scholarly journals A novel computational approach to the silencing of Sugarcane Bacilliform Guadeloupe A Virus determines potential host-derived MicroRNAs in sugarcane (Saccharum officinarum L.)

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8359
Author(s):  
Fakiha Ashraf ◽  
Muhammad Aleem Ashraf ◽  
Xiaowen Hu ◽  
Shuzhen Zhang

Sugarcane Bacilliform Guadeloupe A Virus (SCBGAV, genus Badnavirus, family Caulimoviridae) is an emerging, deleterious pathogen of sugarcane which presents a substantial barrier to producing high sugarcane earnings. Sugarcane bacilliform viruses (SCBVs) are one of the main species that infect sugarcane. During the last 30 years, significant genetic changes in SCBV strains have been observed with a high risk of disease incidence associated with crop damage. SCBV infection may lead to significant losses in biomass production in susceptible sugarcane cultivars. The circular, double-stranded (ds) DNA genome of SCBGAV (7.4 Kb) is composed of three open reading frames (ORFs) on the positive strand that replicate by a reverse transcriptase. SCBGAV can infect sugarcane in a semipersistent manner via the insect vectors sugarcane mealybug species. In the current study, we used miRNA target prediction algorithms to identify and comprehensively analyze the genome-wide sugarcane (Saccharum officinarum L.)-encoded microRNA (miRNA) targets against the SCBGAV. Mature miRNA target sequences were retrieved from the miRBase (miRNA database) and were further analyzed for hybridization to the SCBGAV genome. Multiple computational approaches—including miRNA-target seed pairing, multiple target positions, minimum free energy, target site accessibility, maximum complementarity, pattern recognition and minimum folding energy for attachments—were considered by all algorithms. Among them, sof-miR396 was identified as the top effective candidate, capable of targeting the vital ORF3 of the SCBGAV genome. miRanda, RNA22 and RNAhybrid algorithms predicted hybridization of sof-miR396 at common locus position 3394. The predicted sugarcane miRNAs against viral mRNA targets possess antiviral activities, leading to translational inhibition by mRNA cleavage. Interaction network of sugarcane-encoded miRNAs with SCBGAV genes, created using Circos, allow analyze new targets. The finding of the present study acts as a first step towards the creation of SCBGAV-resistant sugarcane through the expression of the identified miRNAs.

2019 ◽  
Author(s):  
Fakiha Ashraf ◽  
Muhammad Aleem Ashraf ◽  
Xiaowen Hu ◽  
Shuzhen Zhang

Sugarcane Bacilliform Guadeloupe A Virus (SCBGAV, genus Badnavirus, family Caulimoviridae) is an emerging, deleterious pathogen of sugarcane which presents a substantial barrier to producing high sugarcane earnings. The circular, double-stranded (ds) DNA genome of SCBGAV (7.4 Kb) is composed of three open reading frames (ORF) that replicate by a reverse transcriptase. In the current study, we used miRNA target prediction algorithms to identify and comprehensively analyze the genome-wide sugarcane (Saccharum officinarum L.)-encoded microRNA (miRNA) targets against the SCBGAV. A total of 28 potential mature target miRNAs were retrieved from the miRBase database and were further analyzed for hybridization to the SCBGAV genome. Multiple computational approaches—including miRNA-target seed pairing, multiple target positions, minimum free energy, target site accessibility, maximum complementarity, pattern recognition and minimum folding energy for attachments— were considered by all algorithms. Only 4 sugarcane miRNAs are selected for SCBGAV silencing. Among those 4, sof-miR396 was identified as the top effective candidate, capable of targeting the vital ORF3 which encodes polyprotein of the SCBGAV genome. miRanda, RNA22 and RNAhybrid algorithms predicted hybridization of sof-miR396 at common locus position 3394. A Circos plot was created to study the network visualization of sugarcane-encoded miRNAs with SCBGAV genes determines detailed evidence for any ideal targets of SCBGAV ORFs by precise miRNAs. The present study concludes a comprehensive report towards the creation of SCBGAV-resistant sugarcane through the expression analysis of the identified miRNAs.


