Objective:To study the genetic diversity of Murray Valley encephalitis virus(MVEV) in Australia and Papua New Guinea.Methods:MVEV envelope gene sequences were aligned using Clustal X and manual editing was performed w...Objective:To study the genetic diversity of Murray Valley encephalitis virus(MVEV) in Australia and Papua New Guinea.Methods:MVEV envelope gene sequences were aligned using Clustal X and manual editing was performed with Bioedit.ModelTest v.3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data.Maximum likelihood analysis was performed using PhyML.The phylogenetic signal of the dataset wa.s investigated by the likelihood mapping analysis.The Bayesian phylogenetic tree was built using BEAST.Results:The phylogenetic trees showed two main clades.The clade Ⅰincluding eight strains isolated from West Australia.The clade Ⅱ was characterized by at least four epidemic entries,three of which localized in Northern West Australia and one in Papua New Guinea.The estimated mean evolutionary rate value of the MVEV envelope gene wa.s0.407 × 10^(-3) substitution/site/year(95%HPD:0.623 × 10~4-0.780× 10^(-3)).Population dynamics defines a relative constant population until the year 2000.when a reduction occurred,probably due to a bottleneck.Conclusions:This study has been useful in supporting the probable connection between climate changes and viral evolution also by the vector point of view:multidisciplinary monitoring studies are important to prevent new viral epidemics inside and outside new endemic areas.展开更多
Objective: To evaluate the evolution of the pathogen Mayaro virus, causing Mayaro fever(a mosquito-borne disease) and to perform selective pressure analysis and homology modelling.Methods: Nine different datasets were...Objective: To evaluate the evolution of the pathogen Mayaro virus, causing Mayaro fever(a mosquito-borne disease) and to perform selective pressure analysis and homology modelling.Methods: Nine different datasets were built, one for each protein(from protein C to non-structural protein 4) and the last one for the complete genome. Selective pressure and homology modelling analyses were applied. Results: Two main clades(A and B) were pointed in the maximum likelihood tree. The clade A included five Brazilian sequences sampled from 1955 to 2015. The Brazilian sequence sampled in 2014 significantly clustered with the Haitian sequence sampled in 2015. The clade B included the remaining 27 sequences sampled in the Central and Southern America from 1957 to 2013. Selective pressure analysis revealed several sites under episodic diversifying selection in envelope surface glycoprotein El, non-structural protein 1 and nonstructural protein 3 with a posterior probability P≤0.01. Homology modelling showed different sites modified by selective pressure and some protein-protein interaction sites at high interaction propensity. Conclusion: Maximum likelihood analysis confirmed the Mayaro virus previous circulation in Haiti and the successful spread to the Caribbean and USA. Selective pressure analysis revealed a strong presence of negatively selected sites, suggesting a probable purging of deleterious polymorphisms in functional genes. Homology model showed the position 31, under selective pressure, located in the edge of the ADP-ribose binding site predicting to possess a high potential of protein-protein interaction and suggesting the possible chance for a protective vaccine,thus preventing Mayaro virus urbanization as with Chikungunya virus.展开更多
Background:Phylodynamics,the study of the interaction between epidemiological and pathogen evolutionary processes within and among populations,was originally defined in the context of rapidly evolving viruses and used...Background:Phylodynamics,the study of the interaction between epidemiological and pathogen evolutionary processes within and among populations,was originally defined in the context of rapidly evolving viruses and used to characterize transmission dynamics.The concept of phylodynamics has evolved since the early 21^(st)century,extending its reach to slower-evolving pathogens,including bacteria and fungi,and to the identification of influential factors in disease spread and pathogen population dynamics.Results:The phylodynamic approach has now become a fundamental building block for the development of comparative phylogenetic tools capable of incorporating epidemiological surveillance data with molecular sequences into a single statistical framework.These innovative tools have greatly enhanced scientific investigations of the temporal and geographical origins,evolutionary history,and ecological risk factors associated with the growth and spread of viruses such as human immunodeficiency virus(HIV),Zika,and dengue and bacteria such as Methicillin-resistant Staphylococcus aureus.Conclusions:Capitalizing on an extensive review of the literature,we discuss the evolution of the field of infectious disease epidemiology and recent accomplishments,highlighting the advancements in phylodynamics,as well as the challenges and limitations currently facing researchers studying emerging pathogen epidemics across the globe.展开更多
