Ultrafast Sample placement on Existing tRees (UShER) enables real-time phylogenetics for the SARS-CoV-2 pandemic.
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ABSTRACT:
SUBMITTER: Turakhia Y
PROVIDER: S-EPMC9248294 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Phylogenetics has been central to the genomic surveillance, epidemiology and contact tracing efforts during the COVD-19 pandemic. But the massive scale of genomic sequencing has rendered the pre-pandemic tools inadequate for comprehensive phylogenetic analyses. Here, we discuss the phylogenetic package that we developed to address the needs imposed by this pandemic. The package incorporates several pandemic-specific optimization and parallelization techniques and comprises four programs: UShER, matOptimize, RIPPLES and matUtils. Using high-performance computing, UShER and matOptimize maintain and refine daily a massive mutation-annotated phylogenetic tree consisting of all SARS-CoV-2 sequences available in online repositories. With UShER and RIPPLES, individual labs - even with modest compute resources - incorporate newly-sequenced SARS-CoV-2 genomes on this phylogeny and discover evidence for recombination in real-time. With matUtils, they rapidly query and visualize massive SARS-CoV-2 phylogenies. These tools have empowered scientists worldwide to study the SARS-CoV-2 evolution and transmission at an unprecedented scale, resolution and speed.
| S-EPMC8679213 | biostudies-literature
Project description:Phylogenetics plays a crucial role in the interpretation of genomic data1. Phylogenetic analyses of SARS-CoV-2 genomes have allowed the detailed study of the virus's origins2, of its international3,4 and local4-9 spread, and of the emergence10 and reproductive success11 of new variants, among many applications. These analyses have been enabled by the unparalleled volumes of genome sequence data generated and employed to study and help contain the pandemic12. However, preferred model-based phylogenetic approaches including maximum likelihood and Bayesian methods, mostly based on Felsenstein's 'pruning' algorithm13,14, cannot scale to the size of the datasets from the current pandemic4,15, hampering our understanding of the virus's evolution and transmission16. We present new approaches, based on reworking Felsenstein's algorithm, for likelihood-based phylogenetic analysis of epidemiological genomic datasets at unprecedented scales. We exploit near-certainty regarding ancestral genomes, and the similarities between closely related and densely sampled genomes, to greatly reduce computational demands for memory and time. Combined with new methods for searching amongst candidate evolutionary trees, this results in our MAPLE ('MAximum Parsimonious Likelihood Estimation') software giving better results than popular approaches such as FastTree 217, IQ-TREE 218, RAxML-NG19 and UShER15. Our approach therefore allows complex and accurate probabilistic phylogenetic analyses of millions of microbial genomes, extending the reach of genomic epidemiology. Future epidemiological datasets are likely to be even larger than those currently associated with COVID-19, and other disciplines such as metagenomics and biodiversity science are also generating huge numbers of genome sequences20-22. Our methods will permit continued use of preferred likelihood-based phylogenetic analyses.
| S-EPMC8963701 | biostudies-literature
Project description:The outcome of a light-matter interaction depends on both the state of matter and the state of light. It is thus a natural setting for implementing bilinear classical logic. A description of the state of a time-varying system requires measuring an (ideally complete) set of time-dependent observables. Typically, this is prohibitive, but in weak-field spectroscopy we can move toward this goal because only a finite number of levels are accessible. Recent progress in nonlinear spectroscopies means that nontrivial measurements can be implemented and thereby give rise to interesting logic schemes where the outputs are functions of the observables. Lie algebra offers a natural tool for generating the outcome of the bilinear light-matter interaction. We show how to synthesize these ideas by explicitly discussing three-photon spectroscopy of a bichromophoric molecule for which there are four accessible states. Switching logic would use the on-off occupancies of these four states as outcomes. Here, we explore the use of all 16 observables that define the time-evolving state of the bichromophoric system. The bilinear laser-system interaction with the three pulses of the setup of a 2D photon echo spectroscopy experiment can be used to generate a rich parallel logic that corresponds to the implementation of a molecular decision tree. Our simulations allow relaxation by weak coupling to the environment, which adds to the complexity of the logic operations.
