Quality control of large genome datasets.

The 1000 Genomes Project (TGP) is a foundational resource that serves the biomedical community as a standard reference cohort for human genetic variation. There are now seven public versions of these genomes. The TGP Consortium produced the first by mapping its final data release against human reference sequence GRCh37, then "lifted over" these genomes to the improved reference sequence (GRCh38) when it was released, and remapped the original data to GRCh38 with two similar pipelines. As best-practice quality validation, the pipelines that generated these versions were benchmarked against the Genome In A Bottle Consortium's "platinum quality" genome (NA12878). The New York Genome Center recently released the results of independently resequencing the cohort at greater depth (30×), a phased version informed by the inclusion of related individuals, and independently remapped the original variant calls to GRCh38. We performed a cross-comparison evaluation of all seven versions using genome fingerprinting, which supports ultrafast genome comparison even across reference versions. We noted multiple issues, including discrepancies in cohort membership, disagreement on the overall level of variation, evidence of substandard pipeline performance on specific genomes and in specific regions of the genome, cryptic relationships between individuals, inconsistent phasing, and annotation distortions caused by the history of the reference genome itself. We therefore recommend global quality assessment by rapid genome comparisons, alongside benchmarking as part of best-practice quality assessment of large genome datasets. Our observations also help inform the decision of which version to use, to support analyses by individual researchers.

Biolink Model: A universal schema for knowledge graphs in clinical, biomedical, and translational science.

Within clinical, biomedical, and translational science, an increasing number of projects are adopting graphs for knowledge representation. Graph-based data models elucidate the interconnectedness among core biomedical concepts, enable data structures to be easily updated, and support intuitive queries, visualizations, and inference algorithms. However, knowledge discovery across these "knowledge graphs" (KGs) has remained difficult. Data set heterogeneity and complexity; the proliferation of ad hoc data formats; poor compliance with guidelines on findability, accessibility, interoperability, and reusability; and, in particular, the lack of a universally accepted, open-access model for standardization across biomedical KGs has left the task of reconciling data sources to downstream consumers. Biolink Model is an open-source data model that can be used to formalize the relationships between data structures in translational science. It incorporates object-oriented classification and graph-oriented features. The core of the model is a set of hierarchical, interconnected classes (or categories) and relationships between them (or predicates) representing biomedical entities such as gene, disease, chemical, anatomic structure, and phenotype. The model provides class and edge attributes and associations that guide how entities should relate to one another. Here, we highlight the need for a standardized data model for KGs, describe Biolink Model, and compare it with other models. We demonstrate the utility of Biolink Model in various initiatives, including the Biomedical Data Translator Consortium and the Monarch Initiative, and show how it has supported easier integration and interoperability of biomedical KGs, bringing together knowledge from multiple sources and helping to realize the goals of translational science.

Assessment of the availability of technology for trauma care in Nepal.

BACKGROUND: We sought to assess the availability of technology-related equipment for trauma care in Nepal and to identify factors leading to optimal availability as well as deficiencies. We also sought to identify potential solutions addressing the deficits in terms of health systems management and product development. METHODS: Thirty-two items for large hospitals and sixteen items for small hospitals related to the technological aspect of trauma care were selected from the World Health Organization's Guidelines for Essential Trauma Care for the current study. Fifty-six small and 29 large hospitals were assessed for availability of these items in the study area. Site visits included direct inspection and interviews with administrative, clinical, and bioengineering staff. RESULTS: Deficiencies of many specific items were noted, including many that were inexpensive and which could have been easily supplied. Shortage of electricity was identified as a major infrastructural deficiency present in all parts of the country. Deficiencies of pulse oximetry and ventilators were observed in most hospitals, attributed in most part to frequent breakdowns and long downtimes because of lack of vendor-based service contracts or in-house maintenance staff. Sub-optimal oxygen supply was identified as a major and frequent deficiency contributing to disruption of services. All equipment was imported except for a small percent of suction machines and haemoglobinometers. CONCLUSIONS: The study identified a range of items which were deficient and whose availability could be improved cost-effectively and sustainably by better planning and organisation. The electricity deficit has been dealt with successfully in a few hospitals via direct feeder lines and installation of solar panels; wider implementation of these methods would help solve a large portion of the technological deficiencies. From a health systems management view-point, strengthening procurement and stocking of low cost items especially in remote parts of the country is needed. From a product development view-point, there is a need for robust pulse-oximeters and ventilators that are lower cost and which have longer durability and less need for repairs. Increasing capabilities for local manufacture is another potential method to increase availability of a range of equipment and spare parts.