Background: Since its discovery in 2012, over 1700 confirmed cases of Middle East Respiratory Syndrome (MERS)have been documented worldwide and more than a third of those cases have died. While the greatest number ofc...Background: Since its discovery in 2012, over 1700 confirmed cases of Middle East Respiratory Syndrome (MERS)have been documented worldwide and more than a third of those cases have died. While the greatest number ofcases has occurred in Saudi Arabia, the recent export of MERS-coronavirus (MERS-CoV) to Republic of Korea showedthat a pandemic is a possibility that cannot be ignored. Due to the deficit of knowledge in transmissionmethodology, targeted treatment and possible vaccines, understanding this virus should be a priority. Our aim wasto combine epidemiological data from literature with genetic information from viruses sequenced around theworld to present a phylodynamic picture of MERS spread molecular level to global scale.Methods: We performed a qualitative meta-analysis of all laboratory confirmed cases worldwide to date based onliterature, with emphasis on international transmission and healthcare associated infections. In parallel, we usedpublicly available MERS-CoV genomes from GenBank to create a phylogeographic tree, detailing geospatial timelineof viral evolution.Results: Several healthcare associated outbreaks starting with the retrospectively identified hospital outbreak inJordan to the most recent outbreak in Riyadh, Saudi Arabia have occurred. MERS has also crossed many oceans,entering multiple nations in eight waves between 2012 and 2015. In this paper, the spatiotemporal history of MERScases, as documented epidemiologically, was examined by Bayesian phylogenetic analysis. Distribution ofsequences into geographic clusters and interleaving of MERS-CoV sequences from camels among those isolatedfrom humans indicated that multiple zoonotic introductions occurred in endemic nations. We also report asummary of basic reproduction numbers for MERS-CoV in humans and camels.Conclusion: Together, these analyses can help us identify factors associated with viral evolution and spread as wellas establish efficacy of infection control measures. The results are especially pertinent to countries without currentMERS-CoV endemic, since their unfamiliarity makes them particularly susceptible to uncontrollable spread of a virusthat may be imported by travelers.展开更多
This work investigates frequency distributions of strings within a text. The mathematical derivation accounts for variable alphabet size, character probabilities, and string/text lengths, under both the Bernoullian an...This work investigates frequency distributions of strings within a text. The mathematical derivation accounts for variable alphabet size, character probabilities, and string/text lengths, under both the Bernoullian and the Markovian model for string generation. The analysis is limited to the set of nonclumpable strings, that cannot overlap with them selves. Two formulae (exact and approximated) are derived, calculating the frequency distribution of a string of length m found inside a text of length n (with m 〈: n). The approximated formula has a constant complexity (in contrast to an exponential com plexity of the exact) and makes it applicable to very long texts. The proposed formulae were applied to analyze string frequencies in a portion of the human genome, and to recalculate frequencies of known repeated motif within genes, associated to genetic dis eases. A comparison with stateoftheart methods was provided. The formulae presentedhere can be of use in the statistical evaluation of specific motif frequencies within very long texts (e.g. genes or genomes) and help in characterizing motifs in pathologic conditions.展开更多
文摘Objective:To study the genetic diversity of Murray Valley encephalitis virus(MVEV) in Australia and Papua New Guinea.Methods:MVEV envelope gene sequences were aligned using Clustal X and manual editing was performed with Bioedit.ModelTest v.3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data.Maximum likelihood analysis was performed using PhyML.The phylogenetic signal of the dataset wa.s investigated by the likelihood mapping analysis.The Bayesian phylogenetic tree was built using BEAST.Results:The phylogenetic trees showed two main clades.The clade Ⅰincluding eight strains isolated from West Australia.The clade Ⅱ was characterized by at least four epidemic entries,three of which localized in Northern West Australia and one in Papua New Guinea.The estimated mean evolutionary rate value of the MVEV envelope gene wa.s0.407 × 10^(-3) substitution/site/year(95%HPD:0.623 × 10~4-0.780× 10^(-3)).Population dynamics defines a relative constant population until the year 2000.when a reduction occurred,probably due to a bottleneck.Conclusions:This study has been useful in supporting the probable connection between climate changes and viral evolution also by the vector point of view:multidisciplinary monitoring studies are important to prevent new viral epidemics inside and outside new endemic areas.
文摘Objective: To evaluate the evolution of the pathogen Mayaro virus, causing Mayaro fever(a mosquito-borne disease) and to perform selective pressure analysis and homology modelling.Methods: Nine different datasets were built, one for each protein(from protein C to non-structural protein 4) and the last one for the complete genome. Selective pressure and homology modelling analyses were applied. Results: Two main clades(A and B) were pointed in the maximum likelihood tree. The clade A included five Brazilian sequences sampled from 1955 to 2015. The Brazilian sequence sampled in 2014 significantly clustered with the Haitian sequence sampled in 2015. The clade B included the remaining 27 sequences sampled in the Central and Southern America from 1957 to 2013. Selective pressure analysis revealed several sites under episodic diversifying selection in envelope surface glycoprotein El, non-structural protein 1 and nonstructural protein 3 with a posterior probability P≤0.01. Homology modelling showed different sites modified by selective pressure and some protein-protein interaction sites at high interaction propensity. Conclusion: Maximum likelihood analysis confirmed the Mayaro virus previous circulation in Haiti and the successful spread to the Caribbean and USA. Selective pressure analysis revealed a strong presence of negatively selected sites, suggesting a probable purging of deleterious polymorphisms in functional genes. Homology model showed the position 31, under selective pressure, located in the edge of the ADP-ribose binding site predicting to possess a high potential of protein-protein interaction and suggesting the possible chance for a protective vaccine,thus preventing Mayaro virus urbanization as with Chikungunya virus.
