TY  - JOUR
A1  - Guziolowski, Carito
A1  - Videla, Santiago
A1  - Eduati, Federica
A1  - Thiele, Sven
A1  - Cokelaer, Thomas
A1  - Siegel, Anne
A1  - Saez-Rodriguez, Julio
T1  - Exhaustively characterizing feasible logic models of a signaling network using Answer Set Programming
JF  - Bioinformatics
N2  - Motivation: Logic modeling is a useful tool to study signal transduction across multiple pathways. Logic models can be generated by training a network containing the prior knowledge to phospho-proteomics data. The training can be performed using stochastic optimization procedures, but these are unable to guarantee a global optima or to report the complete family of feasible models. This, however, is essential to provide precise insight in the mechanisms underlaying signal transduction and generate reliable predictions.
 Results: We propose the use of Answer Set Programming to explore exhaustively the space of feasible logic models. Toward this end, we have developed caspo, an open-source Python package that provides a powerful platform to learn and characterize logic models by leveraging the rich modeling language and solving technologies of Answer Set Programming. We illustrate the usefulness of caspo by revisiting a model of pro-growth and inflammatory pathways in liver cells. We show that, if experimental error is taken into account, there are thousands (11 700) of models compatible with the data. Despite the large number, we can extract structural features from the models, such as links that are always (or never) present or modules that appear in a mutual exclusive fashion. To further characterize this family of models, we investigate the input-output behavior of the models. We find 91 behaviors across the 11 700 models and we suggest new experiments to discriminate among them. Our results underscore the importance of characterizing in a global and exhaustive manner the family of feasible models, with important implications for experimental design.
Y1  - 2013
U6  - https://doi.org/10.1093/bioinformatics/btt393
SN  - 1367-4803
VL  - 29
IS  - 18
SP  - 2320
EP  - 2326
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Kaminski, Roland
A1  - Schaub, Torsten H.
A1  - Siegel, Anne
A1  - Videla, Santiago
T1  - Minimal intervention strategies in logical signaling networks with ASP
JF  - Theory and practice of logic programming
N2  - Proposing relevant perturbations to biological signaling networks is central to many problems in biology and medicine because it allows for enabling or disabling certain biological outcomes. In contrast to quantitative methods that permit fine-grained (kinetic) analysis, qualitative approaches allow for addressing large-scale networks. This is accomplished by more abstract representations such as logical networks. We elaborate upon such a qualitative approach aiming at the computation of minimal interventions in logical signaling networks relying on Kleene's three-valued logic and fixpoint semantics. We address this problem within answer set programming and show that it greatly outperforms previous work using dedicated algorithms.
Y1  - 2013
U6  - https://doi.org/10.1017/S1471068413000422
SN  - 1471-0684
VL  - 13
SP  - 675
EP  - 690
PB  - Cambridge Univ. Press
CY  - New York
ER  -