Characterization of Reachable Attractors Using Petri Net Unfoldings

International audienceAttractors of network dynamics represent the long-term behaviours of the modelled system. Their characterization is therefore crucial for understanding the response and differentiation capabilities of a dynamical system. In the scope of qualitative models of interaction networks, the computation of attractors reachable from a given state of the network faces combinatorial issues due to the state space explosion. In this paper, we present a new algorithm that exploits the concurrency between transitions of parallel acting components in order to reduce the search space. The algorithm relies on Petri net unfoldings that can be used to compute a compact representation of the dynamics. We illustrate the applicability of the algorithm with Petri net models of cell signalling and regulation networks, Boolean and multi-valued. The proposed approach aims at being complementary to existing methods for deriving the attractors of Boolean models, while being %so far more generic since it applies to any safe Petri net

Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers

Small molecule splicing modifiers have been previously described that target the general splicing machinery and thus have low specificity for individual genes. Several potent molecules correcting the splicing deficit of the SMN2 (survival of motor neuron 2) gene have been identified and these molecules are moving towards a potential therapy for spinal muscular atrophy (SMA). Here by using a combination of RNA splicing, transcription, and protein chemistry techniques, we show that these molecules directly bind to two distinct sites of the SMN2 pre-mRNA, thereby stabilizing a yet unidentified ribonucleoprotein (RNP) complex that is critical to the specificity of these small molecules for SMN2 over other genes. In addition to the therapeutic potential of these molecules for treatment of SMA, our work has wide-ranging implications in understanding how small molecules can interact with specific quaternary RNA structures

Using rules of thumb for repairing inconsistent answer set programs

Answer set programming is a form of declarative programming that can be used to elegantly model various systems. When the available knowledge about these systems is imperfect, however, the resulting programs can be inconsistent. In such cases, it is of interest to find plausible repairs, i.e. plausible modifications to the original program that ensure the existence of at least one answer set. Although several approaches to this end have already been proposed, most of them merely find a repair which is in some sense minimal. In many applications, however, expert knowledge is available which could allow us to identify better repairs. In this paper, we analyze the potential of using expert knowledge in this way, by focusing on a specific case study: gene regulatory networks. We show how we can identify the repairs that best agree with insights about such networks that have been reported in the literature, and experimentally compare this strategy against the baseline strategy of identifying minimal repairs

Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers

Small molecule splicing modifiers have been previously described that target the general splicing machinery and thus have low specificity for individual genes. Several potent molecules correcting the splicing deficit of the SMN2 (survival of motor neuron 2) gene have been identified and these molecules are moving towards a potential therapy for spinal muscular atrophy (SMA). Here by using a combination of RNA splicing, transcription, and protein chemistry techniques, we show that these molecules directly bind to two distinct sites of the SMN2 pre-mRNA, thereby stabilizing a yet unidentified ribonucleoprotein (RNP) complex that is critical to the specificity of these small molecules for SMN2 over other genes. In addition to the therapeutic potential of these molecules for treatment of SMA, our work has wide-ranging implications in understanding how small molecules can interact with specific quaternary RNA structures.ISSN:2041-172