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000165276 1001_ $$0P:(DE-2719)9001303$$aCarraro, Caterina$$b0$$udzne
000165276 245__ $$aDecoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state.
000165276 260__ $$aCambridge$$beLife Sciences Publications$$c2022
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000165276 520__ $$aOmics-based technologies are driving major advances in precision medicine, but efforts are still required to consolidate their use in drug discovery. In this work, we exemplify the use of multi-omics to support the development of 3-chloropiperidines, a new class of candidate anticancer agents. Combined analyses of transcriptome and chromatin accessibility elucidated the mechanisms underlying sensitivity to test agents. Furthermore, we implemented a new versatile strategy for the integration of RNA- and ATAC-seq (Assay for Transposase-Accessible Chromatin) data, able to accelerate and extend the standalone analyses of distinct omic layers. This platform guided the construction of a perturbation-informed basal signature predicting cancer cell lines' sensitivity and to further direct compound development against specific tumor types. Overall, this approach offers a scalable pipeline to support the early phases of drug discovery, understanding of mechanisms, and potentially inform the positioning of therapeutics in the clinic.
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000165276 650_7 $$2Other$$achromatin accessibility
000165276 650_7 $$2Other$$acomputational biology
000165276 650_7 $$2Other$$adrug candidate
000165276 650_7 $$2Other$$ahuman
000165276 650_7 $$2Other$$amechanism of action
000165276 650_7 $$2Other$$amulti-omics
000165276 650_7 $$2Other$$asensitivity ML prediction
000165276 650_7 $$2Other$$asystems biology
000165276 650_7 $$2Other$$atranscriptome
000165276 650_7 $$2NLM Chemicals$$aChromatin
000165276 650_7 $$063231-63-0$$2NLM Chemicals$$aRNA
000165276 650_7 $$0EC 2.7.7.-$$2NLM Chemicals$$aTransposases
000165276 650_2 $$2MeSH$$aChromatin
000165276 650_2 $$2MeSH$$aPrecision Medicine
000165276 650_2 $$2MeSH$$aRNA
000165276 650_2 $$2MeSH$$aTranscriptome
000165276 650_2 $$2MeSH$$aTransposases: metabolism
000165276 7001_ $$0P:(DE-2719)9001512$$aBonaguro, Lorenzo$$b1$$udzne
000165276 7001_ $$0P:(DE-2719)9001500$$aSchulte-Schrepping, Jonas$$b2$$udzne
000165276 7001_ $$0P:(DE-2719)9002161$$aHorne, Arik$$b3$$udzne
000165276 7001_ $$0P:(DE-2719)9002070$$aOestreich, Marie$$b4$$udzne
000165276 7001_ $$0P:(DE-2719)9001511$$aWarnat-Herresthal, Stefanie$$b5$$udzne
000165276 7001_ $$00000-0002-1284-3254$$aHelbing, Tim$$b6
000165276 7001_ $$aDe Franco, Michele$$b7
000165276 7001_ $$0P:(DE-2719)2812735$$aHändler, Kristian$$b8$$udzne
000165276 7001_ $$0P:(DE-2719)2811372$$aMukherjee, Sach$$b9$$udzne
000165276 7001_ $$0P:(DE-2719)9000845$$aUlas, Thomas$$b10$$udzne
000165276 7001_ $$aGandin, Valentina$$b11
000165276 7001_ $$aGoettlich, Richard$$b12
000165276 7001_ $$0P:(DE-2719)2812913$$aAschenbrenner, Anna Christin$$b13$$udzne
000165276 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b14$$udzne
000165276 7001_ $$00000-0001-9465-6913$$aGatto, Barbara$$b15
000165276 773__ $$0PERI:(DE-600)2687154-3$$a10.7554/eLife.78012$$gVol. 11, p. e78012$$pe78012$$teLife$$v11$$x2050-084X$$y2022
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