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Modelling Signalling Networks from Perturbation Data

By Mathurin Dorel, Bertram Klinger, Anja Sieber, Anirudh Prahallad, Torsten Gross, Evert Bosdriesz, Lodewyk Wessels, Nils Bluethgen

Posted 05 Jan 2018
bioRxiv DOI: 10.1101/243600 (published DOI: 10.1093/bioinformatics/bty473)

Intracellular signalling is realized by complex signalling networks which are almost impossible to understand without network models, especially if feedbacks are involved. Modular Response Analysis (MRA) is a convenient modelling method to study signalling networks in various contexts. We developed a derivative of MRA that is suited to model signalling networks from incomplete perturbation schemes and multi-perturbation data. We applied the method to study the effect of SHP2, a protein that has been implicated in resistance to targeted therapy in colon cancer, using data from a knock out and parental colon cancer cell line. We find that SHP2 is required for MAPK signalling, whereas AKT signalling only partially depends on SHP2. An R-package is available at https://github.com/MathurinD/STASNet

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