Evaluating biological activity of compounds by transcription factor activity profiling.
Sci Adv
; 4(9): eaar4666, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30263952
ABSTRACT
Assessing the biological activity of compounds is an essential objective of biomedical research. We show that one can infer the bioactivity of compounds by assessing the activity of transcription factors (TFs) that regulate gene expression. Using a multiplex reporter system, the FACTORIAL, we characterized cell response to a compound by a quantitative signature, the TF activity profile (TFAP). We found that perturbagens of biological pathways elicited distinct TFAP signatures in human cells. Unexpectedly, perturbagens of the same pathway all produced identical TFAPs, regardless of where or how they interfered. We found invariant TFAPs for mitochondrial, histone deacetylase, and ubiquitin/proteasome pathway inhibitors; cytoskeleton disruptors; and DNA-damaging agents. Using these invariant signatures permitted straightforward identification of compounds with specified bioactivities among uncharacterized chemicals. Furthermore, this approach allowed us to assess the multiple bioactivities of polypharmacological drugs. Thus, TF activity profiling affords straightforward assessment of the bioactivity of compounds through the identification of perturbed biological pathways.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Biomarcadores Tumorais
/
Drogas em Investigação
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Regulação Neoplásica da Expressão Gênica
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Carcinoma Hepatocelular
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Transcriptoma
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Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos