vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding
Abstract Background As antibiotic resistance creates a significant global health threat, we need not only to accelerate the development of novel antibiotics but also to develop better treatment strategies using existing drugs to improve their efficacy and prevent the selection of further resistance....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12859-021-04536-3 |
| _version_ | 1798034507834589184 |
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| author | Vi Ngoc-Nha Tran Alireza Shams Sinan Ascioglu Antal Martinecz Jingyi Liang Fabrizio Clarelli Rafal Mostowy Ted Cohen Pia Abel zur Wiesch |
| author_facet | Vi Ngoc-Nha Tran Alireza Shams Sinan Ascioglu Antal Martinecz Jingyi Liang Fabrizio Clarelli Rafal Mostowy Ted Cohen Pia Abel zur Wiesch |
| author_sort | Vi Ngoc-Nha Tran |
| collection | DOAJ |
| description | Abstract Background As antibiotic resistance creates a significant global health threat, we need not only to accelerate the development of novel antibiotics but also to develop better treatment strategies using existing drugs to improve their efficacy and prevent the selection of further resistance. We require new tools to rationally design dosing regimens from data collected in early phases of antibiotic and dosing development. Mathematical models such as mechanistic pharmacodynamic drug-target binding explain mechanistic details of how the given drug concentration affects its targeted bacteria. However, there are no available tools in the literature that allow non-quantitative scientists to develop computational models to simulate antibiotic-target binding and its effects on bacteria. Results In this work, we have devised an extension of a mechanistic binding-kinetic model to incorporate clinical drug concentration data. Based on the extended model, we develop a novel and interactive web-based tool that allows non-quantitative scientists to create and visualize their own computational models of bacterial antibiotic target-binding based on their considered drugs and bacteria. We also demonstrate how Rifampicin affects bacterial populations of Tuberculosis bacteria using our vCOMBAT tool. Conclusions The vCOMBAT online tool is publicly available at https://combat-bacteria.org/ . |
| first_indexed | 2024-04-11T20:45:08Z |
| format | Article |
| id | doaj.art-3dd0590bae834732ad088cd1ab86823b |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-04-11T20:45:08Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-3dd0590bae834732ad088cd1ab86823b2022-12-22T04:04:03ZengBMCBMC Bioinformatics1471-21052022-01-0123111510.1186/s12859-021-04536-3vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-bindingVi Ngoc-Nha Tran0Alireza Shams1Sinan Ascioglu2Antal Martinecz3Jingyi Liang4Fabrizio Clarelli5Rafal Mostowy6Ted Cohen7Pia Abel zur Wiesch8Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of NorwayPolytechnique MontréalIntegrated Digital Media Department, New York UniversityDepartment of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of NorwayDepartment of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of NorwayDepartment of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of NorwayMalopolska Centre of Biotechnology, Jagiellonian UniversityDepartment of Epidemiology of Microbial Diseases, Yale School of Public HealthDepartment of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of NorwayAbstract Background As antibiotic resistance creates a significant global health threat, we need not only to accelerate the development of novel antibiotics but also to develop better treatment strategies using existing drugs to improve their efficacy and prevent the selection of further resistance. We require new tools to rationally design dosing regimens from data collected in early phases of antibiotic and dosing development. Mathematical models such as mechanistic pharmacodynamic drug-target binding explain mechanistic details of how the given drug concentration affects its targeted bacteria. However, there are no available tools in the literature that allow non-quantitative scientists to develop computational models to simulate antibiotic-target binding and its effects on bacteria. Results In this work, we have devised an extension of a mechanistic binding-kinetic model to incorporate clinical drug concentration data. Based on the extended model, we develop a novel and interactive web-based tool that allows non-quantitative scientists to create and visualize their own computational models of bacterial antibiotic target-binding based on their considered drugs and bacteria. We also demonstrate how Rifampicin affects bacterial populations of Tuberculosis bacteria using our vCOMBAT tool. Conclusions The vCOMBAT online tool is publicly available at https://combat-bacteria.org/ .https://doi.org/10.1186/s12859-021-04536-3Web-based toolComputational modelAntibioticPharmacodynamicsPharmacokineticsBinding kinetics |
| spellingShingle | Vi Ngoc-Nha Tran Alireza Shams Sinan Ascioglu Antal Martinecz Jingyi Liang Fabrizio Clarelli Rafal Mostowy Ted Cohen Pia Abel zur Wiesch vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding BMC Bioinformatics Web-based tool Computational model Antibiotic Pharmacodynamics Pharmacokinetics Binding kinetics |
| title | vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding |
| title_full | vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding |
| title_fullStr | vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding |
| title_full_unstemmed | vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding |
| title_short | vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding |
| title_sort | vcombat a novel tool to create and visualize a computational model of bacterial antibiotic target binding |
| topic | Web-based tool Computational model Antibiotic Pharmacodynamics Pharmacokinetics Binding kinetics |
| url | https://doi.org/10.1186/s12859-021-04536-3 |
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