Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Characterizing Long COVID: Deep Phenotype of a Complex Condition

Since late 2019, the novel coronavirus SARS-CoV-2 has introduced a wide array of health challenges globally. In addition to a complex acute presentation that can affect multiple organ systems, increasing evidence points to long-term sequelae being common and impactful. The worldwide scientific community is forging ahead to characterize a wide range of outcomes associated with SARS-CoV-2 infection; however the underlying assumptions in these studies have varied so widely that the resulting data are difficult to compareFormal definitions are needed in order to design robust and consistent studies of Long COVID that consistently capture variation in long-term outcomes. Even the condition itself goes by three terms, most widely "Long COVID", but also "COVID-19 syndrome (PACS)" or, "post-acute sequelae of SARS-CoV-2 infection (PASC)". In the present study, we investigate the definitions used in the literature published to date and compare them against data available from electronic health records and patient-reported information collected via surveys. Long COVID holds the potential to produce a second public health crisis on the heels of the pandemic itself. Proactive efforts to identify the characteristics of this heterogeneous condition are imperative for a rigorous scientific effort to investigate and mitigate this threat.

https://www.medrxiv.org/content/medrxiv/early/2021/03/26/2021.03.20.21253896.full.pdf

Challenges in defining Long COVID: Striking differences across literature, Electronic Health Records, and patient-reported information

Summary The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.

GA4GH: International policies and standards for data sharing across genomic research and healthcare

The Human Disease Ontology (DO) (www.disease-ontology.org) database, has significantly expanded the disease content and enhanced our userbase and website since the DO's 2018 Nucleic Acids Research DATABASE issue paper. Conservatively, based on available resource statistics, terms from the DO have been annotated to over 1.5 million biomedical data elements and citations, a 10× increase in the past 5 years. The DO, funded as a NHGRI Genomic Resource, plays a key role in disease knowledge organization, representation, and standardization, serving as a reference framework for multiscale biomedical data integration and analysis across thousands of clinical, biomedical and computational research projects and genomic resources around the world. This update reports on the addition of 1,793 new disease terms, a 14% increase of textual definitions and the integration of 22 137 new SubClassOf axioms defining disease to disease connections representing the DO's complex disease classification. The DO's updated website provides multifaceted etiology searching, enhanced documentation and educational resources.

https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkab1063/41120327/gkab1063.pdf

The Human Disease Ontology 2022 update.

The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.

/pdf/the-human-phenotype-ontology-in-2021-1tdig2slrx.pdf

The Human Phenotype Ontology in 2021

A woman in her 70s presented to her general practitioner (GP) with a 3-month history of left upper arm pain and weakness. A significant difference in bilateral blood pressures was noted and a further history elicited coolness in her left arm without functional compromise. A CT angiography revealed variant subclavian steal syndrome with a subclavian arterial stenosis, which was proximal to both the internal mammary and thyrocervical trunk and her left vertebral artery originating from the aortic arch. She was referred to a vascular surgeon but declined surgical intervention. Her symptoms remain stable with 6-month follow-up from her GP. This case highlights the importance of considering vascular aetiologies in upper limb pain and weakness. Our case reviews the differential diagnoses of upper limb pain and weakness, consequently leading to the discussion of an interesting variant of subclavian stenosis.

Shahmir A. Rind

Papers

The Human Phenotype Ontology in 2021

Variant of subclavian steal syndrome: unusual anatomical relationship between left subclavian artery and left vertebral artery