Author(s):  
Longjian Gao ◽  
Chengzhen Xu ◽  
Wangan Song ◽  
Feng Xiao ◽  
Xiaomin Wu ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
High Throughput Sequencing ◽  
Structural Information ◽  
Dynamic Programming Algorithm ◽  
Structure Alignment ◽  
Programming Algorithm ◽  
Structure Information ◽  
Alignment Algorithms

Background: With increasing applications and development of high-throughput sequencing, knowledge of the primary structure of RNA has expanded exponentially. Moreover, the function of RNA is determined by the secondary or higher RNA structure, and similar structures are related to similar functions, such as the secondary clover structure of tRNA. Therefore, RNA structure alignment is an important subject in computational biology and bioinformatics to accurately predict function. However, the traditional RNA structure alignment algorithms have some drawbacks such as high complexity and easy loss of secondary structure information. Objective: To study RNA secondary structure alignment according to the shortcomings of existing secondary structure alignment algorithms and the characteristics of RNA secondary structure. Method: We propose a new digital sequence RNA structure representation algorithm named “DSARna” . Then based on a dynamic programming algorithm, the scoring matrix and binary path matrix are simultaneously constructed. The backtracking path is identified in the path matrix, and the optimal result is predicted according to the path length. Conclusions: Upon comparison with the existing SimTree algorithm through experimental analysis, the proposed method showed higher accuracy and could ensure that the structural information is not easily lost in terms of improved specificity, sensitivity, and the Matthews correlation coefficient.

scholarly journals Accurate prediction of genome-wide RNA secondary structure profile based on extreme gradient boosting

2020 ◽  
Vol 36 (17) ◽  
pp. 4576-4582
Author(s):  
Yaobin Ke ◽  
Jiahua Rao ◽  
Huiying Zhao ◽  
Yutong Lu ◽  
Nong Xiao ◽  
...  
Keyword(s):  
Secondary Structure ◽  
High Throughput ◽  
Rna Secondary Structure ◽  
High Throughput Sequencing ◽  
Supplementary Information ◽  
Gradient Boosting ◽  
Synonymous Mutations ◽  
Periodic Distribution ◽  
Genome Wide ◽  
Extreme Gradient Boosting

Abstract Motivation RNA secondary structure plays a vital role in fundamental cellular processes, and identification of RNA secondary structure is a key step to understand RNA functions. Recently, a few experimental methods were developed to profile genome-wide RNA secondary structure, i.e. the pairing probability of each nucleotide, through high-throughput sequencing techniques. However, these high-throughput methods have low precision and cannot cover all nucleotides due to limited sequencing coverage. Results Here, we have developed a new method for the prediction of genome-wide RNA secondary structure profile from RNA sequence based on the extreme gradient boosting technique. The method achieves predictions with areas under the receiver operating characteristic curve (AUC) >0.9 on three different datasets, and AUC of 0.888 by another independent test on the recently released Zika virus data. These AUCs are consistently >5% greater than those by the CROSS method recently developed based on a shallow neural network. Further analysis on the 1000 Genome Project data showed that our predicted unpaired probabilities are highly correlated (>0.8) with the minor allele frequencies at synonymous, non-synonymous mutations, and mutations in untranslated regions, which were higher than those generated by RNAplfold. Moreover, the prediction over all human mRNA indicated a consistent result with previous observation that there is a periodic distribution of unpaired probability on codons. The accurate predictions by our method indicate that such model trained on genome-wide experimental data might be an alternative for analytical methods. Availability and implementation The GRASP is available for academic use at https://github.com/sysu-yanglab/GRASP. Supplementary information Supplementary data are available online.

scholarly journals The role of different serotypes and dengue virus concentration in the prognosis of dengue shock syndrome in children

2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Tram Van Ta ◽  
Hai Thanh Tran ◽  
Quyen Nguyen Than Ha ◽  
Xuong Tuyet Nguyen ◽  
Vu Kien Tran ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Infection ◽  
Dengue Shock Syndrome ◽  
Denv Infection ◽  
Virus Concentration ◽  
Denv Serotypes ◽  
Significant Difference ◽  
Almost All ◽  
The Relationship

Dengue haemorrhagic fever (DHF) is a burden of disease in tropical countries, caused by any one of four-dengue virus (DENV) serotypes (DENV-1 to DENV-4). Although there have been many studies on patients with DHF, many things remain unclear, including the role of DENV serotypes and DENV concentration. The objective of this study was to determine the role of different serotypes and DENV concentration in the prognosis of dengue shock syndrome. This was a prospective cohort study, conducted to show information relating to patients’ conditions, such as hematocrit, platelet, leukocytes, and DENV concentration and the differences between DENV serotypes. The study also expressed the relationship between two groups, DHF without shock and DHF with shock, in terms of immune status, different DENV serotypes, and DENV concentration. Two-hundred and thirty-four patients were serologically confirmed as having a DENV infection. On hospital admission day (fever within 72 hours), results showed that almost all patients had a secondary dengue infection (76.5 %). DENV-1 accounted for the highest number of cases (61.11%), and DENV-4 accounted for the lowest (0.43%). No statistically significant difference was found when comparing the two groups (DHF with shock and DHF without shock) or when comparing the groups of different DENV serotypes. The study concluded that different DENV serotypes or DENV concentration in the first day of hospitalization (fever within 72 hours) cannot be used for prognostic of DSS.

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