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  1. Article ; Online: Recombination-aware phylogenetic analysis sheds light on the evolutionary origin of SARS-CoV-2.

    Esquivel Gomez, Luis Roger / Weber, Ariane / Kocher, Arthur / Kühnert, Denise

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 541

    Abstract: SARS-CoV-2 can infect human cells through the recognition of the human angiotensin-converting enzyme 2 receptor. This affinity is given by six amino acid residues located in the variable loop of the receptor binding domain (RBD) within the Spike protein. ...

    Abstract SARS-CoV-2 can infect human cells through the recognition of the human angiotensin-converting enzyme 2 receptor. This affinity is given by six amino acid residues located in the variable loop of the receptor binding domain (RBD) within the Spike protein. Genetic recombination involving bat and pangolin Sarbecoviruses, and natural selection have been proposed as possible explanations for the acquisition of the variable loop and these amino acid residues. In this study we employed Bayesian phylogenetics to jointly reconstruct the phylogeny of the RBD among human, bat and pangolin Sarbecoviruses and detect recombination events affecting this region of the genome. A recombination event involving RaTG13, the closest relative of SARS-CoV-2 that lacks five of the six residues, and an unsampled Sarbecovirus lineage was detected. This result suggests that the variable loop of the RBD didn't have a recombinant origin and the key amino acid residues were likely present in the common ancestor of SARS-CoV-2 and RaTG13, with the latter losing five of them probably as the result of recombination.
    MeSH term(s) Animals ; Humans ; SARS-CoV-2/genetics ; Phylogeny ; COVID-19 ; Chiroptera ; Pangolins ; Bayes Theorem ; Recombination, Genetic ; Amino Acids/genetics
    Chemical Substances Amino Acids
    Language English
    Publishing date 2024-01-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-50952-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Reconstructing relative transmission rates in Bayesian phylodynamics: Two-fold transmission advantage of Omicron in Berlin, Germany during December 2021.

    Weber, Ariane / Översti, Sanni / Kühnert, Denise

    Virus evolution

    2023  Volume 9, Issue 2, Page(s) vead070

    Abstract: Phylodynamic methods have lately played a key role in understanding the spread of infectious diseases. During the coronavirus disease (COVID-19) pandemic, large scale genomic surveillance has further increased the potential of dynamic inference from ... ...

    Abstract Phylodynamic methods have lately played a key role in understanding the spread of infectious diseases. During the coronavirus disease (COVID-19) pandemic, large scale genomic surveillance has further increased the potential of dynamic inference from viral genomes. With the continual emergence of novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, explicitly allowing transmission rate differences between simultaneously circulating variants in phylodynamic inference is crucial. In this study, we present and empirically validate an extension to the BEAST2 package birth-death skyline model (BDSKY), BDSKY[Formula: see text], which introduces a scaling factor for the transmission rate between independent, jointly inferred trees. In an extensive simulation study, we show that BDSKY[Formula: see text] robustly infers the relative transmission rates under different epidemic scenarios. Using publicly available genome data of SARS-CoV-2, we apply BDSKY[Formula: see text] to quantify the transmission advantage of the Omicron over the Delta variant in Berlin, Germany. We find the overall transmission rate of Omicron to be scaled by a factor of two with pronounced variation between the individual clusters of each variant. These results quantify the transmission advantage of Omicron over the previously circulating Delta variant, in a crucial period of pre-established non-pharmaceutical interventions. By inferring variant- as well as cluster-specific transmission rate scaling factors, we show the differences in transmission dynamics for each variant. This highlights the importance of incorporating lineage-specific transmission differences in phylodynamic inference.
    Language English
    Publishing date 2023-11-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/vead070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Online ; Thesis: Elucidating the (re-)emergence of human pathogens with Bayesian phylogenetics

    Esquivel Gómez, Luis Roger [Verfasser] / Krause, Johannes [Gutachter] / Kühnert, Denise [Gutachter] / Scholz, Holger [Gutachter]

    2024  

    Author's details Luis Roger Esquivel Gómez ; Gutachter: Johannes Krause, Denise Kühnert, Holger Scholz
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Friedrich-Schiller-Universität Jena
    Publishing place Jena
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  4. Article ; Online: Phylogenetic meta-analysis of chronic SARS-CoV-2 infections in immunocompromised patients shows no evidence of elevated evolutionary rates

    Oversti, Sanni / Gaul, Emily / Jensen, Bjorn-Erik Ole / Kuhnert, Denise

    bioRxiv

    Abstract: Genomic sequences from rapidly evolving pathogens, sampled over time, hold information on disease origin, transmission, and evolution. Together with their sampling times, sequences can be used to estimate the rates of molecular evolution and date ... ...

