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At least 1,207 records · Page 67

MINE 2.0: enhanced biochemical coverage for peak identification in untargeted metabolomics

Abstract Summary Although advances in untargeted metabolomics have made it possible to gather data on thousands of cellular metabolites in parallel, identification of novel metabolites from these datasets remains challenging. To address this need, Metabolic in silico Network Expansions (MINEs) were developed. A MINE is an expansion of known biochemistry which can be used as a list of potential structures for unannotated metabolomics peaks. Here, we present MINE 2.0, which utilizes a new set of biochemical transformation rules that covers 93% of MetaCyc reactions (compared to 25% in MINE 1.0). This results in a 17-fold increase in database size and a 40% increase in MINE database compounds matching unannotated peaks from an untargeted metabolomics dataset. MINE 2.0 is thus a significant improvement to this community resource. Availability and implementation The MINE 2.0 website can be accessed at https://minedatabase.ci.northwestern.edu. The MINE 2.0 web API documentation can be accessed at https://mine-api.readthedocs.io/en/latest/. The data and code underlying this article are available in the MINE-2.0-Paper repository at https://github.com/tyo-nu/MINE-2.0-Paper. MINE 2.0 source code can be accessed at https://github.com/tyo-nu/MINE-Database (MINE construction), https://github.com/tyo-nu/MINE-Server (backend web API) and https://github.com/tyo-nu/MINE-app (web app). Supplementary information Supplementary data are available at Bioinformatics online.

59 BASIC BIOLOGICAL SCIENCES↗

A reversible Renilla luciferase protein complementation assay for rapid identification of protein-protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus

A growing body of evidence suggests that protein–protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. We tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. In conclusion, our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta.

59 BASIC BIOLOGICAL SCIENCES↗

Dark Energy Survey Identification of A Low-Mass Active Galactic Nucleus at Redshift 0.823 from Optical Variability

We report the identification of a low-mass active galactic nucleus (AGN), DES J0218−0430, in a redshift z = 0.823 galaxy in the Dark Energy Survey (DES) Supernova field. We select DES J0218−0430 as an AGN candidate by characterizing its long-term optical variability alone based on DES optical broad-band light curves spanning over 6 yr. An archival optical spectrum from the fourth phase of the Sloan Digital Sky Survey shows both broad Mg ii and broad H β lines, confirming its nature as a broad-line AGN. Archival XMM–Newton X-ray observations suggest an intrinsic hard X-ray luminosity of |$L_{{\rm 2-12\, keV}}\approx 7.6\pm 0.4\times 10^{43}$| erg s^−1, which exceeds those of the most X-ray luminous starburst galaxies, in support of an AGN driving the optical variability. Based on the broad H β from SDSS spectrum, we estimate a virial black hole (BH) mass of M_• ≈ 10^6.43–10^6.72 M_⊙ (with the error denoting the systematic uncertainty from different calibrations), consistent with the estimation from OzDES, making it the lowest mass AGN with redshift > 0.4 detected in optical. We estimate the host galaxy stellar mass to be M_* ≈ 10^10.5 ± 0.3 M_⊙ based on modelling the multiwavelength spectral energy distribution. DES J0218−0430 extends the M_•–M_* relation observed in luminous AGNs at z ∼ 1 to masses lower than being probed by previous work. Our work demonstrates the feasibility of using optical variability to identify low-mass AGNs at higher redshift in deeper synoptic surveys with direct implications for the upcoming Legacy Survey of Space and Time at Vera C. Rubin Observatory.

