State Reachability and Parameter Identifiability in Synthetic Gene Networks through Edge Modification

Despite the current node-centric approaches of analysis, measurement, and perturbation of pathways, network edges are central to the function and stability of biological pathways. In an effort to examine the potential for new opportunities in therapeutic intervention by edge modifications, we define the parameter identifiability and state reachability of two synthetic gene networks. Specifically, we uncover that the phenomenological rates of mRNA degradation, protein degradation, and protein production can be uniquely determined (i.e. identified) from experimental data collected from a microRNA inhibition network using single and high-throughput edge edits. Additionally, we characterize the achievable steady states of a single input multiple output (SIMO) synthetic network, where the input is a microRNA and the outputs are two regulated fluorescent proteins, upon both node perturbation and edge modification. We find that the reachable states of the SIMO network upon input inhibition correspond to a trajectory-bound subset of the reachable states obtained through edge modification, indicating that edge intervention results in a higher degree of controllability of the SIMOs network outputs.

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