Transcriptome Analysis Reveals Dynamic Changes of Inflammation and Stress Responses during Different Infected Stages with Burkholderia pseudomallei

2020 ◽  
Author(s):  
Chenglong Rao(Former Corresponding Author) ◽  
Chan Mao ◽  
Yupei Xia ◽  
Meijuan Zhang ◽  
Zhiqiang Hu ◽  
...  
Keyword(s):  
Stress Responses ◽  
Burkholderia Pseudomallei ◽  
Cellular Response ◽  
Cell Model ◽  
Mrna Level ◽  
A549 Cells ◽  
Enrichment Analysis ◽  
Host Cells ◽  
P Value ◽  
Pathway Enrichment Analysis

Abstract Background: Burkholderia pseudomallei causes melioidosis and usually affects patients’ lungs, its persistent infection promotes the fusion of host cells, leading to the formation of multinucleated giant cells (MGCs) at the late infected stage. In this study, the global transcriptomic responses of B. pseudomallei infection of a human lung epithelial A549 cell model with different infected stages were investigated by means of microarray analysis to further elucidate the host cellular factors involved in the occurrence and development of the event. Results: A set of 35 common differential expression genes (DEGs) in EI and LI on the mRNA level applying a cut-off level of 1.5-fold change and a p-value < 0.05 were observed. Microarray data were further verified by Real-Time quantitative PCR (RT-qPCR). GO classification and pathway enrichment analysis revealed these DEGs mainly involved in inflammatory response related processes, such as cellular response to tumor necrosis factor, cellular response to lipopolysaccharide, positive regulation of NF-κB transcription factor activity. p-eIF2α, ATF4,NF-κB2(p52) and IL-1β were next selected to be validated by western bloting, which indicated B. pseudomallei could activate the eIF2α-ATF4 axis and NF-κB2 pathway in A549 cells. Conclusion: Our data shed light on the transcriptome dynamics of A549 cells which persistently infected with B. pseudomallei and suggested that the formation of MGCs may be a means for B. pseudomallei to manipulate the host's inflammation and stress response to adapt to intracellular life.

scholarly journals Lipidomics profiling of goose granulosa cell model of stearoyl-CoA desaturase function identifies a pattern of lipid droplets associated with follicle development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Yuan ◽  
Shenqiang Hu ◽  
Liang Li ◽  
Chunchun Han ◽  
Hehe Liu ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Lipid Droplets ◽  
Cell Model ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Follicle Development ◽  
Microscopy Analysis ◽  
Stearoyl Coa Desaturase ◽  
Underlying Mechanisms

Abstract Background Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese. Results Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism. Conclusions This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.

scholarly journals Tissue-based metabolomics profiling reveals metabolic signatures and major metabolic pathways of gastric cancer

2021 ◽  
Author(s):  
Yaqin Wang ◽  
Wenchao Chen ◽  
Kun Li ◽  
Gang Wu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Predictive Ability ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Pentose Phosphate ◽  
P Value ◽  
Pathway Enrichment Analysis ◽  
Dodecanoic Acid ◽  
Orthogonal Projections ◽  
Latent Structures

Abstract Purpose This study was aimed to screen differential metabolites between gastric cancer (GC) and paracancerous (PC) tissues and find new biomarkers of GC. Methods GC (n = 28) and matched PC (n = 28) tissues were collected and LC-MS/MS analyses were performed to detect metabolites of GC and PC tissues in positive and negative models. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminate analysis (OPLS-DA) were conducted to describe distribution of origin data and general separation and estimate the robustness and the predictive ability of our mode. Differential metabolites were screened based on criterion of variables with p value < 0.05 and VIP (variable importance in the projection) > 1.0. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of differential metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to search for metabolite pathways and MetaboAnalyst was used for pathway enrichment analysis. Results Several metabolites were significantly changed in GC group compared with PC group. Thirteen metabolites with high VIP were chose and among which 1-methylnicotinamide, dodecanoic acid and sphinganine possessed high AUC values (AUC > 0.8) indicating an excellent discriminatory ability on GC. Pathways such as pentose phosphate pathway and histidine metabolism were focused based on differential metabolites demonstrating their effects on progress of GC. Conclusions In conclusion, we investigated the tissue-based metabolomics profile of GC and several differential metabolites and signaling pathways were focused. Further study is needed to verify those results.

