A Neural Networks Committee for the Contextual Bandit Problem

This paper presents a new contextual bandit algorithm, NeuralBandit, which does not need hypothesis on stationarity of contexts and rewards. Several neural networks are trained to modelize the value of rewards knowing the context. Two variants, based on multi-experts approach, are proposed to choose online the parameters of multi-layer perceptrons. The proposed algorithms are successfully tested on a large dataset with and without stationarity of rewards.Comment: 21st International Conference on Neural Information Processin

VFISV: Very Fast Inversion of the Stokes Vector for the Helioseismic and Magnetic Imager

In this paper we describe in detail the implementation and main properties of a new inversion code for the polarized radiative transfer equation (VFISV: Very Fast inversion of the Stokes vector). VFISV will routinely analyze pipeline data from the Helioseismic and Magnetic Imager (HMI) on-board of the Solar Dynamics Observatory (SDO). It will provide full-disk maps (4096$\times$4096 pixels) of the magnetic field vector on the Solar Photosphere every 10 minutes. For this reason VFISV is optimized to achieve an inversion speed that will allow it to invert 16 million pixels every 10 minutes with a modest number (approx. 50) of CPUs. Here we focus on describing a number of important details, simplifications and tweaks that have allowed us to significantly speed up the inversion process. We also give details on tests performed with data from the spectropolarimeter on-board of the Hinode spacecraft.Comment: 23 pages, 9 figures (2 color). Submitted for publication to Solar Physic

A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate multiple functional annotations. In non-gene-centric analysis, STAARpipeline uses SCANG-STAAR to incorporate dynamic window sizes and multiple functional annotations. We apply STAARpipeline to identify noncoding RV sets associated with four lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several of them in an additional 9,123 TOPMed samples. We also analyze five non-lipid TOPMed traits

Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program

Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n = 109,122 individuals. We identified 59 sentinel variants (p < 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that the independent signals colocalized with cell-type-specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

BACKGROUND: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. METHODS: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. RESULTS: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. CONCLUSIONS: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer

Stress response to chronic inflammation in the horse

Five clinically healthy Thoroughbred geldings were injected with Freund's adjuvant 3 times to induce a chronic inflammatory response. Blood was collected at various times before and after adjuvant administration. Clinical responses (rectal temperature and general demeanour) were also monitored. Adjuvant injection induced increases in rectal temperature and plasma fibrinogen concentration (maximum levels measured were mean ± s.d. 39.7 ± 0.5°C and 8.2 ± 03 g/l, respectively), indicative of an inflammatory response. A mild clinical depression was also observed in the horses for 24 h after the first injection of adjuvant only. Plasma Cortisol levels decreased significantly from control levels of mean ± s.d. 187.7 ± 24.3 nmol/l to a minimum of 80.2 ± 22.1 nmol/l (P<0.01) 9 days after the first injection of adjuvant. Conversely, plasma insulin levels increased after the first injection of adjuvant to a maximum (96.7 ± 15.2 iu/ml; P<0.01) 12 days later, while plasma glucose concentrations tended to decline. A control group of horses to rule out contemporary environmental influences on the physiological and biochemical indices measured was not included in this study. The results show that chronic inflammation in the horse depressed resting plasma Cortisol concentrations

Nesting biology of the Black-bellied Wren (Thryothorus fasciatoventris) in central Panama

We describe the nest and nest site, and provide the first description of the eggs and nesting behavior of the Black-bellied Wren (Thryothorus fasciatoventris) in central Panama. Nine nests were found near tree-fall gaps, swamps, and roads in moist tropical forests. Nests were dome-shaped with a circular side entrance. They were composed chiefly of strips of dead palm fronds, and were generally built in places where leaf litter and other debris had accumulated at the convergence of several vines near the forest floor. Both males and females participated in building the nest. Clutch size was three, and eggs were laid on consecutive days. Egg color varied from creamy to beige with faint to dark brown speckles that were more concentrated at the blunt end. Females were the sole incubators, but males fed the incubating females. Only the female brooded the nestlings once they hatched, but both parents fed the nestlings