Polygenic risk scores for cigarettes smoked per day do not generalize to a Native American population

Recent studies have demonstrated the utility of polygenic risk scores (PRSs) for exploring the genetic etiology of psychiatric phenotypes and the genetic correlations between them. To date, these studies have been conducted almost exclusively using participants of European ancestry, and thus, there is a need for similar studies conducted in other ancestral populations. However, given that the predictive ability of PRSs are sensitive to differences in linkage disequilibrium (LD) patterns and minor allele frequencies across discovery and target samples, the applicability of PRSs developed in European ancestry samples to other ancestral populations has yet to be determined. Therefore, the current study derived PRSs for cigarettes per day (CPD) from predominantly European-ancestry samples and examined their ability to predict nicotine dependence (ND) in a Native American (NA) population sample

VisualDecisionLinc: A visual analytics approach for comparative effectiveness-based clinical decision support in psychiatry

Comparative Effectiveness Research (CER) is designed to provide research evidence on the effectiveness and risks of different therapeutic options on the basis of data compiled from subpopulations of patients with similar medical conditions. Electronic Health Record (EHR) system contain large volumes of patient data that could be used for CER, but the data contained in EHR system are typically accessible only in formats that are not conducive to rapid synthesis and interpretation of therapeutic outcomes. In the time-pressured clinical setting, clinicians faced with large amounts of patient data in formats that are not readily interpretable often feel 'information overload'. Decision support tools that enable rapid access at the point of care to aggregate data on the most effective therapeutic outcomes derived from CER would greatly aid the clinical decision-making process and individualize patient care. In this manuscript, we highlight the role that visual analytics can play in CER-based clinical decision support. We developed a 'VisualDecisionLinc' (VDL) tool prototype that uses visual analytics to provide summarized CER-derived data views to facilitate rapid interpretation of large amounts of data. We highlight the flexibility that visual analytics offers to gain an overview of therapeutic options and outcomes and if needed, to instantly customize the evidence to the needs of the patient or clinician. The VDL tool uses visual analytics to help the clinician evaluate and understand the effectiveness and risk of different therapeutic options for different subpopulations of patients

Patient Electronic Health Data-Driven Approach to Clinical Decision Support

This article presents a novel visual analytics (VA)‐based clinical decision support (CDS) tool prototype that was designed as a collaborative work between Renaissance Computing Institute and Duke University. Using Major Depressive Disorder data from MindLinc electronic health record system at Duke, the CDS tool shows an approach to leverage data from comparative population (patients with similar medical profile) to enhance a clinicians’ decision making process at the point of care. The initial work is being extended in collaboration with the University of North Carolina CTSA to address the key challenges of CDS, as well as to show the use of VA to derive insight from large volumes of Electronic Health Record patient data. Clin Trans Sci 2011; Volume 4: 369–37

Shocks in supersonic sand

We measure time-averaged velocity, density, and temperature fields for steady granular flow past a wedge and calculate a speed of granular pressure disturbances (sound speed) equal to 10% of the flow speed. The flow is supersonic, forming shocks nearly identical to those in a supersonic gas. Molecular dynamics simulations of Newton's laws and Monte Carlo simulations of the Boltzmann equation yield fields in quantitative agreement with experiment. A numerical solution of Navier-Stokes-like equations agrees with a molecular dynamics simulation for experimental conditions excluding wall friction.Comment: 4 pages, 5 figure

Pre-calculated protein structure alignments at the RCSB PDB website: Fig. 1.

Summary: With the continuous growth of the RCSB Protein Data Bank (PDB), providing an up-to-date systematic structure comparison of all protein structures poses an ever growing challenge. Here, we present a comparison tool for calculating both 1D protein sequence and 3D protein structure alignments. This tool supports various applications at the RCSB PDB website. First, a structure alignment web service calculates pairwise alignments. Second, a stand-alone application runs alignments locally and visualizes the results. Third, pre-calculated 3D structure comparisons for the whole PDB are provided and updated on a weekly basis. These three applications allow users to discover novel relationships between proteins available either at the RCSB PDB or provided by the user

Association and ancestry analysis of sequence variants in ADH and ALDH using alcohol-related phenotypes in a Native American community sample

Higher rates of alcohol use and other drug-dependence have been observed in some Native American populations relative to other ethnic groups in the U.S. Previous studies have shown that alcohol dehydrogenase (ADH) genes and aldehyde dehydrogenase (ALDH) genes may affect the risk of development of alcohol dependence, and that polymorphisms within these genes may differentially affect risk for the disorder depending on the ethnic group evaluated. We evaluated variations in the ADH and ALDH genes in a large study investigating risk factors for substance use in a Native American population. We assessed ancestry admixture and tested for associations between alcohol-related phenotypes in the genomic regions around the ADH1-7 and ALDH2 and ALDH1A1 genes. Seventy-two (72) ADH variants showed significant evidence of association with a severity level of alcohol drinking-related dependence symptoms phenotype. These significant variants spanned across the entire 7 ADH gene cluster regions. Two significant associations, one in ADH and one in ALDH2, were observed with alcohol dependence diagnosis. Seventeen (17) variants showed significant association with the largest number of alcohol drinks ingested during any 24-hour period. Variants in or near ADH7 were significantly negatively associated with alcohol-related phenotypes, suggesting a potential protective effect of this gene. In addition, our results suggested that a higher degree of Native American ancestry is associated with higher frequencies of potential risk variants and lower frequencies of potential protective variants for alcohol dependence phenotypes

