Evidence map›Paper›PMID 36043458›Full record

ArticleeLife2022

Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state.

Caterina Carraro, Lorenzo Bonaguro, Jonas Schulte-Schrepping, Arik Horne, Marie Oestreich, Stefanie Warnat-Herresthal, Tim Helbing, Michele De Franco, Kristian Haendler, Sach Mukherjee and 6 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Tackling neurodegenerationFrontiers in molecular neuroscience · 2024
    Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 6 countries.

Caterina CarraroDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.ORCID https://orcid.org/0000-0002-3039-4675
Lorenzo BonaguroSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.ORCID https://orcid.org/0000-0001-9675-7208
Jonas Schulte-SchreppingSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.
Arik HorneSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.
Marie OestreichSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.
Stefanie Warnat-HerresthalSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.
Tim HelbingInstitute of Organic Chemistry, Justus Liebig University Giessen, Giessen, Germany.ORCID https://orcid.org/0000-0002-1284-3254
Michele De FrancoDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Kristian HaendlerSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.
Sach MukherjeeStatistics and Machine Learning, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.
Thomas UlasSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.
Valentina GandinDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Richard GoettlichInstitute of Organic Chemistry, Justus Liebig University Giessen, Giessen, Germany.
Anna C AschenbrennerSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.ORCID https://orcid.org/0000-0002-9429-5457
Joachim L SchultzeSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Bonn, Germany.
Barbara GattoDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.ORCID https://orcid.org/0000-0001-9465-6913
University of Bonn · DEUniversity of Padua · ITGerman Center for Neurodegenerative Diseases · DEJustus-Liebig-Universität Gießen · DEUniversity of Cambridge · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

ChromatinTranscriptomePrecision MedicineRNATransposasesChromatinRNATransposaseschromatin accessibilitycomputational biologydrug candidatehumanmechanism of actionmulti-omicssensitivity ML predictionsystems biologytranscriptome

Identifiers

PMID36043458
PMCPMC9433094
OpenAlexW4293765007

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.