Development of a targeted amplicon sequencing method for genotyping from fresh produce and clinical samples with enhanced genomic resolution and sensitivity.

Outbreaks of cyclosporiasis, an enteric illness caused by the parasite , have been associated with consumption of various types of fresh produce. Although a method is in use for genotyping from clinical specimens, the very low abundance of in food and environmental samples presents a greater challenge. To complement epidemiological investigations, a molecular surveillance tool is needed for use in genetic linkage of food vehicles to cyclosporiasis illnesses, estimation of the scope of outbreaks or clusters of illness, and determination of geographical areas involved.

Patterns of antiemetic medication use during pregnancy: A multi-country retrospective cohort study.

Objective: To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014.

Methods: We constructed population-based cohorts of pregnant women using administrative healthcare data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan), the Clinical Practice Research Datalink from the United Kingdom, and the IBM MarketScan Research Databases from the United States. We included pregnancies ending in live births, stillbirth, spontaneous abortion, or induced abortion.

DSIF modulates RNA polymerase II occupancy according to template G + C content.

The DSIF complex comprising the Supt4h and Supt5h transcription elongation proteins clamps RNA polymerase II (RNAPII) onto DNA templates, facilitating polymerase processivity. Lowering DSIF components can differentially decrease expression of alleles containing nucleotide repeat expansions, suggesting that RNAPII transit through repeat expansions is dependent on DSIF functions. To globally identify sequence features that affect dependence of the polymerase on DSIF in human cells, we used ultra-deep ChIP-seq analysis and RNA-seq to investigate and quantify the genome-wide effects of Supt4h loss on template occupancy and transcript production.

A comprehensive HPV-STI NGS assay for detection of 29 HPV types and 14 non-HPV sexually transmitted infections.

Background: Sexually transmitted infections (STIs) are prevalent throughout the world and impose a significant burden on individual health and public health systems. Missed diagnosis and late treatment of STIs can lead to serious complications such as infertility and cervical cancer. Although sexually transmitted co-infections are common, most commercial assays target one or a few STIs.

Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort.

Importance: Ondansetron is frequently used to treat nausea and vomiting during pregnancy. Although some studies reported important safety signals, few studies have been sufficiently large to assess rare pregnancy outcomes.

Objective: To study the association between ondansetron exposure during pregnancy and the risks of spontaneous abortion, stillbirth, and major congenital malformations.

CTLA-4 expression by B-1a B cells is essential for immune tolerance.

CTLA-4 is an important regulator of T-cell function. Here, we report that expression of this immune-regulator in mouse B-1a cells has a critical function in maintaining self-tolerance by regulating these early-developing B cells that express a repertoire enriched for auto-reactivity. Selective deletion of CTLA-4 from B cells results in mice that spontaneously develop autoantibodies, T follicular helper (Tfh) cells and germinal centers (GCs) in the spleen, and autoimmune pathology later in life.

Estimated GFR and Incidence of Major Surgery: A Population-Based Cohort Study.

Rationale & Objective: Kidney disease is associated with an increased risk for postoperative morbidity and mortality. However, the incidence of major surgery on a population level is unknown. We aimed to determine the incidence of major surgery by level of kidney function.

Association between change in physician remuneration and use of peritoneal dialysis: a population-based cohort analysis.

Background: Health care payers are interested in policy-level interventions to increase peritoneal dialysis use in end-stage renal disease. We examined whether increases in physician remuneration for peritoneal dialysis were associated with greater peritoneal dialysis use.

Methods: We studied a cohort of patients in Alberta who started long-term dialysis with at least 90 days of preceding nephrologist care between Jan.

Association of Specialist Physician Payment Model With Visit Frequency, Quality, and Costs of Care for People With Chronic Disease.

Importance: Specialist physicians are key members of chronic care management teams; to date, however, little is known about the association between specialist payment models and outcomes for patients with chronic diseases.

Objective: To examine the association of payment model with visit frequency, quality of care, and costs for patients with chronic diseases seen by specialists.

Design, Setting, And Participants: A retrospective cohort study using propensity-score matching in patients seen by a specialist physician was conducted between April 1, 2011, and September 31, 2014.

Genome-wide effects of social status on DNA methylation in the brain of a cichlid fish, Astatotilapia burtoni.

Background: Successful social behavior requires real-time integration of information about the environment, internal physiology, and past experience. The molecular substrates of this integration are poorly understood, but likely modulate neural plasticity and gene regulation. In the cichlid fish species Astatotilapia burtoni, male social status can shift rapidly depending on the environment, causing fast behavioral modifications and a cascade of changes in gene transcription, the brain, and the reproductive system.

Association of Mental Health Disorders With Health Care Utilization and Costs Among Adults With Chronic Disease.

Importance: A population-based study using validated algorithms to estimate the costs of treating people with chronic disease with and without mental health disorders is needed.

Objective: To determine the association of mental health disorders with health care costs among people with chronic diseases.

Design, Setting, And Participants: This population-based cohort study in the Canadian province of Alberta collected data from April 1, 2012, to March 31, 2015, among 991 445 adults 18 years and older with a chronic disease (ie, asthma, congestive heart failure, myocardial infarction, diabetes, epilepsy, hypertension, chronic pulmonary disease, or chronic kidney disease).

The association between payment model and specialist physicians' selection of patients with diabetes: a descriptive study.

Background: As the number of people with chronic diseases increases, understanding the impact of payment model on the types of patients seen by specialists has implications for improving the quality and value of care. We sought to determine if there is an association between specialist physician payment model and the types of patients seen.

