Evidence of a dysregulated Vitamin D pathway in SARS-CoV-2 infected patient’s lung cells
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Abstract
Although a defective vitamin D pathway has been widely suspected to be associated in SARS-CoV-2 pathobiology, the status of the vitamin D pathway and vitamin D-modulated genes in lung cells of patients infected with SARS-CoV-2 remains unknown. To understand the significance of the vitamin D pathway in SARS-CoV-2 pathobiology, computational approaches were applied to transcriptomic datasets from bronchoalveolar lavage fluid (BALF) cells of such patients or healthy individuals. Levels of vitamin D receptor, retinoid X receptor, and CYP27A1 in BALF cells of patients infected with SARS-CoV-2 were found to be reduced. Additionally, 107 differentially expressed, predominantly downregulated genes modulated by vitamin D were identified in transcriptomic datasets from patient’s cells. Further analysis of differentially expressed genes provided eight novel genes with a conserved motif with vitamin D-responsive elements, implying the role of both direct and indirect mechanisms of gene expression by the dysregulated vitamin D pathway in SARS-CoV-2-infected cells. Network analysis of differentially expressed vitamin D-modulated genes identified pathways in the immune system, NF-KB/cytokine signaling, and cell cycle regulation as top predicted pathways that might be affected in the cells of such patients. In brief, the results provided computational evidence to implicate a dysregulated vitamin D pathway in the pathobiology of SARS-CoV-2 infection.
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SciScore for 10.1101/2020.12.21.423733: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources A549), transformed lung-derived Calu-3 cells mock treated or infected with SARS-CoV-2 (USA-WA1/2020), data was accessed from Gene Expression Omnibus under the accession GSE14750731. A549suggested: NoneCalu-3suggested: NonePAK silenced transcriptome data: The gene expression profiles of MCF10A.B2 cells (MCF10A cells expressing a chemically activatable form of Her2) stably expressing a Tet inducible shRNA directed against Pak1 gene was … SciScore for 10.1101/2020.12.21.423733: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources A549), transformed lung-derived Calu-3 cells mock treated or infected with SARS-CoV-2 (USA-WA1/2020), data was accessed from Gene Expression Omnibus under the accession GSE14750731. A549suggested: NoneCalu-3suggested: NonePAK silenced transcriptome data: The gene expression profiles of MCF10A.B2 cells (MCF10A cells expressing a chemically activatable form of Her2) stably expressing a Tet inducible shRNA directed against Pak1 gene was accessed from Gene Expression Omnibus under the accession GSE7128391. MCF10A.B2suggested: NoneMCF10Asuggested: NoneSoftware and Algorithms Sentences Resources PAK silenced transcriptome data: The gene expression profiles of MCF10A.B2 cells (MCF10A cells expressing a chemically activatable form of Her2) stably expressing a Tet inducible shRNA directed against Pak1 gene was accessed from Gene Expression Omnibus under the accession GSE7128391. Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)Differential Expression Analysis and Data: Differential expression data available as supplementary data were collected and differential expression analysis was performed for the gene count provided under the accession GSE147507 using BioJupies92. BioJupies92suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.12.21.423733: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources A549), transformed lung-derived Calu-3 cells mock treated or infected with SARS- CoV-2 (USA-WA1/2020), data was accessed from Gene Expression Omnibus under the accession GSE14750731. A549suggested: NoneCalu-3suggested: NonePAK silenced transcriptome data The gene expression profiles of MCF10A.B2 cells (MCF10A cells expressing a chemically … SciScore for 10.1101/2020.12.21.423733: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources A549), transformed lung-derived Calu-3 cells mock treated or infected with SARS- CoV-2 (USA-WA1/2020), data was accessed from Gene Expression Omnibus under the accession GSE14750731. A549suggested: NoneCalu-3suggested: NonePAK silenced transcriptome data The gene expression profiles of MCF10A.B2 cells (MCF10A cells expressing a chemically activatable form of Her2) stably expressing a Tet inducible shRNA directed against Pak1 gene was accessed from Gene Expression Omnibus under the accession GSE7128389. MCF10A.B2suggested: NoneMCF10Asuggested: NoneSoftware and Algorithms Sentences Resources Second study reports that BALF cell transcriptome indicates robust innate immune responses in SARS-CoV-2 patients30 and the remaining studies provided the transcriptomic data ofSARS-CoV-2 deceased patient, the data has accessed from Gene Expression Omnibus under the accession GSE147507, GSE153970, GSE150316 and GSE152075. Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)Differential Expression Analysis and Data Differential expression data available with from the supplementary data were collected and differential expression analysis was performed for the gene count provided under the accession GSE147507 using BioJupies90 BioJupies90suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
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