Description:
Drug repositioning can save considerable time and resources and significantly speed upthe drug development process. The increasing availability of drug action and disease-associatedtranscriptome data makes it an attractive source for repositioning studies. Here, we have developed atranscriptome-guided approach for drug/biologics repositioning based on multi-layer self-organizingmaps (ml-SOM). It allows for analyzing multiple transcriptome datasets by segmenting them intolayers of drug action- and disease-associated transcriptome data. A comparison of expression changesin clusters of functionally related genes across the layers identifies “drug target” spots in disease layersand evaluates the repositioning possibility of a drug. The repositioning potential for two approvedbiologics drugs (infliximab and brodalumab) confirmed the drugs’ action for approved diseases(ulcerative colitis and Crohn’s disease for infliximab and psoriasis for brodalumab). We showedthe potential efficacy of infliximab for the treatment of sarcoidosis, but not chronic obstructivepulmonary disease (COPD). Brodalumab failed to affect dysregulated functional gene clusters inCrohn’s disease (CD) and systemic juvenile idiopathic arthritis (SJIA), clearly indicating that it maynot be effective in the treatment of these diseases. In conclusion, ml-SOM offers a novel approach fortranscriptome-guided drug repositioning that could be particularly useful for biologics drugs.