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Master Regulators Connectivity Map: A Transcription Factors-Centered Approach to
Drug Repositioning
#MMPMID30034338
De Bastiani MA
; Pfaffenseller B
; Klamt F
Front Pharmacol
2018[]; 9
(?): 697
PMID30034338
show ga
Drug discovery is a very expensive and time-consuming endeavor. Fortunately,
recent omics technologies and Systems Biology approaches introduced interesting
new tools to achieve this task, facilitating the repurposing of already known
drugs to new therapeutic assignments using gene expression data and
bioinformatics. The inherent role of transcription factors in gene expression
modulation makes them strong candidates for master regulators of phenotypic
transitions. However, transcription factors expression itself usually does not
reflect its activity changes due to post-transcriptional modifications and other
complications. In this aspect, the use of high-throughput transcriptomic data may
be employed to infer transcription factors-targets interactions and assess their
activity through co-expression networks, which can be further used to search for
drugs capable of reverting the gene expression profile of pathological phenotypes
employing the connectivity maps paradigm. Following this idea, we argue that a
module-oriented connectivity map approach using transcription factors-centered
networks would aid the query for new repositioning candidates. Through a brief
case study, we explored this idea in bipolar disorder, retrieving known drugs
used in the usual clinical scenario as well as new candidates with potential
therapeutic application in this disease. Indeed, the results of the case study
indicate just how promising our approach may be to drug repositioning.
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