Navigating the Terrain of Cancer Data: The JAX

Clinical Knowledgebase (JAX-CKB)

August 8, 2016

Cara Statz, PhDClinical Analyst

Cara.statz@jax.org

Comprehensive Genomic Database

KEY COMPONENTS

• Published somatic variants

• Relevant drugs and therapies with supporting efficacy evidence

• Clinical trials

Addressing the Challenge in Precision Oncology

The JAX Clinical Knowledgebase (JAX-CKB), enables rapid access of clinically relevant data

Disease Ontology

Therapy

Treatment Approach

Clinical TrialGene

(HGNC)

Gene Variant(HGVS)

JAX-CKB Timeline: From Past to Present

2014 2015 2016

CKB build implemented inearly 2014

Launch of CKB user interface for curation

CKB validated for clinical reporting of JAX-CTP

Launch of JAX-CKB Open Access at ASCO

Feb 22, 2016 Jackson Lab Describes Model Clinical Interpretation Infrastructure for Use in Oncology ContextsInterview based on: Patterson et al., Hum. Genomics 2016, Jan 16;10(1):4.

Poster Presentations:2015: 17 posters presented at national meetings including ASCO, USCAP, AMP

Mar, 2016 Podcast for Clinical ChemistryInterview based on: Mockus et al., Clin. Chem. 2016, 62(3):442-448.

July, 2016 Somatic gene mutation analysis of triple negative breast cancers. Dillon JL, et al.Breast. 2016, Jul 7

July, 2016 mTOR Inhibitors in Castration Resistant Prostate Cancer: A Systematic Review. Statz, C et al., Targeted Oncology. In Press

Pathology Report to NGS Clinical Report

Pathology Report Diagnosis

eLIMS(Disease Ontology

DOID)

SNPeffVariant Calls

JAX-CKB

Mapping and Query Tools

Clinical Report• Gene Variant Descriptions• Therapies

• Efficacy Evidence• Ranking

• Clinical Trials• Therapy based• Molecular criteria

based• References

Match DOIDs

Match Variants

Bioinformatics Pipeline

• ~24,000 variants• ~6,300 efficacy evidence• ~1,600 therapies• ~3,800 clinical trials

Decision Matrix: Gene Variants

Gain of Function(Activating)

Gain of Function-Predicted

(Inferred Activating)

Loss of Function(Inactivating)

Loss of Function-Predicted

(Inferred inactivating)

No Effect(Benign)

Unknown

The specific type of gene alteration as well as its location is similar to that of another alteration in the same gene that has been functionally characterized as a gain of function within peer-reviewed published literature.

Peer-reviewed published literature demonstrating functional evidence that the gene alteration present results in increased INTRINSIC activity of the protein.

Peer-reviewed published literature demonstrating functional evidence that the gene alteration present results in decreased INTRINSIC activity of the protein.

The specific type of gene alteration as well as its location is similar to that of another alteration in the same gene that has been functionally characterized as a loss of function within peer-reviewed published literature. If all known functional domains or a key domain are lost, is also appropriate.

Peer-reviewed published literature demonstrating functional evidence that the gene alteration present results in activity similar to that of wild-type and does not demonstrate tumorigenic attributes.

There is no peer-reviewed published literature demonstrating the gene alteration present affects the intrinsic activity of the protein.

JAX-CKB Open Access• 82 genes- commonly found on hotspot panels

– More than 8,000 related gene variants

• Characterized gene variants linked to over 1,000 available targeted therapies, more than 2,000 clinical trials, and nearly 4,500 efficacy evidence lines

Basic Search- Explore by Gene

Gene names are HGNC approved, but synonyms are also included. Gene description is provided below.

Basic Search- Explore by Gene

Entrez Id for BRAF- links out to NCBI gene

# of annotated variants associated with BRAF

# of annotated molecular profiles associated with BRAF

# of annotated efficacy evidence lines related to BRAF

Allows filtering and sorting within each of the tabs

Advanced Search

Allows one to search on multiple attributes at once

Advanced Search

Tab indicates 18 associated efficacy evidence lines that are actionable

JAX-CKB Demo

Acknowledgements

Computational SciencesDaniel DurkinAnuradha LakshminarayanaAsha ThadikemallaRoger Liu, Ph.D.

LeadershipEdison Liu, M.D.Charles Lee, Ph.D.

Clinical GenomicsSusan Mockus, Ph.D.Sara Patterson, Ph.D.Taofei Yin, Ph.D.Blake Palculict, Ph.D.Sean Eddy, Ph.D.

Contact Info for JAX-CKB: ckbsupport@jax.org