XY sex determination in a cnidarian.

Background: Sex determination occurs across animal species, but most of our knowledge about its mechanisms comes from only a handful of bilaterian taxa. This limits our ability to infer the evolutionary history of sex determination within animals.

Results: In this study, we generated a linkage map of the genome of the colonial cnidarian Hydractinia symbiolongicarpus and used it to demonstrate that this species has an XX/XY sex determination system.

Genotype first: Clinical genomics research through a reverse phenotyping approach.

Although genomic research has predominantly relied on phenotypic ascertainment of individuals affected with heritable disease, the falling costs of sequencing allow consideration of genomic ascertainment and reverse phenotyping (the ascertainment of individuals with specific genomic variants and subsequent evaluation of physical characteristics). In this research modality, the scientific question is inverted: investigators gather individuals with a genomic variant and test the hypothesis that there is an associated phenotype via targeted phenotypic evaluations. Genomic ascertainment research is thus a model of predictive genomic medicine and genomic screening.

HLA-associated outcomes in peanut oral immunotherapy trials identify mechanistic and clinical determinants of therapeutic success.

Rationale: Previous studies identified an interaction between HLA and oral peanut exposure. HLA-DQA1*01:02 had a protective role with the induction of Ara h 2 epitope-specific IgG4 associated with peanut consumption during the LEAP clinical trial for prevention of peanut allergy, while it was a risk allele for peanut allergy in the peanut avoidance group. We have now evaluated this gene-environment interaction in two subsequent peanut oral immunotherapy (OIT) trials - IMPACT and POISED - to better understand the potential for the HLA-DQA1*01:02 allele as an indicator of higher likelihood of desensitization, sustained unresponsiveness, and peanut allergy remission.

A Chromosome-Length Assembly of the Hawaiian Monk Seal (): A History of "Genetic Purging" and Genomic Stability.

The Hawaiian monk seal (HMS) is the single extant species of tropical earless seals of the genus The species survived a severe bottleneck in the late 19th century and experienced subsequent population declines until becoming the subject of a NOAA-led species recovery effort beginning in 1976 when the population was fewer than 1000 animals. Like other recovering species, the Hawaiian monk seal has been reported to have reduced genetic heterogeneity due to the bottleneck and subsequent inbreeding. Here, we report a chromosomal reference assembly for a male animal produced using a variety of methods.

Mango: Exploratory Data Analysis for Large-Scale Sequencing Datasets.

The decreasing cost of DNA sequencing over the past decade has led to an explosion of sequencing datasets, leaving us with petabytes of data to analyze. However, current sequencing visualization tools are designed to run on single machines, which limits their scalability and interactivity on modern genomic datasets. Here, we leverage the scalability of Apache Spark to provide Mango, consisting of a Jupyter notebook and genome browser, which removes scalability and interactivity constraints by leveraging multi-node compute clusters to allow interactive analysis over terabytes of sequencing data.

Tools for annotation and comparison of structural variation.

The impact of structural variants (SVs) on a variety of organisms and diseases like cancer has become increasingly evident. Methods for SV detection when studying genomic differences across cells, individuals or populations are being actively developed. Currently, just a few methods are available to compare different SVs callsets, and no specialized methods are available to annotate SVs that account for the unique characteristics of these variant types.

International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases.

Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their "diagnostic odyssey," improves disease management, and fosters genetic counseling with respect to recurrence risks while assuring reproductive choices. In a general clinical genetics setting, the current diagnostic rate is approximately 50%, but for those who do not receive a molecular diagnosis after the initial genetics evaluation, that rate is much lower. Diagnostic success for these more challenging affected individuals depends to a large extent on progress in the discovery of genes associated with, and mechanisms underlying, rare diseases.

Open Targets: a platform for therapeutic target identification and validation.

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources.

Highly sensitive and ultrafast read mapping for RNA-seq analysis.

