Full Catalog Research Articles

The Locus Algorithm: The design, implementation and performance characterisation of a software and grid computing system to optimise the quality of fields of view for differential photometry

We present the development and software implementation of the Locus Algorithm, a novel algorithm designed to maximise the performance of differential photometry analyses by optimising the number and quality of reference stars in the Field of View with the target. Firstly, we state the design requirements, constraints and ambitions of the system. Initial testing showed the necessity for a High Performance Computing system such that the software system could be scaled to analysis of the full SDSS Catalogue in a practical timescale. The National Grid Infrastructure at Grid Ireland was selected to fulfil this need. Then, a detailed software design is presented for the system in operation. Next, the data design including file structures used and the data environment required for the system are defined. We present an analysis of the performance characteristics of this system, including an assessment of the scalability of the solution. We conclude that the balance in our system between I/O and processing time varies between I/O dominant and balanced depending on the inputs. Therefore, we note that for our future projects, such as applying this analysis to larger datasets such as LSST or Gaia, we may not be able to rely solely on factors such as algorithmic complexity when predicting system requirements. Instead, experimental testing of runtime and careful analysis of optimisations such as data reuse are critical.

Star-spots and magnetism: testing the activity paradigm in the Pleiades and M67

ABSTRACT We measure star-spot filling fractions for 240 stars in the Pleiades and M67 open star clusters using APOGEE high-resolution H-band spectra. For this work, we developed a modified spectroscopic pipeline which solves for star-spot filling fraction and star-spot temperature contrast. We exclude binary stars, finding that the large majority of binaries in these clusters (80 per cent) can be identified from Gaia DR3 and APOGEE criteria – important for field star applications. Our data agree well with independent activity proxies, indicating that this technique recovers real star-spot signals. In the Pleiades, filling fractions saturate at a mean level of 0.248 ± 0.005 for active stars with a decline at slower rotation; we present fitting functions as a function of Rossby number. In M67, we recover low mean filling fractions of 0.030 ± 0.008 and 0.003 ± 0.002 for main sequence GK stars and evolved red giants, respectively, confirming that the technique does not produce spurious spot signals in inactive stars. Star-spots also modify the derived spectroscopic effective temperatures and convective overturn time-scales. Effective temperatures for active stars are offset from inactive ones by −109 ± 11 K, in agreement with the Pecaut & Mamajek empirical scale. Star-spot filling fractions at the level measured in active stars changes their inferred overturn time-scale, which biases the derived threshold for saturation. Finally, we identify a population of stars statistically discrepant from mean activity–Rossby relations and present evidence that these are genuine departures from a Rossby scaling. Our technique is applicable to the full APOGEE catalogue, with broad applications to stellar, galactic, and exoplanetary astrophysics.

The Arecibo Galaxy Environment Survey (AGES)

Context. Many galaxy properties are known to correlate with the environment in which the galaxies are embedded. Their cold, neutral gas content, which is usually assessed through 21 cm H I observations, is related to many other galaxy properties as it is the underlying fuel for star formation. With its high sensitivity and broad sky coverage the blind Arecibo Galaxy Environment Survey (AGES) brings significant improvement to the census of H I properties of galaxies in a wide range of environments, from voids to the core of a massive cluster. Here we present an H I census over a volume of ∼44 000 Mpc3 towards the merging cluster Abell 1367 and extending well beyond. Aims. We measure the effects that different environments have on the H I content of their constituent galaxies. Methods. We use AGES- a deep, blind, H I survey carried out with the Arecibo radio telescope, which covers 20 square degrees on the sky centred on the merging cluster Abell 1367, mapping the large-scale structure (LSS) surrounding the cluster out to cz = 20 000 km s−1. The survey is sensitive down to a column density of NH I = 1.5 × 1017 cm−2 for emission filling the beam and a line width of 10 km s−1. As an approximate mass sensitivity limit, a member of A1367 (at a distance of 92 Mpc), containing MH I = 2.7 × 108 M⊙ distributed over a top-hat profile of 50 km s−1 width would be detected at 4σ. The results are analysed in combination with optical spectroscopy data from SDSS which we use to estimate the local galaxy density based on the Voronoi-Delaunay method. Results. We present the results of the complete AGES survey of the A1367 field. In total, we detect 457 H I sources, 213 of which are detected for the first time by the AGES survey, and 134 of which are presented in this article for the first time. Of the 457 detections, 225 are in the cluster and 232 are in the remaining volume surveyed. Here we present the full catalogue of H I detections and their basic properties, including optical ones. We concentrate on the difference between the cluster and the foreground and background LSS, revealing a continuous correlation of H I-detected fraction (and H I deficiency) with local galaxy density, independent of global environment.

