Multiscale statistical physics of the pan-viral interactome unravels the systemic nature of SARS-CoV-2 infections
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Abstract
Protein–protein interaction networks have been used to investigate the influence of SARS-CoV-2 viral proteins on the function of human cells, laying out a deeper understanding of COVID–19 and providing ground for applications, such as drug repurposing. Characterizing molecular (dis)similarities between SARS-CoV-2 and other viral agents allows one to exploit existing information about the alteration of key biological processes due to known viruses for predicting the potential effects of this new virus. Here, we compare the novel coronavirus network against 92 known viruses, from the perspective of statistical physics and computational biology. We show that regulatory spreading patterns, physical features and enriched biological pathways in targeted proteins lead, overall, to meaningful clusters of viruses which, across scales, provide complementary perspectives to better characterize SARS-CoV-2 and its effects on humans. Our results indicate that the virus responsible for COVID–19 exhibits expected similarities, such as to Influenza A and Human Respiratory Syncytial viruses, and unexpected ones with different infection types and from distant viral families, like HIV1 and Human Herpes virus. Taken together, our findings indicate that COVID–19 is a systemic disease with potential effects on the function of multiple organs and human body sub-systems.
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SciScore for 10.1101/2020.09.06.20189266: (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
Software and Algorithms Sentences Resources The human interactome used in this study combines protein-protein interactions (PPI) from two of the largest repository publicly available to date, namely STRING v11.041 — publicly available at https://string-db.org/cgi/download.pl — and BIOGRID v3.5.18242,43 — publicly available at https://downloads.thebiogrid.org/ BioGRID/Release-Archive/BIOGRID-3.5.182/). STRINGsuggested: (STRING, RRID:SCR_005223)BIOGRIDsuggested: (BioGrid Australia, RRID:SCR_006334)Other relevant targets (See Fig. 2) include GK (Glycerol Kinase, NCBI Gene ID: 2710), an important enzyme contributing to regulate … SciScore for 10.1101/2020.09.06.20189266: (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
Software and Algorithms Sentences Resources The human interactome used in this study combines protein-protein interactions (PPI) from two of the largest repository publicly available to date, namely STRING v11.041 — publicly available at https://string-db.org/cgi/download.pl — and BIOGRID v3.5.18242,43 — publicly available at https://downloads.thebiogrid.org/ BioGRID/Release-Archive/BIOGRID-3.5.182/). STRINGsuggested: (STRING, RRID:SCR_005223)BIOGRIDsuggested: (BioGrid Australia, RRID:SCR_006334)Other relevant targets (See Fig. 2) include GK (Glycerol Kinase, NCBI Gene ID: 2710), an important enzyme contributing to regulate metabolism and glycerol uptake, and its mutations are associated with glycerol kinase deficiency; TBP (TATA-box Binding Protein, NCBI Gene ID: 6908), which composes the transcription factor IID, which coordinates the activities of more than 70 polypeptides to initiate the transcription by RNA polymerase II; TLR4 (Toll Like Receptor 4, NCBI Gene ID: 7099), relevant for recognizing pathogens and activating innate immunity; STAT2 (Signal Transducer and Activator of Transcription 2, NCBI Gene ID: 6773), acting as a transcription activator within the cell nucleus: it is likely that it contributes to block interferon-alpha response by adenovirus; PTGS2 (Prostaglandin-endoperoxide Synthase 2, NCBI Gene ID: 5743), a key enzyme involved in the process of prostaglandin biosynthesis; IFIH1 (Interferon Induced with Helicase C domain 1, NCBI Gene ID: 64135), encoding MDA5, an intracellular sensor of viral RNA responsible for triggering the innate immune response: it is fundamental for activating the process of pro-inflammatory response that includes interferons, for this reason it is targeted by several virus families which are able to hinder the innate immune response by evading its specific interferon response. NCBI Genesuggested: NoneResults 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.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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