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@ARTICLE{ElHarouni:177744,
author = {D. ElHarouni$^*$ and Y. Berker$^*$ and H. Peterziel$^*$ and
A. Gopisetty$^*$ and L. Turunen and S. Kreth$^*$ and S. A.
Stainczyk$^*$ and I. Oehme$^*$ and V. Pietiäinen and N.
Jäger$^*$ and O. Witt$^*$ and M. Schlesner$^*$ and S.
Oppermann$^*$},
title = {i{TR}e{X}: {I}nteractive exploration of mono- and
combination therapy dose response profiling data.},
journal = {Pharmacological research},
volume = {175},
issn = {0031-6989},
address = {London},
publisher = {Academic Press},
reportid = {DKFZ-2021-02785},
pages = {105996},
year = {2022},
note = {#EA:B062#LA:B310# / 2022 Jan;175:105996},
abstract = {High throughput screening methods, measuring the
sensitivity and resistance of tumor cells to drug treatments
have been rapidly evolving. Not only do these screens allow
correlating response profiles to tumor genomic features for
developing novel predictors of treatment response, but they
can also add evidence for therapy decision making in
precision oncology. Recent analysis methods developed for
either assessing single agents or combination drug
efficacies enable quantification of dose-response curves
with restricted symmetric fit settings. Here, we introduce
iTReX, a user-friendly and interactive Shiny/R application,
for both the analysis of mono- and combination therapy
responses. The application features an extended version of
the drug sensitivity score (DSS) based on the integral of an
advanced five-parameter dose-response curve model and a
differential DSS for combination therapy profiling.
Additionally, iTReX includes modules that visualize drug
target interaction networks and support the detection of
matches between top therapy hits and the sample omics
features to enable the identification of druggable targets
and biomarkers. iTReX enables the analysis of various
quantitative drug or therapy response readouts (e.g.
luminescence, fluorescence microscopy) and multiple
treatment strategies (drug treatments, radiation). Using
iTReX we validate a cost-effective drug combination
screening approach and reveal the application's ability to
identify potential sample-specific biomarkers based on drug
target interaction networks. The iTReX web application is
accessible at (https://itrex.kitz-heidelberg.de).},
keywords = {Therapy response profiling and exploration (Other) /
asymmetric sensitivity scoring (Other) / differential
combination sensitivity scoring (Other) / drug target
networks (Other) / interactive drug screen analysis (Other)
/ personalized medicine (Other)},
cin = {B062 / B310 / B087 / B240 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)B310-20160331 /
I:(DE-He78)B087-20160331 / I:(DE-He78)B240-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34848323},
doi = {10.1016/j.phrs.2021.105996},
url = {https://inrepo02.dkfz.de/record/177744},
}