Drug repositioning can save considerable time and resources and significantly speed up the drug development process. The increasing availability of drug action and disease-associated transcriptome data makes it an attractive source for repositioning studies. Here, we have developed a transcriptome-guided approach for drug/biologics repositioning based on multi-layer self-organizing maps (ml-SOM). It allows for analyzing multiple transcriptome datasets by segmenting them into layers of drug action- and disease-associated transcriptome data. A comparison of expression changes in clusters of functionally related genes across the layers identifies "drug target" spots in disease layers and evaluates the repositioning possibility of a drug. The repositioning potential for two approved biologics drugs (infliximab and brodalumab) confirmed the drugs' action for approved diseases (ulcerative colitis and Crohn's disease for infliximab and psoriasis for brodalumab). We showed the potential efficacy of infliximab for the treatment of sarcoidosis, but not chronic obstructive pulmonary disease (COPD). Brodalumab failed to affect dysregulated functional gene clusters in Crohn's disease (CD) and systemic juvenile idiopathic arthritis (SJIA), clearly indicating that it may not be effective in the treatment of these diseases. In conclusion, ml-SOM offers a novel approach for transcriptome-guided drug repositioning that could be particularly useful for biologics drugs.
PubMed ID: 31842375
Projects: oBIG - omics Bioinformatics for Health
Publication type: Journal article
Journal: Pharmaceutics
Human Diseases: No Human Disease specified
Citation: Pharmaceutics. 2019 Dec 12;11(12). pii: pharmaceutics11120677. doi: 10.3390/pharmaceutics11120677.
Date Published: 12th Dec 2019
Registered Mode: by PubMed ID
Views: 2338
Created: 20th Jan 2022 at 13:22
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