A cosmological underdensity does not solve the Hubble tension

A potential solution to the Hubble tension is the hypothesis that the Milky Way is located near the center of a matter underdensity. We model this scenario through the Lemaître-Tolman-Bondi formalism with the inclusion of a cosmological constant (ΛLTB) and consider a generalized Gaussian parametrization for the matter density profile. We constrain the underdensity and the background cosmology with a combination of data sets: the Pantheon Sample of type Ia supernovae (both the full catalogue and a redshift-binned version of it), a collection of baryon acoustic oscillations data points and the distance priors extracted from the latest Planck data release. The analysis with the binned supernovae suggests a preference for a -13 % density drop with a size of approximately 300 Mpc, interestingly matching the prediction for the so-called KBC void already identified on the basis of independent analyses using galaxy distributions. The constraints obtained with the full Pantheon Sample are instead compatible with a homogeneous cosmology and we interpret this radically different result as a cautionary tale about the potential bias introduced by employing a binned supernova data set. We quantify the level of improvement on the Hubble tension by analyzing the constraints on the B-band absolute magnitude of the supernovae, which provides the calibration for the local measurements of H 0. Since no significant difference is observed with respect to an analogous fit performed with a standard ΛCDM cosmology, we conclude that the potential presence of a local underdensity does not resolve the tension and does not significantly degrade current supernova constraints on H 0.

The Extreme Scarcity of Dust-enshrouded Red Supergiants: Consequences for Producing Stripped Stars via Winds

Quiescent mass loss during the red supergiant (RSG) phase has been shown to be far lower than prescriptions typically employed in single-star evolutionary models. Importantly, RSG winds are too weak to drive the production of Wolf-Rayet (WR) stars and stripped-envelope supernovae (SE-SNe) at initial masses of roughly 20–40 M ⊙. If single stars are to make WR stars and SE-SNe, this shifts the burden of mass loss to rare dust-enshrouded RSGs (DE-RSGs), objects claimed to represent a short-lived, high-mass-loss phase. Here, we take a fresh look at the purported DE-RSGs. By modeling the mid-IR excesses of the full sample of RSGs in the Large Magellanic Cloud, we find that only one RSG has both a high mass-loss rate ( ≥ 10−4 M ⊙ yr−1) and a high optical circumstellar dust extinction (7.92 mag). This RSG is WOH G64, and it is the only one of the 14 originally proposed DE-RSGs that is actually dust enshrouded. The rest appear to be either normal RSGs without strong IR excess, or lower-mass asymptotic giant branch stars. Only one additional object in the full catalog of RSGs (not previously identified as a DE-RSG) shows strong mid-IR excess. We conclude that if DE-RSGs do represent a pre-SN phase of enhanced in single stars, it is extremely short-lived, only capable of removing ≤2 M ⊙ of material. This rules out the single-star post-RSG pathway for the production of WR stars, luminous blue variables, and SE-SNe. Single-star models should not employ -prescriptions based on these extreme objects for any significant fraction of the RSG phase.

