Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that caused the coronavirus disease 2019 (COVID-19) pandemic. Though previous studies have suggested that SARS-CoV-2 cellular tropism depends on the host-cell-expressed proteins, whether transcriptional regulation controls SAR...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/4/837 |
| _version_ | 1797443125627584512 |
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| author | Haonan Tong Hao Chen Cranos M. Williams |
| author_facet | Haonan Tong Hao Chen Cranos M. Williams |
| author_sort | Haonan Tong |
| collection | DOAJ |
| description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that caused the coronavirus disease 2019 (COVID-19) pandemic. Though previous studies have suggested that SARS-CoV-2 cellular tropism depends on the host-cell-expressed proteins, whether transcriptional regulation controls SARS-CoV-2 tropism factors in human lung cells remains unclear. In this study, we used computational approaches to identify transcription factors (TFs) regulating SARS-CoV-2 tropism for different types of lung cells. We constructed transcriptional regulatory networks (TRNs) controlling SARS-CoV-2 tropism factors for healthy donors and COVID-19 patients using lung single-cell RNA-sequencing (scRNA-seq) data. Through differential network analysis, we found that the altered regulatory role of TFs in the same cell types of healthy and SARS-CoV-2-infected networks may be partially responsible for differential tropism factor expression. In addition, we identified the TFs with high centralities from each cell type and proposed currently available drugs that target these TFs as potential candidates for the treatment of SARS-CoV-2 infection. Altogether, our work provides valuable cell-type-specific TRN models for understanding the transcriptional regulation and gene expression of SARS-CoV-2 tropism factors. |
| first_indexed | 2024-03-09T12:51:32Z |
| format | Article |
| id | doaj.art-0030ab1bd1e441a2afc6aa0dce578cc2 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T12:51:32Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-0030ab1bd1e441a2afc6aa0dce578cc22023-11-30T22:04:24ZengMDPI AGViruses1999-49152022-04-0114483710.3390/v14040837Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human LungsHaonan Tong0Hao Chen1Cranos M. Williams2Electrical and Computer Engineering, North Carolina State University, Raleigh, NC 27695, USAProgram in Genetics, Department of Plant and Microbial Biology, North Carolina State University, Raleigh, NC 27695, USAElectrical and Computer Engineering, North Carolina State University, Raleigh, NC 27695, USASevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that caused the coronavirus disease 2019 (COVID-19) pandemic. Though previous studies have suggested that SARS-CoV-2 cellular tropism depends on the host-cell-expressed proteins, whether transcriptional regulation controls SARS-CoV-2 tropism factors in human lung cells remains unclear. In this study, we used computational approaches to identify transcription factors (TFs) regulating SARS-CoV-2 tropism for different types of lung cells. We constructed transcriptional regulatory networks (TRNs) controlling SARS-CoV-2 tropism factors for healthy donors and COVID-19 patients using lung single-cell RNA-sequencing (scRNA-seq) data. Through differential network analysis, we found that the altered regulatory role of TFs in the same cell types of healthy and SARS-CoV-2-infected networks may be partially responsible for differential tropism factor expression. In addition, we identified the TFs with high centralities from each cell type and proposed currently available drugs that target these TFs as potential candidates for the treatment of SARS-CoV-2 infection. Altogether, our work provides valuable cell-type-specific TRN models for understanding the transcriptional regulation and gene expression of SARS-CoV-2 tropism factors.https://www.mdpi.com/1999-4915/14/4/837SARS-CoV-2single-cell RNA-seqdifferential network analysis |
| spellingShingle | Haonan Tong Hao Chen Cranos M. Williams Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs Viruses SARS-CoV-2 single-cell RNA-seq differential network analysis |
| title | Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs |
| title_full | Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs |
| title_fullStr | Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs |
| title_full_unstemmed | Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs |
| title_short | Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs |
| title_sort | identification of transcription factors regulating sars cov 2 tropism factor expression by inferring cell type specific transcriptional regulatory networks in human lungs |
| topic | SARS-CoV-2 single-cell RNA-seq differential network analysis |
| url | https://www.mdpi.com/1999-4915/14/4/837 |
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