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Claus Kadelka

Publications and source records attributed to Claus Kadelka.

At least 19 recordsLinked to original sources

Permutation theory governs long-term dynamics of critical Boolean networks

Boolean networks are widely used to model gene regulatory Attractors of Boolean networks model stable gene-expression patterns, yet deriving their properties from network structure remains an open problem. We solve this problem for critical $K=1$ networks by showing that their feedback loops induce a permutation whose order bounds the average attractor length both above and below by universal constant factors. This correspondence allows classical results from combinatorics and number theory to be applied directly to Boolean network dynamics. We find three distinct asymptotic scales for both average and maximum attractor lengths: typical networks scale as $\exp[(1/8+o(1))(\ln N)^2]$, the ensemble means grow as $\exp[N^{1/3+o(1)}]$, and extremal networks attain $\exp[(1+o(1))\sqrt{N\ln N}]$. Thus, ensemble averages are governed by rare network realizations and are unrepresentative of typical dynamics.

q-bio.MN

Dynamics Decomposition of Boolean Networks: An algebraic foundation

Understanding the dynamics of Boolean networks is central to problems such as network reduction, design, control, and reverse engineering. As Boolean network models continue to grow in size and complexity, it becomes increasingly important to decompose networks into modules in a manner that is compatible with their dynamics. In this paper, we show that endowing the space of possible dynamics with a semiring structure enables a systematic decomposition of the dynamics of any Boolean network in terms of the dynamics of its constituent modules. This algebraic framework provides a systematic way to analyze how local dynamical behaviors combine to produce global dynamics. Our results establish a concrete algebraic foundation for network modularity and introduce new mathematical tools for the study of complex Boolean networks, and opens the door to the application of algebraic methods to problems of network analysis, decomposition, and control.

q-bio.QM

Correcting hidden sampling biases in null models of canalizing Boolean networks

Boolean networks are widely used to model gene regulatory systems. Their structural and dynamical properties are commonly interpreted by comparison with ensembles of random Boolean networks generated by sampling Boolean functions for individual nodes. Canalizing and nested canalizing functions, in which one or more regulatory inputs dominate the output, capture an important feature of gene regulation. These functions are typically generated by sampling their defining parameters uniformly at random. Because multiple parameterizations can represent the same Boolean function, however, this procedure induces a biased distribution over functions and consequently over null models. We develop efficient algorithms for uniformly sampling Boolean functions with prescribed canalizing depth, thereby correcting this systematic bias. Using these unbiased null models, we show that the sampling measure substantially alters function- and network-level properties. Whereas parameter-uniform sampling yields nested canalizing functions with expected average sensitivity one, these sensitivities increase with degree under function-uniform sampling and approach 1.183. These differences alter expectations for robustness, attractor structure, and stability. Reanalysis of 122 published Boolean gene regulatory network models reveals substantially stronger enrichment of low-sensitivity canalizing architectures than previously recognized. Widely used parameter-based null models therefore systematically underestimate baseline sensitivity and overestimate the stabilizing role of canalization.

q-bio.MN

Canalization as a stabilizing principle of gene regulatory networks: a discrete dynamical systems perspective

Gene regulatory networks exhibit remarkable stability, maintaining functional phenotypes despite genetic and environmental perturbations. Discrete dynamical models, such as Boolean networks, provide systems biologists with a tractable framework to explore the mathematical underpinnings of this robustness. A key mechanism conferring stability is canalization. This perspective synthesizes historical insights, formal definitions of canalization in discrete dynamical models, quantitative measures of stability, illustrative applications, and emerging challenges at the interface of theory and experiment.

q-bio.MN

On the number of non-degenerate canalizing Boolean functions

Canalization is a key organizing principle in complex systems, particularly in gene regulatory networks. It describes how certain input variables exert dominant control over a function's output, thereby imposing hierarchical structure and conferring robustness to perturbations. Degeneracy, in contrast, captures redundancy among input variables and reflects the complete dominance of some variables by others. Both properties influence the stability and dynamics of discrete dynamical systems, yet their combinatorial underpinnings remain incompletely understood. Here, we derive recursive formulas for counting Boolean functions with prescribed numbers of essential variables and given canalizing properties. In particular, we determine the number of non-degenerate canalizing Boolean functions -- that is, functions for which all variables are essential and at least one variable is canalizing. Our approach extends earlier enumeration results on canalizing and nested canalizing functions. It provides a rigorous foundation for quantifying how frequently canalization occurs among random Boolean functions and for assessing its pronounced over-representation in biological network models, where it contributes to both robustness and to the emergence of distinct regulatory roles.

