Sequential Reprogramming of Boolean Networks Made Practical

We address the sequential reprogramming of gene regulatory networks modelled as Boolean networks. We develop an attractor-based sequential reprogramming method to compute all sequential reprogramming paths from a source attractor to a target attractor, where only attractors of the network are used as intermediates. Our method is more practical than existing reprogramming methods as it incorporates several practical constraints: (1) only biologically observable states, viz. attractors, can act as intermediates; (2) certain attractors, such as apoptosis, can be avoided as intermediates; (3) certain nodes can be avoided to perturb as they may be essential for cell survival or difficult to perturb with biomolecular techniques; and (4) given a threshold k, all sequential reprogramming paths with no more than k perturbations are computed. We compare our method with the minimal one-step reprogramming and the minimal sequential reprogramming on a variety of biological networks. The results show that our method can greatly reduce the number of perturbations compared to the one-step reprogramming, while having comparable results with the minimal sequential reprogramming. Moreover, our implementation is scalable for networks of more than 60 nodes.