79 ASTRONOMY AND ASTROPHYSICS↗

El-CID: a filter for gravitational-wave electromagnetic counterpart identification

ABSTRACT As gravitational-wave (GW) interferometers become more sensitive and probe ever more distant reaches, the number of detected binary neutron star mergers will increase. However, detecting more events farther away with GWs does not guarantee corresponding increase in the number of electromagnetic counterparts of these events. Current and upcoming wide-field surveys that participate in GW follow-up operations will have to contend with distinguishing the kilonova (KN) from the ever increasing number of transients they detect, many of which will be consistent with the GW sky-localization. We have developed a novel tool based on a temporal convolutional neural network architecture, trained on sparse early-time photometry and contextual information for Electromagnetic Counterpart Identification (El-CID). The overarching goal for El-CID is to slice through list of new transient candidates that are consistent with the GW sky localization, and determine which sources are consistent with KNe, allowing limited target-of-opportunity resources to be used judiciously. In addition to verifying the performance of our algorithm on an extensive testing sample, we validate it on AT2017gfo – the only EM counterpart of a binary neutron star merger discovered to date – and AT2019npv – a supernova that was initially suspected as a counterpart of the GW event, GW190814, but was later ruled out after further analysis.

79 ASTRONOMY AND ASTROPHYSICS↗

SDSS-IV MaNGA: Identification and multiwavelength properties of Type-1 AGN in the DR15 sample

ABSTRACT We present a method to identify type-1 active galactic nuclei (AGNs) in the central 3 arcsec integrated spectra of galaxies in the MaNGA DR15 sample. It is based on flux ratios estimates in spectral bands flanking the expected h α broad component h αBC. The high signal-to-noise ratio obtained (mean S/N = 84) permits the identification of h αBC without prior subtraction of the host galaxy (HG) stellar component. A final sample of 47 type-1 AGN is reported out of 4700 galaxies at z < 0.15. The results were compared with those from other methods based on the SDSS DR7 and MaNGA data. Detection of type-1 AGN in those works compared to our method goes from 26 per cent to 81 per cent. Spectral indexes were used to classify the type-1 AGN spectra according to different levels of AGN-HG contribution, finding 9 AGN-dominated, 14 intermediate, and 24 HG-dominated objects. Complementary data in NIR-MIR allowed us to identify type I AGN-dominated objects as blue and HG-dominated as red in the WISE colours. From NVSS and FIRST radio continuum data, we identify 5 HERGs (high-excitation radio galaxies) and 4 LERGs (low-excitation radio galaxies), three showing evidence of radio-jets in the FIRST maps. Additional X-ray data from ROSAT allowed us to build [O iii] and h αBC versus X-ray, NIR-MIR, and radio continuum diagrams, showing that L(h αBC) and L([O iii]) provide good correlations. The range in h αBC luminosity is wide 38 < logL(h αBC) < 44, with log FWHM(h αBC) ∼ 3–4, covering a range of Eddington ratios of −5.15 < log Lbol/LEdd < 0.70. Finally, we also identify and report ten possible changing-look AGN candidates.

Cortes-Suárez, Edgar↗

Identification and characterization of the WYL BrxR protein and its gene as separable regulatory elements of a BREX phage restriction system

Bacteriophage exclusion (‘BREX’) phage restriction systems are found in a wide range of bacteria. Various BREX systems encode unique combinations of proteins that usually include a site-specific methyltransferase; none appear to contain a nuclease. Here we describe the identification and characterization of a Type I BREX system from Acinetobacter and the effect of deleting each BREX ORF on growth, methylation, and restriction. We identified a previously uncharacterized gene in the BREX operon that is dispensable for methylation but involved in restriction. Biochemical and crystallographic analyses of this factor, which we term BrxR (‘BREX Regulator’), demonstrate that it forms a homodimer and specifically binds a DNA target site upstream of its transcription start site. Deletion of the BrxR gene causes cell toxicity, reduces restriction, and significantly increases the expression of BrxC. In contrast, the introduction of a premature stop codon into the BrxR gene, or a point mutation blocking its DNA binding ability, has little effect on restriction, implying that the BrxR coding sequence and BrxR protein play independent functional roles. We speculate that elements within the BrxR coding sequence are involved in cis regulation of anti-phage activity, while the BrxR protein itself plays an additional regulatory role, perhaps during horizontal transfer.

