scholarly journals Dual RNA-Seq analysis of SARS-CoV-2 correlates specific human transcriptional response pathways directly to viral expression

2021 ◽  
Author(s):  
Nathan D Maulding ◽  
Spencer Seiler ◽  
Alex Pearson ◽  
Nick Kreusser ◽  
Josh Stuart
Keyword(s):  
Drug Targets ◽  
Tissue Specificity ◽  
Differential Expression Analysis ◽  
Transcriptional Response ◽  
Therapeutic Interventions ◽  
Host Responses ◽  
Rna Seq ◽  
Therapeutic Research ◽  
First Time ◽  
Therapeutic Considerations

AbstractThe SARS-CoV-2 pandemic has challenged humankind’s ability to quickly determine the cascade of health effects caused by a novel infection. Even with the unprecedented speed at which vaccines were developed and introduced into society, identifying therapeutic interventions and drug targets for patients infected with the virus remains important as new strains of the virus may evolve, or future coronaviruses may emerge, that are resistant to current vaccines. The application of transcriptomic RNA sequencing of infected samples may shed new light on the pathways involved in viral mechanisms and host responses. We describe the application of “dual RNA-seq” analysis to consider both the host and pathogen transcriptomes simultaneously, to investigate for the first time the co-regulation of human and SARS-CoV-2 genes. Together with differential expression analysis, we describe the tissue specificity of SARS-CoV-2 expression, an inferred lipopolysaccharide response, and co-regulation of CXCL’s, SPRR’s, S100’s with SARS-CoV-2 expression. Lipopolysaccharide response pathways in particular offer promise for future therapeutic research and the prospect of subgrouping patients based on chemokine expression that may help explain the vastly different reactions patients have to infection. Taken together these findings illuminate previously unappreciated SARS-CoV-2 expression signatures, identify new therapeutic considerations, and contribute a pipeline for studying multi-transcriptome systems.

scholarly journals Dual RNA-Seq Analysis of SARS-CoV-2 Correlates Specific Human Transcriptional Response Pathways Directly to Viral Expression

2021 ◽  
Author(s):  
Nathan Maulding ◽  
Spencer Seiler ◽  
Alexander Pearson ◽  
Nicholas Kreusser ◽  
Joshua Stuart
Keyword(s):  
Drug Targets ◽  
Tissue Specificity ◽  
Differential Expression Analysis ◽  
Transcriptional Response ◽  
Therapeutic Interventions ◽  
Host Responses ◽  
Rna Seq ◽  
Therapeutic Research ◽  
First Time ◽  
Therapeutic Considerations

Abstract The SARS-CoV-2 pandemic has challenged humankind’s ability to quickly determine the cascade of health effects caused by a novel infection. Even with the unprecedented speed at which vaccines were developed and introduced into society, identifying therapeutic interventions and drug targets for patients infected with the virus remains important as new strains of the virus may evolve, or future coronaviruses may emerge, that are resistant to current vaccines. The application of transcriptomic RNA sequencing of infected samples may shed new light on the pathways involved in viral mechanisms and host responses. We describe the application of “dual RNA-seq” analysis to consider both the host and pathogen transcriptomes simultaneously, to investigate for the first time the co-regulation of human and SARS-CoV-2 genes. Together with differential expression analysis, we describe the tissue specificity of SARS-CoV-2 expression, an inferred lipopolysaccharide response, and co-regulation of CXCL’s, SPRR’s, S100’s with SARS-CoV-2 expression. Lipopolysaccharide response pathways in particular offer promise for future therapeutic research and the prospect of subgrouping patients based on chemokine expression that may help explain the vastly different reactions patients have to infection. Taken together these findings illuminate previously unappreciated SARS-CoV-2 expression signatures, identify new therapeutic considerations, and contribute a pipeline for studying multi-transcriptome systems.

scholarly journals Common virulence gene expression in adult first-time infected malaria patients and severe cases

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jan Stephan Wichers ◽  
Gerry Tonkin-Hill ◽  
Thorsten Thye ◽  
Ralf Krumkamp ◽  
Benno Kreuels ◽  
...  
Keyword(s):  
Severe Malaria ◽  
De Novo ◽  
Differential Expression Analysis ◽  
Virulence Gene ◽  
Host Responses ◽  
Rna Seq ◽  
Endothelial Protein C Receptor ◽  
Virulence Gene Expression ◽  
Infected Adult ◽  
First Time

