Drug Repurposing Prediction for Immune-Mediated Cutaneous Diseases using a Word-Embedding–Based Machine Learning Approach

• Published in: Journal of investigative dermatology Vol. 139; no. 3; pp. 683 - 691
• Main Authors: Patrick, Matthew T., Raja, Kalpana, Miller, Keylonnie, Sotzen, Jason, Gudjonsson, Johann E., Elder, James T., Tsoi, Lam C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2019
• Subjects: Algorithms; Cohort Studies; Computational Biology; Drug Repositioning - methods; Humans; Immune System Diseases - drug therapy; Machine Learning; PubMed; ROC Curve; Skin - drug effects; Skin - immunology; Skin Diseases - drug therapy; Transcriptome; CTD; GloVe; Th; NDF-RT; AUROC; PLS-DA; LSA
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1016/j.jid.2018.09.018

Immune-mediated diseases affect more than 20% of the population, and many autoimmune diseases affect the skin. Drug repurposing (or repositioning) is a cost-effective approach for finding drugs that can be used to treat diseases for which they are currently not prescribed. We implemented an efficient bioinformatics approach using word embedding to summarize drug information from more than 20 million articles and applied machine learning to model the drug-disease relationship. We trained our drug repurposing approach separately on nine cutaneous diseases (including psoriasis, atopic dermatitis, and alopecia areata) and eight other immune-mediated diseases and obtained a mean area under the receiver operating characteristic of 0.93 in cross-validation. Focusing in particular on psoriasis, a chronic inflammatory condition of skin that affects more than 100 million people worldwide, we were able to confirm drugs that are known to be effective for psoriasis and to identify potential candidates used to treat other diseases. Furthermore, the targets of drug candidates predicted by our approach were significantly enriched among genes differentially expressed in psoriatic lesional skin from a large-scale RNA sequencing cohort. Although our algorithm cannot be used to determine clinical efficacy, our work provides an approach for suggesting drugs for repurposing to immune-mediated cutaneous diseases.