59 BASIC BIOLOGICAL SCIENCES↗

Catalytic site identification—a web server to identify catalytic site structural matches throughout PDB

The catalytic site identification web server provides the innovative capability to find structural matches to a user-specified catalytic site among all Protein Data Bank proteins rapidly (in less than a minute). The server also can examine a user-specified protein structure or model to identify structural matches to a library of catalytic sites. Finally, the server provides a database of pre-calculated matches between all Protein Data Bank proteins and the library of catalytic sites. The database has been used to derive a set of hypothesized novel enzymatic function annotations. In all cases, matches and putative binding sites (protein structure and surfaces) can be visualized interactively online. The website can be accessed at http://catsid.llnl. gov.

59 BASIC BIOLOGICAL SCIENCES↗

Metabolic Source Isotopic Pair Labeling and Genome-Wide Association Are Complementary Tools for the Identification of Metabolite-Gene Associations in Plants

The optimal extraction of information from untargeted metabolomics analyses is a continuing challenge. Here, we describe an approach that combines stable isotope labeling, liquid chromatography– mass spectrometry (LC–MS), and a computational pipeline to automatically identify metabolites produced from a selected metabolic precursor. Here, we identified the subset of the soluble metabolome generated from phenylalanine (Phe) in Arabidopsis thaliana, which we refer to as the Phe-derived metabolome (FDM) In addition to identifying Phe-derived metabolites present in a single wild-type reference accession, the FDM was established in nine enzymatic and regulatory mutants in the phenylpropanoid pathway. To identify genes associated with variation in Phe-derived metabolites in Arabidopsis, MS features collected by untargeted metabolite profiling of an Arabidopsis diversity panel were retrospectively annotated to the FDM and natural genetic variants responsible for differences in accumulation of FDM features were identified by genome-wide association. Large differences in Phe-derived metabolite accumulation and presence/absence variation of abundant metabolites were observed in the nine mutants as well as between accessions from the diversity panel. Many Phe-derived metabolites that accumulated in mutants also accumulated in non-Col-0 accessions and was associated to genes with known or suspected functions in the phenylpropanoid pathway as well as genes with no known functions. Overall, we show that cataloguing a biochemical pathway’s products through isotopic labeling across genetic variants can substantially contribute to the identification of metabolites and genes associated with their biosynthesis.

09 BIOMASS FUELS↗

Bayesian differential programming for robust systems identification under uncertainty

This paper presents a machine learning framework for Bayesian systems identification from noisy, sparse and irregular observations of nonlinear dynamical systems. The proposed method takes advantage of recent developments in differentiable programming to propagate gradient information through ordinary differential equation solvers and perform Bayesian inference with respect to unknown model parameters using Hamiltonian Monte Carlo sampling. This allows an efficient inference of the posterior distributions over plausible models with quantified uncertainty, while the use of sparsity-promoting priors enables the discovery of interpretable and parsimonious representations for the underlying latent dynamics. A series of numerical studies is presented to demonstrate the effectiveness of the proposed methods, including nonlinear oscillators, predator–prey systems and examples from systems biology. Taken together, our findings put forth a flexible and robust workflow for data-driven model discovery under uncertainty. All codes and data accompanying this article are available at https://bit.ly/34FOJMj .

Science & Technology - Other Topics↗

Genomic reconstruction of Bacillus anthracis from complex environmental samples enables high-throughput identification and lineage assignment in Pakistan

