BACKGROUND: Boolean networks (BNs) provide an effective modelling formalism for various complex biochemical phenomena. Their long term behaviour is represented by attractors-subsets of the state space towards which the BN eventually converges. These are then typically linked to different biological phenotypes. Depending on various logical parameters, the structure and quality of attractors can undergo a significant change, known as a bifurcation. We present a methodology for analysing bifurcations in asynchronous parametrised Boolean networks. RESULTS: In this paper, we propose a computational framework employing advanced symbolic graph algorithms that enable the analysis of large networks with hundreds of Boolean variables. To visualise the results of this analysis, we developed a novel interactive presentation technique based on decision trees, allowing us to quickly uncover parameters crucial to the changes in the attractor landscape. As a whole, the methodology is implemented in our tool AEON. We evaluate the method's applicability on a complex human cell signalling network describing the activity of type-1 interferons and related molecules interacting with SARS-COV-2 virion. In particular, the analysis focuses on explaining the potential suppressive role of the recently proposed drug molecule GRL0617 on replication of the virus. CONCLUSIONS: The proposed method creates a working analogy to the concept of bifurcation analysis widely used in kinetic modelling to reveal the impact of parameters on the system's stability. The important feature of our tool is its unique capability to work fast with large-scale networks with a relatively large extent of unknown information. The results obtained in the case study are in agreement with the recent biological findings.

• Klíčová slova
• Attractor bifurcation, Boolean networks, Software tool, Symbolic computation, type-1 interferons,
• MeSH
• algoritmy MeSH
• aniliny MeSH
• benzamidy MeSH
• COVID-19 * MeSH
• genové regulační sítě * MeSH
• lidé MeSH
• modely genetické MeSH
• naftaleny MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 5-amino-2-methyl-N-((R)-1-(1-naphthyl)ethyl)benzamide MeSH Prohlížeč
• aniliny MeSH
• benzamidy MeSH
• naftaleny MeSH