2019 ◽  
Author(s):  
Fakiha Ashraf ◽  
Muhammad Aleem Ashraf ◽  
Xiaowen Hu ◽  
Shuzhen Zhang

Sugarcane Bacilliform Guadeloupe A Virus (SCBGAV, genus Badnavirus, family Caulimoviridae) is an emerging, deleterious pathogen of sugarcane which presents a substantial barrier to producing high sugarcane earnings. The circular, double-stranded (ds) DNA genome of SCBGAV (7.4 Kb) is composed of three open reading frames (ORF) that replicate by a reverse transcriptase. In the current study, we used miRNA target prediction algorithms to identify and comprehensively analyze the genome-wide sugarcane (Saccharum officinarum L.)-encoded microRNA (miRNA) targets against the SCBGAV. A total of 28 potential mature target miRNAs were retrieved from the miRBase database and were further analyzed for hybridization to the SCBGAV genome. Multiple computational approaches—including miRNA-target seed pairing, multiple target positions, minimum free energy, target site accessibility, maximum complementarity, pattern recognition and minimum folding energy for attachments— were considered by all algorithms. Only 4 sugarcane miRNAs are selected for SCBGAV silencing. Among those 4, sof-miR396 was identified as the top effective candidate, capable of targeting the vital ORF3 which encodes polyprotein of the SCBGAV genome. miRanda, RNA22 and RNAhybrid algorithms predicted hybridization of sof-miR396 at common locus position 3394. A Circos plot was created to study the network visualization of sugarcane-encoded miRNAs with SCBGAV genes determines detailed evidence for any ideal targets of SCBGAV ORFs by precise miRNAs. The present study concludes a comprehensive report towards the creation of SCBGAV-resistant sugarcane through the expression analysis of the identified miRNAs.


2018 ◽  
Vol 16 (04) ◽  
pp. 1850013 ◽  
Author(s):  
Mohammad Mohebbi ◽  
Liang Ding ◽  
Russell L. Malmberg ◽  
Cory Momany ◽  
Khaled Rasheed ◽  
...  

miRNAs are involved in many critical cellular activities through binding to their mRNA targets, e.g. in cell proliferation, differentiation, death, growth control, and developmental timing. Accurate prediction of miRNA targets can assist efficient experimental investigations on the functional roles of miRNAs. Their prediction, however, remains a challengeable task due to the lack of experimental data about the tertiary structure of miRNA-target binding duplexes. In particular, correlations of nucleotides in the binding duplexes may not be limited to the canonical Watson Crick base pairs (BPs) as they have been perceived; methods based on secondary structure prediction (typically minimum free energy (MFE)) have only had mix success. In this work, we characterized miRNA binding duplexes with a graph model to capture the correlations between pairs of nucleotides of an miRNA and its target sequences. We developed machine learning algorithms to train the graph model to predict the target sites of miRNAs. In particular, because imbalance between positive and negative samples can significantly deteriorate the performance of machine learning methods, we designed a novel method to re-sample available dataset to produce more informative data learning process. We evaluated our model and miRNA target prediction method on human miRNAs and target data obtained from mirTarBase, a database of experimentally verified miRNA-target interactions. The performance of our method in target prediction achieved a sensitivity of 86% with a false positive rate below 13%. In comparison with the state-of-the-art methods miRanda and RNAhybrid on the test data, our method outperforms both of them by a significant margin. The source codes, test sets and model files all are available at http://rna-informatics.uga.edu/?f=software&p=GraB-miTarget .


2019 ◽  
pp. 1-4
Author(s):  
Tikam Chand ◽  
Tikam Chand

Having role in gene regulation and silencing, miRNAs have been implicated in development and progression of a number of diseases, including cancer. Herein, I present potential miRNAs associated with BAP1 gene identified using in-silico tools such as TargetScan and Exiqon miRNA Target Prediction. I identified fifteen highly conserved miRNA (hsa-miR-423-5p, hsa-miR-3184-5p, hsa-miR-4319, hsa-miR125b-5p, hsa-miR-125a-5p, hsa-miR-6893-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-505-3p.1, hsa-miR-429, hsa-miR-370-3p, hsa-miR-125a-5p, hsa-miR-141-3p, hsa-miR-200a-3p, and hsa-miR-429) associated with BAP1 gene. We also predicted the differential regulation of these twelve miRNAs in different cancer types.


