Andrzej Mizera

Soumya Paul, Cui Su, Jun Pang et al.

We study the problem of computing a minimal subset of nodes of a given asynchronous Boolean network that need to be controlled to drive its dynamics from an initial steady state (or attractor) to a target steady state. Due to the phenomenon of state-space explosion, a simple global approach that performs computations on the entire network, may not scale well for large networks. We believe that efficient algorithms for such networks must exploit the structure of the networks together with their dynamics. Taking such an approach, we derive a decomposition-based solution to the minimal control problem which can be significantly faster than the existing approaches on large networks. We apply our solution to both real-life biological networks and randomly generated networks, demonstrating promising results.

Andrzej Mizera, Jakub Zarzycki

Cellular reprogramming can be used for both the prevention and cure of different diseases. However, the efficiency of discovering reprogramming strategies with classical wet-lab experiments is hindered by lengthy time commitments and high costs. In this study, we develop a novel computational framework based on deep reinforcement learning that facilitates the identification of reprogramming strategies. For this aim, we formulate a control problem in the context of cellular reprogramming for the frameworks of BNs and PBNs under the asynchronous update mode. Furthermore, we introduce the notion of a pseudo-attractor and a procedure for identification of pseudo-attractor state during training. Finally, we devise a computational framework for solving the control problem, which we test on a number of different models.

Andrzej Mizera, Jakub Zarzycki

Cellular reprogramming, the artificial transformation of one cell type into another, has been attracting increasing research attention due to its therapeutic potential for complex diseases. However, identifying effective reprogramming strategies through classical wet-lab experiments is hindered by lengthy time commitments and high costs. In this study, we explore the use of deep reinforcement learning (DRL) to control Boolean network models of complex biological systems, such as gene regulatory and signalling pathway networks. We formulate a novel control problem for Boolean network models under the asynchronous update mode, specifically in the context of cellular reprogramming. To solve it, we devise GATTACA, a scalable computational framework. To facilitate scalability of our framework, we consider previously introduced concept of a pseudo-attractor and improve the procedure for effective identification of pseudo-attractor states. We then incorporate graph neural networks with graph convolution operations into the artificial neural network approximator of the DRL agent's action-value function. This allows us to leverage the available knowledge on the structure of a biological system and to indirectly, yet effectively, encode the system's modelled dynamics into a latent representation. Experiments on several large-scale, real-world biological networks from the literature demonstrate the scalability and effectiveness of our approach.

Andrzej Mizera, Jun Pang, Qixia Yuan

Probabilistic Boolean networks (PBNs) is an important mathematical framework widely used for modelling and analysing biological systems. PBNs are suited for modelling large biological systems, which more and more often arise in systems biology. However, the large system size poses a~significant challenge to the analysis of PBNs, in particular, to the crucial analysis of their steady-state behaviour. Numerical methods for performing steady-state analyses suffer from the state-space explosion problem, which makes the utilisation of statistical methods the only viable approach. However, such methods require long simulations of PBNs, rendering the simulation speed a crucial efficiency factor. For large PBNs and high estimation precision requirements, a slow simulation speed becomes an obstacle. In this paper, we propose a structure-based method for fast simulation of PBNs. This method first performs a network reduction operation and then divides nodes into groups for parallel simulation. Experimental results show that our method can lead to an approximately 10 times speedup for computing steady-state probabilities of a real-life biological network.