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  1. Article: MASCOT-Skyline integrates population and migration dynamics to enhance phylogeographic reconstructions.

    Müller, Nicola F / Bouckaert, Remco R / Wu, Chieh-Hsi / Bedford, Trevor

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The spread of infectious diseases is shaped by spatial and temporal aspects, such as host population structure or changes in the transmission rate or number of infected individuals over time. These spatiotemporal dynamics are imprinted in the genome of ... ...

    Abstract The spread of infectious diseases is shaped by spatial and temporal aspects, such as host population structure or changes in the transmission rate or number of infected individuals over time. These spatiotemporal dynamics are imprinted in the genome of pathogens and can be recovered from those genomes using phylodynamics methods. However, phylodynamic methods typically quantify either the temporal or spatial transmission dynamics, which leads to unclear biases, as one can potentially not be inferred without the other. Here, we address this challenge by introducing a structured coalescent skyline approach, MASCOT-Skyline that allows us to jointly infer spatial and temporal transmission dynamics of infectious diseases using Markov chain Monte Carlo inference. To do so, we model the effective population size dynamics in different locations using a non-parametric function, allowing us to approximate a range of population size dynamics. We show, using a range of different viral outbreak datasets, potential issues with phylogeographic methods. We then use these viral datasets to motivate simulations of outbreaks that illuminate the nature of biases present in the different phylogeographic methods. We show that spatial and temporal dynamics should be modeled jointly even if one seeks to recover just one of the two. Further, we showcase conditions under which we can expect phylogeographic analyses to be biased, particularly different subsampling approaches, as well as provide recommendations of when we can expect them to perform well. We implemented MASCOT-Skyline as part of the open-source software package MASCOT for the Bayesian phylodynamics platform BEAST2.
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.06.583734
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: State-dependent evolutionary models reveal modes of solid tumour growth.

    Lewinsohn, Maya A / Bedford, Trevor / Müller, Nicola F / Feder, Alison F

    Nature ecology & evolution

    2023  Volume 7, Issue 4, Page(s) 581–596

    Abstract: Spatial properties of tumour growth have profound implications for cancer progression, therapeutic resistance and metastasis. Yet, how spatial position governs tumour cell division remains difficult to evaluate in clinical tumours. Here, we demonstrate ... ...

    Abstract Spatial properties of tumour growth have profound implications for cancer progression, therapeutic resistance and metastasis. Yet, how spatial position governs tumour cell division remains difficult to evaluate in clinical tumours. Here, we demonstrate that faster division on the tumour periphery leaves characteristic genetic patterns, which become evident when a phylogenetic tree is reconstructed from spatially sampled cells. Namely, rapidly dividing peripheral lineages branch more extensively and acquire more mutations than slower-dividing centre lineages. We develop a Bayesian state-dependent evolutionary phylodynamic model (SDevo) that quantifies these patterns to infer the differential division rates between peripheral and central cells. We demonstrate that this approach accurately infers spatially varying birth rates of simulated tumours across a range of growth conditions and sampling strategies. We then show that SDevo outperforms state-of-the-art, non-cancer multi-state phylodynamic methods that ignore differential sequence evolution. Finally, we apply SDevo to single-time-point, multi-region sequencing data from clinical hepatocellular carcinomas and find evidence of a three- to six-times-higher division rate on the tumour edge. With the increasing availability of high-resolution, multi-region sequencing, we anticipate that SDevo will be useful in interrogating spatial growth restrictions and could be extended to model non-spatial factors that influence tumour progression.
    MeSH term(s) Humans ; Phylogeny ; Bayes Theorem ; Neoplasms/genetics
    Language English
    Publishing date 2023-03-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2397-334X
    ISSN (online) 2397-334X
    DOI 10.1038/s41559-023-02000-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A Bayesian approach to infer recombination patterns in coronaviruses.

    Müller, Nicola F / Kistler, Kathryn E / Bedford, Trevor

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 4186

    Abstract: As shown during the SARS-CoV-2 pandemic, phylogenetic and phylodynamic methods are essential tools to study the spread and evolution of pathogens. One of the central assumptions of these methods is that the shared history of pathogens isolated from ... ...

    Abstract As shown during the SARS-CoV-2 pandemic, phylogenetic and phylodynamic methods are essential tools to study the spread and evolution of pathogens. One of the central assumptions of these methods is that the shared history of pathogens isolated from different hosts can be described by a branching phylogenetic tree. Recombination breaks this assumption. This makes it problematic to apply phylogenetic methods to study recombining pathogens, including, for example, coronaviruses. Here, we introduce a Markov chain Monte Carlo approach that allows inference of recombination networks from genetic sequence data under a template switching model of recombination. Using this method, we first show that recombination is extremely common in the evolutionary history of SARS-like coronaviruses. We then show how recombination rates across the genome of the human seasonal coronaviruses 229E, OC43 and NL63 vary with rates of adaptation. This suggests that recombination could be beneficial to fitness of human seasonal coronaviruses. Additionally, this work sets the stage for Bayesian phylogenetic tracking of the spread and evolution of SARS-CoV-2 in the future, even as recombinant viruses become prevalent.
    MeSH term(s) Bayes Theorem ; COVID-19 ; Coronavirus 229E, Human ; Humans ; Phylogeny ; Recombination, Genetic ; SARS-CoV-2/genetics
    Language English
    Publishing date 2022-07-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-31749-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Recombination patterns in coronaviruses.

