Mitochondrial DNA haplogroup, genetic ancestry, and susceptibility to Ewing sarcoma.

Based on current studies, the incidence of Ewing sarcoma (ES) varies significantly by race and ethnicity, with the disease being most common in patients of European ancestry. However, race/ethnicity has generally been self-reported rather than formally evaluated at a population level using DNA evidence. Additionally, mitochondrial dysfunction is a hallmark of ES, yet there have been no reported studies of mitochondrial genetics in ES. Thus, we evaluated both the mitochondrial and nuclear ancestries of 420 pediatric ES patients in the United States using whole-genome sequencing. We found that the mitochondrial DNA (mtDNA) genomes of only six (1.4 %) patients belonged to African L haplogroups, while those of 90 % of the patients belonged to macrohaplogroup R, which includes haplogroup H, the most common maternal lineage in Europe. Compared to the general US population, European haplogroups were significantly enriched in ES patients (p < 2.2e-16) and the African haplogroups are significantly impoverished (p < 4.6e-16). Using the ancestry informative markers defined in a National Genographic study, the vast majority of patients exhibited significant nuclear ancestry originating from the Mediterranean, Northern Europe, and Southwest Asia, including all six patients with African L mtDNAs. Very few had primarily African nuclear ancestry. This is the first genomic epidemiology study to simultaneously interrogate the mitochondrial and nuclear ancestries of ES patients. While supporting previous findings of enriched European ancestry in ES patients, these results also suggest alternative hypotheses for the significant contribution of mitochondrial ancestry in ES patients, as well as the protective role of African ancestry.

Projecting the Impacts of a Changing Climate: Tropical Cyclones and Flooding.

PURPOSE OF REVIEW: There is clear evidence that the earth's climate is changing, largely from anthropogenic causes. Flooding and tropical cyclones have clear impacts on human health in the United States at present, and projections of their health impacts in the future will help inform climate policy, yet to date there have been few quantitative climate health impact projections. RECENT FINDINGS: Despite a wealth of studies characterizing health impacts of floods and tropical cyclones, many are better suited for qualitative, rather than quantitative, projections of climate change health impacts. However, a growing number have features that will facilitate their use in quantitative projections, features we highlight here. Further, while it can be difficult to project how exposures to flood and tropical cyclone hazards will change in the future, climate science continues to advance in its capabilities to capture changes in these exposures, including capturing regional variation. Developments in climate epidemiology and climate science are opening new possibilities in projecting the health impacts of floods and tropical cyclones under a changing climate.

Exposure Assessment for Tropical Cyclone Epidemiology.

PURPOSE OF REVIEW: Tropical cyclones impact human health, sometimes catastrophically. Epidemiological research characterizes these health impacts and uncovers pathways between storm hazards and health, helping to mitigate the health impacts of future storms. These studies, however, require researchers to identify people and areas exposed to tropical cyclones, which is often challenging. Here we review approaches, tools, and data products that can be useful in this exposure assessment. RECENT FINDINGS: Epidemiological studies have used various operational measures to characterize exposure to tropical cyclones, including measures of physical hazards (e.g., wind, rain, flooding), measures related to human impacts (e.g., damage, stressors from the storm), and proxy measures of distance from the storm's central track. The choice of metric depends on the research question asked by the study, but there are numerous resources available that can help in capturing any of these metrics of exposure. Each has strengths and weaknesses that may influence their utility for a specific study. Here we have highlighted key tools and data products that can be useful for exposure assessment for tropical cyclone epidemiology. These results can guide epidemiologists as they design studies to explore how tropical cyclones influence human health.

OncoKids: A Comprehensive Next-Generation Sequencing Panel for Pediatric Malignancies.

The OncoKids panel is an amplification-based next-generation sequencing assay designed to detect diagnostic, prognostic, and therapeutic markers across the spectrum of pediatric malignancies, including leukemias, sarcomas, brain tumors, and embryonal tumors. This panel uses low input amounts of DNA (20 ng) and RNA (20 ng) and is compatible with formalin-fixed, paraffin-embedded and frozen tissue, bone marrow, and peripheral blood. The DNA content of this panel covers the full coding regions of 44 cancer predisposition loci, tumor suppressor genes, and oncogenes; hotspots for mutations in 82 genes; and amplification events in 24 genes. The RNA content includes 1421 targeted gene fusions. We describe the validation of this panel by using a large cohort of 192 unique clinical samples that included a wide range of tumor types and alterations. Robust performance was observed for analytical sensitivity, reproducibility, and limit of detection studies. The results from this study support the use of OncoKids for routine clinical testing of a wide variety of pediatric malignancies.

Muscle Logic: New Knowledge Resource for Anatomy Enables Comprehensive Searches of the Literature on the Feeding Muscles of Mammals.

