Intronic regulation of SARS-CoV-2 receptor (ACE2) expression mediated by immune signaling and oxidative stress pathways

  1. Daniel Richard
  2. Pushpanathan Muthuirulan
  3. Jennifer Aguiar
  4. Andrew C. Doxey
  5. Arinjay Banerjee
  6. Karen Mossman
  7. Jeremy Hirota
  8. Terence D. Capellini

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Abstract

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  1. Version published to 10.1016/j.isci.2022.104614
  2. ScreenIT

    SciScore for 10.1101/2021.06.07.447351: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationSequences were subsequently used for de novo motif analysis using HOMER (version 4.10)(22) using a 10x random shuffling as a background set.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    ACE2 co-expression and functional enrichment analysis with public microarray data: Public microarray experiments using Affymetrix chips (HuGene-1.0-st-v1 and HG-U133 Plus 2) on airway epithelial cell samples were obtained from the NCBI Gene Expression Omnibus (GEO) database, as described in our previous work(4).
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    Probe definition files were downloaded from Bioconductor and probes were annotated using Bioconductor’s annotate package.
    Bioconductor
    suggested: (Bioconductor, RRID:SCR_006442)
    Heat maps for top 200 ACE2-correlated genes across samples were generated with the pheatmap R package (version 1.0.12).
    pheatmap
    suggested: (pheatmap, RRID:SCR_016418)
    Terms were ranked within ontologies by FDR-adjusted p value (calculated by Enrichr by running the Fisher exact test for random gene sets in order to compute a mean rank and standard deviation from the expected rank for each term in the gene set library) and the top 3 terms for ontologies of interest were selected.
    Enrichr
    suggested: (Enrichr, RRID:SCR_001575)
    Functional enrichment bar plots were generated with the ggplot2 R pack-age (version 3.2.1).
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    Sequences were subsequently used for de novo motif analysis using HOMER (version 4.10)(22) using a 10x random shuffling as a background set.
    HOMER
    suggested: (HOMER, RRID:SCR_010881)
    The highest-rank motif bore close similarity to the FOSL2::JUN PWM from the JASPAR database (MA1130.1).
    JASPAR
    suggested: (JASPAR, RRID:SCR_003030)
    These were lifted-over to hg19 using the UCSC liftOver utility(21) with sulforaphane and vehicle-treatment datasets pooled and merged for a final set of 919 peaks.
    UCSC liftOver
    suggested: None
    Peak files (hg19) were sorted and merged for overlapping peaks using bedtools.
    bedtools
    suggested: (BEDTools, RRID:SCR_006646)
    DNase, ChIP-seq, and motif hit tracks were loaded into the UCSC Genome Browser(29) for visualization.
    ChIP-seq
    suggested: (ChIP-seq, RRID:SCR_001237)

    Results 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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.06.07.447351v1 on bioRxiv