scholarly journals Identification of Key Genes in ‘Luang Pratahn’, Thai Salt-Tolerant Rice, Based on Time-Course Data and Weighted Co-expression Networks

2021 ◽  
Vol 12 ◽  
Author(s):  
Pajaree Sonsungsan ◽  
Pheerawat Chantanakool ◽  
Apichat Suratanee ◽  
Teerapong Buaboocha ◽  
Luca Comai ◽  
...  
Keyword(s):  
Salt Stress ◽  
Salt Tolerance ◽  
Stress Responses ◽  
Time Course ◽  
Rice Variety ◽  
Enrichment Analysis ◽  
Normal Growth ◽  
Growth Conditions ◽  
Pathway Enrichment Analysis ◽  
Key Genes

Salinity is an important environmental factor causing a negative effect on rice production. To prevent salinity effects on rice yields, genetic diversity concerning salt tolerance must be evaluated. In this study, we investigated the salinity responses of rice (Oryza sativa) to determine the critical genes. The transcriptomes of ‘Luang Pratahn’ rice, a local Thai rice variety with high salt tolerance, were used as a model for analyzing and identifying the key genes responsible for salt-stress tolerance. Based on 3' Tag-Seq data from the time course of salt-stress treatment, weighted gene co-expression network analysis was used to identify key genes in gene modules. We obtained 1,386 significantly differentially expressed genes in eight modules. Among them, six modules indicated a significant correlation within 6, 12, or 48h after salt stress. Functional and pathway enrichment analysis was performed on the co-expressed genes of interesting modules to reveal which genes were mainly enriched within important functions for salt-stress responses. To identify the key genes in salt-stress responses, we considered the two-state co-expression networks, normal growth conditions, and salt stress to investigate which genes were less important in a normal situation but gained more impact under stress. We identified key genes for the response to biotic and abiotic stimuli and tolerance to salt stress. Thus, these novel genes may play important roles in salinity tolerance and serve as potential biomarkers to improve salt tolerance cultivars.

Exploring microRNAs, Target mRNAs and their Functions in Leguminous PlantArachis hypogaea

MicroRNA ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 135-146 ◽  
Author(s):  
Anjana Rajendiran ◽  
Saravanan Vijayakumar ◽  
Archana Pan
Keyword(s):  
Comparative Genomics ◽  
Stress Responses ◽  
Unsaturated Fatty Acids ◽  
Enrichment Analysis ◽  
Antibiotic Biosynthesis ◽  
Pathway Enrichment Analysis ◽  
Transcriptional Level ◽  
Biological Databases ◽  
Biotic And Abiotic Stress ◽  
Genome Survey

Background:MicroRNAs (miRNAs) are a class of small non-coding, endogenous RNAs that regulate gene expression at post-transcriptional level. In plants, miRNAs are usually of 18-24 nucleotide in length and play humongous role by aiding in development, growth, defense, biotic and abiotic stress responses, etc.Objective:Arachis hypogaea is an economically important oil seed crop and human dietary source cultivated mostly in tropical and subtropical regions. In the present study, an initiative was taken to uncover miRNAs, their targets and functions in this important plant species. </P><P> Method: Comparative genomics strategy coupled with bioinformatics approaches was deployed for the identification of miRNAs, their corresponding targets and functions by exploiting biological databases and tools.Results:The study was able to identify 34 conserved miRNA candidates, belonging to 17 miRNA families, contributed by 23 and 3 precursor miRNAs from A. hypogaea Expressed Sequence Tags (EST) and Genome Survey Sequences (GSS), respectively. As well, 495 EST and 917 unigene sequences were predicted as targets for the identified miRNAs. Herein, psRNAtarget server and TargetFinder tool were used to predict unigene targets, whereas comparative genomics strategy was used for identifying EST targets. Functional annotation of the identified targets revealed that the identified miRNAs regulate mRNAs that participate in key biological and metabolic processes. Pathway enrichment analysis using KEGG database also revealed that they regulate important metabolic pathways including antibiotic biosynthesis, biosynthesis of unsaturated fatty acids, amino acids metabolism and flavonoid biosynthesis.Conclusion:The outcome of the study would aid experimental biologists to focus on these miRNAs to facilitate improved crop development and yield.

