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| Status |
Public on Aug 17, 2022 |
| Title |
Perturbation-informed signatures from crosswise integration of transcriptome and chromatin accessibility analyses predict susceptibility to candidate anticancer drugs [ATAC-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Despite the tremendous advances in the use of omic-based technologies to serve the new paradigm of precision medicine, efforts are still required to expedite their routine use in drug discovery. In this work, we present a case study describing the use of multi-omics to push the development of 3-chloropiperidines (3-CePs), a new class of potential anticancer DNA alkylating agents. The combined analyses of transcriptome and chromatin accessibility efficiently identified proteostasis and DNA repair unbalances as the mechanisms underlying the tropism of 3-CePs against a pancreatic adenocarcinoma cell line. Further on, we implemented a new versatile strategy for the integration of RNA-seq and ATAC-seq information, which could be easily exported to accelerate and extend the separate analyses of omic layers. In addition, this platform offered a new anchor for the construction of a perturbation-informed basal signature able to efficiently predict cell lines sensitivity to 3-CePs and to further direct their development against specific tumor types. Overall, this approach offered a clinically-applicable pipeline to support both the early phases of drug discovery and the correct positioning of therapeutics in the medical practice.
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| Overall design |
Chromatin accessibility profile (ATAC) of BxPC-3 and HCT-15 treated with 2 compounds of the 3-chloropiperidines class. The analysis was performed at 2 time-points including untreated control to investigate the dynamic effect of the new molecules.
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| Contributor(s) |
Carraro C, Bonaguro L, Schultze J, Gatto B |
| Citation(s) |
36043458 |
| |
| Submission date |
Jun 28, 2021 |
| Last update date |
Nov 16, 2022 |
| Contact name |
Joachim Schultze |
| E-mail(s) |
j.schultze@uni-bonn.de
|
| Organization name |
LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
|
| Department |
Genomics and Immunoregulation
|
| Street address |
Carl-Troll-Strasse 31
|
| City |
Bonn |
| State/province |
NRW |
| ZIP/Postal code |
53115 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (30)
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| This SubSeries is part of SuperSeries: |
| GSE179064 |
Perturbation-informed signatures from crosswise integration of transcriptome and chromatin accessibility analyses predict susceptibility to candidate anticancer drugs |
|
| Relations |
| BioProject |
PRJNA742038 |
| SRA |
SRP325874 |
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