Understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literature
Abstract Drug resistance caused by mutations is a public health threat for existing and emerging viral diseases. A wealth of evidence about these mutations and their clinically associated phenotypes is scattered across the literature, but a comprehensive perspective is usually lacking. This work aim...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17746-3 |
| _version_ | 1811188835845931008 |
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| author | An Goto Raul Rodriguez-Esteban Sebastian H. Scharf Garrett M. Morris |
| author_facet | An Goto Raul Rodriguez-Esteban Sebastian H. Scharf Garrett M. Morris |
| author_sort | An Goto |
| collection | DOAJ |
| description | Abstract Drug resistance caused by mutations is a public health threat for existing and emerging viral diseases. A wealth of evidence about these mutations and their clinically associated phenotypes is scattered across the literature, but a comprehensive perspective is usually lacking. This work aimed to produce a clinically relevant view for the case of Hepatitis B virus (HBV) mutations by combining a chronic HBV clinical study with a compendium of genetic mutations systematically gathered from the scientific literature. We enriched clinical mutation data by systematically mining 2,472,725 scientific articles from PubMed Central in order to gather information about the HBV mutational landscape. By performing this analysis, we were able to identify mutational hotspots for each HBV genotype (A-E) and gene (C, X, P, S), as well as the location of disulfide bonds associated with these mutations. Through a modelling study, we also identified a mutation position common in both the clinical data and the literature that is located at the binding pocket for a known anti-HBV drug, namely entecavir. The results of this novel approach show the potential of integrated analyses to assist in the development of new drugs for viral diseases that are more robust to resistance. Such analyses should be of particular interest due to the increasing importance of viral resistance in established and emerging viruses, such as for newly developed drugs against SARS-CoV-2. |
| first_indexed | 2024-04-11T14:25:56Z |
| format | Article |
| id | doaj.art-c309742550b34f8fb0a789ce52afb184 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T14:25:56Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c309742550b34f8fb0a789ce52afb1842022-12-22T04:18:53ZengNature PortfolioScientific Reports2045-23222022-08-0112111110.1038/s41598-022-17746-3Understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literatureAn Goto0Raul Rodriguez-Esteban1Sebastian H. Scharf2Garrett M. Morris3Oxford Protein Informatics Group, Department of Statistics, University of OxfordRoche Innovation Center BaselRoche Innovation Center BaselOxford Protein Informatics Group, Department of Statistics, University of OxfordAbstract Drug resistance caused by mutations is a public health threat for existing and emerging viral diseases. A wealth of evidence about these mutations and their clinically associated phenotypes is scattered across the literature, but a comprehensive perspective is usually lacking. This work aimed to produce a clinically relevant view for the case of Hepatitis B virus (HBV) mutations by combining a chronic HBV clinical study with a compendium of genetic mutations systematically gathered from the scientific literature. We enriched clinical mutation data by systematically mining 2,472,725 scientific articles from PubMed Central in order to gather information about the HBV mutational landscape. By performing this analysis, we were able to identify mutational hotspots for each HBV genotype (A-E) and gene (C, X, P, S), as well as the location of disulfide bonds associated with these mutations. Through a modelling study, we also identified a mutation position common in both the clinical data and the literature that is located at the binding pocket for a known anti-HBV drug, namely entecavir. The results of this novel approach show the potential of integrated analyses to assist in the development of new drugs for viral diseases that are more robust to resistance. Such analyses should be of particular interest due to the increasing importance of viral resistance in established and emerging viruses, such as for newly developed drugs against SARS-CoV-2.https://doi.org/10.1038/s41598-022-17746-3 |
| spellingShingle | An Goto Raul Rodriguez-Esteban Sebastian H. Scharf Garrett M. Morris Understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literature Scientific Reports |
| title | Understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literature |
| title_full | Understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literature |
| title_fullStr | Understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literature |
| title_full_unstemmed | Understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literature |
| title_short | Understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literature |
| title_sort | understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literature |
| url | https://doi.org/10.1038/s41598-022-17746-3 |
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