    Abstract Genomic sequences from rapidly evolving pathogens, sampled over time, hold information on disease origin, transmission, and evolution. Together with their sampling times, sequences can be used to estimate the rates of molecular evolution and date evolutionary events through molecular tip-dating. The validity of this approach, however, depends on whether detectable levels of genetic variation have accumulated over the given sampling interval, generating temporal signal. Moreover, different molecular dating methods have demonstrated varying degrees of systematic biases under different biologically realistic scenarios, such as the presence of phylo-temporal clustering. Chronic SARS-CoV-2 infection in immunocompromised patients has been linked to remarkably higher intra-host molecular rates than those of global lineages, facilitating the emergence of novel viral lineages. Yet, most studies reporting accelerated rates lack the evaluation of temporal signal or comparison of multiple methods of inference, both required to reliably estimate molecular rates. In this study, we use 26 previously published longitudinally sampled sequence series obtained from chronically infected immunocompromised patients to re-evaluate the rate of SARS-CoV-2 intrahost evolution. Using a range of methods, we analyse the strength of temporal signal and infer evolutionary rates from tip-calibrated phylogenies. Regardless of heterogeneity in rate estimates between sample series and methods, we find within-host rates to be in good agreement with rates derived from host-to-host transmission chains. Our findings suggest that when certain limitations of the methodology are disregarded, such as the underlying assumption of phylogenetic independence or the method9s sensitivity to phylo-temporal grouping, evolutionary rates can be substantially overestimated. We demonstrate that estimating within-host rates is a challenging question necessitating careful interpretation of findings. While our results do not support faster evolution across the complete viral genome during chronic SARS-CoV-2 infection, prolonged viral shedding together with relapsing viral load dynamics may nevertheless promote the emergence of new viral variants in immunocompromised patients.
    Keywords covid19
    Language English
    Publishing date 2023-11-02
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.11.01.565087
    Database COVID19

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  5. Article: Robust Phylodynamic Analysis of Genetic Sequencing Data from Structured Populations

    Scire, Jérémie / Barido-Sottani, Joëlle / Kühnert, Denise / Vaughan, Timothy G. / Stadler, Tanja

    Viruses. 2022 July 27, v. 14, no. 8

    2022  

    Abstract: The multi-type birth–death model with sampling is a phylodynamic model which enables the quantification of past population dynamics in structured populations based on phylogenetic trees. The BEAST 2 package bdmm implements an algorithm for numerically ... ...

    Abstract The multi-type birth–death model with sampling is a phylodynamic model which enables the quantification of past population dynamics in structured populations based on phylogenetic trees. The BEAST 2 package bdmm implements an algorithm for numerically computing the probability density of a phylogenetic tree given the population dynamic parameters under this model. In the initial release of bdmm, analyses were computationally limited to trees consisting of up to approximately 250 genetic samples. We implemented important algorithmic changes to bdmm which dramatically increased the number of genetic samples that could be analyzed and which improved the numerical robustness and efficiency of the calculations. Including more samples led to the improved precision of parameter estimates, particularly for structured models with a high number of inferred parameters. Furthermore, we report on several model extensions to bdmm, inspired by properties common to empirical datasets. We applied this improved algorithm to two partly overlapping datasets of the Influenza A virus HA sequences sampled around the world—one with 500 samples and the other with only 175—for comparison. We report and compare the global migration patterns and seasonal dynamics inferred from each dataset. In this way, we show the information that is gained by analyzing the bigger dataset, which became possible with the presented algorithmic changes to bdmm. In summary, bdmm allows for the robust, faster, and more general phylodynamic inference of larger datasets.
    Keywords Influenza A virus ; algorithms ; data collection ; models ; phylogeny ; population dynamics ; probability distribution
    Language English
    Dates of publication 2022-0727
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14081648
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Robust Phylodynamic Analysis of Genetic Sequencing Data from Structured Populations.

    Scire, Jérémie / Barido-Sottani, Joëlle / Kühnert, Denise / Vaughan, Timothy G / Stadler, Tanja

    Viruses

    2022  Volume 14, Issue 8

    Abstract: The multi-type birth-death model with sampling is a phylodynamic model which enables the quantification of past population dynamics in structured populations based on phylogenetic trees. The BEAST 2 ... ...

