VICC Meta-KB Published

Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. Dr. Alex Wagner led a study, published today in Nature Genetics, which found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure, and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting.

Dr. Wagner and colleagues developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. This work demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. They subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Their analyses illuminate the need for open, interoperable sharing of variant interpretation data. In addition, they provide a freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.