Agrawal, P and Sambaturu, N and Olgun, G and Hannenhalli, S (2022) A Path-Based Analysis of Infected Cell Line and COVID-19 Patient Transcriptome Reveals Novel Potential Targets and Drugs Against SARS-CoV-2. In: Frontiers in Immunology, 13 .
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Abstract
Most transcriptomic studies of SARS-CoV-2 infection have focused on differentially expressed genes, which do not necessarily reveal the genes mediating the transcriptomic changes. In contrast, exploiting curated biological network, our PathExt tool identifies central genes from the differentially active paths mediating global transcriptomic response. Here we apply PathExt to multiple cell line infection models of SARS-CoV-2 and other viruses, as well as to COVID-19 patient-derived PBMCs. The central genes mediating SARS-CoV-2 response in cell lines were uniquely enriched for ATP metabolic process, G1/S transition, leukocyte activation and migration. In contrast, PBMC response reveals dysregulated cell-cycle processes. In PBMC, the most frequently central genes are associated with COVID-19 severity. Importantly, relative to differential genes, PathExt-identified genes show greater concordance with several benchmark anti-COVID-19 target gene sets. We propose six novel anti-SARS-CoV-2 targets ADCY2, ADSL, OCRL, TIAM1, PBK, and BUB1, and potential drugs targeting these genes, such as Bemcentinib, Phthalocyanine, and Conivaptan.
| Item Type: | Journal Article |
|---|---|
| Publication: | Frontiers in Immunology |
| Publisher: | Frontiers Media S.A. |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | cell lines; DEGs (Differentially Expressed Genes); network analysis; PBMCs (Peripheral Blood Mononuclear Cells); SARS-C0V-2; transcriptome |
| Department/Centre: | Division of Physical & Mathematical Sciences > Mathematics |
| Date Deposited: | 04 Aug 2022 09:51 |
| Last Modified: | 04 Aug 2022 09:51 |
| URI: | https://eprints.iisc.ac.in/id/eprint/75297 |
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