IMaNGA: mock MaNGA galaxies based on IllustrisTNG and MaStar SSPs – I. Construction and analysis of the mock data cubes

ABSTRACT Galaxy formation and evolution simulations are essential tools to probe poorly known astrophysics processes, but particular care is needed to compare simulations with galaxy observations, as observed data need to be modelled as well. We present a method to generate mock galaxies from the hydro-dynamical IllustrisTNG simulations which are suited to compare with integral field spectroscopic observation of galaxies from the SDSS-IV/Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey. First, we include the same instrumental effects and procedures as adopted in the acquisition and analysis of real data. Furthermore, we generate the galaxy spectra from the simulations using new stellar population models based on the MaNGA stellar library (MaStar). In this way, our mock data cubes have the same spatial sampling, cover the same wavelength range (3600–10 300 Å), and share the same spectral resolution (R ≈ 1800) and flux calibration of real MaNGA galaxy spectra. In this first paper, we demonstrate the method over an early- and a late-type simulated galaxy from TNG50. We analyse the correspondent mock MaNGA-like data cubes with the same full spectral fitting code, firefly, which was used for the observed spectra. We find that the intrinsic and recovered age and metallicity gradients are consistent within 1σ, with residuals over all tassels consistent with 0 at the 68 ${{\ \rm per\ cent}}$ confidence level. We also perform the challenging test at comparing intrinsic and recovered star formation histories, finding a close resemblance between input and output. In follow-up papers, we will present a full simulated MaNGA-like catalogue (≈10 000 galaxies) with a comprehensive comparison of TNG50 simulations to MaNGA observational results.

Estimating Video on Demand QoE From Network QoS Through ICMP Probes

With the increasing traffic of Video on Demand (VoD), network providers are seeking to deliver high Quality of Experience (QoE) for their users. Many methods have been proposed to assess VoD-related QoE. Some of them rely on client instrumentation and reporting QoE information to network elements, such as Server and Network Assisted DASH, others are based on statistical methods that make QoE inferences using monitored network conditions, such as throughput and delays. In this article, we present a practical method to estimate QoE for VoD using the widely supported Internet Control Message Protocol (ICMP) probes. Measured network conditions are used as input to a Machine Learning (ML) model that estimates QoE in terms of Mean Opinion Score (MOS), based on the ITU-T P.1203 Recommendation. The estimation encompasses video quality switches and playback stalls. We estimate MOS with an average Root Mean Square Error (RMSE) of 1.05 for a catalog of 25 different videos, training a model with sessions of the shortest video, and evaluating the generalization to the full catalog. We performed experiments using a virtualized setup as well as in a Wide Area Network.

Statistical Modeling of the Seismic Moments via Mathai Distribution.

Mathai’s pathway model is playing an increasingly prominent role in statistical distributions. As a generalization of a great variety of distributions, the pathway model allows the studying of several non-linear dynamics of complex systems. Here, we construct a model, called the Pareto–Mathai distribution, using the fact that the earthquakes’ magnitudes of full catalogues are well-modeled by a Mathai distribution. The Pareto–Mathai distribution is used to study artificially induced microseisms in the mining industry. The fitting of a distribution for entire range of magnitudes allow us to calculate the completeness magnitude (). Mathematical properties of the new distribution are studied. In addition, applying this model to data recorded at a Chilean mine, the magnitude is estimated for several mine sectors and also the entire mine.

Virgo Filaments. II. Catalog and First Results on the Effect of Filaments on Galaxy Properties

Abstract Virgo is the nearest galaxy cluster; it is thus ideal for studies of galaxy evolution in dense environments in the local universe. It is embedded in a complex filamentary network of galaxies and groups, which represents the skeleton of the large-scale Laniakea supercluster. Here we assemble a comprehensive catalog of galaxies extending up to ∼12 virial radii in projection from Virgo to revisit the cosmic-web structure around it. This work is the foundation of a series of papers that will investigate the multiwavelength properties of galaxies in the cosmic web around Virgo. We match spectroscopically confirmed sources from several databases and surveys including HyperLeda, NASA Sloan Atlas, NASA/IPAC Extragalactic Database, and ALFALFA. The sample consists of ∼7000 galaxies. By exploiting a tomographic approach, we identify 13 filaments, spanning several megaparsecs in length. Long >17 h –1 Mpc filaments, tend to be thin (<1 h –1 Mpc in radius) and with a low-density contrast (<5), while shorter filaments show a larger scatter in their structural properties. Overall, we find that filaments are a transitioning environment between the field and cluster in terms of local densities, galaxy morphologies, and fraction of barred galaxies. Denser filaments have a higher fraction of early-type galaxies, suggesting that the morphology–density relation is already in place in the filaments, before galaxies fall into the cluster itself. We release the full catalog of galaxies around Virgo and their associated properties.

