In:
Bioinformatics, Oxford University Press (OUP), Vol. 34, No. 23 ( 2018-12-01), p. 4079-4086
Abstract:
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. Results We developed the software package STASNet (STeady-STate Analysis of Signalling Networks) that provides an augmented and extended version of MRA suited to model signalling networks from incomplete perturbation schemes and multi-perturbation data. Using data from the Dialogue on Reverse Engineering Assessment and Methods challenge, we show that predictions from STASNet models are among the top-performing methods. 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 a novel dataset from the colon cancer cell line Widr and a SHP2-depleted derivative. We find that SHP2 is required for mitogen-activated protein kinase signalling, whereas AKT signalling only partially depends on SHP2. Availability and implementation An R-package is available at https://github.com/molsysbio/STASNet. Supplementary information Supplementary data are available at Bioinformatics online.
Type of Medium:
Online Resource
ISSN:
1367-4803
,
1367-4811
DOI:
10.1093/bioinformatics/bty473
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2018
detail.hit.zdb_id:
1468345-3
SSG:
12