BACKGROUND: In recent years large bibliographic databases have made much of the published literature of biology available for searches. However, the capabilities of the search engines integrated into these databases for text-based bibliographic searches are limited. To enable searches that deliver the results expected by comparative anatomists, an underlying logical structure known as an ontology is required. DEVELOPMENT AND TESTING OF THE ONTOLOGY: Here we present the Mammalian Feeding Muscle Ontology (MFMO), a multi-species ontology focused on anatomical structures that participate in feeding and other oral/pharyngeal behaviors. A unique feature of the MFMO is that a simple, computable, definition of each muscle, which includes its attachments and innervation, is true across mammals. This construction mirrors the logical foundation of comparative anatomy and permits searches using language familiar to biologists. Further, it provides a template for muscles that will be useful in extending any anatomy ontology. The MFMO is developed to support the Feeding Experiments End-User Database Project (FEED, https://feedexp.org/), a publicly-available, online repository for physiological data collected from in vivo studies of feeding (e.g., mastication, biting, swallowing) in mammals. Currently the MFMO is integrated into FEED and also into two literature-specific implementations of Textpresso, a text-mining system that facilitates powerful searches of a corpus of scientific publications. We evaluate the MFMO by asking questions that test the ability of the ontology to return appropriate answers (competency questions). We compare the results of queries of the MFMO to results from similar searches in PubMed and Google Scholar. RESULTS AND SIGNIFICANCE: Our tests demonstrate that the MFMO is competent to answer queries formed in the common language of comparative anatomy, but PubMed and Google Scholar are not. Overall, our results show that by incorporating anatomical ontologies into searches, an expanded and anatomically comprehensive set of results can be obtained. The broader scientific and publishing communities should consider taking up the challenge of semantically enabled search capabilities.

WormBase 2016: expanding to enable helminth genomic research.

WormBase (www.wormbase.org) is a central repository for research data on the biology, genetics and genomics of Caenorhabditis elegans and other nematodes. The project has evolved from its original remit to collect and integrate all data for a single species, and now extends to numerous nematodes, ranging from evolutionary comparators of C. elegans to parasitic species that threaten plant, animal and human health. Research activity using C. elegans as a model system is as vibrant as ever, and we have created new tools for community curation in response to the ever-increasing volume and complexity of data. To better allow users to navigate their way through these data, we have made a number of improvements to our main website, including new tools for browsing genomic features and ontology annotations. Finally, we have developed a new portal for parasitic worm genomes. WormBase ParaSite (parasite.wormbase.org) contains all publicly available nematode and platyhelminth annotated genome sequences, and is designed specifically to support helminth genomic research.

BC4GO: a full-text corpus for the BioCreative IV GO task.

Gene function curation via Gene Ontology (GO) annotation is a common task among Model Organism Database groups. Owing to its manual nature, this task is considered one of the bottlenecks in literature curation. There have been many previous attempts at automatic identification of GO terms and supporting information from full text. However, few systems have delivered an accuracy that is comparable with humans. One recognized challenge in developing such systems is the lack of marked sentence-level evidence text that provides the basis for making GO annotations. We aim to create a corpus that includes the GO evidence text along with the three core elements of GO annotations: (i) a gene or gene product, (ii) a GO term and (iii) a GO evidence code. To ensure our results are consistent with real-life GO data, we recruited eight professional GO curators and asked them to follow their routine GO annotation protocols. Our annotators marked up more than 5000 text passages in 200 articles for 1356 distinct GO terms. For evidence sentence selection, the inter-annotator agreement (IAA) results are 9.3% (strict) and 42.7% (relaxed) in F1-measures. For GO term selection, the IAAs are 47% (strict) and 62.9% (hierarchical). Our corpus analysis further shows that abstracts contain ∼ 10% of relevant evidence sentences and 30% distinct GO terms, while the Results/Experiment section has nearly 60% relevant sentences and >70% GO terms. Further, of those evidence sentences found in abstracts, less than one-third contain enough experimental detail to fulfill the three core criteria of a GO annotation. This result demonstrates the need of using full-text articles for text mining GO annotations. Through its use at the BioCreative IV GO (BC4GO) task, we expect our corpus to become a valuable resource for the BioNLP research community. Database URL: http://www.biocreative.org/resources/corpora/bc-iv-go-task-corpus/.

WormBase 2014: new views of curated biology.

WormBase (http://www.wormbase.org/) is a highly curated resource dedicated to supporting research using the model organism Caenorhabditis elegans. With an electronic history predating the World Wide Web, WormBase contains information ranging from the sequence and phenotype of individual alleles to genome-wide studies generated using next-generation sequencing technologies. In recent years, we have expanded the contents to include data on additional nematodes of agricultural and medical significance, bringing the knowledge of C. elegans to bear on these systems and providing support for underserved research communities. Manual curation of the primary literature remains a central focus of the WormBase project, providing users with reliable, up-to-date and highly cross-linked information. In this update, we describe efforts to organize the original atomized and highly contextualized curated data into integrated syntheses of discrete biological topics. Next, we discuss our experiences coping with the vast increase in available genome sequences made possible through next-generation sequencing platforms. Finally, we describe some of the features and tools of the new WormBase Web site that help users better find and explore data of interest.