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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84657 |
| Date | 11 April 2023 |
| Creators | Arakelyan, Arsen, Nersisyan, Lilit, Nikoghosyan, Maria, Hakobyan, Siras, Simonyan, Arman, Hopp, Lydia, Loeffler-Wirth, Henry, Binder, Hans |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1999-4923, 677 |
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