The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data

  1. João Malato
  2. Franziska Sotzny
  3. Sandra Bauer
  4. Helma Freitag
  5. André Fonseca
  6. Anna D. Grabowska
  7. Luís Graça
  8. Clara Cordeiro
  9. Luís Nacul
  10. Eliana M. Lacerda
  11. Jesus Castro-Marrero
  12. Carmen Scheibenbogen
  13. Francisco Westermeier
  14. Nuno Sepúlveda

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Abstract

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  1. Version published to 10.1016/j.heliyon.2021.e07665
  2. Version published to 10.1101/2021.03.23.21254175v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.03.23.21254175: (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

    Software and Algorithms
    SentencesResources
    To determine the SNPs located in the ACE and ACE2 genes as defined above, we searched the annotation files for the following RefSeq transcript identifiers: ACE - ENST00000290866 (Ensembl identifier) or NM_000789 (National Center for Biotechnology Information (NCBI) Reference
    RefSeq
    suggested: (RefSeq, RRID:SCR_003496)
    Ensembl
    suggested: (Ensembl, RRID:SCR_002344)
    Since these studies did not make their data publicly, our analysis was based on the reported list of SNPs possibly associated with ME/CFS. 2.4 Analysis of case-control EWAS: We focused our analysis on four available case-control EWAS on ME/CFS (Brenu et al., 2014; De Vega et al., 2017, 2014; Trivedi et al., 2018), which were reviewed elsewhere (Almenar-Pérez et al., 2019), and two additional case-control studies published after this review (Helliwell et al., 2020; Herrera et al., 2018) (Table 2).
    ME/CFS.
    suggested: None
    We conducted a joint analysis of the four of the array-based studies which had their data available in the NCBI Gene Expression Omnibus (GEO) data repository (Barrett et al., 2013).
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    In this analysis, we used the following Bioconductor packages: hgu133a.db, hgu133plus2.db, IlluminaHumanMethylation450kanno.ilmn12.hg19, and IlluminaHumanMethylationEPICanno.ilm10b2.hg19 to analyze the annotation files of the GeneChip HG-U133A, GeneChip U133+2
    Bioconductor
    suggested: (Bioconductor, RRID:SCR_006442)
    GeneChip
    suggested: None

    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: We detected the following sentences addressing limitations in the study:
    We attempted to compensate this data limitation with the analysis of a new data from a cohort of German patients. This analysis suggested that the gene expression of ACE or ACE2 in PBMCs were similar between patients and healthy controls. Data scarcity can be explained by five main reasons. Firstly, there were only few GWAS, EWAS, and GES available in the ME/CFS literature. This limited number of studies could be related to a poor societal recognition of ME/CFS as a disease, which ultimately limits the funding available for the respective research. Access to limited research funding could also imply an additional difficulty in assembling multidisciplinary teams required to tackle the various challenging technical aspects of these studies. Secondly, three published case-control GES based on microarray technology were excluded from this investigation, because they used broad or alternative case definitions of ME/CFS. Given the absence of an objective disease biomarker, the research community should aim to use consensual case definitions for research with the intention to make diagnostic comparable across studies while reducing between-studies heterogeneity. In this regard, our requirement for ME/CFS diagnosis was the 1994 CDC/Fukuda definition or the 2003 CCC according to the recommendation for research given by the European Network on ME/CFS (Pheby et al., 2020). Thirdly, four RNA-seq studies were not included in our investigation due to unclear data quality. Issues concerning...

    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.

    About SciScore

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  4. Version published to 10.1101/2021.03.23.21254175v1 on medRxiv