scholarly journals Transcriptome Analysis Reveals Unfolded Protein Response Was Induced During the Early Stage of Burkholderia pseudomallei Infection in A549 Cells

2020 ◽  
Vol 11 ◽  
Author(s):  
Chenglong Rao ◽  
Chan Mao ◽  
Yupei Xia ◽  
Meijuan Zhang ◽  
Zhiqiang Hu ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Burkholderia Pseudomallei ◽  
Cellular Response ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Response Dynamics ◽  
Unfolded Protein ◽  
Lung Epithelial ◽  
Protein Response ◽  
Over Time

Burkholderia pseudomallei is a zoonotic pathogen that usually affects patients' lungs and causes serious melioidosis. The interaction of B. pseudomallei with its hosts is complex, and cellular response to B. pseudomallei infection in humans still remains to be elucidated. In this study, transcriptomic profiling of B. pseudomallei-infected human lung epithelial A549 cells was performed to characterize the cellular response dynamics during the early infection (EI) stage. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the online databases DAVID 6.8 and KOBAS 3.0. Real-time quantitative PCR and western blot were used for validation experiments. Compared with the negative control group (NC), a set of 36 common genes varied over time with a cut-off level of 1.5-fold change, and a P-value &lt; 0.05 was identified. Bioinformatics analysis indicated that the PERK-mediated unfolded protein response (UPR) was enriched as the most noteworthy biological process category, which was enriched as a branch of UPR in the signaling pathway of protein processing in the endoplasmic reticulum. Other categories, such as inflammatory responses, cell migration, and apoptosis, were also focused. The molecular chaperone Bip (GRP78), PERK, and PERK sensor-dependent phosphorylation of eIF2α (p-eIF2α) and ATF4 were verified to be increasing over time during the EI stage, suggesting that B. pseudomallei infection activated the PERK-mediated UPR in A549 cells. Collectively, these results provide important initial insights into the intimate interaction between B. pseudomallei and lung epithelial cells, which can be further explored toward the elucidation of the cellular mechanisms of B. pseudomallei infections in humans.

scholarly journals Elevated Expression of Mir-130a in t(8,21) AML Reinforces the Aberrant Molecular Program of AML1-ETO

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Gabriela Krivdova ◽  
Veronique Voisin ◽  
Sajid Marhon ◽  
Schoof E Erwin ◽  
Martino Gabra ◽  
...  
Keyword(s):  
Stress Responses ◽  
Functional Significance ◽  
De Novo ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Protein Levels ◽  
The Impact