Methods: In this descriptive study, we used administrative data to compare demographic characteristics, illness severity and visit indication of patients with diabetes seen by fee-for-service and salary-based internal medicine and diabetes specialists in Calgary and Edmonton between April 2011 and September 2014.

Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression.

The senescence of mammalian cells is characterized by a proliferative arrest in response to stress and the expression of an inflammatory phenotype. Here we show that histone H2A.J, a poorly studied H2A variant found only in mammals, accumulates in human fibroblasts in senescence with persistent DNA damage.

Warfarin Initiation, Atrial Fibrillation, and Kidney Function: Comparative Effectiveness and Safety of Warfarin in Older Adults With Newly Diagnosed Atrial Fibrillation.

Background: The effectiveness and safety of warfarin use among patients with atrial fibrillation (AF) and reduced kidney function are uncertain.

Study Design: Community-based retrospective cohort study (May 1, 2003, to March 31, 2012) using province-wide laboratory and administrative data in Alberta, Canada.

Setting & Participants: 14,892 adults 66 years or older with new AF and a measurement of kidney function.

Lifetime risk of diabetes among First Nations and non-First Nations people.

Background: Lifetime risk is a relatively straightforward measure used to communicate disease burden, representing the cumulative risk of an outcome during the remainder of an individual's life starting from a disease-free index age. We estimated the lifetime risk of diabetes among men and women in both First Nations and non-First Nations populations using a cohort of adults in a single Canadian province.

Methods: We used a population-based cohort consisting of Alberta residents from 1997 to 2008 who were free of diabetes at cohort entry to estimate the lifetime risk of diabetes among First Nations and non-First Nations people.

Identification of Human Neuronal Protein Complexes Reveals Biochemical Activities and Convergent Mechanisms of Action in Autism Spectrum Disorders.

The prevalence of autism spectrum disorders (ASDs) is rapidly growing, yet its molecular basis is poorly understood. We used a systems approach in which ASD candidate genes were mapped onto the ubiquitous human protein complexes and the resulting complexes were characterized. The studies revealed the role of histone deacetylases (HDAC1/2) in regulating the expression of ASD orthologs in the embryonic mouse brain.

The association between kidney function and major bleeding in older adults with atrial fibrillation starting warfarin treatment: population based observational study.

Objective: To determine rates of major bleeding by level of kidney function for older adults with atrial fibrillation starting warfarin.

Design: Retrospective cohort study.

Setting: Community based, using province wide laboratory and administrative data in Alberta, Canada.

Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.

Autism is a complex disease whose etiology remains elusive. We integrated previously and newly generated data and developed a systems framework involving the interactome, gene expression and genome sequencing to identify a protein interaction module with members strongly enriched for autism candidate genes. Sequencing of 25 patients confirmed the involvement of this module in autism, which was subsequently validated using an independent cohort of over 500 patients.

Principles of regulatory information conservation between mouse and human.

To broaden our understanding of the evolution of gene regulation mechanisms, we generated occupancy profiles for 34 orthologous transcription factors (TFs) in human-mouse erythroid progenitor, lymphoblast and embryonic stem-cell lines. By combining the genome-wide transcription factor occupancy repertoires, associated epigenetic signals, and co-association patterns, here we deduce several evolutionary principles of gene regulatory features operating since the mouse and human lineages diverged. The genomic distribution profiles, primary binding motifs, chromatin states, and DNA methylation preferences are well conserved for TF-occupied sequences.

A comparative encyclopedia of DNA elements in the mouse genome.

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

Insect-induced tree mortality of boreal forests in eastern Canada under a changing climate.

Forest insects are major disturbances that induce tree mortality in eastern coniferous (or fir-spruce) forests in eastern North America. The spruce budworm (SBW) (Choristoneura fumiferana [Clemens]) is the most devastating insect causing tree mortality. However, the relative importance of insect-caused mortality versus tree mortality caused by other agents and how this relationship will change with climate change is not known.

Widespread contribution of transposable elements to the innovation of gene regulatory networks.

Transposable elements (TEs) have been shown to contain functional binding sites for certain transcription factors (TFs). However, the extent to which TEs contribute to the evolution of TF binding sites is not well known. We comprehensively mapped binding sites for 26 pairs of orthologous TFs in two pairs of human and mouse cell lines (representing two cell lineages), along with epigenomic profiles, including DNA methylation and six histone modifications.

Whole-genome haplotyping using long reads and statistical methods.

The rapid growth of sequencing technologies has greatly contributed to our understanding of human genetics. Yet, despite this growth, mainstream technologies have not been fully able to resolve the diploid nature of the human genome. Here we describe statistically aided, long-read haplotyping (SLRH), a rapid, accurate method that uses a statistical algorithm to take advantage of the partially phased information contained in long genomic fragments analyzed by short-read sequencing.

In-depth characterization of microRNA transcriptome in melanoma.

The full repertoire of human microRNAs (miRNAs) that could distinguish common (benign) nevi from cutaneous (malignant) melanomas remains to be established. In an effort to gain further insight into the role of miRNAs in melanoma, we applied Illumina next-generation sequencing (NGS) platform to carry out an in-depth analysis of miRNA transcriptome in biopsies of nevi, thick primary (>4.0 mm) and metastatic melanomas with matched normal skin in parallel to melanocytes and melanoma cell lines (both primary and metastatic) (n=28).

An encyclopedia of mouse DNA elements (Mouse ENCODE).

To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.