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

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

The qualitative transparency deliberations: insights and implications

In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu

Characterization of Suction and CUSA Interaction with Brain Tissue

Basic and ultrasonic aspirators are the most commonly used surgical devices in neurosurgery. In this study, a tissue removal model was adjusted to experimental results of interaction between ultrasonic aspiration and brain tissue-mimicking material. Tissue grasping with a basic aspirator was also further investigated on fresh calf brain tissue obtained from several animals. Tests were conducted on both grey and white matter. The simulation screenshots, compared with the experimental photos, are presented to demonstrate the results.Peer reviewed: YesNRC publication: Ye

Radiation exposure to dwellers due to naturally occurring radionuclides found in selected commercial building materials sold in Nigeria

The activity concentration of 226Ra, 232Th and 40 K was measured in commonly building materials used in Nigeria from commercial supplier using High Purity Germanium Gamma (HPGe) detector. The mean activity concentrations in the samples were found to be 51.5 ± 9.3, 72.46 ± 17.65 and 217.05 ± 44.31 Bqkg-1 for 226Ra, 232Th and 40 K respectively. The highest radium equivalent (Raeq) of 273.9 Bqkg-1 was noted in Perfect Superfix White Cement (Nigeria) but found to be < 370 Bqkg-1 as the recommended dose limiting safe value for bulk media as presumed, the highest value of internal hazard index (Hin) and external hazard index (Hex) of 0.894 and 0.744 respectively were also < 1. The absorbed dose rate (DR) with a value of 122.52 nGyh-1 noted in ceramic tile sample is higher than the weighted population world average value of 80 nGyh-1 by a factor of 1.53. The highest annual effective dose rate (AEDR) of 0.601 mSvy-1 reported in PNT ceramics but was found to be less < 1 mSvy-1 . The investigated materials have the values of Hin, Hex and AEDR greater than 0.5 but less than1, showing that the dose impact exceeds the exemption dose level of 0.3 mSvy-1 for AEDR but complies to the upper limit of dose principle of 1 mSvy-1

Contributions to the correlation and fauna of the permian in Australia and New Zealand

Contributions by a number of authors to a Symposium on the correlation and subdivision of the Australian and New Zealand Permian, at the Canberra Meeting of the Australian and New Zealand Association for the Advancement of Science, held in January 1954, are reviewed, together with some recently published works