Satellitome comparison of two oedipodine grasshoppers highlights the contingent nature of satellite DNA evolution

BackgroundThe full catalog of satellite DNA (satDNA) within a same genome constitutes the satellitome. The Library Hypothesis predicts that satDNA in relative species reflects that in their common ancestor, but the evolutionary mechanisms and pathways of satDNA evolution have never been analyzed for full satellitomes. We compare here the satellitomes of two Oedipodine grasshoppers (Locusta migratoria and Oedaleus decorus) which shared their most recent common ancestor about 22.8 Ma ago.ResultsWe found that about one third of their satDNA families (near 60 in every species) showed sequence homology and were grouped into 12 orthologous superfamilies. The turnover rate of consensus sequences was extremely variable among the 20 orthologous family pairs analyzed in both species. The satDNAs shared by both species showed poor association with sequence signatures and motives frequently argued as functional, except for short inverted repeats allowing short dyad symmetries and non-B DNA conformations. Orthologous satDNAs frequently showed different FISH patterns at both intra- and interspecific levels. We defined indices of homogenization and degeneration and quantified the level of incomplete library sorting between species.ConclusionsOur analyses revealed that satDNA degenerates through point mutation and homogenizes through partial turnovers caused by massive tandem duplications (the so-called satDNA amplification). Remarkably, satDNA amplification increases homogenization, at intragenomic level, and diversification between species, thus constituting the basis for concerted evolution. We suggest a model of satDNA evolution by means of recursive cycles of amplification and degeneration, leading to mostly contingent evolutionary pathways where concerted evolution emerges promptly after lineages split.

The CubeSpec space mission

Context. There is currently a niche for providing high-cadence, high resolution, time-series optical spectroscopy from space, which can be filled by using a low-cost cubesat mission. The Belgian-led ESA/KU Leuven CubeSpec mission is specifically designed to provide space-based, low-cost spectroscopy with specific capabilities that can be optimised for a particular science need. Approved as an ESA in-orbit demonstrator, the CubeSpec satellite’s primary science objective will be to focus on obtaining high-cadence, high resolution optical spectroscopic data to facilitate asteroseismology of pulsating massive stars. Aims. In this first paper, we aim to search for pulsating massive stars suitable for the CubeSpec mission, specifically β Cep stars, which typically require time-series spectroscopy to identify the geometry of their pulsation modes. Methods. Based on the science requirements needed to enable asteroseismology of massive stars with the capabilities of CubeSpec’s spectrograph, we combined a literature study for pulsation with the analysis of recent high-cadence time-series photometry from the Transiting Exoplanet Survey Satellite (TESS) mission to classify the variability for stars brighter than V ≤ 4 mag and between O9 and B3 in spectral type. Results. Among the 90 stars that meet our magnitude and spectral type requirements, we identified 23 promising β Cep stars with high-amplitude (non-)radial pulsation modes with frequencies below 7 d−1. Using further constraints on projected rotational velocities, pulsation amplitudes, and the number of pulsation modes, we devised a prioritised target list for the CubeSpec mission according to its science requirements and the potential of the targets for asteroseismology. The full target catalogue further provides a modern TESS-based review of line profile and photometric variability properties among bright O9–B3 stars.

