Home > Publications Database > Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state. > print

001     165276
005     20230915090615.0
024 7 _ |a 10.7554/eLife.78012
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037 _ _ |a DZNE-2022-01569
041 _ _ |a English
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100 1 _ |a Carraro, Caterina
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245 _ _ |a Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state.
260 _ _ |a Cambridge
|c 2022
|b eLife Sciences Publications
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500 _ _ |a CC BY: https://creativecommons.org/licenses/by/4.0/
520 _ _ |a 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.
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650 _ 7 |a chromatin accessibility
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650 _ 7 |a computational biology
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650 _ 7 |a drug candidate
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650 _ 7 |a human
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650 _ 7 |a mechanism of action
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650 _ 7 |a multi-omics
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650 _ 7 |a sensitivity ML prediction
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650 _ 7 |a systems biology
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650 _ 7 |a transcriptome
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650 _ 7 |a Chromatin
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650 _ 7 |a RNA
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650 _ 7 |a Transposases
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650 _ 2 |a Chromatin
|2 MeSH
650 _ 2 |a Precision Medicine
|2 MeSH
650 _ 2 |a RNA
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Transposases: metabolism
|2 MeSH
700 1 _ |a Bonaguro, Lorenzo
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700 1 _ |a Schulte-Schrepping, Jonas
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700 1 _ |a Horne, Arik
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700 1 _ |a Oestreich, Marie
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700 1 _ |a Warnat-Herresthal, Stefanie
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700 1 _ |a Helbing, Tim
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700 1 _ |a De Franco, Michele
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700 1 _ |a Mukherjee, Sach
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700 1 _ |a Ulas, Thomas
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700 1 _ |a Gandin, Valentina
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700 1 _ |a Goettlich, Richard
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700 1 _ |a Aschenbrenner, Anna Christin
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700 1 _ |a Schultze, Joachim L
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700 1 _ |a Gatto, Barbara
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