PT  - JOURNAL ARTICLE
AU  - Martin, Brian
AU  - Jacob, Howard J.
AU  - Hajduk, Philip
AU  - Wolfe, Elaine
AU  - Chen, Loren
AU  - Crosby, Henry
AU  - Lefever, Matthew
AU  - Wendell, Richard
TI  - Leveraging a Billion-Edge Knowledge Graph for Drug Re-purposing and Target Prioritization using Genomically-Informed Subgraphs
AID  - 10.1101/2022.12.20.521235
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.12.20.521235
4099  - http://biorxiv.org/content/early/2022/12/20/2022.12.20.521235.short
4100  - http://biorxiv.org/content/early/2022/12/20/2022.12.20.521235.full
AB  - Drug development is a resource and time-intensive process resulting in attrition rates of up to 90%. As a result, repurposing existing drugs with established safety and pharmacokinetic profiles is gaining traction as a way of accelerating therapeutics development. Here we have developed unique machine learning-driven Natural Language Processing and biomedical semantic technologies that mine over 53 million biomedical documents to automate the generation of a 911M edge knowledge graph. We then applied subgraph queries that relate drugs to diseases using genetic evidence to identify potential drug repurposing candidates for a broad range of diseases. We use Carney Complex, a disease with no known treatment, to illustrate our approach. This analysis revealed Ruxolitinib (Incyte, trade name Jakafi), a JAK1/2 inhibitor with an established safety and efficacy profile approved to treat myelofibrosis, as a potential candidate for the treatment of Carney Complex through off-target drug activity.Competing Interest StatementBrian Martin, Howard Jacob and Philip Hadjuk are current employees of AbbVie. Elaine Wolfe, Loren Chen, Henry Crosby and Matt Lefever are current employees of tellic LLC. Richard Wendell is the Founder and Owner of tellic LLC.