Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state Article Swipe
Caterina Carraro
,
Lorenzo Bonaguro
,
Jonas Schulte-Schrepping
,
Arik Horne
,
Marie Oestreich
,
Stefanie Warnat‐Herresthal
,
Tim Helbing
,
Michele De Franco
,
Kristian Haendler
,
Sach Mukherjee
,
Thomas Ulas
,
Valentina Gandin
,
Richard Goettlich
,
Anna C. Aschenbrenner
,
Joachim L. Schultze
,
Barbara Gatto
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.7554/elife.78012
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.7554/elife.78012
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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Concepts
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.7554/elife.78012
- https://elifesciences.org/articles/78012.bib
- OA Status
- gold
- Cited By
- 8
- References
- 123
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4293765007
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4293765007Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.7554/elife.78012Digital Object Identifier
- Title
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Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin stateWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-08-16Full publication date if available
- Authors
-
Caterina Carraro, Lorenzo Bonaguro, Jonas Schulte-Schrepping, Arik Horne, Marie Oestreich, Stefanie Warnat‐Herresthal, Tim Helbing, Michele De Franco, Kristian Haendler, Sach Mukherjee, Thomas Ulas, Valentina Gandin, Richard Goettlich, Anna C. Aschenbrenner, Joachim L. Schultze, Barbara GattoList of authors in order
- Landing page
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https://doi.org/10.7554/elife.78012Publisher landing page
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https://elifesciences.org/articles/78012.bibDirect link to full text PDF
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://elifesciences.org/articles/78012.bibDirect OA link when available
- Concepts
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Chromatin, Computational biology, Transcriptome, Computer science, Drug discovery, Bioinformatics, Biology, Genetics, Gene, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
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8Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 3, 2023: 2Per-year citation counts (last 5 years)
- References (count)
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123Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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