Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients

  1. Xinping Chen
  2. Tao Wu
  3. Lingguo Li
  4. Yu Lin
  5. Zhichao Ma
  6. Jinjin Xu
  7. Hui Li
  8. Fanjun Cheng
  9. Ruoyan Chen
  10. Kun Sun
  11. Yuxue Luo
  12. Chen Zhang
  13. Fang Chen
  14. Jiao Wang
  15. Tingyu Kuo
  16. Xiaojuan Li
  17. Chunyu Geng
  18. Feng Lin
  19. Chaojie Huang
  20. Junjie Hu
  21. Jianhua Yin
  22. Ming Liu
  23. Ye Tao
  24. Jiye Zhang
  25. Rijing Ou
  26. Fang Zheng
  27. Yan Jin
  28. Huanming Yang
  29. Jian Wang
  30. Xun Xu
  31. Shengmiao Fu
  32. Hongyan Jiang
  33. Xin Jin
  34. Haiqiang Zhang

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Abstract

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.

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  1. Version published to 10.3389/fgene.2021.663098
  2. ScreenIT

    SciScore for 10.1101/2020.06.08.20124305: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Materials and Methods:
    Methods
    suggested: None

    Results from OddPub: Thank you for sharing your data.

    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.
    • Thank you for including a protocol registration statement.

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  3. Version published to 10.1101/2020.06.08.20124305v1 on medRxiv