AMICO galaxy clusters in KiDS-DR3: measurement of the halo bias and power spectrum normalization from a stacked weak lensing analysis

ABSTRACT Galaxy clusters are biased tracers of the underlying matter density field. At very large radii beyond about 10 Mpc h−1, the shear profile shows evidence of a second-halo term. This is related to the correlated matter distribution around galaxy clusters and proportional to the so-called halo bias. We present an observational analysis of the halo bias–mass relation based on the AMICO galaxy cluster catalogue, comprising around 7000 candidates detected in the third release of the KiDS survey. We split the cluster sample into 14 redshift-richness bins and derive the halo bias and the virial mass in each bin by means of a stacked weak lensing analysis. The observed halo bias–mass relation and the theoretical predictions based on the Lambda cold dark matter standard cosmological model show an agreement within 2σ. The mean measurements of bias and mass over the full catalogue give $M_{200c} = (4.9 \pm 0.3) \times 10^{13}\, {\rm M}_{\odot }/{\it h}$ and $b_h \sigma _8^2 = 1.2 \pm 0.1$. With the additional prior of a bias–mass relation from numerical simulations, we constrain the normalization of the power spectrum with a fixed matter density Ωm = 0.3, finding σ8 = 0.63 ± 0.10.

Gravitational waves from tidal disruption events: an open and comprehensive catalog

ABSTRACT We present an online, open, and comprehensive template library of gravitational waveforms produced during the tidal disruptions of stars by massive black holes, spanning a broad space of parameters. We build this library thanks to a new feature that we implement in the general relativistic version of phantom, a smoothed particle hydrodynamics code for three dimensional simulations in general relativity. We first perform a series of numerical tests to show that the gravitational wave (GW) signal obtained is in excellent agreement with the one expected from theory. This benchmark is done for well studied scenarios (such as binary stellar systems). We then apply our code to calculate the GW signals from tidal disruption events, finding that our results are consistent with the theoretical estimates obtained in previous studies for selected parameters. We illustrate interesting results from the catalog, where we stress how the gravitational signal is affected by variations of some parameters (like black hole spin, stellar orbital eccentricity, and inclination). The full catalog is available online. It is intended to be a living catalog.

Completeness of the Gaia verse – V. Astrometry and radial velocity sample selection functions in Gaia EDR3

ABSTRACT We risk reaching false scientific conclusions if we test our physical theories against subsets of the Gaia catalogue without correcting for the biased process by which stars make it into our sample. In this paper, we produce selection functions for three Gaia science samples to enable the community to correct for this bias. We estimate the probability that a source in Gaia EDR3 will have (i) a reported parallax and proper motion, (ii) an astrometric renormalized unit weight error below 1.4, or (iii) a reported radial velocity. These selectionfunctions are estimated as a function of G-band apparent magnitude and position on the sky, with the latter two also being dependent on G − GRP colour. The inferred selection functions have a non-trivial dependence on these observable parameters, demonstrating the importance of empirically estimating selection functions. We also produce a simple estimate for the selection function of the full Gaia EDR3 source catalogue to be used with the subset selection functions. We make all of our selection functions easily accessible through the GitHub repository selectionfunctions.

The Ultraviolet Deep Imaging Survey of Galaxies in the Bootes Void. I. Catalog, Color–Magnitude Relations, and Star Formation

Abstract We present a deep far and near-ultraviolet (FUV and NUV) wide-field imaging survey of galaxies in the Bootes void using the Ultraviolet Imaging Telescope on board AstroSat. Our data reach 5σ limiting magnitudes for point sources at 23.0 and 24.0 AB mag in the FUV and NUV, respectively. We report a total of six star-forming galaxies residing in the Bootes void alongside the full catalog, and of these, three are newly detected in our FUV observation. Our void galaxy sample spans a range of UV colors (−0.35 mag ≤ FUV−NUV ≤ 0.68 mag) and absolute magnitudes (−14.16 mag ≤ M NUV ≤ −18.65 mag). In addition, Sloan Digital Sky Survey and Two Micron All Sky Survey archival data are being used to study UV, optical, and infrared color–magnitude relations for our galaxies in the void. We investigate the nature of bimodal color distribution, morphologies, and star formation of the void galaxies. Most of the galaxies in our sample are fainter and less massive than L* galaxies, with M r > −20 mag. Our analysis reveals a dominant fraction of bluer galaxies over the red ones in the void region probed. The internal and Galactic extinction corrected FUV star formation rates (SFRs) in our void galaxy catalog varies in a large range of 0.05–51.01 M ⊙ yr−1, with a median of 3.96 M ⊙ yr−1. We find a weak effect of the environment on the SFRs of galaxies. Implications of our findings are discussed.

