Characterizing viral within-host diversity in fast and non-equilibrium demo-genetic dynamics
High-throughput sequencing has opened the route for a deep assessment of within-host genetic diversity that can be used, e.g., to characterize microbial communities and to infer transmission links in infectious disease outbreaks. The performance of such characterizations and inferences cannot be ana...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.983938/full |
| _version_ | 1811243064724815872 |
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| author | Maryam Alamil Maryam Alamil Gaël Thébaud Karine Berthier Samuel Soubeyrand |
| author_facet | Maryam Alamil Maryam Alamil Gaël Thébaud Karine Berthier Samuel Soubeyrand |
| author_sort | Maryam Alamil |
| collection | DOAJ |
| description | High-throughput sequencing has opened the route for a deep assessment of within-host genetic diversity that can be used, e.g., to characterize microbial communities and to infer transmission links in infectious disease outbreaks. The performance of such characterizations and inferences cannot be analytically assessed in general and are often grounded on computer-intensive evaluations. Then, being able to simulate within-host genetic diversity across time under various demo-genetic assumptions is paramount to assess the performance of the approaches of interest. In this context, we built an original model that can be simulated to investigate the temporal evolution of genotypes and their frequencies under various demo-genetic assumptions. The model describes the growth and the mutation of genotypes at the nucleotide resolution conditional on an overall within-host viral kinetics, and can be tuned to generate fast non-equilibrium demo-genetic dynamics. We ran simulations of this model and computed classic diversity indices to characterize the temporal variation of within-host genetic diversity (from high-throughput amplicon sequences) of virus populations under three demographic kinetic models of viral infection. Our results highlight how demographic (viral load) and genetic (mutation, selection, or drift) factors drive variations in within-host diversity during the course of an infection. In particular, we observed a non-monotonic relationship between pathogen population size and genetic diversity, and a reduction of the impact of mutation on diversity when a non-specific host immune response is activated. The large variation in the diversity patterns generated in our simulations suggests that the underlying model provides a flexible basis to produce very diverse demo-genetic scenarios and test, for instance, methods for the inference of transmission links during outbreaks. |
| first_indexed | 2024-04-12T13:59:41Z |
| format | Article |
| id | doaj.art-5145641ff2784780be004123500a3433 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T13:59:41Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-5145641ff2784780be004123500a34332022-12-22T03:30:14ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-10-011310.3389/fmicb.2022.983938983938Characterizing viral within-host diversity in fast and non-equilibrium demo-genetic dynamicsMaryam Alamil0Maryam Alamil1Gaël Thébaud2Karine Berthier3Samuel Soubeyrand4INRAE, BioSP, Avignon, FranceDepartment of Mathematics and Computer Science, Alfaisal University, Riyadh, Saudi ArabiaPHIM Plant Health Institute, INRAE, Univ Montpellier, CIRAD, Institut Agro, IRD, Montpellier, FranceINRAE, Pathologie Végétale, Montfavet, FranceINRAE, BioSP, Avignon, FranceHigh-throughput sequencing has opened the route for a deep assessment of within-host genetic diversity that can be used, e.g., to characterize microbial communities and to infer transmission links in infectious disease outbreaks. The performance of such characterizations and inferences cannot be analytically assessed in general and are often grounded on computer-intensive evaluations. Then, being able to simulate within-host genetic diversity across time under various demo-genetic assumptions is paramount to assess the performance of the approaches of interest. In this context, we built an original model that can be simulated to investigate the temporal evolution of genotypes and their frequencies under various demo-genetic assumptions. The model describes the growth and the mutation of genotypes at the nucleotide resolution conditional on an overall within-host viral kinetics, and can be tuned to generate fast non-equilibrium demo-genetic dynamics. We ran simulations of this model and computed classic diversity indices to characterize the temporal variation of within-host genetic diversity (from high-throughput amplicon sequences) of virus populations under three demographic kinetic models of viral infection. Our results highlight how demographic (viral load) and genetic (mutation, selection, or drift) factors drive variations in within-host diversity during the course of an infection. In particular, we observed a non-monotonic relationship between pathogen population size and genetic diversity, and a reduction of the impact of mutation on diversity when a non-specific host immune response is activated. The large variation in the diversity patterns generated in our simulations suggests that the underlying model provides a flexible basis to produce very diverse demo-genetic scenarios and test, for instance, methods for the inference of transmission links during outbreaks.https://www.frontiersin.org/articles/10.3389/fmicb.2022.983938/fulldiversity indicesgenome evolutionkinetic modelsimulation modelvirus evolutionwithin-host pathogen diversity |
| spellingShingle | Maryam Alamil Maryam Alamil Gaël Thébaud Karine Berthier Samuel Soubeyrand Characterizing viral within-host diversity in fast and non-equilibrium demo-genetic dynamics Frontiers in Microbiology diversity indices genome evolution kinetic model simulation model virus evolution within-host pathogen diversity |
| title | Characterizing viral within-host diversity in fast and non-equilibrium demo-genetic dynamics |
| title_full | Characterizing viral within-host diversity in fast and non-equilibrium demo-genetic dynamics |
| title_fullStr | Characterizing viral within-host diversity in fast and non-equilibrium demo-genetic dynamics |
| title_full_unstemmed | Characterizing viral within-host diversity in fast and non-equilibrium demo-genetic dynamics |
| title_short | Characterizing viral within-host diversity in fast and non-equilibrium demo-genetic dynamics |
| title_sort | characterizing viral within host diversity in fast and non equilibrium demo genetic dynamics |
| topic | diversity indices genome evolution kinetic model simulation model virus evolution within-host pathogen diversity |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.983938/full |
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