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

TitleThe cancer precision medicine knowledge base for structured clinical-grade mutations and interpretations.
Publication TypeJournal Article
Year of Publication2017
AuthorsHuang L, Fernandes H, Zia H, Tavassoli P, Rennert H, Pisapia D, Imielinski M, Sboner A, Rubin MA, Kluk M, Elemento O
JournalJ Am Med Inform Assoc
Date Published2017 May 01
KeywordsDatabases, Genetic, Genomics, Humans, Knowledge Bases, Neoplasms, Online Systems, Precision Medicine, User-Computer Interface

Objective: This paper describes the Precision Medicine Knowledge Base (PMKB; ), an interactive online application for collaborative editing, maintenance, and sharing of structured clinical-grade cancer mutation interpretations.

Materials and Methods: PMKB was built using the Ruby on Rails Web application framework. Leveraging existing standards such as the Human Genome Variation Society variant description format, we implemented a data model that links variants to tumor-specific and tissue-specific interpretations. Key features of PMKB include support for all major variant types, standardized authentication, distinct user roles including high-level approvers, and detailed activity history. A REpresentational State Transfer (REST) application-programming interface (API) was implemented to query the PMKB programmatically.

Results: At the time of writing, PMKB contains 457 variant descriptions with 281 clinical-grade interpretations. The EGFR, BRAF, KRAS, and KIT genes are associated with the largest numbers of interpretable variants. PMKB's interpretations have been used in over 1500 AmpliSeq tests and 750 whole-exome sequencing tests. The interpretations are accessed either directly via the Web interface or programmatically via the existing API.

Discussion: An accurate and up-to-date knowledge base of genomic alterations of clinical significance is critical to the success of precision medicine programs. The open-access, programmatically accessible PMKB represents an important attempt at creating such a resource in the field of oncology.

Conclusion: The PMKB was designed to help collect and maintain clinical-grade mutation interpretations and facilitate reporting for clinical cancer genomic testing. The PMKB was also designed to enable the creation of clinical cancer genomics automated reporting pipelines via an API.

Alternate JournalJ Am Med Inform Assoc
PubMed ID27789569
PubMed Central IDPMC5391733
Grant ListR01 CA194547 / CA / NCI NIH HHS / United States