11 research outputs found
Random-effects substitution models for phylogenetics via scalable gradient approximations
Phylogenetic and discrete-trait evolutionary inference depend heavily on an
appropriate characterization of the underlying character substitution process.
In this paper, we present random-effects substitution models that extend common
continuous-time Markov chain models into a richer class of processes capable of
capturing a wider variety of substitution dynamics. As these random-effects
substitution models often require many more parameters than their usual
counterparts, inference can be both statistically and computationally
challenging. Thus, we also propose an efficient approach to compute an
approximation to the gradient of the data likelihood with respect to all
unknown substitution model parameters. We demonstrate that this approximate
gradient enables scaling of sampling-based inference, namely Bayesian inference
via Hamiltonian Monte Carlo, under random-effects substitution models across
large trees and state-spaces. Applied to a dataset of 583 SARS-CoV-2 sequences,
an HKY model with random-effects shows strong signals of nonreversibility in
the substitution process, and posterior predictive model checks clearly show
that it is a more adequate model than a reversible model. When analyzing the
pattern of phylogeographic spread of 1441 influenza A virus (H3N2) sequences
between 14 regions, a random-effects phylogeographic substitution model infers
that air travel volume adequately predicts almost all dispersal rates. A
random-effects state-dependent substitution model reveals no evidence for an
effect of arboreality on the swimming mode in the tree frog subfamily Hylinae.
Simulations reveal that random-effects substitution models can accommodate both
negligible and radical departures from the underlying base substitution model.
We show that our gradient-based inference approach is over an order of
magnitude more time efficient than conventional approaches
The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2
Understanding the circumstances that lead to pandemics is important for their prevention. Here, we analyze the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted A and B. Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October–8 December), while the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events
The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic
Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports but later this conclusion became controversial. We show the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2 susceptible mammals were sold at the market in late 2019 and, within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. While there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China, and show that the Huanan market was the epicenter of the COVID-19 pandemic
Strain-Specific Metabolic Requirements Revealed by a Defined Minimal Medium for Systems Analyses of Staphylococcus aureus
Defects Formation and Amorphization of Zn-MOF-74 Crystals by Post-Synthetic Interactions with Bidentate Adsorbates
The
controlled introduction of defects into MOFs is a powerful strategy to induce
new physiochemical properties and improve their performance for target
applications. Herein, we present a new strategy for defect formation and
amorphization.<br /
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The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic.
Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing future zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports, but later this conclusion became controversial. We show here that the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2-susceptible mammals were sold at the market in late 2019 and that within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. Although there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred through the live wildlife trade in China and show that the Huanan market was the epicenter of the COVID-19 pandemic
Detection of SARS-CoV-2 intra-host recombination during superinfection with Alpha and Epsilon variants in New York City
Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, detection of recombination is only feasible when genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts reveals that Alpha variant alleles comprise around 75% of the genomes, whereas the Epsilon variant alleles comprise around 20% of the sample. Further investigation reveals the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity
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The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2.
Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted "A" and "B." Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October to 8 December), and the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans before November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events