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Pharmaceutics. 2019 Dec 12;11(12). pii: E677. doi: 10.3390/pharmaceutics11120677.

Transcriptome-Guided Drug Repositioning.

Author information

1
Institute of Biomedicine and Pharmacy, Russian-Armenian University, 0051 Yerevan, Armenia.
2
Group of Bioinformatics, Institute of Molecular Biology NAS RA, 0014 Yerevan, Armenia.
3
Interdisciplinary Centre for Bioinformatics, University of Leipzig, D-04107 Leipzig, Germany.

Abstract

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.

KEYWORDS:

COPD; Crohn’s disease; drug repositioning; psoriasis; sarcoidosis; self-organizing maps; systemic juvenile idiopathic arthritis; transcriptome; ulcerative colitis

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