A Flexible Bayesian Generalized Linear Model for Dichotomous Response Data with an Application to Text Categorization

We present a class of sparse generalized linear models that include probit and logistic regression as special cases and offer some extra flexibility. We provide an EM algorithm for learning the parameters of these models from data. We apply our method in text classification and in simulated data and show that our method outperforms the logistic and probit models and also the elastic net, in general by a substantial margin

Novel loci and Mapuche genetic ancestry are associated with pubertal growth traits in Chilean boys

Puberty is a complex developmental process that varies considerably among individuals and populations. Genetic factors explain a large proportion of the variability of several pubertal traits. Recent genome-wide association studies (GWAS) have identified hundreds of variants involved in traits that result from body growth, like adult height. However, they do not capture many genetic loci involved in growth changes over distinct growth phases. Further, such GWAS have been mostly performed in Europeans, but it is unknown how these findings relate to other continental populations. In this study, we analyzed the genetic basis of three pubertal traits; namely, peak height velocity (PV), age at PV (APV) and height at APV (HAPV). We analyzed a cohort of 904 admixed Chilean children and adolescents with European and Mapuche Native American ancestries. Height was measured on roughly a 6−month basis from childhood to adolescence between 2006 and 2019. We predict that, in average, HAPV is 4.3 cm higher in European than in Mapuche adolescents (P = 0.042), and APV is 0.73 years later in European compared with Mapuche adolescents (P = 0.023). Further, by performing a GWAS on 774, 433 single-nucleotide polymorphisms, we identified a genetic signal harboring 3 linked variants significantly associated with PV in boys (P <5×10−8). This signal has never been associated with growth-related traits

Exploratory Visualization of Astronomical Data on Ultra-high-resolution Wall Displays

International audienceUltra-high-resolution wall displays feature a very high pixel density over a large physical surface, which makes them well-suited to the collaborative, exploratory visualization of large datasets. We introduce FITS-OW, an application designed for such wall displays, that enables astronomers to navigate in large collections of FITS images, query astronomical databases, and display detailed, complementary data and documents about multiple sources simultaneously. We describe how astronomers interact with their data using both the wall's touch-sensitive surface and handheld devices. We also report on the technical challenges we addressed in terms of distributed graphics rendering and data sharing over the computer clusters that drive wall displays

Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia

Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. LCAT sequencing identified rare p.V333 M and p.M404 V missense mutations in compound heterozygous state in the proband, as well the common synonymous p.L363 L variant. LCAT protein was detected in proband’s plasma, but with undetectable enzyme activity compared to control relatives. HEK-293 T transfected cells with vector expression plasmids containing either p.M404 V or p.V333 M cDNA showed detectable LCAT protein expression both in supernatants and lysates from cultured cells, but with much lower enzyme activity compared to cells transfected with the wild-type sequence. Bioinformatic analyses also supported a causal role of such rare variations in LCAT lack of function. Additionally, the proband carried the minor allele of the synonymous p.L363 L variant. However, this variant is unlikely to affect the clinical phenotype of the proband given its relatively high frequency in the Chilean population (4%) and its small putative effect on plasma HDL-cholesterol levels. Conclusion: Genetic, biochemical, in vitro and in silico analyses indicate that the rare mutations p.M404 V and p. V333 M in LCAT gene lead to suppression of LCAT enzyme activity and cause clinical features of familial LCAT deficiency.This work was supported by Proyecto FONDECYT 1150416 and Proyecto Interdisciplina VRI-PUC II15024 from the Dirección de Investigación, Pontificia Universidad Católica de Chile. Genotyping of GOCS was performed in the in the Human Genotyping laboratory at the Spanish National Cancer Research Centre, a member of CeGen (PRB2-ISCIII), and was supported by grant PT13/ 0001/0005 of PE I + D + i 2013-2016 funded by ISCIII and ERDF (Fondo Europeo de Desarrollo Regional). This research was partially supported by the supercomputing infrastructure of the NLHPC (ECM-02). L.V. and C.B. were supported by VRI, Pontificia Universidad Católica de Chile (Proyecto Investigación Interdisciplinaria VRI-PUC II15024). TG was supported by “Beca de Magíster Nacional” CONICYT. L.V. was additionally supported by FONDECYT postdoctoral grant 3170038. We express our gratitude to the proband and relatives

