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Transcriptome-Guided Drug Repositioning

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-g...

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Autores principales: Arakelyan, Arsen, Nersisyan, Lilit, Nikoghosyan, Maria, Hakobyan, Siras, Simonyan, Arman, Hopp, Lydia, Loeffler-Wirth, Henry, Binder, Hans
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969900/
https://www.ncbi.nlm.nih.gov/pubmed/31842375
http://dx.doi.org/10.3390/pharmaceutics11120677
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author Arakelyan, Arsen
Nersisyan, Lilit
Nikoghosyan, Maria
Hakobyan, Siras
Simonyan, Arman
Hopp, Lydia
Loeffler-Wirth, Henry
Binder, Hans
author_facet Arakelyan, Arsen
Nersisyan, Lilit
Nikoghosyan, Maria
Hakobyan, Siras
Simonyan, Arman
Hopp, Lydia
Loeffler-Wirth, Henry
Binder, Hans
author_sort Arakelyan, Arsen
collection PubMed
description 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.
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spelling pubmed-69699002020-02-04 Transcriptome-Guided Drug Repositioning Arakelyan, Arsen Nersisyan, Lilit Nikoghosyan, Maria Hakobyan, Siras Simonyan, Arman Hopp, Lydia Loeffler-Wirth, Henry Binder, Hans Pharmaceutics Article 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. MDPI 2019-12-12 /pmc/articles/PMC6969900/ /pubmed/31842375 http://dx.doi.org/10.3390/pharmaceutics11120677 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arakelyan, Arsen
Nersisyan, Lilit
Nikoghosyan, Maria
Hakobyan, Siras
Simonyan, Arman
Hopp, Lydia
Loeffler-Wirth, Henry
Binder, Hans
Transcriptome-Guided Drug Repositioning
title Transcriptome-Guided Drug Repositioning
title_full Transcriptome-Guided Drug Repositioning
title_fullStr Transcriptome-Guided Drug Repositioning
title_full_unstemmed Transcriptome-Guided Drug Repositioning
title_short Transcriptome-Guided Drug Repositioning
title_sort transcriptome-guided drug repositioning
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969900/
https://www.ncbi.nlm.nih.gov/pubmed/31842375
http://dx.doi.org/10.3390/pharmaceutics11120677
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