Frontiers in Genetics (May 2021)
Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients
- Xinping Chen,
- Tao Wu,
- Lingguo Li,
- Lingguo Li,
- Lingguo Li,
- Yu Lin,
- Zhichao Ma,
- Jinjin Xu,
- Hui Li,
- Fanjun Cheng,
- Ruoyan Chen,
- Kun Sun,
- Kun Sun,
- Yuxue Luo,
- Yuxue Luo,
- Chen Zhang,
- Fang Chen,
- Jiao Wang,
- Tingyu Kuo,
- Tingyu Kuo,
- Xiaojuan Li,
- Chunyu Geng,
- Feng Lin,
- Chaojie Huang,
- Junjie Hu,
- Jianhua Yin,
- Ming Liu,
- Ye Tao,
- Jiye Zhang,
- Rijing Ou,
- Fang Zheng,
- Yan Jin,
- Huanming Yang,
- Huanming Yang,
- Jian Wang,
- Jian Wang,
- Xun Xu,
- Xun Xu,
- Shengmiao Fu,
- Hongyan Jiang,
- Xin Jin,
- Xin Jin,
- Haiqiang Zhang
Affiliations
- Xinping Chen
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Tao Wu
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Lingguo Li
- BGI-Shenzhen, Shenzhen, China
- Lingguo Li
- BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China
- Lingguo Li
- School of Future Technology, University of Chinese Academy of Sciences, Beijing, China
- Yu Lin
- BGI-Shenzhen, Shenzhen, China
- Zhichao Ma
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Jinjin Xu
- BGI-Shenzhen, Shenzhen, China
- Hui Li
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Fanjun Cheng
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ruoyan Chen
- BGI-Shenzhen, Shenzhen, China
- Kun Sun
- BGI-Shenzhen, Shenzhen, China
- Kun Sun
- Shenzhen Bay Laboratory, Shenzhen, China
- Yuxue Luo
- BGI-Shenzhen, Shenzhen, China
- Yuxue Luo
- School of Medicine, South China University of Technology, Guangzhou, China
- Chen Zhang
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Fang Chen
- BGI-Shenzhen, Shenzhen, China
- Jiao Wang
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Tingyu Kuo
- BGI-Shenzhen, Shenzhen, China
- Tingyu Kuo
- BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China
- Xiaojuan Li
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Chunyu Geng
- BGI-Shenzhen, Shenzhen, China
- Feng Lin
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Chaojie Huang
- BGI-Shenzhen, Shenzhen, China
- Junjie Hu
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Jianhua Yin
- BGI-Shenzhen, Shenzhen, China
- Ming Liu
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Ye Tao
- BGI-Shenzhen, Shenzhen, China
- Jiye Zhang
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Rijing Ou
- BGI-Shenzhen, Shenzhen, China
- Fang Zheng
- Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yan Jin
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Huanming Yang
- BGI-Shenzhen, Shenzhen, China
- Huanming Yang
- 0James D. Watson Institute of Genome Sciences, Hangzhou, China
- Jian Wang
- BGI-Shenzhen, Shenzhen, China
- Jian Wang
- 0James D. Watson Institute of Genome Sciences, Hangzhou, China
- Xun Xu
- BGI-Shenzhen, Shenzhen, China
- Xun Xu
- 1Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen, China
- Shengmiao Fu
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Hongyan Jiang
- Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Hainan General Hospital, Hainan Hospital Affiliated to The Hainan Medical College, Haikou, China
- Xin Jin
- BGI-Shenzhen, Shenzhen, China
- Xin Jin
- Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Haiqiang Zhang
- BGI-Shenzhen, Shenzhen, China
- DOI
- https://doi.org/10.3389/fgene.2021.663098
- Journal volume & issue
-
Vol. 12
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.
Keywords