| S-EPMC3808618 | biostudies-literature
Project description:The centrifuge is among the oldest and most widely used pieces of laboratory equipment, with significant applications that include clinical diagnostics and biomedical research. A major limitation of laboratory centrifuges is their "black box" nature, limiting sample observation to before and after centrifugation. Thus, optimized protocols require significant trial and error, while unoptimized protocols waste time by centrifuging longer than necessary or material due to incomplete sedimentation. Here, we developed an instrumented centrifuge tube receptacle compatible with several commercial benchtop centrifuges that can provide real-time sample analysis during centrifugation. We demonstrated the system by monitoring cell separations during centrifugation for different spin speeds, concentrations, buffers, cell types, and temperatures. We show that the collected data are valuable for analytical purposes (e.g. quality control), or as feedback to the user or the instrument. For the latter, we verified an adaptation where complete sedimentation turned off the centrifuge and notified the user by a text message. Our system adds new functionality to existing laboratory centrifuges, saving users time and providing useful feedback. This add-on potentially enables new analytical applications for an instrument that has remained largely unchanged for decades.
| S-EPMC5901991 | biostudies-literature
Project description:MotivationIn most metagenomic sequencing studies, the initial analysis step consists in assessing the evolutionary provenance of the sequences. Phylogenetic (or Evolutionary) Placement methods can be employed to determine the evolutionary position of sequences with respect to a given reference phylogeny. These placement methods do however face certain limitations: The manual selection of reference sequences is labor-intensive; the computational effort to infer reference phylogenies is substantially larger than for methods that rely on sequence similarity; the number of taxa in the reference phylogeny should be small enough to allow for visually inspecting the results.ResultsWe present algorithms to overcome the above limitations. First, we introduce a method to automatically construct representative sequences from databases to infer reference phylogenies. Second, we present an approach for conducting large-scale phylogenetic placements on nested phylogenies. Third, we describe a preprocessing pipeline that allows for handling huge sequence datasets. Our experiments on empirical data show that our methods substantially accelerate the workflow and yield highly accurate placement results.Availability and implementationFreely available under GPLv3 at http://github.com/lczech/gappa.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC6449752 | biostudies-literature
Project description:The non-covalent affinity of photoresponsive molecules to biotargets represents an attractive tool for achieving effective cell photo-stimulation. Here, an amphiphilic azobenzene that preferentially dwells within the plasma membrane is studied. In particular, its isomerization dynamics in different media is investigated. It is found that in molecular aggregates formed in water, the isomerization reaction is hindered, while radiative deactivation is favored. However, once protected by a lipid shell, the photochromic molecule reacquires its ultrafast photoisomerization capacity. This behavior is explained considering collective excited states that may form in aggregates, locking the conformational dynamics and redistributing the oscillator strength. By applying the pump probe technique in different media, an isomerization time in the order of 10 ps is identified and the deactivation in the aggregate in water is also characterized. Finally, it is demonstrated that the reversible modulation of membrane potential of HEK293 cells via illumination with visible light can be indeed related to the recovered trans?cis photoreaction in lipid membrane. These data fully account for the recently reported experiments in neurons, showing that the amphiphilic azobenzenes, once partitioned in the cell membrane, are effective light actuators for the modification of the electrical state of the membrane.
| S-EPMC7175258 | biostudies-literature
Project description:Phylogenetic analyses using genome-scale data sets must confront incongruence among gene trees, which in plants is exacerbated by frequent gene duplications and losses. Gene tree parsimony (GTP) is a phylogenetic optimization criterion in which a species tree that minimizes the number of gene duplications induced among a set of gene trees is selected. The run time performance of previous implementations has limited its use on large-scale data sets. We used new software that incorporates recent algorithmic advances to examine the performance of GTP on a plant data set consisting of 18,896 gene trees containing 510,922 protein sequences from 136 plant taxa (giving a combined alignment length of >2.9 million characters). The relationships inferred from the GTP analysis were largely consistent with previous large-scale studies of backbone plant phylogeny and resolved some controversial nodes. The placement of taxa that were present in few gene trees generally varied the most among GTP bootstrap replicates. Excluding these taxa either before or after the GTP analysis revealed high levels of phylogenetic support across plants. The analyses supported magnoliids sister to a eudicot + monocot clade and did not support the eurosid I and II clades. This study presents a nuclear genomic perspective on the broad-scale phylogenic relationships among plants, and it demonstrates that nuclear genes with a history of duplication and loss can be phylogenetically informative for resolving the plant tree of life.
