A molecular approach to complex adaptive systems

Complex Adaptive Systems (CAS) are dynamical networks of interacting agents which as a whole determine the behavior, adaptivity and cognitive ability of the system. CAS are ubiquitous and occur in a variety of natural and artificial systems (e.g., cells, societies, stock markets). To study CAS, Holland proposed to employ an agent-based system in which Learning Classifier Systems (LCS) were used to determine the agents behavior and adaptivity. We argue that LCS are limited for the study of CAS: the rule-discovery mechanism is pre-specified and may limit the evolvability of CAS. Secondly, LCS distinguish a demarcation between messages and rules, however operations are reflexive in CAS, e.g., in a cell, an agent (a molecule) may both act as a message (substrate) and as a catalyst (rule). To address these issues, we proposed the Molecular Classifier Systems (MCS.b), a string-based Artificial Chemistry based on Holland’s broadcast language. In the MCS.b, no explicit fitness function or rule discovery mechanism is specified, moreover no distinction is made between messages and rules. In the context of the ESIGNET project, we employ the MCS.b to study a subclass of CAS: Cell Signaling Networks (CSNs) which are complex biochemical networks responsible for coordinating cellular activities. As CSNs occur in cells, these networks must replicate themselves prior to cell division. In this paper we present a series of experiments focusing on the self-replication ability of these CAS. Results indicate counter intuitive outcomes as opposed to those inferred from the literature. This work highlights the current deficit of a theoretical framework for the study of Artificial Chemistries

Cellular automaton supercolliders

Gliders in one-dimensional cellular automata are compact groups of non-quiescent and non-ether patterns (ether represents a periodic background) translating along automaton lattice. They are cellular-automaton analogous of localizations or quasi-local collective excitations travelling in a spatially extended non-linear medium. They can be considered as binary strings or symbols travelling along a one-dimensional ring, interacting with each other and changing their states, or symbolic values, as a result of interactions. We analyse what types of interaction occur between gliders travelling on a cellular automaton `cyclotron' and build a catalog of the most common reactions. We demonstrate that collisions between gliders emulate the basic types of interaction that occur between localizations in non-linear media: fusion, elastic collision, and soliton-like collision. Computational outcomes of a swarm of gliders circling on a one-dimensional torus are analysed via implementation of cyclic tag systems

Unifying metabolic networks, regulatory constraints, and resource allocation

Metabolic and gene regulatory networks are two classic models of systems biology. Biologically, gene regulatory networks are the control system of protein expression while metabolic networks, especially the genome-scale reconstructions consist of thousands of enzymatic reactions breaking down nutrients into precursors and energy to support the cellular survival. Metabolic-genetic networks, in addition, include the translational processes as an integrated model of classical metabolic networks and the gene expression machinery. Conversely, genetic regulation is also affected by the metabolic activities that provide feedbacks and precursors to the regulatory system. Thus, the two systems are highly interactive and depend on each other. Up to now, various efforts have been made to bridge the two network types. Yet, the dynamic integration of metabolic networks and genetic regulation remains a major challenge in computational systems biology. This PhD thesis is a contribution to mathematical modeling approaches for studying metabolic-regulatory systems. Inspired by regulatory flux balance analysis (rFBA), we first propose an analytic pipeline to explore the optimal solution space in rFBA. Then, our efforts focus on the dynamic combination of metabolic networks together with enzyme production costs and genetic regulation. For this purpose, we first explore the intuitive idea that incorporates Boolean regulatory rules while iterating resource balance analysis. However, with the iterative strategy, the gene expression states are only updated in discrete time steps. Furthermore, formalizing the metabolic-regulatory networks (MRNs) by hybrid automata provides a new mathematical framework that allows the quantitative integration of the metabolic-genetic network with the genetic regulation in a hybrid discrete-continuous system. For the application of this theoretical formalization, we develop a constraint-based approach regulatory dynamic enzyme-cost flux balance analysis (r-deFBA) as an optimal control strategy for the hybrid automata representing MRNs. This allows the prediction of optimal regulatory state transitions, dynamics of metabolism, and resource allocation capable of achieving a maximal biomass production over a time interval. Finally, this PhD project ends with a chapter on perspectives; we apply the theory of product automata to model the dynamics at population-level, integrating continuous metabolism and discrete regulatory states

