TY - JOUR T1 - Qualitative modeling of signaling networks in replicative senescence by selecting optimal node and arc sets JF - bioRxiv DO - 10.1101/389692 SP - 389692 AU - Theodore Sakellaropoulos AU - Ilona Binenbaum AU - Maria Lefaki AU - Aristotelis Chatziioannou AU - Niki Chondrogianni AU - Leonidas G. Alexopoulos Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/08/10/389692.abstract N2 - Signaling networks are an important tool of modern systems biology and drug development. Here, we present a new methodology to qualitatively model signaling networks by combining experimental data and prior knowledge about protein connectivity. Unlike other methods, our approach does not focus solely on selecting which reactions are involved but also on whether a protein is present. This allows the user to model more complicated experiments and incorporate more knowledge into the model. To demonstrate the capabilities of our method we compared the signaling networks of young and replicative senescent human primary HFL-1 fibroblasts, whose differences are expected to be due mainly to changes in the expression of the proteins rather than the reactions involved. The resulting networks indicate that, compared to young cells, aged cells are not as responsive to insulin stimulation and activate pathways that establish and maintain senescence.Author summary Cells have developed a complex network of biochemical reactions to monitor their environment and react to changes. Although multiple pathways, tuned to identify specific stimuli, have been discovered, it is generally understood that the signaling process typically involves multiple pathways and is context depended. Consequently, reconstructing the signaling network utilized by cells at any given moment is not a trivial task. In this article, we report on a novel logic-based method for identifying signaling network by combining experimental data with prior knowledge about the connectivity of the involved proteins. Unlike other methods proposed so far, our method uses data to evaluate the presence or absence of reactions and proteins alike. We reconstructed and compared the signaling network of human primary HFL-1 fibroblasts as they undergo replicative senescence in the presence of 6 different stimuli. The resulting networks indicate that, compared to young cells, senescent cells are not responsive to insulin stimulation and activate pathways that are known to establish and maintain senescence. ER -