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

BACKGROUND: Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. METHODS: We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. RESULTS: A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. CONCLUSION: The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean famil

THE ACS VIRGO CLUSTER SURVEY XVI. SELECTION PROCEDURE AND CATALOGS OF GLOBULAR CLUSTER CANDIDATES

We present catalogs of globular cluster candidates for the 100 galaxies of the Advanced Camera for Surveys Virgo Cluster Survey, a large program to carry out imaging of early-type members of the Virgo Cluster using the Advanced Camera for Surveys (ACS) on the Hubble Space Telescope. We describe the procedure used to select bona fide globular cluster candidates out of the full list of detections based on model-based clustering methods with the use of expected contamination catalogs constructed using blank field observations and which are customized for each galaxy. We also present the catalogs of expected contaminants for each of our target galaxies. For each detected source we measure its position, magnitudes in the F475W (≈ Sloan g) and F850LP (≈ Sloan z) bandpasses, and half-light radii by fitting point-spread function convolved King models to the observed light distribution. These measurements are presented for 20,375 sources, of which 12,763 are likely to be globular clusters. Finally, we detail the calculation of the aperture corrections adopted for the globular cluster photometry

A Ground-based Optical Transmission Spectrum of WASP-6b

We present a ground-based optical transmission spectrum of the inflated sub-Jupiter-mass planet WASP-6b. The spectrum was measured in 20 spectral channels from 480 nm to 860 nm using a series of 91 spectra over a complete transit event. The observations were carried out using multi-object differential spectrophotometry with the Inamori-Magellan Areal Camera and Spectrograph on the Baade Telescope at Las Campanas Observatory. We model systematic effects on the observed light curves using principal component analysis on the comparison stars and allow for the presence of short and long memory correlation structure in our Monte Carlo Markov Chain analysis of the transit light curves for WASP-6. The measured transmission spectrum presents a general trend of decreasing apparent planetary size with wavelength and lacks evidence for broad spectral features of Na and K predicted by clear atmosphere models. The spectrum is consistent with that expected for scattering that is more efficient in the blue, as could be caused by hazes or condensates in the atmosphere of WASP-6b. WASP-6b therefore appears to be yet another massive exoplanet with evidence for a mostly featureless transmission spectrum, underscoring the importance that hazes and condensates can have in determining the transmission spectra of exoplanets

Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations

Hypertension is a complex disease that affects a large proportion of adult population. Although approximately half of the inter-individual variance in blood pressure (BP) level is heritable, identification of genes responsible for its regulation has remained challenging. Genome-wide association study (GWAS) is a novel approach to search for genetic variants contributing to complex diseases. We conducted GWAS for three BP traits [systolic and diastolic blood pressure (SBP and DBP); hypertension (HYP)] in the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) S3 cohort (n = 1644) recruited from general population in Southern Germany. GWAS with 395 912 single nucleotide polymorphisms (SNPs) identified an association between BP traits and a common variant rs11646213 (T/A) upstream of the CDH13 gene at 16q23.3. The initial associations with HYP and DBP were confirmed in two other European population-based cohorts: KORA S4 (Germans) and HYPEST (Estonians). The associations between rs11646213 and three BP traits were replicated in combined analyses (dominant model: DBP, P = 5.55 × 10–5, effect –1.40 mmHg; SBP, P = 0.007, effect –1.56 mmHg; HYP, P = 5.30 × 10−8, OR = 0.67). Carriers of the minor allele A had a decreased risk of hypertension. A non-significant trend for association was also detected with severe family based hypertension in the BRIGHT sample (British). The novel susceptibility locus, CDH13, encodes for an adhesion glycoprotein T-cadherin, a regulator of vascular wall remodeling and angiogenesis. Its function is compatible with the BP biology and may improve the understanding of the pathogenesis of hypertension