    Abstract The multi-type birth-death model with sampling is a phylodynamic model which enables the quantification of past population dynamics in structured populations based on phylogenetic trees. The BEAST 2 package
    MeSH term(s) Algorithms ; Phylogeny ; Population Dynamics
    Language English
    Publishing date 2022-07-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14081648
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Rapid incidence estimation from SARS-CoV-2 genomes reveals decreased case detection in Europe during summer 2020.

    Smith, Maureen Rebecca / Trofimova, Maria / Weber, Ariane / Duport, Yannick / Kühnert, Denise / von Kleist, Max

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 6009

    Abstract: By October 2021, 230 million SARS-CoV-2 diagnoses have been reported. Yet, a considerable proportion of cases remains undetected. Here, we propose GInPipe, a method that rapidly reconstructs SARS-CoV-2 incidence profiles solely from publicly available, ... ...

    Abstract By October 2021, 230 million SARS-CoV-2 diagnoses have been reported. Yet, a considerable proportion of cases remains undetected. Here, we propose GInPipe, a method that rapidly reconstructs SARS-CoV-2 incidence profiles solely from publicly available, time-stamped viral genomes. We validate GInPipe against simulated outbreaks and elaborate phylodynamic analyses. Using available sequence data, we reconstruct incidence histories for Denmark, Scotland, Switzerland, and Victoria (Australia) and demonstrate, how to use the method to investigate the effects of changing testing policies on case ascertainment. Specifically, we find that under-reporting was highest during summer 2020 in Europe, coinciding with more liberal testing policies at times of low testing capacities. Due to the increased use of real-time sequencing, it is envisaged that GInPipe can complement established surveillance tools to monitor the SARS-CoV-2 pandemic. In post-pandemic times, when diagnostic efforts are decreasing, GInPipe may facilitate the detection of hidden infection dynamics.
    MeSH term(s) COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19/history ; Europe/epidemiology ; Genome, Viral ; History, 21st Century ; Humans ; Incidence ; Pandemics ; Phylogeny ; SARS-CoV-2/classification ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Scotland ; Switzerland ; Victoria
    Language English
    Publishing date 2021-10-14
    Publishing country England
    Document type Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-26267-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Molecular Epidemiology and Transmission Dynamics of the HIV-1 Epidemic in Ethiopia: Epidemic Decline Coincided With Behavioral Interventions Before ART Scale-Up.

    Arimide, Dawit Assefa / Esquivel-Gómez, Luis Roger / Kebede, Yenew / Sasinovich, Sviataslau / Balcha, Taye / Björkman, Per / Kühnert, Denise / Medstrand, Patrik

    Frontiers in microbiology

    2022  Volume 13, Page(s) 821006

    Abstract: Background: Ethiopia is one of the sub-Saharan countries hit hard by the HIV epidemic. Previous studies have shown that subtype C dominates the Ethiopian HIV-1 epidemic, but the evolutionary and temporal dynamics of HIV-1 in Ethiopia have not been ... ...

    Abstract Background: Ethiopia is one of the sub-Saharan countries hit hard by the HIV epidemic. Previous studies have shown that subtype C dominates the Ethiopian HIV-1 epidemic, but the evolutionary and temporal dynamics of HIV-1 in Ethiopia have not been closely scrutinized. Understanding the evolutionary and epidemiological pattern of HIV is vital to monitor the spread, evaluate and implement HIV prevention strategies.
    Methods: We analyzed 1,276 Ethiopian HIV-1 subtype C polymerase (
    Results: Our analysis revealed that the Ethiopian HIV-1 epidemic originated from two independent introductions at the beginning of the 1970s and 1980s from eastern and southern African countries, respectively, followed by epidemic growth reaching its maximum in the early 1990s. We identified three large clusters with a majority of Ethiopian sequences. Phylodynamic analyses revealed that all three clusters were characterized by high transmission rates during the early epidemic, followed by a decline in HIV-1 transmissions after 1990. R
    Conclusion: The rapid decline in the HIV epidemic took place a decade before introducing antiretroviral therapy in Ethiopia and coincided with early behavioral, preventive, and awareness interventions implemented in the country. Our findings highlight the importance of behavioral interventions and antiretroviral therapy scale-up to halt and maintain HIV transmissions at low levels (R
    Language English
    Publishing date 2022-02-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2022.821006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Phylogenetic analysis of the origin and spread of plague in Madagascar.

