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1.
Bioinformatics ; 36(10): 3286-3287, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32022854

RESUMO

MOTIVATION: Approximate Bayesian computation (ABC) is an important framework within which to infer the structure and parameters of a systems biology model. It is especially suitable for biological systems with stochastic and nonlinear dynamics, for which the likelihood functions are intractable. However, the associated computational cost often limits ABC to models that are relatively quick to simulate in practice. RESULTS: We here present a Julia package, GpABC, that implements parameter inference and model selection for deterministic or stochastic models using (i) standard rejection ABC or sequential Monte Carlo ABC or (ii) ABC with Gaussian process emulation. The latter significantly reduces the computational cost. AVAILABILITY AND IMPLEMENTATION: https://github.com/tanhevg/GpABC.jl.


Assuntos
Biologia de Sistemas , Teorema de Bayes , Simulação por Computador , Funções Verossimilhança , Método de Monte Carlo , Distribuição Normal
3.
Commun Biol ; 7(1): 171, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347162

RESUMO

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.


Assuntos
Bactérias , Mucosa , Humanos , Mucosa/microbiologia , Bactérias/genética , Simbiose , Imunidade nas Mucosas , Genômica
4.
Science ; 371(6536)2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33531384

RESUMO

After initial declines, in mid-2020 a resurgence in transmission of novel coronavirus disease (COVID-19) occurred in the United States and Europe. As efforts to control COVID-19 disease are reintensified, understanding the age demographics driving transmission and how these affect the loosening of interventions is crucial. We analyze aggregated, age-specific mobility trends from more than 10 million individuals in the United States and link these mechanistically to age-specific COVID-19 mortality data. We estimate that as of October 2020, individuals aged 20 to 49 are the only age groups sustaining resurgent SARS-CoV-2 transmission with reproduction numbers well above one and that at least 65 of 100 COVID-19 infections originate from individuals aged 20 to 49 in the United States. Targeting interventions-including transmission-blocking vaccines-to adults aged 20 to 49 is an important consideration in halting resurgent epidemics and preventing COVID-19-attributable deaths.


Assuntos
COVID-19/epidemiologia , COVID-19/transmissão , Epidemias , Adolescente , Adulto , Fatores Etários , Número Básico de Reprodução , COVID-19/mortalidade , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Telefone Celular , Criança , Pré-Escolar , Controle de Doenças Transmissíveis , Epidemias/prevenção & controle , Humanos , Lactente , Pessoa de Meia-Idade , Modelos Teóricos , Pandemias/prevenção & controle , Instituições Acadêmicas , Estados Unidos/epidemiologia , Adulto Jovem
5.
Nat Commun ; 11(1): 6189, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33273462

RESUMO

As of 1st June 2020, the US Centres for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available death data within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on the rate of transmission of SARS-CoV-2. We estimate that Rt was only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%-4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.


Assuntos
COVID-19/epidemiologia , Pandemias/estatística & dados numéricos , Teorema de Bayes , COVID-19/transmissão , Humanos , Modelos Estatísticos , Estados Unidos/epidemiologia , Viroses/epidemiologia
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