cs.DM

BoolForge: Controlled Generation and Analysis of Boolean Functions and Networks

Boolean networks are a widely used modeling framework in systems biology for studying gene regulation, signal transduction, and cellular decision-making. Empirical studies indicate that biological Boolean networks exhibit a high degree of canalization, a structural property of Boolean update rules that stabilizes dynamics and constrains state transitions. Despite its central role, existing software packages provide limited support for the systematic generation of Boolean functions and networks with prescribed canalization properties. We present BoolForge, a Python toolbox for the random generation and analysis of Boolean functions and networks, with a particular focus on canalization. BoolForge enables users to (i) generate random Boolean functions with specified canalizing depth, layer structure, and related constraints; (ii) construct Boolean networks with tunable topological and functional properties; and (iii) analyze structural and dynamical features including canalization measures, robustness, modularity, and attractor structure. By enabling controlled generation alongside analysis, BoolForge facilitates ensemble-based investigations of structure-dynamics relationships, benchmarking of theoretical predictions, and construction of biologically informed null models for Boolean network studies. Availability and Implementation: BoolForge is implemented in Python ($\geq$3.10) and can be installed via \texttt{pip install boolforge}. Source code and documentation are available at https://github.com/ckadelka/BoolForge. A PDF tutorial compendium is provided as Supplementary Material.

q-bio.MN

Invasive species control via a discrete model for the Trojan Y-chromosome strategy

Invasive species are a growing threat to ecosystems, particularly in aquatic environments. The Trojan Y Chromosome (TYC) strategy is a promising biological method for reducing invasive populations by introducing genetically modified males (supermales) that produce only male offspring, leading to population decline due to a shortage of females. In this study, we develop a novel discrete--time, age--structured mathematical model to simulate the effects of this strategy. Our model divides the life cycle of species into two stages--egg and maturity--and tracks different sub--populations, including supermales. We analyze the equilibria of the system and prove the existence and stability of extinction and positive equilibrium points. Numerical simulations show that extinction depends on factors such as fecundity, the number of supermales released, and initial population sizes. The model also reveals complex behaviors, such as bistability and thresholds for population collapse. This discrete approach offers a useful framework for understanding and optimizing the TYC strategy and can help guide future field applications of invasive species control.

q-bio.PE

Upper bound for the stability of Boolean networks

Boolean networks, inspired by gene regulatory networks, were developed to understand the complex behaviors observed in biological systems, with network attractors corresponding to biological phenotypes or cell types. In this article, we present a proof for a conjecture by Williadsen, Triesch and Wiles about upper bounds for the stability of basins of attraction in Boolean networks. We further extend this result from a single basin of attraction to the entire network. Specifically, we demonstrate that the asymptotic upper bound for the robustness and the basin entropy of a Boolean network are negatively linearly related.

q-bio.MN

Modular control of Boolean network models

The concept of control is crucial for effectively understanding and applying biological network models. Key structural features relate to control functions through gene regulation, signaling, or metabolic mechanisms, and computational models need to encode these. Applications often focus on model-based control, such as in biomedicine or metabolic engineering. In a recent paper, the authors developed a theoretical framework of modularity in Boolean networks, which lead to a canonical semidirect product decomposition of these systems. In this paper, we present an approach to model-based control that exploits this modular structure, as well as the canalizing features of the regulatory mechanisms. We show how to identify control strategies from the individual modules, and we present a criterion based on canalizing features of the regulatory rules to identify modules that do not contribute to network control and can be excluded. For even moderately sized networks, finding global control inputs is computationally challenging. Our modular approach leads to an efficient approach to solving this problem. We apply it to a published Boolean network model of blood cancer large granular lymphocyte (T-LGL) leukemia to identify a minimal control set that achieves a desired control objective.