AbacusSummit: a massive set of high-accuracy, high-resolution N-body simulations

ABSTRACT We present the public data release of the AbacusSummit cosmological N-body simulation suite, produced with the Abacus N-body code on the Summit supercomputer of the Oak Ridge Leadership Computing Facility. Abacus achieves $\mathcal {O}(10^{-5})$ median fractional force error at superlative speeds, calculating 70M particle updates per second per node at early times, and 45M particle updates per second per node at late times. The simulation suite totals roughly 60 trillion particles, the core of which is a set of 139 simulations with particle mass $2\times 10^{9}\, h^{-1}\, \mathrm{M}_\odot$ in box size $2\, h^{-1}\, \mathrm{Gpc}$. The suite spans 97 cosmological models, including Planck 2018, previous flagship simulation cosmologies, and a linear derivative and cosmic emulator grid. A subsuite of 1883 boxes of size $500\, h^{-1}\, \mathrm{Mpc}$ is available for covariance estimation. AbacusSummit data products span 33 epochs from z = 8 to 0.1 and include light cones, full particle snapshots, halo catalogues, and particle subsets sampled consistently across redshift. AbacusSummit is the largest high-accuracy cosmological N-body data set produced to date.

Ultra-short-period massive black hole binary candidates in LSST as LISA ‘verification binaries’

ABSTRACT The Legacy Survey of Space and Time (LSST) by the Vera C. Rubin Observatory is expected to discover tens of millions of quasars. A significant fraction of these could be powered by coalescing massive black hole (MBH) binaries, since many quasars are believed to be triggered by mergers. We show that under plausible assumptions about the luminosity functions, lifetimes, and binary fractions of quasars, we expect the full LSST quasar catalogue to contain between 20 and 100 million compact MBH binaries with masses M = 105–9M⊙, redshifts z = 0–6, and orbital periods P = 1–70 d. Their light-curves are expected to be distinctly periodic, which can be confidently distinguished from stochastic red-noise variability, because LSST will cover dozens, or even hundreds of cycles. A very small subset of 10–150 ultracompact (P ≲ 1 d) binary quasars among these will, over ∼5–15 yr, evolve into the mHz gravitational-wave frequency band and can be detected by LISA. They can therefore be regarded as ‘LISA verification binaries’, analogous to short-period Galactic compact-object binaries. The practical question is how to find these handful of ‘needles in the haystack’ among the large number of quasars: this will likely require a tailored co-adding analysis optimized for this purpose.

The introduction of clinical genetic testing in Ethiopia: Experiences and lessons learned.

Limited data are available on genetic testing laboratories in low- and middle-income countries including those in sub-Saharan Africa (SSA). To characterize the need for genetic testing in SSA we describe the experience of MRC-ET Advanced Laboratory, a genetic testing laboratory in Ethiopia. Test results were analyzed based on indication(s) for testing, referral category, and diagnostic yield. A total of 1311 tests were run using the full MRC-Holland catalogue of Multiplex-Ligation Probe Amplification assays. Of all samples, 77% were postnatal samples, 15% products of conception (POC), and 8% amniotic samples. Of postnatal samples, the most common testing categories were multiple congenital anomalies (32%), disorders of sex development (17%), and Obstetrics/Gynecology (16%). Forty-three percent of postnatal samples were diagnostic, 11% were variants of uncertain significance (VUS), and 46% were normal with Trisomy 21 the most common diagnosis. Of POC samples, 10% were diagnostic, 34% revealed VUSs, and 55% were normal with Trisomy 18 the most common diagnosis. Of amniotic samples 17.5% were diagnostic, 3% revealed VUSs, and 79% were normal with Trisomy 18 the most common diagnosis. There is increasing demand for genetic testing in Ethiopia. Diagnostic genetic testing in SSA deserves increased attention as testing platforms become more affordable.