Bacillus anthracis, the causative agent of anthrax, is a highly virulent zoonotic pathogen primarily affecting domesticated and wild herbivores. Human exposure to B. anthracis is primarily through contact with infected animals or contaminated animal products. In Pakistan, where livestock vaccines are largely unavailable and infected carcasses are often disposed of improperly, the risk to humans, wildlife and livestock is significant. Currently, the diagnosis of anthrax infections and outbreak tracing necessitates the isolation and culturing of B. anthracis, a process that requires BSL-3 facilities. In this study, we show that positive identification, genome reconstruction and lineage assignment can be accomplished using bioinformatic analysis of DNA extracted directly from environmental samples that would otherwise provide the starting material for isolation and culturing. This approach does not require laboratory target enrichment as is necessary for other pathogens, due in part to the extremely high bacterial load in the bloodstream in the deceased animals. Using these methods, we greatly expand the knowledge of endemic B. anthracis in Pakistan. We provide the first reference B. anthracis genomes from Pakistan since the 1970s and identify A.Br.014 Aust94 as a minor circulating sublineage alongside the dominant A.Br.047 Vollum. Future work will focus on the limits of detection and will determine if this bioinformatic method can be expanded more broadly for B. anthracis or other pathogens to replace typical culture-based methods.

A.Br.047 Vollum↗

Highly boosted dielectron identification in proton-proton collisions at $\sqrt{s}$ = 13 TeV

A new technique is developed to identify dielectrons (e$^+$e$^-$) with Lorentz boost $γ_\mathrm{L}$$\gt$ 20 that produce one single merged cluster in the electromagnetic calorimeter of the CMS detector. The identification uses two multivariate models: one for the case where both electron tracks are reconstructed, and another where only one of the tracks is reconstructed. The efficiency is determined using proton-proton collision data collected at a center-of-mass energy of 13 TeV. Boosted J/$ψ$ mesons decaying into e$^+$e$^-$ pairs are used to estimate the efficiency of the model with two tracks, yielding an overall efficiency of 80%. The Z $\to$ $μ^+μ^-γ$ events, where the photon converts into a collimated dielectron, are used for the model with a single track, yielding an efficiency of about 60%. A dedicated energy correction for dielectron candidates is also developed using B$^\pm$ $\to$ J/$ψ$K$^\pm$ $\to$ e$^+$e$^-$K$^\pm$ data.

Hayrapetyan, A. [Yerevan Phys. Inst.]↗

Identification of open quantum systems from observable time traces

Estimating the parameters that dictate the dynamics of a quantum system is an important task for quantum information processing and quantum metrology, as well as fundamental physics. In our paper we develop a method for parameter estimation for Markovian open quantum systems using a temporal record of measurements on the system. Furthermore, the method is based on system realization theory and is a generalization of our previous work on identification of Hamiltonian parameters.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Interaction networks for the identification of boosted H → $b\overline b$ decays

We develop an algorithm based on an interaction network to identify high-transverse-momentum Higgs bosons decaying to bottom quark-antiquark pairs and distinguish them from ordinary jets that reflect the configurations of quarks and gluons at short distances. The algorithm's inputs are features of the reconstructed charged particles in a jet and the secondary vertices associated with them. Describing the jet shower as a combination of particle-to-particle and particle-to-vertex interactions, the model is trained to learn a jet representation on which the classification problem is optimized. The algorithm is trained on simulated samples of realistic LHC collisions, released by the CMS Collaboration on the CERN Open Data Portal. The interaction network achieves a drastic improvement in the identification performance with respect to state-of-the-art algorithms.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Novel method for the identification of the production flavor of neutral charmed mesons

We propose a new algorithm for the identification of the production flavor of neutral D mesons in the Belle II experiment. The algorithm exploits the correlation between the flavor of a reconstructed neutral D meson (signal D meson) and the electric charges of particles reconstructed in the rest of the e + e – →$c\bar{c}$ event. These include those originating from the decay of the other charm hadron produced in the event, as well as those possibly produced in association with the signal D meson. We develop the algorithm using simulation and calibrate it in data using decay modes that identify the flavor of the decaying neutral D meson. We use a data sample of e + e – collisions, corresponding to 362 fb –1 of integrated luminosity, collected by Belle II at center-of-mass energies near the Υ(4S) mass. The effective tagging efficiency in data is (47.91±0.07 (stat) ±0.51 (syst)) %, independent of the neutral-D-meson decay mode. This charm flavor tagger will approximately double the effective sample size of many CP-violation and charm-mixing measurements that so far have exclusively relied on neutral D mesons originating from D* ± decays. While developed for Belle II, the basic principles underlying the charm flavor tagger can be used in other experiments, including those at hadron colliders.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Angular analysis of B → K * e + e − in the low- q 2 region with new electron identification at Belle