q-bio.MN

Canalization reduces the nonlinearity of regulation in biological networks

Biological networks such as gene regulatory networks possess desirable properties. They are more robust and controllable than random networks. This motivates the search for structural and dynamical features that evolution has incorporated in biological networks. A recent meta-analysis of published, expert-curated Boolean biological network models has revealed several such features, often referred to as design principles. Among others, the biological networks are enriched for certain recurring network motifs, the dynamic update rules are more redundant, more biased and more canalizing than expected, and the dynamics of biological networks are better approximable by linear and lower-order approximations than those of comparable random networks. Since most of these features are interrelated, it is paramount to disentangle cause and effect, that is, to understand which features evolution actively selects for, and thus truly constitute evolutionary design principles. Here, we show that approximability is strongly dependent on the dynamical robustness of a network, and that increased canalization in biological networks can almost completely explain their recently postulated high approximability.

q-bio.MN

Modular Construction of Boolean Networks

Boolean networks have been used in a variety of settings, as models for general complex systems as well as models of specific systems in diverse fields, such as biology, engineering, and computer science. Traditionally, their properties as dynamical systems have been studied through simulation studies, due to a lack of mathematical structure. This paper uses a common mathematical technique to identify a class of Boolean networks with a "simple" structure and describes an algorithm to construct arbitrary extensions of a collection of simple Boolean networks. In this way, all Boolean networks can be obtained from a collection of simple Boolean networks as building blocks. The paper furthermore provides a formula for the number of extensions of given simple networks and, in some cases, provides a parametrization of those extensions. This has potential applications to the construction of networks with particular properties, for instance in synthetic biology, and can also be applied to develop efficient control algorithms for Boolean network models.

math.DS

A meta-analysis of Boolean network models reveals design principles of gene regulatory networks

Gene regulatory networks (GRNs) play a central role in cellular decision-making. Understanding their structure and how it impacts their dynamics constitutes thus a fundamental biological question. GRNs are frequently modeled as Boolean networks, which are intuitive, simple to describe, and can yield qualitative results even when data is sparse. We assembled the largest repository of expert-curated Boolean GRN models. A meta-analysis of this diverse set of models reveals several design principles. GRNs exhibit more canalization, redundancy and stable dynamics than expected. Moreover, they are enriched for certain recurring network motifs. This raises the important question why evolution favors these design mechanisms.

q-bio.MN

Collectively canalizing Boolean functions

This paper studies the mathematical properties of collectively canalizing Boolean functions, a class of functions that has arisen from applications in systems biology. Boolean networks are an increasingly popular modeling framework for regulatory networks, and the class of functions studied here captures a key feature of biological network dynamics, namely that a subset of one or more variables, under certain conditions, can dominate the value of a Boolean function, to the exclusion of all others. These functions have rich mathematical properties to be explored. The paper shows how the number and type of such sets influence a function's behavior and define a new measure for the canalizing strength of any Boolean function. We further connect the concept of collective canalization with the well-studied concept of the average sensitivity of a Boolean function. The relationship between Boolean functions and the dynamics of the networks they form is important in a wide range of applications beyond biology, such as computer science, and has been studied with statistical and simulation-based methods. But the rich relationship between structure and dynamics remains largely unexplored, and this paper is intended as a contribution to its mathematical foundation.

cs.DM

Stability of Linear Boolean Networks

Stability is an important characteristic of network models that has implications for other desirable aspects such as controllability. The stability of a Boolean network depends on various factors, such as the topology of its wiring diagram and the type of the functions describing its dynamics. In this paper, we study the stability of linear Boolean networks by computing Derrida curves and quantifying the number of attractors and cycle lengths imposed by their network topologies. Derrida curves are commonly used to measure the stability of Boolean networks and several parameters such as the average in-degree K and the output bias p can indicate if a network is stable, critical, or unstable. For random unbiased Boolean networks there is a critical connectivity value Kc=2 such that if K Kc networks operate in the chaotic regime. Here, we show that for linear networks, which are the least canalizing and most unstable, the phase transition from order to chaos already happens at an average in-degree of Kc=1. Consistently, we also show that unstable networks exhibit a large number of attractors with very long limit cycles while stable and critical networks exhibit fewer attractors with shorter limit cycles. Additionally, we present theoretical results to quantify important dynamical properties of linear networks. First, we present a formula for the proportion of attractor states in linear systems. Second, we show that the expected number of fixed points in linear systems is 2, while general Boolean networks possess on average one fixed point. Third, we present a formula to quantify the number of bijective linear Boolean networks and provide a lower bound for the percentage of this type of network.