An informatics approach to analyzing the incidentalome

Next-generation sequencing (NGS) has transformed genetic research and is poised to revolutionize clinical diagnosis. However, the vast amount of data and inevitable discovery of incidental findings require novel analytic approaches. We therefore implemented for the first time a strategy that utilizes an a priori structured framework and a conservative threshold for selecting clinically relevant incidental findings

ReQON: a Bioconductor package for recalibrating quality scores from next-generation sequencing data

AbstractBackgroundNext-generation sequencing technologies have become important tools for genome-wide studies. However, the quality scores that are assigned to each base have been shown to be inaccurate. If the quality scores are used in downstream analyses, these inaccuracies can have a significant impact on the results.ResultsHere we present ReQON, a tool that recalibrates the base quality scores from an input BAM file of aligned sequencing data using logistic regression. ReQON also generates diagnostic plots showing the effectiveness of the recalibration. We show that ReQON produces quality scores that are both more accurate, in the sense that they more closely correspond to the probability of a sequencing error, and do a better job of discriminating between sequencing errors and non-errors than the original quality scores. We also compare ReQON to other available recalibration tools and show that ReQON is less biased and performs favorably in terms of quality score accuracy.ConclusionReQON is an open source software package, written in R and available through Bioconductor, for recalibrating base quality scores for next-generation sequencing data. ReQON produces a new BAM file with more accurate quality scores, which can improve the results of downstream analysis, and produces several diagnostic plots showing the effectiveness of the recalibration

ReQON: a Bioconductor package for recalibrating quality scores from next-generation sequencing data

Background Next-generation sequencing technologies have become important tools for genome-wide studies. However, the quality scores that are assigned to each base have been shown to be inaccurate. If the quality scores are used in downstream analyses, these inaccuracies can have a significant impact on the results. Results Here we present ReQON, a tool that recalibrates the base quality scores from an input BAM file of aligned sequencing data using logistic regression. ReQON also generates diagnostic plots showing the effectiveness of the recalibration. We show that ReQON produces quality scores that are both more accurate, in the sense that they more closely correspond to the probability of a sequencing error, and do a better job of discriminating between sequencing errors and non-errors than the original quality scores. We also compare ReQON to other available recalibration tools and show that ReQON is less biased and performs favorably in terms of quality score accuracy. Conclusion ReQON is an open source software package, written in R and available through Bioconductor, for recalibrating base quality scores for next-generation sequencing data. ReQON produces a new BAM file with more accurate quality scores, which can improve the results of downstream analysis, and produces several diagnostic plots showing the effectiveness of the recalibration

Low-Cost Access to the Deep, High-Cadence Sky: the Argus Optical Array

New mass-produced, wide-field, small-aperture telescopes have the potential to revolutionize ground-based astronomy by greatly reducing the cost of collecting area. In this paper, we introduce a new class of large telescope based on these advances: an all-sky, arcsecond-resolution, 1000-telescope array which builds a simultaneously high-cadence and deep survey by observing the entire sky all night. As a concrete example, we describe the Argus Array, a 5m-class telescope with an all-sky field of view and the ability to reach extremely high cadences using low-noise CMOS detectors. Each 55 GPix Argus exposure covers 20% of the entire sky to g=19.6 each minute and g=21.9 each hour; a high-speed mode will allow sub-second survey cadences for short times. Deep coadds will reach g=23.6 every five nights over 47% of the sky; a larger-aperture array telescope, with an \'etendue close to the Rubin Observatory, could reach g=24.3 in five nights. These arrays can build two-color, million-epoch movies of the sky, enabling sensitive and rapid searches for high-speed transients, fast-radio-burst counterparts, gravitational-wave counterparts, exoplanet microlensing events, occultations by distant solar system bodies, and myriad other phenomena. An array of O(1,000) telescopes, however, would be one of the most complex astronomical instruments yet built. Standard arrays with hundreds of tracking mounts entail thousands of moving parts and exposed optics, and maintenance costs would rapidly outpace the mass-produced-hardware cost savings compared to a monolithic large telescope. We discuss how to greatly reduce operations costs by placing all optics in a thermally controlled, sealed dome with a single moving part. Coupled with careful software scope control and use of existing pipelines, we show that the Argus Array could become the deepest and fastest Northern sky survey, with total costs below $20M.Comment: 17 pages, 5 figures, 2 table