RT Journal Article
SR Electronic
T1 Leveraging a Billion-Edge Knowledge Graph for Drug Re-purposing and Target Prioritization using Genomically-Informed Subgraphs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.12.20.521235
DO 10.1101/2022.12.20.521235
A1 Martin, Brian
A1 Jacob, Howard J.
A1 Hajduk, Philip
A1 Wolfe, Elaine
A1 Chen, Loren
A1 Crosby, Henry
A1 Lefever, Matthew
A1 Wendell, Richard
YR 2022
UL http://biorxiv.org/content/early/2022/12/20/2022.12.20.521235.abstract
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.