nlin.CD

Projecting social contact matrices to populations stratified by binary attributes with known homophily

Contact networks are heterogeneous. People with similar characteristics are more likely to interact, a phenomenon called assortative mixing or homophily. While age-assortativity is well-established and social contact matrices for populations stratified by age have been derived through extensive survey work, we lack empirical studies that describe contact patterns of a population stratified by other attributes such as gender, sexual orientation, ethnicity, etc. Accounting for heterogeneities with respect to these attributes can have a profound effect on the dynamics of epidemiological forecasting models. Here, we introduce a new methodology to expand a given e.g. age-based contact matrix to populations stratified by binary attributes with a known level of homophily. We describe a set of linear conditions any meaningful social contact matrix must satisfy and find the optimal matrix by solving a non-linear optimization problem. We show the effect homophily can have on disease dynamics and conclude by briefly describing more complicated extensions. The available Python source code enables any modeler to account for the presence of homophily with respect to binary attributes in contact patterns, ultimately yielding more accurate predictive models.

physics.soc-ph

Decomposition of Boolean networks: An approach to modularity of biological systems

This paper presents the foundation for a decomposition theory for Boolean networks, a type of discrete dynamical system that has found a wide range of applications in the life sciences, engineering, and physics. Given a Boolean network satisfying certain conditions, there is a unique collection of subnetworks so that the network can be reconstructed from these subnetworks by an extension operation. The main result of the paper is that this structural decomposition induces a corresponding decomposition of the network dynamics. The theory is motivated by the search for a mathematical framework to formalize the hypothesis that biological systems are modular, widely accepted in the life sciences, but not well-defined and well-characterized. As an example of how dynamic modularity could be used for the efficient identification of phenotype control, the control strategies for the network can be found by identifying controls in its modules, one at a time.

math.DS

Revealing the canalizing structure of Boolean functions: Algorithms and applications

Boolean functions can be represented in many ways including logical forms, truth tables, and polynomials. Additionally, Boolean functions have different canonical representations such as minimal disjunctive normal forms. Other canonical representation is based on the polynomial representation of Boolean functions where they can be written as a nested product of canalizing layers and a polynomial that contains the noncanalizing variables. In this paper we study the problem of identifying the canalizing layers format of Boolean functions. First, we show that the problem of finding the canalizing layers is NP-hard. Second, we present several algorithms for finding the canalizing layers of a Boolean function, discuss their complexities, and compare their performances. Third, we show applications where the computation of canalizing layers can be used for finding a disjunctive normal form of a nested canalizing function. Another application deals with the reverse engineering of Boolean networks with a prescribed layering format. Finally, implementations of our algorithms in Python and in the computer algebra system Macaulay2 are available at https://github.com/ckadelka/BooleanCanalization.

cs.CC

The Influence of Canalization on the Robustness of Boolean Networks

Time- and state-discrete dynamical systems are frequently used to model molecular networks. This paper provides a collection of mathematical and computational tools for the study of robustness in Boolean network models. The focus is on networks governed by $k$-canalizing functions, a recently introduced class of Boolean functions that contains the well-studied class of nested canalizing functions. The activities and sensitivity of a function quantify the impact of input changes on the function output. This paper generalizes the latter concept to $c$-sensitivity and provides formulas for the activities and $c$-sensitivity of general $k$-canalizing functions as well as canalizing functions with more precisely defined structure. A popular measure for the robustness of a network, the Derrida value, can be expressed as a weighted sum of the $c$-sensitivities of the governing canalizing functions, and can also be calculated for a stochastic extension of Boolean networks. These findings provide a computationally efficient way to obtain Derrida values of Boolean networks, deterministic or stochastic, that does not involve simulation.

math.DS