We perform an angular analysis of the B → K * e + e − decay for the dielectron mass squared, q 2 , range of 0.0008 – 1.1200 GeV 2 / c 4 using the full Belle dataset in the K * 0 → K + π − and K * + → K S 0 π + channels, incorporating new methods of electron identification to improve the statistical power of the dataset. This analysis is sensitive to contributions from right-handed currents from physics beyond the Standard Model by constraining the Wilson coefficients C 7 ( ′ ) . We perform a fit to the B → K * e + e − differential decay rate and measure the imaginary component of the transversality amplitude to be A T Im = − 1.27 ± 0.52 ± 0.12 , and the K * transverse asymmetry to be A T ( 2 ) = 0.52 ± 0.53 ± 0.11 , with F L and A T Re fixed to the Standard Model values. The resulting constraints on the value of C 7 ′ are consistent with the Standard Model within a 2 σ confidence interval. Published by the American Physical Society 2024

Ferlewicz, D. (ORCID:0000000243741234)↗

Probing the top-quark width using the charge identification of b jets

We propose a new method for measuring the top-quark width based on the on-/off-shell ratio of b -charge asymmetry in pp → Wbj production at the LHC. The charge asymmetry removes virtually all backgrounds and related uncertainties, while remaining systematic and theoretical uncertainties can be taken under control by the ratio of cross sections. Limited only by statistical error, in an optimistic scenario, we find that our approach leads to good precision at high integrated luminosity, at a few hundred MeV assuming 300 – 3000 fb -1 at the LHC. The approach directly probes the total width, in such a way that model-dependence can be minimized. It is complementary to existing cross section measurements which always leave a degeneracy between the total rate and the branching ratio, and provides valuable information about the properties of the top quark. Here, the proposal opens up new opportunities for precision top measurements using a b-charge identification algorithm.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Machine learning for the identification of phase transitions in interacting agent-based systems: A Desai-Zwanzig example

Deriving closed-form analytical expressions for reduced-order models, and judiciously choosing the closures leading to them, has long been the strategy of choice for studying phase- and noise-induced transitions for agent-based models (ABMs). In this paper, we propose a data-driven framework that pinpoints phase transitions for an ABM—the Desai-Zwanzig model—in its mean-field limit, using a smaller number of variables than traditional closed-form models. To this end, we use the manifold learning algorithm Diffusion Maps to identify a parsimonious set of data-driven latent variables, and we show that they are in one-to-one correspondence with the expected theoretical order parameter of the ABM. We then utilize a deep learning framework to obtain a conformal reparametrization of the data-driven coordinates that facilitates, in our example, the identification of a single parameter-dependent ordinary differential equation (ODE) in these coordinates. Additionally, we identify this ODE through a residual neural network inspired by a numerical integration scheme (forward Euler). We then use the identified ODE—enabled through an odd symmetry transformation—to construct the bifurcation diagram exhibiting the phase transition.

97 MATHEMATICS AND COMPUTING↗

Identification of the New Isotope 244 Md

In an experiment performed at Lawrence Berkeley National Laboratory’s 88-inch cyclotron, the isotope Md 244 was produced in the Bi 209 ( Ar 40 , 5 n ) reaction. Decay properties of Md 244 were measured at the focal plane of the Berkeley Gas-filled Separator, and the mass number assignment of A = 244 was confirmed with the apparatus for the identification of nuclide A . The isotope Md 244 is reported to have one, possibly two, α -decaying states with α energies of 8.66(2) and 8.31(2) MeV and half-lives of 0.4 – 0.1 + 0.4 and ~ 6 s , respectively. Furtermore, first evidence of the α decay of Bk 236 was observed and is reported.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