Sequestration of Plasmodium falciparum-infected erythrocytes to host endothelium through the parasite-derived PfEMP1 adhesion proteins is central to the development of malaria pathogenesis. PfEMP1 proteins have diversified and expanded to encompass many sequence variants conferring each parasite a similar array of human endothelial receptor binding phenotypes. Here, we analyzed RNA-seq profiles of parasites isolated from 32 P. falciparum infected adult travelers returning to Germany. Patients were categorized into either malaria naïve (n=15) or pre-exposed (n=17), and into severe (n=8) or non-severe (n=24) cases. For differential expression analysis of PfEMP1-encoding var gene transcripts were de novo assembled from RNA-seq data and, in parallel, var expressed sequence tags were analyzed and used to predict the encoded domain composition of the transcripts. Both approaches showed in concordance that severe malaria was associated with PfEMP1 containing the endothelial protein C receptor (EPCR)-binding CIDRα1 domain, whereas CD36-binding PfEMP1 was linked to non-severe malaria outcomes. First-time infected adults were more likely to develop severe symptoms and tended to be infected for a longer period. Thus, parasites with more pathogenic PfEMP1 variants are more common in patients with a naïve immune status and/or adverse inflammatory host responses to first infections favors growth of EPCR-binding parasites.

scholarly journals SARS-CoV-2 infection initiates interleukin-17-enriched transcriptional response in different cells from multiple organs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Md Zobaer Hasan ◽  
Syful Islam ◽  
Kenichi Matsumoto ◽  
Taro Kawai
Keyword(s):  
Signaling Pathway ◽  
Transcriptional Response ◽  
Drug Repurposing ◽  
Cellular Level ◽  
Therapeutic Interventions ◽  
Interleukin 17 ◽  
Global Public Health ◽  
Rna Seq ◽  
Multiple Organs ◽  
Transcriptomic Signature

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a pandemic. Paucity of information concerning the virus and therapeutic interventions have made SARS-CoV-2 infection a genuine threat to global public health. Therefore, there is a growing need for understanding the molecular mechanism of SARS-CoV-2 infection at cellular level. To address this, we undertook a systems biology approach by analyzing publicly available RNA-seq datasets of SARS-CoV-2 infection of different cells and compared with other lung pathogenic infections. Our study identified several key genes and pathways uniquely associated with SARS-CoV-2 infection. Genes such as interleukin (IL)-6, CXCL8, CCL20, CXCL1 and CXCL3 were upregulated, which in particular regulate the cytokine storm and IL-17 signaling pathway. Of note, SARS-CoV-2 infection strongly activated IL-17 signaling pathway compared with other respiratory viruses. Additionally, this transcriptomic signature was also analyzed to predict potential drug repurposing and small molecule inhibitors. In conclusion, our comprehensive data analysis identifies key molecular pathways to reveal underlying pathological etiology and potential therapeutic targets in SARS-CoV-2 infection.

scholarly journals Depicting the battle between nectarine and Monilinia laxa: the fruit developmental stage dictates the effectiveness of the host defenses and the pathogen’s infection strategies

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Marta Balsells-Llauradó ◽  
Christian J. Silva ◽  
Josep Usall ◽  
Núria Vall-llaura ◽  
Sandra Serrano-Prieto ◽  
...  
Keyword(s):  
Transcriptional Response ◽  
Brown Rot ◽  
Host Responses ◽  
Post Inoculation ◽  
Monilinia Laxa ◽  
Rna Seq ◽  
Mature Fruit ◽  
Immature Fruit ◽  
Hormone Responses ◽  
Functional Analyses

Abstract Infections by the fungus Monilinia laxa, the main cause of brown rot in Europe, result in considerable losses of stone fruit. Herein, we present a comprehensive transcriptomic approach to unravel strategies deployed by nectarine fruit and M. laxa during their interaction. We used M. laxa-inoculated immature and mature fruit, which was resistant and susceptible to brown rot, respectively, to perform a dual RNA-Seq analysis. In immature fruit, host responses, pathogen biomass, and pathogen transcriptional activity peaked at 14–24 h post inoculation (hpi), at which point M. laxa appeared to switch its transcriptional response to either quiescence or death. Mature fruit experienced an exponential increase in host and pathogen activity beginning at 6 hpi. Functional analyses in both host and pathogen highlighted differences in stage-dependent strategies. For example, in immature fruit, M. laxa unsuccessfully employed carbohydrate-active enzymes (CAZymes) for penetration, which the fruit was able to combat with tightly regulated hormone responses and an oxidative burst that challenged the pathogen’s survival at later time points. In contrast, in mature fruit, M. laxa was more dependent on proteolytic effectors than CAZymes, and was able to invest in filamentous growth early during the interaction. Hormone analyses of mature fruit infected with M. laxa indicated that, while jasmonic acid activity was likely useful for defense, high ethylene activity may have promoted susceptibility through the induction of ripening processes. Lastly, we identified M. laxa genes that were highly induced in both quiescent and active infections and may serve as targets for control of brown rot.