    Müller, Nicola F / Kistler, Kathryn E / Bedford, Trevor

    bioRxiv : the preprint server for biology

    2022  

    Abstract: As shown during the SARS-CoV-2 pandemic, phylogenetic and phylodynamic methods are essential tools to study the spread and evolution of pathogens. One of the central assumptions of these methods is that the shared history of pathogens isolated from ... ...

    Abstract As shown during the SARS-CoV-2 pandemic, phylogenetic and phylodynamic methods are essential tools to study the spread and evolution of pathogens. One of the central assumptions of these methods is that the shared history of pathogens isolated from different hosts can be described by a branching phylogenetic tree. Recombination breaks this assumption. This makes it problematic to apply phylogenetic methods to study recombining pathogens, including, for example, coronaviruses. Here, we introduce a Markov chain Monte Carlo approach that allows inference of recombination networks from genetic sequence data under a template switching model of recombination. Using this method, we first show that recombination is extremely common in the evolutionary history of SARS-like coronaviruses. We then show how recombination rates across the genome of the human seasonal coronaviruses 229E, OC43 and NL63 vary with rates of adaptation. This suggests that recombination could be beneficial to fitness of human seasonal coronaviruses. Additionally, this work sets the stage for Bayesian phylogenetic tracking of the spread and evolution of SARS-CoV-2 in the future, even as recombinant viruses become prevalent.
    Language English
    Publishing date 2022-02-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.04.28.441806
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Adaptive Metropolis-coupled MCMC for BEAST 2.

    Müller, Nicola F / Bouckaert, Remco R

    PeerJ

    2020  Volume 8, Page(s) e9473

    Abstract: With ever more complex models used to study evolutionary patterns, approaches that facilitate efficient inference under such models are needed. Metropolis-coupled Markov chain Monte Carlo (MCMC) has long been used to speed up phylogenetic analyses and to ...

    Abstract With ever more complex models used to study evolutionary patterns, approaches that facilitate efficient inference under such models are needed. Metropolis-coupled Markov chain Monte Carlo (MCMC) has long been used to speed up phylogenetic analyses and to make use of multi-core CPUs. Metropolis-coupled MCMC essentially runs multiple MCMC chains in parallel. All chains are heated except for one cold chain that explores the posterior probability space like a regular MCMC chain. This heating allows chains to make bigger jumps in phylogenetic state space. The heated chains can then be used to propose new states for other chains, including the cold chain. One of the practical challenges using this approach, is to find optimal temperatures of the heated chains to efficiently explore state spaces. We here provide an adaptive Metropolis-coupled MCMC scheme to Bayesian phylogenetics, where the temperature difference between heated chains is automatically tuned to achieve a target acceptance probability of states being exchanged between individual chains. We first show the validity of this approach by comparing inferences of adaptive Metropolis-coupled MCMC to MCMC on several datasets. We then explore where Metropolis-coupled MCMC provides benefits over MCMC. We implemented this adaptive Metropolis-coupled MCMC approach as an open source package licenced under GPL 3.0 to the Bayesian phylogenetics software BEAST 2, available from https://github.com/nicfel/CoupledMCMC.
    Language English
    Publishing date 2020-09-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.9473
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Application of phylodynamics to identify spread of antimicrobial-resistant Escherichia coli between humans and canines in an urban environment.

    Walas, Nikolina / Müller, Nicola F / Parker, Emily / Henderson, Abigail / Capone, Drew / Brown, Joe / Barker, Troy / Graham, Jay P

    The Science of the total environment

    2024  Volume 916, Page(s) 170139

    Abstract: The transmission of antimicrobial resistant bacteria in the urban environment is poorly understood. We utilized genomic sequencing and phylogenetics to characterize the transmission dynamics of antimicrobial resistant Escherichia coli (AMR-Ec) cultured ... ...

    Abstract The transmission of antimicrobial resistant bacteria in the urban environment is poorly understood. We utilized genomic sequencing and phylogenetics to characterize the transmission dynamics of antimicrobial resistant Escherichia coli (AMR-Ec) cultured from putative canine (canine
    MeSH term(s) Animals ; Humans ; Dogs ; Escherichia coli ; Escherichia coli Infections/epidemiology ; Bayes Theorem ; Anti-Bacterial Agents/pharmacology ; Anti-Infective Agents ; Drug Resistance, Bacterial/genetics
    Chemical Substances Anti-Bacterial Agents ; Anti-Infective Agents
    Language English
    Publishing date 2024-01-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2024.170139
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Joint Inference of Migration and Reassortment Patterns for Viruses with Segmented Genomes.

    Stolz, Ugnė / Stadler, Tanja / Müller, Nicola F / Vaughan, Timothy G

    Molecular biology and evolution

    2021  Volume 39, Issue 1

    Abstract: The structured coalescent allows inferring migration patterns between viral subpopulations from genetic sequence data. However, these analyses typically assume that no genetic recombination process impacted the sequence evolution of pathogens. For ... ...

