Search Engine for Antimicrobial Resistance: A Cloud Compatible Pipeline and Web Interface for Rapidly Detecting Antimicrobial Resistance Genes Directly from Sequence Data.

BACKGROUND: Antimicrobial resistance remains a growing and significant concern in human and veterinary medicine. Current laboratory methods for the detection and surveillance of antimicrobial resistant bacteria are limited in their effectiveness and scope. With the rapidly developing field of whole genome sequencing beginning to be utilised in clinical practice, the ability to interrogate sequencing data quickly and easily for the presence of antimicrobial resistance genes will become increasingly important and useful for informing clinical decisions. Additionally, use of such tools will provide insight into the dynamics of antimicrobial resistance genes in metagenomic samples such as those used in environmental monitoring. RESULTS: Here we present the Search Engine for Antimicrobial Resistance (SEAR), a pipeline and web interface for detection of horizontally acquired antimicrobial resistance genes in raw sequencing data. The pipeline provides gene information, abundance estimation and the reconstructed sequence of antimicrobial resistance genes; it also provides web links to additional information on each gene. The pipeline utilises clustering and read mapping to annotate full-length genes relative to a user-defined database. It also uses local alignment of annotated genes to a range of online databases to provide additional information. We demonstrate SEAR's application in the detection and abundance estimation of antimicrobial resistance genes in two novel environmental metagenomes, 32 human faecal microbiome datasets and 126 clinical isolates of Shigella sonnei. CONCLUSIONS: We have developed a pipeline that contributes to the improved capacity for antimicrobial resistance detection afforded by next generation sequencing technologies, allowing for rapid detection of antimicrobial resistance genes directly from sequencing data. SEAR uses raw sequencing data via an intuitive interface so can be run rapidly without requiring advanced bioinformatic skills or resources. Finally, we show that SEAR is effective in detecting antimicrobial resistance genes in metagenomic and isolate sequencing data from both environmental metagenomes and sequencing data from clinical isolates.This research was funded by GlaxoSmithKline, the Centre for Environment, Fisheries and Aquaculture Science and the Biotechnology and Biological Sciences Research Council under an industrial CASE studentship. The funder Centre for Environment, Fisheries and Aquaculture Science provided support in the form of salaries, research materials and facilities for authors DVJ and CBA, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder GlaxoSmithKline provided support in the form of salaries for author JR, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version. It was first published by PLOS at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133492

The formation of bulges, discs and two-component galaxies in the CANDELS Survey at z < 3

We examine a sample of 1495 galaxies in the CANDELS fields to determine the evolution of two-component galaxies, including bulges and discs, within massive galaxies at the epoch 1 < z < 3 when the Hubble sequence forms. We fit all of our galaxies’ light profiles with a single Sersic fit, as well as with a combination of exponential and Sersic profiles. The latter is done in order to describe a galaxy with an inner and an outer component, or bulge and disc component. We develop and use three classification methods (visual, F-test and the residual flux fraction) to separate our sample into one-component galaxies (disc/spheroids-like galaxies) and two-component galaxies (galaxies formed by an ‘inner part’ or bulge and an ‘outer part’ or disc). We then compare the results from using these three different ways to classify our galaxies. We find that the fraction of galaxies selected as two-component galaxies increases on average 50 per cent from the lowest mass bin to the most massive galaxies, and decreases with redshift by a factor of 4 from z = 1 to 3. We find that single Sersic ‘disc-like’ galaxies have the highest relative number densities at all redshifts, and that two-component galaxies have the greatest increase and become at par with Sersic discs by z = 1. We also find that the systems we classify as two-component galaxies have an increase in the sizes of their outer components, or ‘discs’, by about a factor of 3 from z = 3 to 1.5, while the inner components or ‘bulges’ stay roughly the same size. This suggests that these systems are growing from the inside out, whilst the bulges or protobulges are in place early in the history of these galaxies. This is also seen to a lesser degree in the growth of single ‘disc-like’ galaxies versus ‘spheroid-like’ galaxies over the same epoch

Comparative metagenomics reveals a diverse range of antimicrobial resistance genes in effluents entering a river catchment.

The aquatic environment has been implicated as a reservoir for antimicrobial resistance genes (ARGs). In order to identify sources that are contributing to these gene reservoirs, it is crucial to assess effluents that are entering the aquatic environment. Here we describe a metagenomic assessment for two types of effluent entering a river catchment. We investigated the diversity and abundance of resistance genes, mobile genetic elements (MGEs) and pathogenic bacteria. Findings were normalised to a background sample of river source water. Our results show that effluent contributed an array of genes to the river catchment, the most abundant being tetracycline resistance genes tetC and tetW from farm effluents and the sulfonamide resistance gene sul2 from wastewater treatment plant (WWTP) effluents. In nine separate samples taken across 3 years, we found 53 different genes conferring resistance to seven classes of antimicrobial. Compared to the background sample taken up river from effluent entry, the average abundance of genes was three times greater in the farm effluent and two times greater in the WWTP effluent. We conclude that effluents disperse ARGs, MGEs and pathogenic bacteria within a river catchment, thereby contributing to environmental reservoirs of ARGs.This research was funded by the Centre for Environment, Fisheries and Aquaculture Science, GlaxoSmithKline and the Biotechnology and Biological Sciences Research Council. Metagenomic sequencing was performed by the Sequencing Service and Wellcome Trust Biomedical Informatics Hub, Exeter (UK).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by IWA Publishing

The JWST Hubble Sequence: The Rest-frame Optical Evolution of Galaxy Structure at 1.5 < z < 6.5