scholarly journals Best practices on the differential expression analysis of multi-species RNA-seq

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Matthew Chung ◽  
Vincent M. Bruno ◽  
David A. Rasko ◽  
Christina A. Cuomo ◽  
José F. Muñoz ◽  
...  
Keyword(s):  
Best Practices ◽  
Differential Expression ◽  
Expression Analysis ◽  
Differential Expression Analysis ◽  
Single Species ◽  
Rna Seq ◽  
Species Analysis ◽  
Differential Gene ◽  
Multiple Species ◽  
Downstream Analysis

AbstractAdvances in transcriptome sequencing allow for simultaneous interrogation of differentially expressed genes from multiple species originating from a single RNA sample, termed dual or multi-species transcriptomics. Compared to single-species differential expression analysis, the design of multi-species differential expression experiments must account for the relative abundances of each organism of interest within the sample, often requiring enrichment methods and yielding differences in total read counts across samples. The analysis of multi-species transcriptomics datasets requires modifications to the alignment, quantification, and downstream analysis steps compared to the single-species analysis pipelines. We describe best practices for multi-species transcriptomics and differential gene expression.

scholarly journals Gene Expression Profile and Co-Expression Network of Pearl Gentian Grouper under Cold Stress by Integrating Illumina and PacBio Sequences

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1745
Author(s):  
Ben-Ben Miao ◽  
Su-Fang Niu ◽  
Ren-Xie Wu ◽  
Zhen-Bang Liang ◽  
Bao-Gui Tang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cold Stress ◽  
Differential Expression Analysis ◽  
Endocrine System ◽  
Control Group ◽  
Regulation Mechanism ◽  
Rna Seq ◽  
Cold Tolerant ◽  
Stress Signals ◽  
Membrane Changes

Pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) is a fish of high commercial value in the aquaculture industry in Asia. However, this hybrid fish is not cold-tolerant, and its molecular regulation mechanism underlying cold stress remains largely elusive. This study thus investigated the liver transcriptomic responses of pearl gentian grouper by comparing the gene expression of cold stress groups (20, 15, 12, and 12 °C for 6 h) with that of control group (25 °C) using PacBio SMRT-Seq and Illumina RNA-Seq technologies. In SMRT-Seq analysis, a total of 11,033 full-length transcripts were generated and used as reference sequences for further RNA-Seq analysis. In RNA-Seq analysis, 3271 differentially expressed genes (DEGs), two low-temperature specific modules (tan and blue modules), and two significantly expressed gene sets (profiles 0 and 19) were screened by differential expression analysis, weighted gene co-expression networks analysis (WGCNA), and short time-series expression miner (STEM), respectively. The intersection of the above analyses further revealed some key genes, such as PCK, ALDOB, FBP, G6pC, CPT1A, PPARα, SOCS3, PPP1CC, CYP2J, HMGCR, CDKN1B, and GADD45Bc. These genes were significantly enriched in carbohydrate metabolism, lipid metabolism, signal transduction, and endocrine system pathways. All these pathways were linked to biological functions relevant to cold adaptation, such as energy metabolism, stress-induced cell membrane changes, and transduction of stress signals. Taken together, our study explores an overall and complex regulation network of the functional genes in the liver of pearl gentian grouper, which could benefit the species in preventing damage caused by cold stress.

scholarly journals Differential Expression Analysis of Phytohormone-Related Genes of Korean Wheat (Triticum aestivum) in Response to Preharvest Sprouting and Abscisic Acid (ABA)

2021 ◽  
Vol 11 (8) ◽  
pp. 3562
Author(s):  
Yong Jin Lee ◽  
Sang Yong Park ◽  
Dae Yeon Kim ◽  
Jae Yoon Kim
Keyword(s):  
Abscisic Acid ◽  
Differential Expression Analysis ◽  
Preharvest Sprouting ◽  
Global Changes ◽  
Rna Seq ◽  
Hormone Metabolism ◽  
Global Issue ◽  
End Use ◽  
Transcriptomic Changes

