TY  - CONF
A1  - Hiort, Pauline
A1  - Hugo, Julian
A1  - Zeinert, Justus
A1  - Müller, Nataniel
A1  - Kashyap, Spoorthi
A1  - Rajapakse, Jagath C.
A1  - Azuaje, Francisco
A1  - Renard, Bernhard Y.
A1  - Baum, Katharina
T1  - DrDimont: explainable drug response prediction from differential analysis of multi-omics networks
T2  - Bioinformatics
N2  - Motivation:
While it has been well established that drugs affect and help patients differently, personalized drug response predictions remain challenging. 
Solutions based on single omics measurements have been proposed, and networks provide means to incorporate molecular interactions into reasoning. 
However, how to integrate the wealth of information contained in multiple omics layers still poses a complex problem. 

Results: 
We present DrDimont, Drug response prediction from Differential analysis of multi-omics networks. 
It allows for comparative conclusions between two conditions and translates them into differential drug response predictions. 
DrDimont focuses on molecular interactions. 
It establishes condition-specific networks from correlation within an omics layer that are then reduced and combined into heterogeneous, multi-omics molecular networks. A novel semi-local, path-based integration step ensures integrative conclusions. Differential predictions are derived from comparing the condition-specific integrated networks. 
DrDimont's predictions are explainable, i.e. molecular differences that are the source of high differential drug scores can be retrieved. We predict differential drug response in breast cancer using transcriptomics, proteomics, phosphosite and metabolomics measurements and contrast estrogen receptor positive and receptor negative patients. DrDimont performs better than drug prediction based on differential protein expression or PageRank when evaluating it on ground truth data from cancer cell lines. We find proteomic and phosphosite layers to carry most information for distinguishing drug response.
Y1  - 2022
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/65347
SN  - 1367-4803
SN  - 1367-4811
VL  - 38
SP  - ii113
EP  - ii119
PB  - Oxford Univ. Press
CY  - Oxford
ER  -