As sequencing technologies progress, the amount of data produced grows exponentially, shifting the bottleneck of discovery towards the data analysis phase. In particular, currently available mapping solutions for RNA-seq leave room for improvement in terms of sensitivity and performance, hindering an efficient analysis of transcriptomes by massive sequencing. Here, we present an innovative approach that combines re-engineering, optimization and parallelization.

The Matchmaker Exchange: a platform for rare disease gene discovery.

There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be a reliable or scalable approach in science.

The European Genome-phenome Archive of human data consented for biomedical research.

The European Genome-phenome Archive (EGA) is a permanent archive that promotes distribution and sharing of genetic and phenotype data consented for specific approved uses, but not fully open public distribution. The EGA follows strict protocols for information management, data storage, security and dissemination. Authorized access to the data is managed in partnership with the data providing organizations.

Truncation of the flash-lag effect by a fixed spatial landmark.

The flash-lag effect is a visual illusion where a moving image is perceived to be advanced in its spatial location relative to a flashed image. Multiple studies have shown that the flash-lag effect can be enhanced by increasing the uncertainty of the moving and/or flashed images. However, little is known about the effect of task-irrelevant visual objects on the flash-lag effect.

RD-Connect: an integrated platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research.

Research into rare diseases is typically fragmented by data type and disease. Individual efforts often have poor interoperability and do not systematically connect data across clinical phenotype, genomic data, biomaterial availability, and research/trial data sets. Such data must be linked at both an individual-patient and whole-cohort level to enable researchers to gain a complete view of their disease and patient population of interest.

Paraproteinemic maculopathy.

Purpose: Paraproteinemia relates to monoclonal gammopathy-producing pathologic antibodies with serous macular detachment being an uncommon ocular manifestation. We ascertained the clinical course of maculopathy in paraproteinemia and investigated the effect of various therapeutic methods on the resolution of subretinal deposits.

Design: Multicenter, retrospective, observational case series.

DbVar and DGVa: public archives for genomic structural variation.

Much has changed in the last two years at DGVa (http://www.ebi.ac.

Pitfalls of merging GWAS data: lessons learned in the eMERGE network and quality control procedures to maintain high data quality.

Genome-wide association studies (GWAS) are a useful approach in the study of the genetic components of complex phenotypes. Aside from large cohorts, GWAS have generally been limited to the study of one or a few diseases or traits. The emergence of biobanks linked to electronic medical records (EMRs) allows the efficient reuse of genetic data to yield meaningful genotype-phenotype associations for multiple phenotypes or traits.

Assessing and managing risk when sharing aggregate genetic variant data.

Access to genetic data across studies is an important aspect of identifying new genetic associations through genome-wide association studies (GWASs). Meta-analysis across multiple GWASs with combined cohort sizes of tens of thousands of individuals often uncovers many more genome-wide associated loci than the original individual studies; this emphasizes the importance of tools and mechanisms for data sharing. However, even sharing summary-level data, such as allele frequencies, inherently carries some degree of privacy risk to study participants.

An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities.

Purpose: Copy number variants have emerged as a major cause of human disease such as autism and intellectual disabilities. Because copy number variants are common in normal individuals, determining the functional and clinical significance of rare copy number variants in patients remains challenging. The adoption of whole-genome chromosomal microarray analysis as a first-tier diagnostic test for individuals with unexplained developmental disabilities provides a unique opportunity to obtain large copy number variant datasets generated through routine patient care.

Quality control procedures for genome-wide association studies.

Genome-wide association studies (GWAS) are being conducted at an unprecedented rate in population-based cohorts and have increased our understanding of the pathophysiology of complex disease. Regardless of context, the practical utility of this information will ultimately depend upon the quality of the original data. Quality control (QC) procedures for GWAS are computationally intensive, operationally challenging, and constantly evolving.

Quality control and quality assurance in genotypic data for genome-wide association studies.

Genome-wide scans of nucleotide variation in human subjects are providing an increasing number of replicated associations with complex disease traits. Most of the variants detected have small effects and, collectively, they account for a small fraction of the total genetic variance. Very large sample sizes are required to identify and validate findings.