Trap spaces of Boolean networks are conflict-free siphons of their Petri net encoding

Boolean network modeling of gene regulation but also of post-transcriptomic systems has proven over the years that it can bring powerful analyses and corresponding insight to the many cases where precise biological data is not sufficiently available to build a detailed quantitative model. Besides simulation, the analysis of such models is mostly based on attractor computation, since those correspond roughly to observable biological phenotypes. The recent use of trap spaces made a real breakthrough in that field allowing to consider medium-sized models that used to be out of reach. However, with the continuing increase in model size and complexity of Boolean update functions, the state-of-the-art computation of minimal trap spaces based on prime implicants shows its limits due to the difficulty of the prime-implicant computation. In this article we explore and prove for the first time a connection between trap spaces of a general Boolean network and siphons of its Petri net encoding. Besides important theoretical applications in studying properties of trap spaces, the connection enables us to propose an alternative approach to compute minimal trap spaces, and hence complex attractors, of a general Boolean network. It replaces the need for prime implicants by a completely different technique, namely the enumeration of maximal siphons in the Petri net encoding of the original model. We then demonstrate its efficiency and compare it to the state-of-the-art methods on a large collection of real-world and randomly generated models.& COPY; 2023 Elsevier B.V. All rights reserved.