    Abstract The structured coalescent allows inferring migration patterns between viral subpopulations from genetic sequence data. However, these analyses typically assume that no genetic recombination process impacted the sequence evolution of pathogens. For segmented viruses, such as influenza, that can undergo reassortment this assumption is broken. Reassortment reshuffles the segments of different parent lineages upon a coinfection event, which means that the shared history of viruses has to be represented by a network instead of a tree. Therefore, full genome analyses of such viruses are complex or even impossible. Although this problem has been addressed for unstructured populations, it is still impossible to account for population structure, such as induced by different host populations, whereas also accounting for reassortment. We address this by extending the structured coalescent to account for reassortment and present a framework for investigating possible ties between reassortment and migration (host jump) events. This method can accurately estimate subpopulation dependent effective populations sizes, reassortment, and migration rates from simulated data. Additionally, we apply the new model to avian influenza A/H5N1 sequences, sampled from two avian host types, Anseriformes and Galliformes. We contrast our results with a structured coalescent without reassortment inference, which assumes independently evolving segments. This reveals that taking into account segment reassortment and using sequencing data from several viral segments for joint phylodynamic inference leads to different estimates for effective population sizes, migration, and clock rates. This new model is implemented as the Structured Coalescent with Reassortment package for BEAST 2.5 and is available at https://github.com/jugne/SCORE.
    MeSH term(s) Animals ; Genome, Viral ; Humans ; Influenza A Virus, H5N1 Subtype/genetics ; Influenza, Human ; Phylogeny ; Reassortant Viruses/genetics
    Language English
    Publishing date 2021-12-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 998579-7
    ISSN 1537-1719 ; 0737-4038
    ISSN (online) 1537-1719
    ISSN 0737-4038
    DOI 10.1093/molbev/msab342
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Phylodynamics Uncovers the Transmission of Antibiotic-Resistant

    Walas, Nikolina / Müller, Nicola F / Parker, Emily / Henderson, Abigail / Capone, Drew / Brown, Joe / Barker, Troy / Graham, Jay P

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The role of canines in transmitting antibiotic resistant bacteria to humans in the urban environment is poorly understood. To elucidate this role, we utilized genomic sequencing and phylogenetics to characterize the burden and transmission dynamics of ... ...

    Abstract The role of canines in transmitting antibiotic resistant bacteria to humans in the urban environment is poorly understood. To elucidate this role, we utilized genomic sequencing and phylogenetics to characterize the burden and transmission dynamics of antibiotic resistant
    Language English
    Publishing date 2023-06-01
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.01.543064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Impact and mitigation of sampling bias to determine viral spread: Evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations.

    Layan, Maylis / Müller, Nicola F / Dellicour, Simon / De Maio, Nicola / Bourhy, Hervé / Cauchemez, Simon / Baele, Guy

    Virus evolution

    2023  Volume 9, Issue 1, Page(s) vead010

    Abstract: Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies, which enables reconstruction of the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling ... ...

    Abstract Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies, which enables reconstruction of the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (Bayesian structured coalescent approximation [BASTA] and marginal approximation of the structured coalescent [MASCOT]). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on the simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for the CTMC model. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for the CTMC model, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing the sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data.
    Language English
    Publishing date 2023-02-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/vead010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Inferring time-dependent migration and coalescence patterns from genetic sequence and predictor data in structured populations.

    Müller, Nicola F / Dudas, Gytis / Stadler, Tanja

    Virus evolution

    2019  Volume 5, Issue 2, Page(s) vez030

    Abstract: Population dynamics can be inferred from genetic sequence data by using phylodynamic methods. These methods typically quantify the dynamics in unstructured populations or assume migration rates and effective population sizes to be constant through time ... ...

    Abstract Population dynamics can be inferred from genetic sequence data by using phylodynamic methods. These methods typically quantify the dynamics in unstructured populations or assume migration rates and effective population sizes to be constant through time in structured populations. When considering rates to vary through time in structured populations, the number of parameters to infer increases rapidly and the available data might not be sufficient to inform these. Additionally, it is often of interest to know what predicts these parameters rather than knowing the parameters themselves. Here, we introduce a method to  infer the predictors for time-varying migration rates and effective population sizes by using a generalized linear model (GLM) approach under the marginal approximation of the structured coalescent. Using simulations, we show that our approach is able to reliably infer the model parameters and its predictors from phylogenetic trees. Furthermore, when simulating trees under the structured coalescent, we show that our new approach outperforms the discrete trait GLM model. We then apply our framework to a previously described Ebola virus dataset, where we infer the parameters and its predictors from genome sequences while accounting for phylogenetic uncertainty. We infer weekly cases to be the strongest predictor for effective population size and geographic distance the strongest predictor for migration. This approach is implemented as part of the BEAST2 package MASCOT, which allows us to jointly infer population dynamics, i.e. the parameters and predictors, within structured populations, the phylogenetic tree, and evolutionary parameters.
    Language English
    Publishing date 2019-08-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/vez030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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