title: The cancer precision medicine knowledge base for structured clinical-grade mutations and interpretations.
abstract: OBJECTIVE
  This paper describes the Precision Medicine Knowledge Base (PMKB; https://pmkb.weill.cornell.edu ), an interactive online application for collaborative editing, maintenance, and sharing of structured clinical-grade cancer mutation interpretations.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute for Precision Medicine.|Institute for Computational Biomedicine.
authors: Linda
authors: L
authors: Huang
authors: Institute for Precision Medicine.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
authors: Helen
authors: H
authors: Fernandes
authors: Institute for Precision Medicine.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
authors: Hamid
authors: H
authors: Zia
authors: Institute for Precision Medicine.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
authors: Peyman
authors: P
authors: Tavassoli
authors: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
authors: Hanna
authors: H
authors: Rennert
authors: Institute for Precision Medicine.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
authors: David
authors: D
authors: Pisapia
authors: Institute for Precision Medicine.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
authors: Marcin
authors: M
authors: Imielinski
authors: Institute for Precision Medicine.|Institute for Computational Biomedicine.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
authors: Andrea
authors: A
authors: Sboner
authors: Institute for Precision Medicine.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
authors: Mark A
authors: MA
authors: Rubin
authors: Institute for Precision Medicine.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
authors: Michael
authors: M
authors: Kluk
authors: Institute for Precision Medicine.|Institute for Computational Biomedicine.
authors: Olivier
authors: O
authors: Elemento
mesh_terms: D030541:Databases, Genetic; D023281:Genomics; D006801:Humans; D051188:Knowledge Bases; D009369:Neoplasms / Q000235:genetics*; D009862:Online Systems; D057285:Precision Medicine; D014584:User-Computer Interface
keywords: application-programming interface; cancer genomics; clinical reporting; database; pathology; precision medicine