2021 ◽  
Vol 22 (15) ◽  
pp. 8193
Author(s):  
Daniel Pérez-Cremades ◽  
Ana B. Paes ◽  
Xavier Vidal-Gómez ◽  
Ana Mompeón ◽  
Carlos Hermenegildo ◽  
...  

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a comprehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miRNA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17β-estradiol (E2) (1 nmol/L, 24 h). miRNA–mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miRNA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA–target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship according to miRNA target prediction databases. The analysis identified 588 miRNA–target interactions between 102 miRNAs and 588 targets. Specifically, 63 upregulated miRNAs interacted with 295 downregulated targets, while 39 downregulated miRNAs were paired with 293 upregulated mRNA targets. Functional characterization of miRNA/mRNA association analysis highlighted hypoxia signaling, integrin, ephrin receptor signaling and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Transcription factors and downstream genes analysis revealed eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhesion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Syarifah Faezah Syed Mohamad ◽  
Marjanu Hikmah Elias

Abstract Background Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the expression of the BCR-ABL1 fusion gene. Tyrosine kinase inhibitors (TKI) are used to treat CML, but mutations in the tyrosine kinase domain contribute to CML chemo-resistance. Therefore, finding alternative molecular-targeted therapy is important for the comprehensive treatment of CML. MicroRNAs (miRNA) are small non-coding regulatory RNAs which suppress the expression of their target genes by binding to the 3′ untranslated region (3′UTR) of the target mRNA. Hypothetically, the miRNA-mRNA interaction would suppress BCR-ABL1 expression and consequently reduce and inhibit CML cell proliferation. Thus, our objective was to determine the target interaction of human and plant miRNAs targeting the 3′UTR region of BCR-ABL1 in terms of miRNA binding conformity, protein interaction network, and pathways using in silico analysis. The 3′UTR sequence of BCR-ABL1 is obtained from Ensembl Genome Browser while the binding conformity was determined using the PsRNATarget Analysis Server, RNA22, Target Rank Server, and DIANA TOOLS. Protein-protein interaction network and pathway analysis are determined using STRING, Cytoscape, and KEGG pathway analysis. Results Five plants and five human miRNAs show strong binding conformity with 3′UTR of BCR-ABL1. The strongest binding conformity was shown by Oryza sativa’s Osa-miR1858a and osa-miR1858b with −24.4 kcal/mol folding energy and a p value of 0.0077. Meanwhile, in human miRNA, the hsa-miR-891a-3p shows the highest miTG score of 0.99 with −12 kcal/mol folding energy and a p value of 0.037. Apart from ABL1, osa-miR1858a/osa-miR1858b and hsa-miR891a-3p also target other 720 and 645 genes, respectively. The interaction network of Osa-miR1858a/osa-miR1858b and hsa-miR891a-3p identifies nineteen and twelve ABL1’s immediate neighboring proteins, respectively. The pathways analysis focuses on the RAS, MAPK, CML, and hematopoietic cell lineage pathway. Conclusion Both plant and human miRNAs tested in this study could be a potential therapeutic prospect in CML treatment, but thermodynamically, osa-miR1858a/osa-miR1858b binding to ABL1 is more favorable. However, it is important to carry out more research in vitro and in vivo and clinical studies to assess its efficacy as a targeted therapy for CML. Graphical abstract


2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110167
Author(s):  
Xing-Pan Wu ◽  
Tian-Shun Wang ◽  
Zi-Xin Yuan ◽  
Yan-Fang Yang ◽  
He-Zhen Wu