Estimating colocalization probability from limited summary statistics

BackgroundColocalization is a statistical method used in genetics to determine whether the same variant is causal for multiple phenotypes, for example, complex traits and gene expression. It provides stronger mechanistic evidence than shared significance, which can be produced through separate causal variants in linkage disequilibrium. Current colocalization methods require full summary statistics for both traits, limiting their use with the majority of reported GWAS associations (e.g. GWAS Catalog). We propose a new approximation to the popular coloc method that can be applied when limited summary statistics are available.Our method (POint EstiMation of Colocalization, POEMColoc) imputes missing summary statistics for one or both traits using LD structure in a reference panel, and performs colocalization using the imputed summary statistics.ResultsWe evaluate the performance of POEMColoc using real (UK Biobank phenotypes and GTEx eQTL) and simulated datasets. We show good correlation between posterior probabilities of colocalization computed from imputed and observed datasets and similar accuracy in simulation. We evaluate scenarios that might reduce performance and show that multiple independent causal variants in a region and imputation from a limited subset of typed variants have a larger effect while mismatched ancestry in the reference panel has a modest effect. Further, we find that POEMColoc is a better approximation of coloc when the imputed association statistics are from a well powered study (e.g., relatively larger sample size or effect size). Applying POEMColoc to estimate colocalization of GWAS Catalog entries and GTEx eQTL, we find evidence for colocalization of 150,000 trait-gene-tissue triplets.ConclusionsWe find that colocalization analysis performed with full summary statistics can be closely approximated when only the summary statistics of the top SNP are available for one or both traits. When applied to the full GWAS Catalog and GTEx eQTL, we find that colocalized trait-gene pairs are enriched in tissues relevant to disease etiology and for matches to approved drug mechanisms. POEMColoc R package is available at https://github.com/AbbVie-ComputationalGenomics/POEMColoc.

Novel Pathogenic Variants in LHX3, LHX4 and GLI2 Identified in Pediatric Patients With Congenital Hypopituitarism: From Variant Calling To Variant Testing

Congenital hypopituitarism (CH), septo-optic dysplasia (SOD), and holoprosencephaly (HPE) constitute an important group of structural birth defects that cause significant morbidity and life-long consequences for quality of life and care. The genetic causes are highly overlapping. As such, these disorders can be considered as a spectrum of related disorders. Improved insight into genetic causes would be valuable for patients, families, and medical geneticists. Very few systematic genetic screens have been carried out for patients with CH. We implemented genetic screening using single-molecule molecular inversion probes sequencing to identify causative mutations in a set of 67 genes previously reported in CH patients and the spectrum encompassing SOD and HPE. We captured genomic DNA from 170 Argentinean pediatric patients with CH, and 54% of the patients in this cohort have craniofacial, ophthalmologic, and/or central nervous system defects. We found candidate pathogenic, likely pathogenic and variants uncertain significance (VUS) in 23% of the cases. In order to evaluate the functional consequences of VUS in LHX3, LHX4, and GLI2, we performed in-vitro functional assays to study the activity of the mutated proteins. To test LHX3/4 variants we co-transfected HEK293T cells with wild type (WT) or mutated LHX3/4 variant plasmids and luciferase reporter genes driven by the ɑGSU promoter or GH1 promoter and assayed for luciferase activity. For GLI2 functional analysis we used the cell line NIH/3T3-CG, stably transfected to express GFP under the presence of GLI2 activated form. Endogenous Gli2 was knocked out by CRISPR-Cas9 and clones were selected for absence of GFP expression upon activation of the sonic hedgehog pathway. We tested the ability of transfected WT or mutated GLI2 expression plasmids to restore GFP fluorescence. We concluded that variants LHX3:p.Pro187Ser LHX4:p.Arg84His, p.Gln100His and p.Trp204Leu and GLI2:p.1404Lfs impair activation of the reporter gene, while the LHX3:p.Leu220Met and GLI2:p.L761P have WT activity on their respective assays. Identification of disease-causing variants in CH is complicated by phenotypic variation, incomplete penetrance, and VUS. Functional testing of potentially pathogenic variants is critical to arrive at a definitive molecular diagnosis. A full catalogue of variant effects in known causative genes would be invaluable for clinicians in order to simplify the interpretation of novel variants and reduce the diagnostic odyssey that families often experience.