Coloured Petri nets for multi-level, multiscale, and multi-dimensional modelling of biological systems

Owing to the availability of data of one biological phenomenon at different levels/scales, modelling of biological systems is moving from single level/scale to multiple levels/scales, which introduces a number of challenges. Coloured Petri nets (ColPNs) have been successfully applied to multilevel, multiscale and multidimensional modelling of some biological systems, addressing many of these challenges. In this article, we first review the basics of ColPNs and some popular extensions, and then their applications for multilevel, multiscale and multidimensional modelling of biological systems. This understanding of how to use ColPNs for modelling biological systems will assist readers in selecting appropriate ColPN classes for specific modelling circumstances

Toward Accessible Multilevel Modeling in Systems Biology: A Rule-based Language Concept

Promoted by advanced experimental techniques for obtaining high-quality data and the steadily accumulating knowledge about the complexity of life, modeling biological systems at multiple interrelated levels of organization attracts more and more attention recently. Current approaches for modeling multilevel systems typically lack an accessible formal modeling language or have major limitations with respect to expressiveness. The aim of this thesis is to provide a comprehensive discussion on associated problems and needs and to propose a concrete solution addressing them

A diversity-aware computational framework for systems biology

L'abstract è presente nell'allegato / the abstract is in the attachmen

Emergence of the mitochondrial reticulum from fission and fusion dynamics

Mitochondria form a dynamic tubular reticulum within eukaryotic cells. Currently, quantitative understanding of its morphological characteristics is largely absent, despite major progress in deciphering the molecular fission and fusion machineries shaping its structure. Here we address the principles of formation and the large-scale organization of the cell-wide network of mitochondria. On the basis of experimentally determined structural features we establish the tip-to-tip and tip-to-side fission and fusion events as dominant reactions in the motility of this organelle. Subsequently, we introduce a graph-based model of the chondriome able to encompass its inherent variability in a single framework. Using both mean-field deterministic and explicit stochastic mathematical methods we establish a relationship between the chondriome structural network characteristics and underlying kinetic rate parameters. The computational analysis indicates that mitochondrial networks exhibit a percolation threshold. Intrinsic morphological instability of the mitochondrial reticulum resulting from its vicinity to the percolation transition is proposed as a novel mechanism that can be utilized by cells for optimizing their functional competence via dynamic remodeling of the chondriome. The detailed size distribution of the network components predicted by the dynamic graph representation introduces a relationship between chondriome characteristics and cell function. It forms a basis for understanding the architecture of mitochondria as a cell-wide but inhomogeneous organelle. Analysis of the reticulum adaptive configuration offers a direct clarification for its impact on numerous physiological processes strongly dependent on mitochondrial dynamics and organization, such as efficiency of cellular metabolism, tissue differentiation and aging

From modularity to emergence: a primer on the design and science of complex systems

Electrical networks, flocking birds, transportation hubs, weather patterns, commercial organisations, swarming robots... Increasingly, many of the systems that we want to engineer or understand are said to be ‘complex’. These systems are often considered to be intractable because of their unpredictability, non-linearity, interconnectivity, heterarchy and ‘emergence’. Such attributes are often framed as a problem, but can also be exploited to encourage systems to efficiently exhibit intelligent, robust, self-organising behaviours. But what does it mean to describe systems as complex? How do these complex systems differ from the more easily understood ‘modular’ systems that we are familiar with? What are the underlying similarities between different systems, whether modular or complex? Answering these questions is a first step in approaching the design and science of complexity. However, to do so, it is necessary to look beyond the specifics of any particular system or field of study. We need to consider the fundamental nature of systems, looking for a common way to view ostensibly different phenomena. This primer introduces a domain-neutral framework and diagrammatic scheme for characterising the ways in which systems are modular or complex. Rather than seeing modularity and complexity as inherent attributes of systems, we instead see them as ways in which those systems are characterised by those who are interested in them. The framework is not tied to any established mode of representation (e.g. networks, equations, formal modelling languages) nor to any domain-specific terminology (e.g. ‘vertex’, ‘eigenvector’, ‘entropy’). Instead, it consists of basic system constructs and three fundamental attributes of modular system architecture, namely structural encapsulation, function-structure mapping and interfacing. These constructs and attributes encourage more precise descriptions of different aspects of complexity (e.g. emergence, self-organisation, heterarchy). This allows researchers and practitioners from different disciplines to share methods, theories and findings related to the design and study of different systems, even when those systems appear superficially dissimilar

Toward a formal theory for computing machines made out of whatever physics offers: extended version

Approaching limitations of digital computing technologies have spurred research in neuromorphic and other unconventional approaches to computing. Here we argue that if we want to systematically engineer computing systems that are based on unconventional physical effects, we need guidance from a formal theory that is different from the symbolic-algorithmic theory of today's computer science textbooks. We propose a general strategy for developing such a theory, and within that general view, a specific approach that we call "fluent computing". In contrast to Turing, who modeled computing processes from a top-down perspective as symbolic reasoning, we adopt the scientific paradigm of physics and model physical computing systems bottom-up by formalizing what can ultimately be measured in any physical substrate. This leads to an understanding of computing as the structuring of processes, while classical models of computing systems describe the processing of structures.Comment: 76 pages. This is an extended version of a perspective article with the same title that will appear in Nature Communications soon after this manuscript goes public on arxi

Aging and Health

Aging is a major risk factor for chronic diseases, which in turn can provide information about the aging of a biological system. This publication serves as an introduction to systems biology and its application to biological aging. Key pathways and processes that impinge on aging are reviewed, and how they contribute to health and disease during aging is discussed. The evolution of this situation is analyzed, and the consequences for the study of genetic effects on aging are presented. Epigenetic programming of aging, as a continuation of development, creates an interface between the genome and the environment. New research into the gut microbiome describes how this interface may operate in practice with marked consequences for a variety of disorders. This analysis is bolstered by a view of the aging organism as a whole, with conclusions about the mechanisms underlying resilience of the organism to change, and is expanded with a discussion of circadian rhythms in aging

Industrial Applications: New Solutions for the New Era

This book reprints articles from the Special Issue "Industrial Applications: New Solutions for the New Age" published online in the open-access journal Machines (ISSN 2075-1702). This book consists of twelve published articles. This special edition belongs to the "Mechatronic and Intelligent Machines" section