A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Stress corrosion of ASTM Grade-2 and Grade-12 titanium in simulated rock salt brines at 83/sup 0/C

Slow-strain-rate tests have been conducted on Grade-2 and Grade-12 titanium in simulated rock salt brines at 83/sup 0/C. Although neither metal shows stress corrosion cracking, total elongation and reduction in area show some decrease. Optical and SEM results are discussed to elucidate the fracture mechanism

Technique for characterizing crevice corrosion under hydrothermal conditions

The current/potential results show that the crevice corrosion incubation period for a Grade-12 titanium crevice formed between two Teflon plates is about two days at 150/sup 0/C. Optical and SEM observations show that the corrosion starts as isolated pitting which spreads along the surface as shallow pits. The corrosion conditions change significantly as the TiO/sub 2/ corrosion product fills the crevice, and the rate of corrosion may be greatly reduced after several days. The rate of crevice corrosion of commercial purity (Grade-2) titanium under similar consitions is approximately three orders of magnitude higher. In this case, active dissolution of metal starts during the initial heating of the autoclave and the incubation period is negligible

Studies of rubidium aluminosilicates as thermionic emitters of Rb+ ions

International Journal of Mass Spectrometry and Ion Processes1342-3221-228IJMP

Nuclear waste management technical support in the development of nuclear waste form criteria for the NRC. Task 1. Waste package overview

In this report the current state of waste package development for high level waste, transuranic waste, and spent fuel in the US and abroad has been assessed. Specifically, reviewed are recent and on-going research on various waste forms, container materials and backfills and tentatively identified those which are likely to perform most satisfactorily in the repository environment. Radiation effects on the waste package components have been reviewed and the magnitude of these effects has been identified. Areas requiring further research have been identified. The important variables affecting radionuclide release from the waste package have been described and an evaluation of regulatory criteria for high level waste and spent fuel is presented. Finally, for spent fuel, high level, and TRU waste, components which could be used to construct a waste package having potential to meet NRC performance requirements have been described and identified