| S-EPMC3038350 | biostudies-literature
Project description:BackgroundTropical rain forests are the most diverse terrestrial ecosystems on the planet. How this diversity evolved remains largely unexplained. In Africa, rain forests are situated in two geographically isolated regions: the West-Central Guineo-Congolian region and the coastal and montane regions of East Africa. These regions have strong floristic affinities with each other, suggesting a former connection via an Eocene pan-African rain forest. High levels of endemism observed in both regions have been hypothesized to be the result of either 1) a single break-up followed by a long isolation or 2) multiple fragmentation and reconnection since the Oligocene. To test these hypotheses the evolutionary history of endemic taxa within a rain forest restricted African lineage of the plant family Annonaceae was studied. Molecular phylogenies and divergence dates were estimated using a Bayesian relaxed uncorrelated molecular clock assumption accounting for both calibration and phylogenetic uncertainties.ResultsOur results provide strong evidence that East African endemic lineages of Annonaceae have multiple origins dated to significantly different times spanning the Oligocene and Miocene epochs. Moreover, these successive origins (c. 33, 16 and 8 million years--Myr) coincide with known periods of aridification and geological activity in Africa that would have recurrently isolated the Guineo-Congolian rain forest from the East African one. All East African taxa were found to have diversified prior to Pleistocene times.ConclusionMolecular phylogenetic dating analyses of this large pan-African clade of Annonaceae unravels an interesting pattern of diversification for rain forest restricted trees co-occurring in West/Central and East African rain forests. Our results suggest that repeated reconnections between the West/Central and East African rain forest blocks allowed for biotic exchange while the break-ups induced speciation via vicariance, enhancing the levels of endemicity. These results provide an explanation for present day distribution patterns and origins of endemicity for African rain forest trees. Moreover, given the pre-Pleistocene origins of all the studied endemic East African genera and species, these results also offer important insights for setting conservation priorities in these highly diversified but threatened ecosystems.
| S-EPMC2628871 | biostudies-literature
Project description:The use of genetic data to reconstruct the transmission tree of infectious disease epidemics and outbreaks has been the subject of an increasing number of studies, but previous approaches have usually either made assumptions that are not fully compatible with phylogenetic inference, or, where they have based inference on a phylogeny, have employed a procedure that requires this tree to be fixed. At the same time, the coalescent-based models of the pathogen population that are employed in the methods usually used for time-resolved phylogeny reconstruction are a considerable simplification of epidemic process, as they assume that pathogen lineages mix freely. Here, we contribute a new method that is simultaneously a phylogeny reconstruction method for isolates taken from an epidemic, and a procedure for transmission tree reconstruction. We observe that, if one or more samples is taken from each host in an epidemic or outbreak and these are used to build a phylogeny, a transmission tree is equivalent to a partition of the set of nodes of this phylogeny, such that each partition element is a set of nodes that is connected in the full tree and contains all the tips corresponding to samples taken from one and only one host. We then implement a Monte Carlo Markov Chain (MCMC) procedure for simultaneous sampling from the spaces of both trees, utilising a newly-designed set of phylogenetic tree proposals that also respect node partitions. We calculate the posterior probability of these partitioned trees based on a model that acknowledges the population structure of an epidemic by employing an individual-based disease transmission model and a coalescent process taking place within each host. We demonstrate our method, first using simulated data, and then with sequences taken from the H7N7 avian influenza outbreak that occurred in the Netherlands in 2003. We show that it is superior to established coalescent methods for reconstructing the topology and node heights of the phylogeny and performs well for transmission tree reconstruction when the phylogeny is well-resolved by the genetic data, but caution that this will often not be the case in practice and that existing genetic and epidemiological data should be used to configure such analyses whenever possible. This method is available for use by the research community as part of BEAST, one of the most widely-used packages for reconstruction of dated phylogenies.
| S-EPMC4701012 | biostudies-literature
Project description:Rechargeable metal-air batteries and water splitting are highly competitive options for a sustainable energy future, but their commercialization is hindered by the absence of cost-effective, highly efficient and stable catalysts for the oxygen evolution reaction. Here we report the rational design and synthesis of a double perovskite PrBa0.5Sr0.5Co1.5Fe0.5O5+δ nanofiber as a highly efficient and robust catalyst for the oxygen evolution reaction. Co-doping of strontium and iron into PrBaCo2O5+δ is found to be very effective in enhancing intrinsic activity (normalized by the geometrical surface area, ∼4.7 times), as validated by electrochemical measurements and first-principles calculations. Further, the nanofiber morphology enhances its mass activity remarkably (by ∼20 times) as the diameter is reduced to ∼20 nm, attributed to the increased surface area and an unexpected intrinsic activity enhancement due possibly to a favourable eg electron filling associated with partial surface reduction, as unravelled from chemical titration and electron energy-loss spectroscopy.
| S-EPMC5333368 | biostudies-literature