The Algorithmic Origins of Life

Although it has been notoriously difficult to pin down precisely what it is that makes life so distinctive and remarkable, there is general agreement that its informational aspect is one key property, perhaps the key property. The unique informational narrative of living systems suggests that life may be characterized by context-dependent causal influences, and in particular, that top-down (or downward) causation -- where higher-levels influence and constrain the dynamics of lower-levels in organizational hierarchies -- may be a major contributor to the hierarchal structure of living systems. Here we propose that the origin of life may correspond to a physical transition associated with a shift in causal structure, where information gains direct, and context-dependent causal efficacy over the matter it is instantiated in. Such a transition may be akin to more traditional physical transitions (e.g. thermodynamic phase transitions), with the crucial distinction that determining which phase (non-life or life) a given system is in requires dynamical information and therefore can only be inferred by identifying causal architecture. We discuss some potential novel research directions based on this hypothesis, including potential measures of such a transition that may be amenable to laboratory study, and how the proposed mechanism corresponds to the onset of the unique mode of (algorithmic) information processing characteristic of living systems.Comment: 13 pages, 1 tabl

Cellular automata simulation of topological effects on the dynamics of feed-forward motifs

<p>Abstract</p> <p>Background</p> <p>Feed-forward motifs are important functional modules in biological and other complex networks. The functionality of feed-forward motifs and other network motifs is largely dictated by the connectivity of the individual network components. While studies on the dynamics of motifs and networks are usually devoted to the temporal or spatial description of processes, this study focuses on the relationship between the specific architecture and the overall rate of the processes of the feed-forward family of motifs, including double and triple feed-forward loops. The search for the most efficient network architecture could be of particular interest for regulatory or signaling pathways in biology, as well as in computational and communication systems.</p> <p>Results</p> <p>Feed-forward motif dynamics were studied using cellular automata and compared with differential equation modeling. The number of cellular automata iterations needed for a 100% conversion of a substrate into a target product was used as an inverse measure of the transformation rate. Several basic topological patterns were identified that order the specific feed-forward constructions according to the rate of dynamics they enable. At the same number of network nodes and constant other parameters, the bi-parallel and tri-parallel motifs provide higher network efficacy than single feed-forward motifs. Additionally, a topological property of isodynamicity was identified for feed-forward motifs where different network architectures resulted in the same overall rate of the target production.</p> <p>Conclusion</p> <p>It was shown for classes of structural motifs with feed-forward architecture that network topology affects the overall rate of a process in a quantitatively predictable manner. These fundamental results can be used as a basis for simulating larger networks as combinations of smaller network modules with implications on studying synthetic gene circuits, small regulatory systems, and eventually dynamic whole-cell models.</p

Systems Biology of Cancer: A Challenging Expedition for Clinical and Quantitative Biologists

A systems-biology approach to complex disease (such as cancer) is now complementing traditional experience-based approaches, which have typically been invasive and expensive. The rapid progress in biomedical knowledge is enabling the targeting of disease with therapies that are precise, proactive, preventive, and personalized. In this paper, we summarize and classify models of systems biology and model checking tools, which have been used to great success in computational biology and related fields. We demonstrate how these models and tools have been used to study some of the twelve biochemical pathways implicated in but not unique to pancreatic cancer, and conclude that the resulting mechanistic models will need to be further enhanced by various abstraction techniques to interpret phenomenological models of cancer progression

Frontiers of Membrane Computing: Open Problems and Research Topics

This is a list of open problems and research topics collected after the Twelfth Conference on Membrane Computing, CMC 2012 (Fontainebleau, France (23 - 26 August 2011), meant initially to be a working material for Tenth Brainstorming Week on Membrane Computing, Sevilla, Spain (January 30 - February 3, 2012). The result was circulated in several versions before the brainstorming and then modified according to the discussions held in Sevilla and according to the progresses made during the meeting. In the present form, the list gives an image about key research directions currently active in membrane computing