Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state.
Elife
; 112022 08 31.
Article
em En
| MEDLINE
| ID: mdl-36043458
ABSTRACT
Omics-based technologies are driving major advances in precision medicine, but efforts are still required to consolidate their use in drug discovery. In this work, we exemplify the use of multi-omics to support the development of 3-chloropiperidines, a new class of candidate anticancer agents. Combined analyses of transcriptome and chromatin accessibility elucidated the mechanisms underlying sensitivity to test agents. Furthermore, we implemented a new versatile strategy for the integration of RNA- and ATAC-seq (Assay for Transposase-Accessible Chromatin) data, able to accelerate and extend the standalone analyses of distinct omic layers. This platform guided the construction of a perturbation-informed basal signature predicting cancer cell lines' sensitivity and to further direct compound development against specific tumor types. Overall, this approach offers a scalable pipeline to support the early phases of drug discovery, understanding of mechanisms, and potentially inform the positioning of therapeutics in the clinic.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Transcriptoma
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article