The cancer precision medicine knowledge base for structured clinical-grade mutations and interpretations

Area of Science:

• Genomic Medicine
• Bioinformatics
• Oncology

Background:

• Precision medicine relies on accurate interpretation of genomic alterations.
• A centralized, up-to-date knowledge base is crucial for clinical decision-making in cancer genomics.
• Existing resources may lack structured, collaborative features for mutation interpretation.

Purpose of the Study:

• To describe the Precision Medicine Knowledge Base (PMKB), an interactive online application.
• To facilitate collaborative editing, maintenance, and sharing of structured, clinical-grade cancer mutation interpretations.
• To enable programmatic access to cancer mutation data via an API for automated reporting.

Main Methods:

• Developed using the Ruby on Rails Web application framework.
• Implemented a data model linking variants to tumor- and tissue-specific interpretations, adhering to Human Genome Variation Society standards.
• Incorporated features like support for major variant types, standardized authentication, distinct user roles, and a REST API.

Main Results:

• PMKB contains 457 variant descriptions and 281 clinical-grade interpretations.
• EGFR, BRAF, KRAS, and KIT genes have the most interpretable variants.
• Interpretations have been utilized in over 1500 AmpliSeq and 750 whole-exome sequencing tests.

Conclusions:

• The open-access, programmatically accessible PMKB is a valuable resource for oncology precision medicine.
• PMKB aids in collecting and maintaining clinical-grade mutation interpretations for cancer genomic testing.
• The API facilitates automated reporting pipelines in clinical cancer genomics.