Background: Deregulation of self-renewal and differentiation programs are central to the pathogenesis of hematologic malignancies. MicroRNAs (miRNAs) represent a large class of post-transcriptional regulators that mediate repression of multiple target mRNAs and are frequently deregulated in acute myeloid leukemia (AML). From our previous in vivo miRNA enforced expression screen in human hematopoietic stem and progenitor cells (HSPC), we identified miR-130a as a regulator of self-renewal and lineage specification. Enforced expression of miR-130a in human cord blood (CB) derived HSPC caused an expansion of HSC, block in erythroid differentiation and abnormal myelopoiesis in xenografts. Thus, we examined miR-130a expression in AML and found miR-130a to be specifically upregulated in t(8,21) AML. The translocation t(8,21) is one of the most common karyotypic abnormalities in AML, accounting up to 10% of all AML cases. The consequence of this translocation is a fusion of AML1 and ETO genes, resulting in a formation of the AML1-ETO (AE) oncofusion protein, which acts as a dominant repressor of the wild type AML1/RUNX1. The ETO moiety mediates the recruitment of the nuclear corepressor (NCoR) and histone deacetylases (HDAC1-3) to block RUNX1 target gene expression. This prevents myeloid maturation, apoptosis and promotes leukemogenesis. Here we investigated the molecular mechanism of miR-130a in t(8,21) AML and how it contributes to the leukemogenesis of this AML subtype. Results: Using the TCGA dataset and our PMCC patient cohort, we identified miR-130a to be upregulated in t(8,21) AML and high miR-130a expression was associated with worse patient overall survival. To interrogate the functional significance of elevated miR-130a in t(8,21) AML, we performed knock-down (KD) experiments in the Kasumi-1 cell line, which represents a well characterized model system for t(8,21) AML. Notably, KD of miR-130a induced a significant reduction in the CD34+ cell population and an increase in differentiated CD11b+CD15+ and pro-apoptotic annexin V+ cells. We next examined the impact of miR-130a KD in CD34+ blasts from primary t(8,21) AML patient samples. In line with our findings in the Kasumi-1 cells, miR-130a KD decreased the proportion of CD34+ cells and increased the proportion of differentiated CD11b+CD15+ blasts. To investigate the effect of miR-130a KD on leukemic engraftment in vivo, we transduced CD34+ blasts from 2 patient samples and transplanted them into NSG-GF mice. miR-130a KD decreased leukemic engraftment and the proportion of transduced cells, corroborating the functional significance of high miR-130a expression in t(8,21) AML. To investigate the mechanistic action of miR-130a, we performed label-free semi-quantitative proteomics in human CB derived HSPC to uncover miR-130a targets. Surprisingly, we found the beta subunit of RUNX1, CBFb, and Transducin Beta Like 1 X-Linked Receptor 1, TBL1XR1, to be among the most repressed targets. TBL1XR1 is a component of the nuclear receptor corepressor (NCoR) complex and is involved in NCoR degradation. Thus, we performed western and immunoprecipitations (IP) assays in Flag-AE Kasumi-1 cells following miR-130a KD to examine changes in the expression of proteins associated with the AE complex. We observed increased expression of CBFβ, TBL1XR1 and CEBPA with miR-130a KD. Notably, miR-130a KD resulted in a dramatic decrease of NCoR protein levels. IP of Flag-AE showed decreased association of CBFβ and NCoR with AE, despite unaltered protein levels of AE. To investigate changes in binding occupancy of Flag-AE after miR-130a KD, we performed Cleavage Under the Targets and Release Using Nuclease (CUT&RUN) assay. Surprisingly, we observed 2-fold gain of AE sites in miR-130a KD sample compared to control. De novo motif enrichment analysis showed loss of motives for ETS and HOX transcription factors known to associate with AE following miR-130a KD. Genomic distribution of the peaks revealed a dramatic shift of AE peaks away from the promoter region to introns in miR-130a KD. Pathway enrichment analysis of the unique peaks gained in miR-130a KD showed stress responses and organelle disassembly, in line with the differentiation phenotype observed with miR-130a KD. Collectively, we uncovered a novel mechanism by which miR-130a reinforces the aberrant AE molecular program by controlling the composition and binding of the AE complex. Disclosures Dick: Bristol-Myers Squibb/Celgene: Research Funding.

scholarly journals Transcriptome responses of intestinal epithelial cells induced by membrane vesicles of Listeria monocytogenes unveil novel insights into the host-pathogen cross talk

2019 ◽  
Author(s):  
Raman Karthikeyan ◽  
Pratapa Gayathri ◽  
Paramasamy Gunasekaran ◽  
Medicharla V. Jagannadham ◽  
Jeyaprakash Rajendhran
Keyword(s):  
Cell Cycle ◽  
Listeria Monocytogenes ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Enrichment Analysis ◽  
Membrane Vesicles ◽  
Host Cells ◽  
Mitogen Activated Protein Kinase ◽  
Pathway Enrichment Analysis ◽  
Whole Cells