Preharvest sprouting (PHS) is a key global issue in production and end-use quality of cereals, particularly in regions where the rainfall season overlaps the harvest. To investigate transcriptomic changes in genes affected by PHS-induction and ABA-treatment, RNA-seq analysis was performed in two wheat cultivars that differ in PHS tolerance. A total of 123 unigenes related to hormone metabolism and signaling for abscisic acid (ABA), gibberellic acid (GA), indole-3-acetic acid (IAA), and cytokinin were identified and 1862 of differentially expressed genes were identified and divided into 8 groups by transcriptomic analysis. DEG analysis showed the majority of genes were categorized in sugar related processes, which interact with ABA signaling in PHS tolerant cultivar under PHS-induction. Thus, genes related to ABA are key regulators of dormancy and germination. Our results give insight into global changes in expression of plant hormone related genes in response to PHS.

movAPA: modeling and visualization of dynamics of alternative polyadenylation across biological samples

2020 ◽  
Author(s):  
Wenbin Ye ◽  
Tao Liu ◽  
Hongjuan Fu ◽  
Congting Ye ◽  
Guoli Ji ◽  
...  
Keyword(s):  
Biological Samples ◽  
Tissue Specificity ◽  
Single Cells ◽  
Alternative Polyadenylation ◽  
R Package ◽  
Supplementary Information ◽  
Rna Seq ◽  
Mouse Sperm ◽  
High Scalability ◽  
A Site

Abstract Motivation Alternative polyadenylation (APA) has been widely recognized as a widespread mechanism modulated dynamically. Studies based on 3′ end sequencing and/or RNA-seq have profiled poly(A) sites in various species with diverse pipelines, yet no unified and easy-to-use toolkit is available for comprehensive APA analyses. Results We developed an R package called movAPA for modeling and visualization of dynamics of alternative polyadenylation across biological samples. movAPA incorporates rich functions for preprocessing, annotation and statistical analyses of poly(A) sites, identification of poly(A) signals, profiling of APA dynamics and visualization. Particularly, seven metrics are provided for measuring the tissue-specificity or usages of APA sites across samples. Three methods are used for identifying 3′ UTR shortening/lengthening events between conditions. APA site switching involving non-3′ UTR polyadenylation can also be explored. Using poly(A) site data from rice and mouse sperm cells, we demonstrated the high scalability and flexibility of movAPA in profiling APA dynamics across tissues and single cells. Availability and implementation https://github.com/BMILAB/movAPA. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

2021 ◽  
Vol 22 (3) ◽  
pp. 1407
Author(s):  
Hongxia Liu ◽  
Wang Zheng ◽  
Qianping Chen ◽  
Yuchuan Zhou ◽  
Yan Pan ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Line ◽  
Malignant Tumors ◽  
Underlying Mechanism ◽  
Mtor Pathway ◽  
Rna Seq ◽  
Cellular Autophagy ◽  
First Time

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

scholarly journals The long and the short of it: unlocking nanopore long-read RNA sequencing data with short-read differential expression analysis tools

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Xueyi Dong ◽  
Luyi Tian ◽  
Quentin Gouil ◽  
Hasaru Kariyawasam ◽  
Shian Su ◽  
...  
Keyword(s):  
Differential Expression ◽  
Expression Analysis ◽  
Differential Expression Analysis ◽  
Transcriptomic Analysis ◽  
Statistical Testing ◽  
Rna Seq ◽  
Sequencing Data ◽  
Short Read ◽  
Sequencing Platform ◽  
Long Read

Abstract Application of Oxford Nanopore Technologies’ long-read sequencing platform to transcriptomic analysis is increasing in popularity. However, such analysis can be challenging due to the high sequence error and small library sizes, which decreases quantification accuracy and reduces power for statistical testing. Here, we report the analysis of two nanopore RNA-seq datasets with the goal of obtaining gene- and isoform-level differential expression information. A dataset of synthetic, spliced, spike-in RNAs (‘sequins’) as well as a mouse neural stem cell dataset from samples with a null mutation of the epigenetic regulator Smchd1 was analysed using a mix of long-read specific tools for preprocessing together with established short-read RNA-seq methods for downstream analysis. We used limma-voom to perform differential gene expression analysis, and the novel FLAMES pipeline to perform isoform identification and quantification, followed by DRIMSeq and limma-diffSplice (with stageR) to perform differential transcript usage analysis. We compared results from the sequins dataset to the ground truth, and results of the mouse dataset to a previous short-read study on equivalent samples. Overall, our work shows that transcriptomic analysis of long-read nanopore data using long-read specific preprocessing methods together with short-read differential expression methods and software that are already in wide use can yield meaningful results.

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