Reviving the Two-State Markov Chain Approach.

Probabilistic Boolean networks (PBNs) is a well-established computational framework for modelling biological systems. The steady-state dynamics of PBNs is of crucial importance in the study of such systems. However, for large PBNs, which often arise in systems biology, obtaining the steady-state distribution poses a significant challenge. In this paper, we revive the two-state Markov chain approach to solve this problem. This paper contributes in three aspects. First, we identify a problem of generating biased results with the approach and we propose a few heuristics to avoid such a pitfall. Second, we conduct an extensive experimental comparison of the extended two-state Markov chain approach and another approach based on the Skart method. We analyze the results with machine learning techniques and we show that statistically the two-state Markov chain approach has a better performance. Finally, we demonstrate the potential of the extended two-state Markov chain approach on a case study of a large PBN model of apoptosis in hepatocytes.