文摘Background:Phylodynamics,the study of the interaction between epidemiological and pathogen evolutionary processes within and among populations,was originally defined in the context of rapidly evolving viruses and used to characterize transmission dynamics.The concept of phylodynamics has evolved since the early 21^(st)century,extending its reach to slower-evolving pathogens,including bacteria and fungi,and to the identification of influential factors in disease spread and pathogen population dynamics.Results:The phylodynamic approach has now become a fundamental building block for the development of comparative phylogenetic tools capable of incorporating epidemiological surveillance data with molecular sequences into a single statistical framework.These innovative tools have greatly enhanced scientific investigations of the temporal and geographical origins,evolutionary history,and ecological risk factors associated with the growth and spread of viruses such as human immunodeficiency virus(HIV),Zika,and dengue and bacteria such as Methicillin-resistant Staphylococcus aureus.Conclusions:Capitalizing on an extensive review of the literature,we discuss the evolution of the field of infectious disease epidemiology and recent accomplishments,highlighting the advancements in phylodynamics,as well as the challenges and limitations currently facing researchers studying emerging pathogen epidemics across the globe.
基金supported by the Virogenesis projectfunding from the European Union’s Horizon 2020 research and innovation program under grant agreement No.634650.
文摘Background: Since its discovery in 2012, over 1700 confirmed cases of Middle East Respiratory Syndrome (MERS)have been documented worldwide and more than a third of those cases have died. While the greatest number ofcases has occurred in Saudi Arabia, the recent export of MERS-coronavirus (MERS-CoV) to Republic of Korea showedthat a pandemic is a possibility that cannot be ignored. Due to the deficit of knowledge in transmissionmethodology, targeted treatment and possible vaccines, understanding this virus should be a priority. Our aim wasto combine epidemiological data from literature with genetic information from viruses sequenced around theworld to present a phylodynamic picture of MERS spread molecular level to global scale.Methods: We performed a qualitative meta-analysis of all laboratory confirmed cases worldwide to date based onliterature, with emphasis on international transmission and healthcare associated infections. In parallel, we usedpublicly available MERS-CoV genomes from GenBank to create a phylogeographic tree, detailing geospatial timelineof viral evolution.Results: Several healthcare associated outbreaks starting with the retrospectively identified hospital outbreak inJordan to the most recent outbreak in Riyadh, Saudi Arabia have occurred. MERS has also crossed many oceans,entering multiple nations in eight waves between 2012 and 2015. In this paper, the spatiotemporal history of MERScases, as documented epidemiologically, was examined by Bayesian phylogenetic analysis. Distribution ofsequences into geographic clusters and interleaving of MERS-CoV sequences from camels among those isolatedfrom humans indicated that multiple zoonotic introductions occurred in endemic nations. We also report asummary of basic reproduction numbers for MERS-CoV in humans and camels.Conclusion: Together, these analyses can help us identify factors associated with viral evolution and spread as wellas establish efficacy of infection control measures. The results are especially pertinent to countries without currentMERS-CoV endemic, since their unfamiliarity makes them particularly susceptible to uncontrollable spread of a virusthat may be imported by travelers.
文摘This work investigates frequency distributions of strings within a text. The mathematical derivation accounts for variable alphabet size, character probabilities, and string/text lengths, under both the Bernoullian and the Markovian model for string generation. The analysis is limited to the set of nonclumpable strings, that cannot overlap with them selves. Two formulae (exact and approximated) are derived, calculating the frequency distribution of a string of length m found inside a text of length n (with m 〈: n). The approximated formula has a constant complexity (in contrast to an exponential com plexity of the exact) and makes it applicable to very long texts. The proposed formulae were applied to analyze string frequencies in a portion of the human genome, and to recalculate frequencies of known repeated motif within genes, associated to genetic dis eases. A comparison with stateoftheart methods was provided. The formulae presentedhere can be of use in the statistical evaluation of specific motif frequencies within very long texts (e.g. genes or genomes) and help in characterizing motifs in pathologic conditions.