Journal article

Authors list: Carraro, Caterina; Bonaguro, Lorenzo; Schulte-Schrepping, Jonas; Horne, Arik; Oestreich, Marie; Warnat-Herresthal, Stefanie; Helbing, Tim; De Franco, Michele; Haendler, Kristian; Mukherjee, Sach; Ulas, Thomas; Gandin, Valentina; Goettlich, Richard; Aschenbrenner, Anna C.; Schultze, Joachim L.; Gatto, Barbara

Publication year: 2022

Journal: eLife

Volume number: 11

ISSN: 2050-084X

Open access status: Gold

DOI Link: https://doi.org/10.7554/eLife.78012

Publisher: eLife Sciences Publications

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.

Harvard Citation style: Carraro, C., Bonaguro, L., Schulte-Schrepping, J., Horne, A., Oestreich, M., Warnat-Herresthal, S., et al. (2022) Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state, eLife, 11, Article e78012. https://doi.org/10.7554/eLife.78012

APA Citation style: Carraro, C., Bonaguro, L., Schulte-Schrepping, J., Horne, A., Oestreich, M., Warnat-Herresthal, S., Helbing, T., De Franco, M., Haendler, K., Mukherjee, S., Ulas, T., Gandin, V., Goettlich, R., Aschenbrenner, A., Schultze, J., & Gatto, B. (2022). Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state. eLife. 11, Article e78012. https://doi.org/10.7554/eLife.78012