AbstractMembrane vesicles (MVs) serve as a vital source of virulence factors in many pathogenic organisms. The release of MVs by Listeria monocytogenes is only recently recognized, but its role in the pathogenesis is poorly understood. Here, we investigated the role of MVs of L. monocytogenes in virulence and host interactions. Proteomic analyses of whole cells and MVs of L. monocytogenes were performed using LC/MS/MS. A total of 1376 and 456 proteins were identified in the L. monocytogenes cells and MVs, respectively. Also, we have found that MVs contains active pore-forming listeriolysin (LLO), internalin B (inlB), phosphatidylinositol-specific phospholipase C (PI-PLC-A). We have previously reported that MVs of L. monocytogenes can infect and induce cytotoxicity in Caco-2 cells. In this study, we report the transcriptome response of Caco-2 cells upon infection with MVs as well as L. monocytogenes. In particular, we observed the up-regulation of autophagy-related genes in the early phase of infection with MVs. Transcription of inflammatory cytokines (CCL2, CXCL6, CXCL8, CXCL15, CXCL5, CXCL10) peaked at four h of infection. A large number of differentially expressed genes was associated with actin cytoskeleton rearrangement, autophagy, cell cycle arrest, and induction of oxidative stress. At a later time point, transcriptional programs generated upon infection with MVs point toward to evade innate immune signals, by modulating the expression of anti-inflammatory genes. KEGG pathway enrichment analysis revealed that MVs induce several signaling pathways such as PI3k-Akt signaling pathway, mitogen-activated protein kinase (MAPK) pathway, NOD-like receptor signaling pathway, cAMP signaling pathway, TNF, and NF-kB signaling pathway. Moreover, MVs induced the expression of cell cycle regulatory genes, which may result in the ability to prolong host cell survival, thus protecting the replicative niche for L. monocytogenes. Notably, we identified several non-coding RNAs (ncRNAs) are regulated during infection, suggesting that an early manipulation of the host gene expression may be essential for L. monocytogenes persistence and replication in host cells.

MFN2 might be a risk factor for lung adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13007-e13007
Author(s):  
Yuqing Lou ◽  
Yanwei Zhang ◽  
Jianlin Xu ◽  
Ping Gu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Lung Adenocarcinoma ◽  
A549 Cells ◽  
Enrichment Analysis ◽  
Tumor Formation ◽  
Normal Lung ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Functional Pathway

e13007 Background: Genetic mutations in Mitofusin-2(MFN2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A( Nature, December 2016). MFN2 was initially identified as a hypertension-associated gene and implicated in the pathogenesis of multiple cancer types. However, underlying mechanisms of MFN2 in lung adenocarcinoma was unclear. Methods: MFN2 expression at protein level was examined in 30 pair lung adenocarcinoma/adjacent normal lung samples with immunohistochemistry staining. Then MFN2 knocked down in human lung adenocarcinoma cells A549 with lentiviral-mediated shRNA strategy. The effects of MFN2 knockdown on cell proliferation, cell cycle process, cell migration and invasion was investigated in A549 cells. MFN2-knockdown induced gene expression changes was analyzed by microarray assay and then functional pathway enrichment analysis was performed to identify critical pathways involved in MFN2-mediated lung adenocarcinoma development. The expression changes of downstream factors were determined by western blot. Furthermore, tumor models in nude mice were generated. Tumor formation and progression in these mice were analyzed. Results: As compared to adjacent normal lung tissues, MFN2 expression was significantly higher in lung adenocarcinoma tissues with positive MFN2 signals in 90% (27/30) lung adenocarcinoma tissues and only in 26.7% (8/30) adjacent normal tissues. Furthermore, MFN2 knockdown inhibited cell proliferation, induced cell cycle arrest and blocked invasion behavior in A549 cells. MFN2-knockdown induced gene expression changes in A549 cells was analyzed by microarray assay. Functional pathway enrichment analysis revealed that 6 pathways were enriched in deregulated genes including Cell cycle, DNA replication, ECM-receptor interaction, Focal adhesion, MAPK signaling pathway and Chemokine signaling pathway. Downregulation of RAP1A and upregulation of RALB and ITGA2 identified in MFN2-knockdown cells by microarray analysis were confirmed by western blot. In vivo, tumor formation and progression in nude mice showed that MFN2 knockdown reduced tumorigenesis of A549 cells. Conclusions: MFN2 overexpression run a risk of lung adenocarcinoma.