Objective To explore the anti-COVID-19 active components and mechanism of Compound Houttuynia mixture by using network pharmacology and molecular docking. Methods First, the main chemical components of Compound Houttuynia mixture were obtained by using the TCMSP database and referring to relevant chemical composition literature. The components were screened for OB ≥30% and DL ≥0.18 as the threshold values. Then Swiss Target Prediction database was used to predict the target of the active components and map the targets of COVID-19 obtained through GeneCards database to obtain the gene pool of the potential target of COVID-19 resistance of the active components of Compound Houttuynia mixture. Next, DAVID database was used for GO enrichment and KEGG pathway annotation of targets function. Cytoscape 3.8.0 software was used to construct a “components-targets-pathways” network. Then String database was used to construct a “protein-protein interaction” network. Finally, the core targets, SARS-COV-2 3 Cl, ACE2 and the core active components of Compound Houttuyna Mixture were imported into the Discovery Studio 2016 Client database for molecular docking verification. Results Eighty-two active compounds, including Xylostosidine, Arctiin, ZINC12153652 and ZINC338038, were screened from Compound Houttuyniae mixture. The key targets involved 128 targets, including MAPK1, MAPK3, MAPK8, MAPK14, TP53, TNF, and IL6. The HIF-1 signaling, VEGF signaling, TNF signaling and another 127 signaling pathways associated with COVID-19 were affected ( P < 0.05). From the results of molecular docking, the binding ability between the selected active components and the core targets was strong. Conclusion Through the combination of network pharmacology and molecular docking technology, this study revealed that the therapeutic effect of Compound Houttuynia mixture on COVID-19 was realized through multiple components, multiple targets and multiple pathways, which provided a certain scientific basis of the clinical application of Compound Houttuynia mixture.


Author(s):  
Chikaire JU ◽  
◽  
Ajaero JO ◽  

The study investigated the effect of climate change on human and social livelihood assets of rural farm families in Orlu agricultural zone of Imo State, Nigeria. The specific objectives were to ascertain rural farmers’ awareness of climate change, and identify sources of information on climate change and to describe the effect of climate change on the human and social livelihood assets of the rural farmers. A purposive sampling technique was adopted in selecting a sample size of 120 farm families. Data were collected with structured questionnaire and mean, percentage were used to analyze the data. The result showed that the major evidence of climate change include increased temperature, unpredictable rainfall pattern, drought, flooding, increased precipitation, crop damage and among others. Climate change affects the livelihood of rural people and can be seen in the effects it has on their human and social capita assets in the following ways - loss of human lives, food shortage, hunger and malnutrition, increased disease incidence, reduction in household. Other effects includes prevention of assistance from members of social groups to farmers and rural people at large, interruption of familiar social linkages of the poor, widows, disruption of linkages to formal and informal community organization.


2019 ◽  
Vol 14 (5) ◽  
pp. 432-445 ◽  
Author(s):  
Muniba Faiza ◽  
Khushnuma Tanveer ◽  
Saman Fatihi ◽  
Yonghua Wang ◽  
Khalid Raza

Background: MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression at the post-transcriptional level through complementary base pairing with the target mRNA, leading to mRNA degradation and blocking translation process. Many dysfunctions of these small regulatory molecules have been linked to the development and progression of several diseases. Therefore, it is necessary to reliably predict potential miRNA targets. Objective: A large number of computational prediction tools have been developed which provide a faster way to find putative miRNA targets, but at the same time, their results are often inconsistent. Hence, finding a reliable, functional miRNA target is still a challenging task. Also, each tool is equipped with different algorithms, and it is difficult for the biologists to know which tool is the best choice for their study. Methods: We analyzed eleven miRNA target predictors on Drosophila melanogaster and Homo sapiens by applying significant empirical methods to evaluate and assess their accuracy and performance using experimentally validated high confident mature miRNAs and their targets. In addition, this paper also describes miRNA target prediction algorithms, and discusses common features of frequently used target prediction tools. Results: The results show that MicroT, microRNA and CoMir are the best performing tool on Drosopihla melanogaster; while TargetScan and miRmap perform well for Homo sapiens. The predicted results of each tool were combined in order to improve the performance in both the datasets, but any significant improvement is not observed in terms of true positives. Conclusion: The currently available miRNA target prediction tools greatly suffer from a large number of false positives. Therefore, computational prediction of significant targets with high statistical confidence is still an open challenge.


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