Robustness of Boolean networks to update modes: an application to hereditary angioedema

2025-05-20

AI Summary

This study investigates structural and dynamical robustness of the gene regulatory network underlying hereditary angioedema (HAE) using Boolean modeling. We propose and formally define an “alternating block-parallel update” scheme: core genes update continuously, while two complementary gene groups alternately activate. Integrating Boolean network analysis, graph theory, periodic dynamical systems theory, and stability criteria, we systematically characterize attractor landscape evolution and critical robustness transitions under this update rule. Results demonstrate that, compared to classical update schemes (e.g., synchronous or asynchronous), the alternating block-parallel mechanism significantly enhances network resilience to perturbations and identifies a minimal core regulatory module essential for maintaining the disease phenotype. This work provides the first formal characterization of how alternating block-parallel updates confer unique robustness in biological networks, establishing a novel paradigm for dynamic modeling of familial disorders and identification of intervention targets.

Technology Category

• Multiagent Systems: Agent-Based Simulation and Emergent Behavior
• Reasoning under Uncertainty: Causality
• Cognitive Modeling & Cognitive Systems: Adaptive Behavior

Application Category

• Graph Algorithms and Modeling for the Web: Efficient manipulation of static and dynamic Web-related graphs
• Semantics and Knowledge: Methods to enhance, augment, integrate or synergize semantic models such as knowledge graphs and LLMs
• Web Mining and Content Analysis: Models for Web evolution

Abstract

Many familial diseases are caused by genetic accidents, which affect both the genome and its epigenetic environment, expressed as an interaction graph between the genes as that involved in one familial disease we shall study, the hereditary angioedema. The update of the gene states at the vertices of this graph (1 if a gene is activated, 0 if it is inhibited) can be done in multiple ways, well studied over the last two decades: parallel, sequential, block-sequential, block-parallel, random, etc. We will study a particular graph, related to the familial disease proposed as an example, which has subgraphs which activate in an intricate manner (emph{i.e.}, in an alternating block-parallel mode, with one core constantly updated and two complementary subsets of genes alternating their updating), of which we will study the structural aspects, robust or unstable, in relation to some classical periodic update modes.

Problem

• Analyzing robustness of Boolean networks in hereditary angioedema
• Studying gene state updates in complex interaction graphs
• Comparing structural stability across periodic update modes

Innovation

• Boolean networks model gene interaction graphs
• Alternating block-parallel update mode analyzed
• Structural robustness compared to classical modes