scholarly journals Tetraspanins are involved in Burkholderia pseudomallei-induced cell-to-cell fusion of phagocytic and non-phagocytic cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tanes Sangsri ◽  
Natnaree Saiprom ◽  
Alisa Tubsuwan ◽  
Peter Monk ◽  
Lynda J. Partridge ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Severe Disease ◽  
A549 Cells ◽  
Host Cells ◽  
Phagocytic Cells ◽  
Tropical Regions ◽  
Cellular Factors ◽  
Large Extracellular Loop

Abstract Tetraspanins are four-span transmembrane proteins of host cells that facilitate infections by many pathogens. Burkholderia pseudomallei is an intracellular bacterium and the causative agent of melioidosis, a severe disease in tropical regions. This study investigated the role of tetraspanins in B. pseudomallei infection. We used flow cytometry to determine tetraspanins CD9, CD63, and CD81 expression on A549 and J774A.1 cells. Their roles in B. pseudomallei infection were investigated in vitro using monoclonal antibodies (MAbs) and recombinant large extracellular loop (EC2) proteins to pretreat cells before infection. Knockout of CD9 and CD81 in cells was performed using CRISPR Cas9 to confirm the role of tetraspanins. Pretreatment of A549 cells with MAb against CD9 and CD9-EC2 significantly enhanced B. pseudomallei internalization, but MAb against CD81 and CD81-EC2 inhibited MNGC formation. Reduction of MNGC formation was consistently observed in J774.A1 cells pretreated with MAbs specific to CD9 and CD81 and with CD9-EC2 and CD81-EC2. Data from knockout experiments confirmed that CD9 enhanced bacterial internalization and that CD81 inhibited MNGC formation. Our data indicate that tetraspanins are host cellular factors that mediated internalization and membrane fusion during B. pseudomallei infection. Tetraspanins may be the potential therapeutic targets for melioidosis.

scholarly journals SARS-CoV-2 Infections - Gene Expression Omnibus (GEO) Data Mining, Pathway Enrichment Analysis, and Prediction of Repurposable Drugs/Compounds

2020 ◽  
Author(s):  
Srilakshmi Chaparala ◽  
Carrie L Iwema ◽  
Ansuman Chattopadhyay
Keyword(s):  
Gene Expression ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Host Cells ◽  
In Vivo Studies ◽  
Pathway Enrichment Analysis ◽  
Gene Expressions ◽  
Pathway Enrichment

The COVID-19 global pandemic has created dire consequences with an alarming rate of morbidity and mortality. There are not yet vaccine or efficacious treatment options to combat the causative SARS-CoV-2 infection. This paper describes the identification of potentially repurposable drugs for COVID-19 treatment by conducting pathway enrichment analysis on publicly available Gene Expression Omnibus datasets. We first determined SARS-CoV-2 infection-induced alterations of host gene expressions and pathways. We then identified drugs or compounds that target and counter virus-triggered cellular perturbations, suggesting their potential repurposing for COVID-19 treatment. The key findings are that SARS-CoV-2 infection in host cells induces mitochondrial dysfunction, inhibits oxidative phosphorylation, and activates several immune response and pro-inflammatory pathways. Triptolide, the major bioactive component of a traditional Chinese medicine herb, may rescue mitochondrial dysfunction by activating oxidative phosphorylation. Further in vitro and in vivo studies are necessary to verify these results prior to clinical application.

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