© 2023. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/We present results on the morphological and structural evolution of a total of 3956 galaxies observed with JWST at 1.5 109 M ⊙ at z > 3 are not dominated by irregular and peculiar structures, either visually or quantitatively, as previously thought. We find a strong dominance of morphologically selected disk galaxies up to z = 6 in this mass range. We also find that the stellar mass and star formation rate densities are dominated by disk galaxies up to z ∼ 6, demonstrating that most stars in the Universe were likely formed in a disk galaxy. We compare our results to theory to show that the fraction of types we find is predicted by cosmological simulations, and that the Hubble Sequence was already in place as early as one billion years after the Big Bang. Additionally, we make our visual classifications public for the community.Peer reviewe

Quantum Tricritical Points in NbFe2_2

Quantum critical points (QCPs) emerge when a 2nd order phase transition is suppressed to zero temperature. In metals the quantum fluctuations at such a QCP can give rise to new phases including unconventional superconductivity. Whereas antiferromagnetic QCPs have been studied in considerable detail ferromagnetic (FM) QCPs are much harder to access. In almost all metals FM QCPs are avoided through either a change to 1st order transitions or through an intervening spin-density-wave (SDW) phase. Here, we study the prototype of the second case, NbFe$_2$. We demonstrate that the phase diagram can be modelled using a two-order-parameter theory in which the putative FM QCP is buried within a SDW phase. We establish the presence of quantum tricritical points (QTCPs) at which both the uniform and finite $q$ susceptibility diverge. The universal nature of our model suggests that such QTCPs arise naturally from the interplay between SDW and FM order and exist generally near a buried FM QCP of this type. Our results promote NbFe$_2$ as the first example of a QTCP, which has been proposed as a key concept in a range of narrow-band metals, including the prominent heavy-fermion compound YbRh$_2$Si$_2$.Comment: 21 pages including S

A self-consistent method to estimate the rate of compact binary coalescences with a Poisson mixture model

The recently published GWTC-1 - a journal article summarizing the search for gravitational waves (GWs) from coalescing compact binaries in data produced by the LIGO-Virgo network of ground-based detectors during their first and second observing runs - quoted estimates for the rates of binary neutron star, neutron star black hole binary, and binary black hole mergers, as well as assigned probabilities of astrophysical origin for various significant and marginal GW candidate events. In this paper, we delineate the formalism used to compute these rates and probabilities, which assumes that triggers above a low ranking statistic threshold, whether of terrestrial or astrophysical origin, occur as independent Poisson processes. In particular, we include an arbitrary number of astrophysical categories by redistributing, via mass-based template weighting, the foreground probabilities of candidate events, across source classes. We evaluate this formalism on synthetic GW data, and demonstrate that this method works well for the kind of GW signals observed during the first and second observing runs.Comment: 19 pages, 5 figure

A self-consistent method to estimate the rate of compact binary coalescences with a Poisson mixture model

The recently published GWTC-1 (Abbott B P et al (LIGO Scientific Collaboration and Virgo Collaboration) 2019 Phys. Rev. X 9 031040)—a journal article summarizing the search for gravitational waves (GWs) from coalescing compact binaries in data produced by the LIGO-Virgo network of ground-based detectors during their first and second observing runs—quoted estimates for the rates of binary neutron star, neutron star black hole binary, and binary black hole mergers, as well as assigned probabilities of astrophysical origin for various significant and marginal GW candidate events. In this paper, we delineate the formalism used to compute these rates and probabilities, which assumes that triggers above a low ranking statistic threshold, whether of terrestrial or astrophysical origin, occur as independent Poisson processes. In particular, we include an arbitrary number of astrophysical categories by redistributing, via mass-based template weighting, the foreground probabilities of candidate events, across source classes. We evaluate this formalism on synthetic GW data, and demonstrate that this method works well for the kind of GW signals observed during the first and second observing runs

A self-consistent method to estimate the rate of compact binary coalescences with a Poisson mixture model

The recently published GWTC-1 - a journal article summarizing the search for gravitational waves (GWs) from coalescing compact binaries in data produced by the LIGO-Virgo network of ground-based detectors during their first and second observing runs - quoted estimates for the rates of binary neutron star, neutron star black hole binary, and binary black hole mergers, as well as assigned probabilities of astrophysical origin for various significant and marginal GW candidate events. In this paper, we delineate the formalism used to compute these rates and probabilities, which assumes that triggers above a low ranking statistic threshold, whether of terrestrial or astrophysical origin, occur as independent Poisson processes. In particular, we include an arbitrary number of astrophysical categories by redistributing, via mass-based template weighting, the foreground probabilities of candidate events, across source classes. We evaluate this formalism on synthetic GW data, and demonstrate that this method works well for the kind of GW signals observed during the first and second observing runs.Comment: 19 pages, 5 figure

Curvature and flatness in a Brans-Dicke universe

The evolution of a universe with Brans-Dicke gravity and nonzero curvature is investigated here. We find solutions to the equations of motion during the radiation dominated era. In a Friedman-Robertson-Walker cosmology we show explicitly that the three possible values of curvature [kappa] = + 1,0, - 1 divide the evolution of the Brans-Dicke universe into dynamically distinct classes just as for the standard model. Subsequently we discuss the flatness problem which exist in Brans-Dicke gravity as it does in the standard model. We also demonstrate a flatness problem in MAD Brans-Dicke gravity. In general, in any model that addresses the horizon problem, including inflation, there are two components to the flatness issue: (i) at the Planck epoch curvature gains importance, and (ii) during accelerated expansion curvature becomes less important and the universe flattens. In many cases the universe must be very flat at the Planck scale in order for the accelerated epoch to be reached; thus there can be a residual flatness problem.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31492/1/0000414.pd