Comparing Ancestry Standardization Approaches for a Transancestry Colorectal Cancer Polygenic Risk Score.

Colorectal cancer (CRC) is a complex disease with monogenic, polygenic and environmental risk factors. Polygenic risk scores (PRSs) aim to identify high polygenic risk individuals. Due to differences in genetic background, PRS distributions vary by ancestry, necessitating standardization.

A blended genome and exome sequencing method captures genetic variation in an unbiased, high-quality, and cost-effective manner.

We deployed the Blended Genome Exome (BGE), a DNA library blending approach that generates low pass whole genome (1-4× mean depth) and deep whole exome (30-40× mean depth) data in a single sequencing run. This technology is cost-effective, empowers most genomic discoveries possible with deep whole genome sequencing, and provides an unbiased method to capture the diversity of common SNP variation across the globe. To evaluate this new technology at scale, we applied BGE to sequence >53,000 samples from the Populations Underrepresented in Mental Illness Associations Studies (PUMAS) Project, which included participants across African, African American, and Latin American populations.

Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations.

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer.

Detection of Copy-Number Variation in Circulating Cell-Free DNA in Patients With Uveal Melanoma.

Purpose: Somatic chromosomal alterations, particularly monosomy 3 and 8q gains, have been associated with metastatic risk in uveal melanoma (UM). Whole genome-scale evaluation of detectable alterations in cell-free DNA (cfDNA) in UM could provide valuable prognostic information. Our pilot study evaluates the correlation between genomic information using ultra-low-pass whole-genome sequencing (ULP-WGS) of cfDNA in UM and associated clinical outcomes.

Comparing ancestry calibration approaches for a trans-ancestry colorectal cancer polygenic risk score.

Background: Colorectal cancer (CRC) is a complex disease with monogenic, polygenic and environmental risk factors. Polygenic risk scores (PRS) are being developed to identify high polygenic risk individuals. Due to differences in genetic background, PRS distributions vary by ancestry, necessitating calibration.

Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations.

Background: Type 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association studies (GWAS), polygenic risk scores (PRS) have shown promise to complement established clinical risk factors and intervention paradigms, and improve early diagnosis and prevention of T2D. However, to date, T2D PRS have been most widely developed and validated in individuals of European descent.

Genome-wide polygenic score to predict chronic kidney disease across ancestries.

Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-wide association studies (GWAS) of kidney function, we designed, optimized and validated a genome-wide polygenic score (GPS) for CKD.

Whole-genome sequencing as an investigational device for return of hereditary disease risk and pharmacogenomic results as part of the All of Us Research Program.

Background: The All of Us Research Program (AoURP, "the program") is an initiative, sponsored by the National Institutes of Health (NIH), that aims to enroll one million people (or more) across the USA. Through repeated engagement of participants, a research resource is being created to enable a variety of future observational and interventional studies. The program has also committed to genomic data generation and returning important health-related information to participants.

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun.

Search for Nucleon and Dinucleon Decays with an Invisible Particle and a Charged Lepton in the Final State at the Super-Kamiokande Experiment.

Search results for nucleon decays p→e^{+}X, p→μ^{+}X, n→νγ (where X is an invisible, massless particle) as well as dinucleon decays np→e^{+}ν, np→μ^{+}ν, and np→τ^{+}ν in the Super-Kamiokande experiment are presented. Using single-ring data from an exposure of  273.4  kton·yr, a search for these decays yields a result consistent with no signal.

The effect of age and teat order on alpha1-acid glycoprotein, neutrophil-to-lymphocyte ratio, cortisol, and average daily gain in commercial growing pigs.

The objectives of the study were to evaluate age and teat order on a performance trait, average daily gain, and on physiological stress indicators, alpha1-acid glycoprotein (AGP), neutrophil-to-lymphocyte ratio (N:L), and cortisol in commercial growing pigs from weaning to market age. Pigs (n = 129) from five commercial California farms were weighed and blood-sampled at 28-d intervals from 28 to 168 d of age. Laboratory assays were performed from blood samples to quantify cortisol, AGP, and N:L.

Comparison of sampling and culture methods for the diagnosis of Tritrichomonas foetus infection in bulls.

Sampling methods for preputial secretions and culture methods for Tritrichomonas foetus were compared in a two-by-two factorial experiment. Fourteen bulls were confirmed as infected by repeated weekly sampling and culture on Diamond's medium over the course of 10 months. In a six-week test of alternative methods of diagnosis, the bulls were randomly assigned to have their preputial contents sampled weekly either by washing or by scraping of the preputial membrane.

Secondhand cigarette smoke as a cause of chronic carbon monoxide poisoning.

Symptoms of carbon monoxide poisoning in a nonsmoking patient continued for several years until her husband stopped smoking cigarettes near her. Carbon monoxide poisoning should be considered in non-smokers when characteristic toxic symptoms occur (ie, lethargy, irritability, headache, blurred vision, slowed reaction time, and decreased concentration). Toxicity may develop simply from breathing second-hand smoke.