Developing a disease-specific annotation protocol for VHL gene curation using Hypothes.is.

Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant disorder that predisposes individuals to developing tumors in many organs. There is significant phenotypic variability and genetic variants encountered within this syndrome, posing a considerable challenge to patient care. The lack of VHL variant data sharing paired with the absence of aggregated genotype-phenotype information results in an arduous process, when characterizing genetic variants and predicting patient prognosis. To address these gaps in knowledge, the Clinical Genome Resource (ClinGen) VHL Variant Curation Expert Panel (VCEP) has been resolving a list of variants of uncertain significance within the VHL gene. Through community curation, we crowdsourced the laborious task of variant annotation by modifying the ClinGen Community Curation (C3)-developed Baseline Annotation protocol and annotating all published VHL cases with the reported genotype-phenotype information in Hypothes.is, an open-access web annotation tool. This process, incorporated into the ClinGen VCEP's workflow, will aid in their curation efforts. To facilitate the curation at all levels of genetics expertise, our team developed a 4-day biocuration training protocol and resource guide. To date, 91.3% of annotations have been completed by undergraduate and high-school students without formal academic genetics specialization. Here, we present our VHL-specific annotation protocol utilizing Hypothes.is, which offers a standardized method to present case-resolution data, and our biocuration training protocol, which can be adapted for other rare disease platforms. By facilitating training for community curation of VHL disease, we increased student engagement with clinical genetics while enhancing knowledge translation in the field of hereditary cancer. Database URL: https://hypothes.is/groups/dKymJJpZ/vhl-hypothesis-annotation.

CIViCdb 2022: evolution of an open-access cancer variant interpretation knowledgebase.

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC's functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing >3200 variants in >470 genes from >3100 publications.

Wearable Inertial Sensors for Gait Analysis in Adults with Osteoarthritis-A Scoping Review.

Our objective was to conduct a scoping review which summarizes the growing body of literature using wearable inertial sensors for gait analysis in lower limb osteoarthritis. We searched six databases using predetermined search terms which highlighted the broad areas of inertial sensors, gait, and osteoarthritis. Two authors independently conducted title and abstract reviews, followed by two authors independently completing full-text screenings. Study quality was also assessed by two independent raters and data were extracted by one reviewer in areas such as study design, osteoarthritis sample, protocols, and inertial sensor outcomes. A total of 72 articles were included, which studied the gait of 2159 adults with osteoarthritis (OA) using inertial sensors. The most common location of OA studied was the knee (n = 46), followed by the hip (n = 22), and the ankle (n = 7). The back (n = 41) and the shank (n = 40) were the most common placements for inertial sensors. The three most prevalent biomechanical outcomes studied were: mean spatiotemporal parameters (n = 45), segment or joint angles (n = 33), and linear acceleration magnitudes (n = 22). Our findings demonstrate exceptional growth in this field in the last 5 years. Nevertheless, there remains a need for more longitudinal study designs, patient-specific models, free-living assessments, and a push for "Code Reuse" to maximize the unique capabilities of these devices and ultimately improve how we diagnose and treat this debilitating disease.