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

Area of Science:

Genetics and Genomics
Rare Diseases
Bioinformatics

Background:

Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant disorder causing tumors in multiple organs, characterized by significant genetic and phenotypic variability.
Challenges in VHL disease patient care stem from limited VHL variant data sharing and lack of aggregated genotype-phenotype information, complicating variant characterization and prognosis prediction.

Purpose of the Study:

To address knowledge gaps in VHL disease by establishing a community-driven variant annotation process.
To develop and implement a standardized protocol for annotating VHL genetic variants and associated phenotypes.
To create a scalable biocuration training program to facilitate broader participation in VHL variant curation.

Main Methods:

Modified the ClinGen Community Curation (C3)-developed Baseline Annotation protocol for VHL variant annotation.
Utilized Hypothes.is, an open-access web annotation tool, to crowdsource genotype-phenotype data from published VHL cases.
Developed a 4-day biocuration training protocol and resource guide for individuals with varying levels of genetics expertise.

Main Results:

Successfully crowdsourced the annotation of VHL cases, completing 91.3% of annotations with contributions from students lacking formal genetics specialization.
Established a standardized VHL-specific annotation protocol using Hypothes.is for consistent case-resolution data presentation.
Demonstrated the effectiveness of the biocuration training protocol in engaging students and facilitating knowledge translation.

Conclusions:

The developed VHL annotation protocol and training program provide a standardized, community-driven approach to VHL variant curation.
This initiative enhances data sharing and knowledge translation in VHL disease, improving the characterization of genetic variants and patient prognosis.
The biocuration training protocol is adaptable for other rare disease platforms, promoting wider community involvement in genetic research.