    Esquivel Gomez, Luis Roger / Savin, Cyril / Andrianaivoarimanana, Voahangy / Rahajandraibe, Soloandry / Randriantseheno, Lovasoa Nomena / Zhou, Zhemin / Kocher, Arthur / Didelot, Xavier / Rajerison, Minoarisoa / Kühnert, Denise

    PLoS neglected tropical diseases

    2023  Volume 17, Issue 5, Page(s) e0010362

    Abstract: Background: Plague is a zoonotic disease caused by the bacterium Yersinia pestis, highly prevalent in the Central Highlands, a mountainous region in the center of Madagascar. After a plague-free period of over 60 years in the northwestern coast city of ... ...

    Abstract Background: Plague is a zoonotic disease caused by the bacterium Yersinia pestis, highly prevalent in the Central Highlands, a mountainous region in the center of Madagascar. After a plague-free period of over 60 years in the northwestern coast city of Mahajanga, the disease reappeared in 1991 and caused several outbreaks until 1999. Previous research indicates that the disease was reintroduced to the city of Mahajanga from the Central Highlands instead of reemerging from a local reservoir. However, it is not clear how many reintroductions occurred and when they took place.
    Methodology/principal findings: In this study we applied a Bayesian phylogeographic model to detect and date migrations of Y. pestis between the two locations that could be linked to the re-emergence of plague in Mahajanga. Genome sequences of 300 Y. pestis strains sampled between 1964 and 2012 were analyzed. Four migrations from the Central Highlands to Mahajanga were detected. Two resulted in persistent transmission in humans, one was responsible for most of the human cases recorded between 1995 and 1999, while the other produced plague cases in 1991 and 1992. We dated the emergence of the Y. pestis sub-branch 1.ORI3, which is only present in Madagascar and Turkey, to the beginning of the 20th century, using a Bayesian molecular dating analysis. The split between 1.ORI3 and its ancestor lineage 1.ORI2 was dated to the second half of the 19th century.
    Conclusions/significance: Our results indicate that two independent migrations from the Central Highlands caused the plague outbreaks in Mahajanga during the 1990s, with both introductions occurring during the early 1980s. They happened over a decade before the detection of human cases, thus the pathogen likely survived in wild reservoirs until the spillover to humans was possible. This study demonstrates the value of Bayesian phylogenetics in elucidating the re-emergence of infectious diseases.
    MeSH term(s) Animals ; Humans ; Phylogeny ; Madagascar/epidemiology ; Bayes Theorem ; Zoonoses ; Phylogeography ; Yersinia pestis/genetics
    Language English
    Publishing date 2023-05-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0010362
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Importations of SARS-CoV-2 lineages decline after nonpharmaceutical interventions in phylogeographic analyses

    Goliaei, Sama / Foroughmand-Araabi, Mohammad-Hadi / Roddy, Aideen / Weber, Ariane / Oeversti, Sanni / Kuehnert, Denise / McHardy, Alice Carolyn

    medRxiv

    Abstract: The onset of the SARS-CoV-2 pandemic marked a period of substantial challenges as the virus and its variants rapidly spread, placing enormous strain on both society and healthcare systems. Prior to the widespread availability of vaccines, non- ... ...

    Abstract The onset of the SARS-CoV-2 pandemic marked a period of substantial challenges as the virus and its variants rapidly spread, placing enormous strain on both society and healthcare systems. Prior to the widespread availability of vaccines, non-pharmaceutical interventions such as reducing contacts, antigenic testing, or travel restrictions were the primary means of reducing viral transmission and case numbers, and quantifying the success of these measures is therefore key for future pandemic preparedness. Using SARS-CoV-2 genomes collected in systematic surveillance, we studied lineage importations for the third, pandemic wave in Germany, employing a large-scale Bayesian phylogenetic and phylogeographic analysis coupled to a longitudinal assessment of lineage importation dynamics over multiple sampling strategies. We evaluated the effect of twelve major nationwide nonpharmaceutical interventions (NPIs) on lineage importations and dissemination within the country. All NPIs were followed by reduced lineage importations, with the most substantial decreases seen for the provision of free rapid tests, the strengthening of regulations on mask-wearing in public transport and stores, as well as on internal movements and gatherings. Most SARS-CoV-2 lineages first appeared in the three states with the largest populations and most cases, and from there spread within the country. Importations began to rise before and peaked shortly after the Christmas holidays. Analysis of SARS-CoV-2 data revealed the substantial effects of free rapid tests and obligatory medical/surgical mask-wearing, suggesting these as key for pandemic preparedness, given their relatively few, negative socioeconomic effects. The approach quantifies the relationships between environmental factors at the host population level to viral lineage dissemination from genomic surveillance data, facilitating similar analyses of rapidly evolving pathogens in the future.
    Keywords covid19
    Language English
    Publishing date 2023-11-10
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2023.11.10.23298337
    Database COVID19

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