UNASSIGNED: Aberrant activation of sonic Hegdehog ( @entity4851 ) signaling has been found to disrupt cellular differentiation in many @entity1 @entity5 and to increase proliferation. The @entity4851 pathway is known to cross-talk with @entity470 dependent signaling. Recent studies experimentally addressed this interplay in @entity1 cells, which are presumable a model system for @entity2946 , a highly malignant brain @entity5 that predominately occurs in @entity1 . Currently ongoing are several clinical trials for different solid @entity5 , which are designed to validate the clinical benefits of targeting the @entity4851 in combination with other pathways. This has motivated us to investigate interactions between @entity470 and @entity4851 dependent signaling in greater depth. To our knowledge, there is no mathematical model describing the interplay between @entity470 and @entity4851 dependent signaling in @entity2946 so far. Here we come up with a fully probabilistic approach using Dynamic Bayesian Networks (DBNs). To build our model, we made use of literature based knowledge describing @entity4851 and @entity470 signaling and integrated gene expression (Illumina) and cellular location dependent time series protein expression data (Reverse Phase Protein Arrays). We validated our model by sub-sampling training data and making Bayesian predictions on the left out test data. Our predictions focusing on key transcription factors and @entity15080 , showed a high level of concordance with experimental data. Furthermore, the stability of our model was tested by a parametric bootstrap approach. Stable network features were in agreement with published data. Altogether we believe that our model improved our understanding of the interplay between two highly oncogenic signaling pathways in @entity1 cells. This may open new perspectives for the future therapy of Hedghog/EGF-dependent solid @entity5 .

Dynamic Bayesian Network Modeling of the Interplay between XXXX and Hedgehog Signaling.

@entity1 :: ('9606', 'Species') :: ['children', 'human', 'Daoy'] @entity15080 :: ('6198', 'Gene') :: ['p70S6K'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancers', 'tumors'] @entity470 :: ('1956', 'Gene') :: ['EGFR'] @entity4851 :: ('6469', 'Gene') :: ['SHH'] @entity2946 :: ('MESH:D008527', 'Disease') :: ['medulloblastoma']
@entity470 :: (1956,Gene) :: ['EGFR']
