Modular organisation of interaction networks based on asymptotic dynamics

This paper investigates questions related to the modularity in discrete models of biological interaction networks. We develop a theoretical framework based on the analysis of their asymptotic dynamics. More precisely, we exhibit formal conditions under which agents of interaction networks can be grouped into modules. As a main result, we show that the usual decomposition in strongly connected components fulfils the conditions of being a modular organisation. Furthermore, we point out that our framework enables a finer analysis providing a decomposition in elementary modules

Perspective: network-guided pattern formation of neural dynamics

The understanding of neural activity patterns is fundamentally linked to an understanding of how the brain's network architecture shapes dynamical processes. Established approaches rely mostly on deviations of a given network from certain classes of random graphs. Hypotheses about the supposed role of prominent topological features (for instance, the roles of modularity, network motifs, or hierarchical network organization) are derived from these deviations. An alternative strategy could be to study deviations of network architectures from regular graphs (rings, lattices) and consider the implications of such deviations for self-organized dynamic patterns on the network. Following this strategy, we draw on the theory of spatiotemporal pattern formation and propose a novel perspective for analyzing dynamics on networks, by evaluating how the self-organized dynamics are confined by network architecture to a small set of permissible collective states. In particular, we discuss the role of prominent topological features of brain connectivity, such as hubs, modules and hierarchy, in shaping activity patterns. We illustrate the notion of network-guided pattern formation with numerical simulations and outline how it can facilitate the understanding of neural dynamics

The stability of a graph partition: A dynamics-based framework for community detection

Recent years have seen a surge of interest in the analysis of complex networks, facilitated by the availability of relational data and the increasingly powerful computational resources that can be employed for their analysis. Naturally, the study of real-world systems leads to highly complex networks and a current challenge is to extract intelligible, simplified descriptions from the network in terms of relevant subgraphs, which can provide insight into the structure and function of the overall system. Sparked by seminal work by Newman and Girvan, an interesting line of research has been devoted to investigating modular community structure in networks, revitalising the classic problem of graph partitioning. However, modular or community structure in networks has notoriously evaded rigorous definition. The most accepted notion of community is perhaps that of a group of elements which exhibit a stronger level of interaction within themselves than with the elements outside the community. This concept has resulted in a plethora of computational methods and heuristics for community detection. Nevertheless a firm theoretical understanding of most of these methods, in terms of how they operate and what they are supposed to detect, is still lacking to date. Here, we will develop a dynamical perspective towards community detection enabling us to define a measure named the stability of a graph partition. It will be shown that a number of previously ad-hoc defined heuristics for community detection can be seen as particular cases of our method providing us with a dynamic reinterpretation of those measures. Our dynamics-based approach thus serves as a unifying framework to gain a deeper understanding of different aspects and problems associated with community detection and allows us to propose new dynamically-inspired criteria for community structure.Comment: 3 figures; published as book chapte

Inference of the genetic network regulating lateral root initiation in Arabidopsis thaliana

Regulation of gene expression is crucial for organism growth, and it is one of the challenges in Systems Biology to reconstruct the underlying regulatory biological networks from transcriptomic data. The formation of lateral roots in Arabidopsis thaliana is stimulated by a cascade of regulators of which only the interactions of its initial elements have been identified. Using simulated gene expression data with known network topology, we compare the performance of inference algorithms, based on different approaches, for which ready-to-use software is available. We show that their performance improves with the network size and the inclusion of mutants. We then analyse two sets of genes, whose activity is likely to be relevant to lateral root initiation in Arabidopsis, by integrating sequence analysis with the intersection of the results of the best performing methods on time series and mutants to infer their regulatory network. The methods applied capture known interactions between genes that are candidate regulators at early stages of development. The network inferred from genes significantly expressed during lateral root formation exhibits distinct scale-free, small world and hierarchical properties and the nodes with a high out-degree may warrant further investigation

Transformations in the Scale of Behaviour and the Global Optimisation of Constraints in Adaptive Networks

The natural energy minimisation behaviour of a dynamical system can be interpreted as a simple optimisation process, finding a locally optimal resolution of problem constraints. In human problem solving, high-dimensional problems are often made much easier by inferring a low-dimensional model of the system in which search is more effective. But this is an approach that seems to require top-down domain knowledge; not one amenable to the spontaneous energy minimisation behaviour of a natural dynamical system. However, in this paper we investigate the ability of distributed dynamical systems to improve their constraint resolution ability over time by self-organisation. We use a ‘self-modelling’ Hopfield network with a novel type of associative connection to illustrate how slowly changing relationships between system components can result in a transformation into a new system which is a low-dimensional caricature of the original system. The energy minimisation behaviour of this new system is significantly more effective at globally resolving the original system constraints. This model uses only very simple, and fully-distributed positive feedback mechanisms that are relevant to other ‘active linking’ and adaptive networks. We discuss how this neural network model helps us to understand transformations and emergent collective behaviour in various non-neural adaptive networks such as social, genetic and ecological networks

Data-driven modelling of biological multi-scale processes

Biological processes involve a variety of spatial and temporal scales. A holistic understanding of many biological processes therefore requires multi-scale models which capture the relevant properties on all these scales. In this manuscript we review mathematical modelling approaches used to describe the individual spatial scales and how they are integrated into holistic models. We discuss the relation between spatial and temporal scales and the implication of that on multi-scale modelling. Based upon this overview over state-of-the-art modelling approaches, we formulate key challenges in mathematical and computational modelling of biological multi-scale and multi-physics processes. In particular, we considered the availability of analysis tools for multi-scale models and model-based multi-scale data integration. We provide a compact review of methods for model-based data integration and model-based hypothesis testing. Furthermore, novel approaches and recent trends are discussed, including computation time reduction using reduced order and surrogate models, which contribute to the solution of inference problems. We conclude the manuscript by providing a few ideas for the development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and Multiscale Dynamics (American Scientific Publishers

On the foundations of cancer modelling: selected topics, speculations, & perspectives

This paper presents a critical review of selected topics related to the modelling of cancer onset, evolution and growth, with the aim of illustrating, to a wide applied mathematical readership, some of the novel mathematical problems in the field. This review attempts to capture, from the appropriate literature, the main issues involved in the modelling of phenomena related to cancer dynamics at all scales which characterise this highly complex system: from the molecular scale up to that of tissue. The last part of the paper discusses the challenge of developing a mathematical biological theory of tumour onset and evolution