Computational Mapping of the Human-SARS-CoV-2 Protein-RNA Interactome

  1. Marc Horlacher
  2. Svitlana Oleshko
  3. Yue Hu
  4. Mahsa Ghanbari
  5. Giulia Cantini
  6. Patrick Schinke
  7. Ernesto Elorduy Vergara
  8. Florian Bittner
  9. Nikola S. Mueller
  10. Uwe Ohler
  11. Lambert Moyon
  12. Annalisa Marsico

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Abstract

Strong evidence suggests that human human RNA-binding proteins (RBPs) are critical factors for viral infection, yet there is no feasible experimental approach to map exact binding sites of RBPs across the SARS-CoV-2 genome systematically at a large scale. We investigated the role of RBPs in the context of SARS-CoV-2 by constructing the first in silico map of human RBP / viral RNA interactions at nucleotide-resolution using two deep learning methods (pysster and DeepRiPe) trained on data from CLIP-seq experiments. We evaluated conservation of RBP binding between 6 other human pathogenic coronaviruses and identified sites of conserved and differential binding in the UTRs of SARS-CoV-1, SARS-CoV-2 and MERS. We scored the impact of variants from 11 viral strains on protein-RNA interaction, identifying a set of gain-and loss of binding events. Lastly, we linked RBPs to functional data and OMICs from other studies, and identified MBNL1, FTO and FXR2 as potential clinical biomarkers. Our results contribute towards a deeper understanding of how viruses hijack host cellular pathways and are available through a comprehensive online resource ( https://sc2rbpmap.helmholtz-muenchen.de ).

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  1. ScreenIT

    SciScore for 10.1101/2021.12.22.472458: (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
    SentencesResources
    3.1 Data and Preprocessing: Enhanced CLIP (eCLIP) datasets were obtained from the ENCODE project database, which comprises 223 eCLIP experiments of 150 RBPs across two cell lines, HepG2 and K562.
    HepG2
    suggested: None
    K562
    suggested: NCI-DTP Cat# K-562, RRID:CVCL_0004)
    3.13 Comparative Analysis of Human coronaviruses: Besides SARS-CoV-2, we obtained reference sequences for 6 other human coronaviruses, including SARS-CoV-1, MERS, HCoV-229E, HCoV-HKU1, HCoV-NL63 and HCoV-OC43 from NCBI [Sayers et al. (2021)].
    HCoV-NL63
    suggested: RRID:CVCL_RW88)
    Software and Algorithms
    SentencesResources
    Peaks of each RBP were taken directly from ENCODE and preprocessing was performed as follows.
    ENCODE
    suggested: (Encode, RRID:SCR_015482)
    For each of the two replicates of a given eCLIP experiment, peaks were first intersected with protein-coding transcript locations obtained from the GENCODE database (Release 35) and only those peaks overlapping with a mRNA transcript were retained.
    GENCODE
    suggested: (GENCODE, RRID:SCR_014966)
    3.3 Pysster Model: The pysster Python library [Budach and Marsico (2018)] was used for implementation of the model which consists of three 1D convolutional layers, each with 150 filters of size 18, followed by a single fully connected layer with 100 units.
    Python
    suggested: (IPython, RRID:SCR_001658)

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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

    About SciScore

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