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pmid:33354650
Host-Viral Interactions Revealed among Shared Transcriptomics Signatures of ARDS and Thrombosis: A Clue into COVID-19 Pathogenesis.
Aastha Mishra · Shankar Chanchal · Mohammad Z Ashraf
TH open : companion journal to thrombosis and haemostasis · 2020 doi:10.1055/s-0040-1721706
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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These consistent observations may have serious implications for the treatment and management of this highly pathogenic disease. As a consequence, the anticoagulant therapeutic strategies, such as low molecular weight heparin, have shown some encouraging results. Cytokine burst leading to sepsis which is one of the primary reasons for acute respiratory distress syndrome (ARDS) drive that could be worsened with the accumulation of coagulation factors in the lungs of COVID-19 patients. However, the obscurity of this syndrome remains a hurdle in making decisive treatment choices. Therefore, an attempt to characterize shared biological mechanisms between ARDS and thrombosis using comprehensive transcriptomics meta-analysis is made. We conducted an integrated gene expression meta-analysis of two independently publicly available datasets of ARDS and venous thromboembolism (VTE). Datasets GSE76293 and GSE19151 derived from National Centre for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database were used for ARDS and VTE, respectively. Integrative meta-analysis of expression data (INMEX) tool preprocessed the datasets and effect size combination with random effect modeling was used for obtaining differentially expressed genes (DEGs). Network construction was done for hub genes and pathway enrichment analysis. Our meta-analysis identified a total of 1,878 significant DEGs among the datasets, which when subjected to enrichment analysis suggested inflammation-coagulation-hypoxemia convolutions in COVID-19 pathogenesis. The top hub genes of our study such as tumor protein 53 (TP53), lysine acetyltransferase 2B (KAT2B), DExH-box helicase 9 (DHX9), REL-associated protein (RELA), RING-box protein 1 (RBX1), and proteasome 20S subunit beta 2 (PSMB2) gave insights into the genes known to be participating in the host-virus interactions that could pave the way to understand the various strategies deployed by the virus to improve its replication and spreading.", "claims": [{"id": "claim-method", "statement": "The differential expression meta-analysis across the diseases and healthy controls was performed by the random effects model (REM) based on combining the effect sizes (ESs) or changes of gene expression from the different studies and obtaining an overall mean with a significance level of p < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33354650", "locator": "sections[5] \"Identification of Shared Differentially Expressed Genes\" paragraph 2", "quote": "The differential expression meta-analysis across the diseases and healthy controls was performed by the random effects model (REM) based on combining the effect sizes (ESs) or changes of gene expression from the different studies and obtaining an overall mean with a significance level of p < 0.05."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33354650"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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