Gene networks under circadian control exhibit diurnal organization in primate organs

  1. Jie Li
  2. Pengxing Nie
  3. Christoph W. Turck
  4. Guang-Zhong Wang

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Abstract

Mammalian organs are individually controlled by autonomous circadian clocks. At the molecular level, this process is defined by the cyclical co-expression of both core transcription factors and their downstream targets across time. While interactions between these molecular clocks are necessary for proper homeostasis, these features remain undefined. Here, we utilize integrative analysis of a baboon diurnal transcriptome atlas to characterize the properties of gene networks under circadian control. We found that 53.4% (8120) of baboon genes are oscillating body-wide. Additionally, two basic network modes were observed at the systems level: daytime and nighttime mode. Daytime networks were enriched for genes involved in metabolism, while nighttime networks were enriched for genes associated with growth and cellular signaling. A substantial number of diseases only form significant disease modules at either daytime or nighttime. In addition, a majority of SARS-CoV-2-related genes and modules are rhythmically expressed, which have significant network proximities with circadian regulators. Our data suggest that synchronization amongst circadian gene networks is necessary for proper homeostatic functions and circadian regulators have close interactions with SARS-CoV-2 infection.

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  1. Version published to 10.1038/s42003-022-03722-0
  2. ScreenIT

    SciScore for 10.1101/2021.09.17.460870: (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
    Primate diurnal gene expression atlas: FPKM expression values from 756 samples were downloaded from NCBI’s Gene Expression Omnibus, with GEO accession number: GSE98965 (Mure et al. 2018).
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    JTK_CYCLE (Hughes et al. 2010; Wu et al. 2016) was employed to detect the global rhythmic parameters, such as amplitude, phase period, and the significance level.
    JTK_CYCLE
    suggested: (JTK_CYCLE, RRID:SCR_017962)
    Next, ComBat was used to eliminate the variations among organs (Johnson et al. 2007) and the JTK_CYCLE was used to detect global cycling genes.
    ComBat
    suggested: (ComBat, RRID:SCR_010974)
    Protein-protein interactions were obtained from the STRING (Szklarczyk et al. 2019) and HIPPIE (Alanis-Lobato et al. 2017) databases; genetic interactions were downloaded from the BioGRID (Oughtred et al. 2019) database, and functional relevant interactions were downloaded from the KEGG pathway database (Kanehisa and Goto 2000).
    STRING
    suggested: (STRING, RRID:SCR_005223)
    BioGRID
    suggested: (BioGrid Australia, RRID:SCR_006334)
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    Functional enrichment analysis: The function annotation of global cycling genes was performed by g:Profiler (Raudvere et al. 2019).
    g:Profiler
    suggested: (G:Profiler, RRID:SCR_006809)

    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.

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  3. Version published to 10.1101/2021.09.17.460870v1 on bioRxiv