All rights reserved.ĭrug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic-COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). Our study provides new insights which bridge barley drought tolerance to PCD through MC1 and TSN1 pathway. Machine learning and correspondence analysis revealed a significant relationship between drought tolerance and measured characteristics in the context of PCD. Identified genotypes exhibited different physiochemical characteristics, including proline content, chlorophylls concentration, percentage of electrolyte leakage (EL%) and malondialdehyde (MDA) content as well as expression profiles of MC1 and TSN1 genes. Based on the field trial, a drought‐tolerant and a drought‐susceptible barley genotype was identified from eight tested cultivars. Gene network topology analysis highlighted two programmed cell death (PCD) modulating genes, (Metacaspase 1) MC1 and (Tudor‐SN 1) TSN1, as important (hub) genes in the predicted network. A gene network was derived from the DEGs, which comprised of a total of 131 nodes and 257 edges. RNA‐seq analysis identified a total of 665 differentially expressed genes (DEGs) belonging to diverse functional categories. ![]() To that, we combined RNA‐seq data analysis with field and greenhouse drought experiments in a systems biology approach. This study was designed to address such important details and to gain insights into molecular responses of barley (Hordeum vulgare L.) to drought stress. Despite extensive studies in this area, there are still many details to be uncovered, such as the importance of each gene involved in the stress response as well as the relationship between these genes and the physiochemical processes governing stress tolerance. Studying the drought‐responsive transcriptome is of high interest since it can serve as a blueprint for stress adaptation strategies. In conclusion, our study unravels a rapid approach for applying next-generation knowledge discovery (NGKD) platforms to discover small molecules with therapeutic potential against COVID-19 and its related disease pathologies. Furthermore, the gene set enrichment analysis (GSEA) preranked method and Metascape web tool were used to decipher and annotate the gene signatures that were potentially reversed by these small molecules. In addition, withaferin A, trichostatin A, narciclasine, camptothecin, and JQ1 have the potential to reverse Neuro-COVID gene signatures. ![]() We uncovered small molecules such as camptothecin, importazole, and withaferin A, which can potentially reverse COVID-19 associated gene signatures. L1000 fireworks display (L1000FWD) and L1000 characteristic direction signature search engine (L1000 CDS2) web tools were used to uncover the small molecules that could potentially reverse the COVID-19 and Neuro-COVID-associated gene signatures. ![]() Additionally, single-cell transcriptomics data (GSE163005) of meta clusters of immune cells from the cerebrospinal fluid (CSF), such as T-cells/natural killer cells (NK) (TcMeta), dendritic cells (DCMeta), and monocytes/granulocyte (monoMeta) cell types for comparison, namely, Neuro-COVID versus idiopathic intracranial hypertension (IIH), were analyzed using iPathwayGuide. Here, we used the raw RNA-seq reads (Single-End) in quadruplicates derived using Illumina Next Seq 500 from SARS-CoV-infected primary human bronchial epithelium (NHBE) and mock-treated NHBE cells obtained from the Gene Expression Omnibus (GEO) (GSE147507), and the quality control (QC) was evaluated using the CLC Genomics Workbench 20.0 (Qiagen, United States) before the RNA-seq analysis using BioJupies web tool and iPathwayGuide for gene ontologies (GO), pathways, upstream regulator genes, small molecules, and natural products. The gene expression profiles of COVID-19 infection models can be used to decipher potential therapeutics for COVID-19 and related pathologies, such as Neuro-COVID. SARS-CoV-2 is the causative agent for coronavirus disease-19 (COVID-19) and belongs to the family Coronaviridae that causes sickness varying from the common cold to more severe illnesses such as severe acute respiratory syndrome, sudden stroke, neurological complications (Neuro-COVID), multiple organ failure, and mortality in some patients.
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