Decoding mechanism of action and susceptibility to drug candidates from integrated transcriptome and chromatin state
Published in BioRxiv, 2022
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 (3-CePs), a new class of candidate anticancer agents. Combined analyses of transcriptome and chromatin accessibility elucidated the mechanisms underlying sensitivity to test agents. Further, we implemented a new versatile strategy for the integration of RNA-seq and ATAC-seq data, able to accelerate and extend the standalone analyses of distinct omic layers. This platform guided the construction of a perturbation-informed basal signature able to predict cancer cell lines’ sensitivity and to further direct compound development against specific tumor types. Overall, this approach offered a scalable pipeline to support the early phases of drug discovery, understanding of mechanism and potentially inform the positioning of therapeutics in the clinic.
Recommended citation: Caterina Carraro, Lorenzo Bonaguro, Jonas Schulte-Schrepping, Arik Horne, Marie Oestreich, Stefanie Warnat-Herresthal, Tim Helbing, Michele De Franco, Kristian Händler, Sach Mukherjee, Thomas Ulas, Valentina Gandin, Richard Göttlich, Anna C Aschenbrenner, Joachim L Schultze, Barbara Gatto. (2022). "Decoding mechanism of action and susceptibility to drug candidates from integrated transcriptome and chromatin state; BioRxiv.
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