Categorical Ontology of Complex Systems, Meta-Systems and Theory of Levels: The Emergence of Life, Human Consciousness and Society

Single cell interactomics in simpler organisms, as well as somatic cell interactomics in multicellular organisms, involve biomolecular interactions in complex signalling pathways that were recently represented in modular terms by quantum automata with ‘reversible behavior’ representing normal cell cycling and division. Other implications of such quantum automata, modular modeling of signaling pathways and cell differentiation during development are in the fields of neural plasticity and brain development leading to quantum-weave dynamic patterns and specific molecular processes underlying extensive memory, learning, anticipation mechanisms and the emergence of human consciousness during the early brain development in children. Cell interactomics is here represented for the first time as a mixture of ‘classical’ states that determine molecular dynamics subject to Boltzmann statistics and ‘steady-state’, metabolic (multi-stable) manifolds, together with ‘configuration’ spaces of metastable quantum states emerging from complex quantum dynamics of interacting networks of biomolecules, such as proteins and nucleic acids that are now collectively defined as quantum interactomics. On the other hand, the time dependent evolution over several generations of cancer cells --that are generally known to undergo frequent and extensive genetic mutations and, indeed, suffer genomic transformations at the chromosome level (such as extensive chromosomal aberrations found in many colon cancers)-- cannot be correctly represented in the ‘standard’ terms of quantum automaton modules, as the normal somatic cells can. This significant difference at the cancer cell genomic level is therefore reflected in major changes in cancer cell interactomics often from one cancer cell ‘cycle’ to the next, and thus it requires substantial changes in the modeling strategies, mathematical tools and experimental designs aimed at understanding cancer mechanisms. Novel solutions to this important problem in carcinogenesis are proposed and experimental validation procedures are suggested. From a medical research and clinical standpoint, this approach has important consequences for addressing and preventing the development of cancer resistance to medical therapy in ongoing clinical trials involving stage III cancer patients, as well as improving the designs of future clinical trials for cancer treatments.\ud \ud \ud KEYWORDS: Emergence of Life and Human Consciousness;\ud Proteomics; Artificial Intelligence; Complex Systems Dynamics; Quantum Automata models and Quantum Interactomics; quantum-weave dynamic patterns underlying human consciousness; specific molecular processes underlying extensive memory, learning, anticipation mechanisms and human consciousness; emergence of human consciousness during the early brain development in children; Cancer cell ‘cycling’; interacting networks of proteins and nucleic acids; genetic mutations and chromosomal aberrations in cancers, such as colon cancer; development of cancer resistance to therapy; ongoing clinical trials involving stage III cancer patients’ possible improvements of the designs for future clinical trials and cancer treatments. \ud \u

Exploring multiple viewshed analysis using terrain features and optimisation techniques

The calculation of viewsheds is a routine operation in geographic information systems and is used in a wide range of applications. Many of these involve the siting of features, such as radio masts, which are part of a network and yet the selection of sites is normally done separately for each feature. The selection of a series of locations which collectively maximise the visual coverage of an area is a combinatorial problem and as such cannot be directly solved except for trivial cases. In this paper, two strategies for tackling this problem are explored. The first is to restrict the search to key topographic points in the landscape such as peaks, pits and passes. The second is to use heuristics which have been applied to other maximal coverage spatial problems such as location-allocation. The results show that the use of these two strategies results in a reduction of the computing time necessary by two orders of magnitude, but at the cost of a loss of 10% in the area viewed. Three different heuristics were used, of which Simulated Annealing produced the best results. However the improvement over a much simpler fast-descent swap heuristic was very slight, but at the cost of greatly increased running times. © 2004 Elsevier Ltd. All rights reserved

Stochastic reaction networks with input processes: Analysis and applications to reporter gene systems

Stochastic reaction network models are widely utilized in biology and chemistry to describe the probabilistic dynamics of biochemical systems in general, and gene interaction networks in particular. Most often, statistical analysis and inference of these systems is addressed by parametric approaches, where the laws governing exogenous input processes, if present, are themselves fixed in advance. Motivated by reporter gene systems, widely utilized in biology to monitor gene activation at the individual cell level, we address the analysis of reaction networks with state-affine reaction rates and arbitrary input processes. We derive a generalization of the so-called moment equations where the dynamics of the network statistics are expressed as a function of the input process statistics. In stationary conditions, we provide a spectral analysis of the system and elaborate on connections with linear filtering. We then apply the theoretical results to develop a method for the reconstruction of input process statistics, namely the gene activation autocovariance function, from reporter gene population snapshot data, and demonstrate its performance on a simulated case study

An introduction to Biomodel engineering, illustrated for signal transduction pathways

BioModel Engineering is the science of designing, constructing and analyzing computational models of biological systems. It is inspired by concepts from software engineering and computing science. This paper illustrates a major theme in BioModel Engineering, namely that identifying a quantitative model of a dynamic system means building the structure, finding an initial state, and parameter fitting. In our approach, the structure is obtained by piecewise construction of models from modular parts, the initial state is obtained by analysis of the structure and parameter fitting comprises determining the rate parameters of the kinetic equations. We illustrate this with an example in the area of intracellular signalling pathways

Stochastic approach to molecular interactions and computational theory of metabolic and genetic regulations

Binding and unbinding of ligands to specific sites of a macromolecule are one of the most elementary molecular interactions inside the cell that embody the computational processes of biological regulations. The interaction between transcription factors and the operators of genes and that between ligands and binding sites of allosteric enzymes are typical examples of such molecular interactions. In order to obtain the general mathematical framework of biological regulations, we formulate these interactions as finite Markov processes and establish a computational theory of regulatory activities of macromolecules based mainly on graphical analysis of their state transition diagrams. The contribution is summarized as follows: (1) Stochastic interpretation of Michaelis-Menten equation is given. (2) Notion of \textit{probability flow} is introduced in relation to detailed balance. (3) A stochastic analogy of \textit{Wegscheider condition} is given in relation to loops in the state transition diagram. (4) A simple graphical method of computing the regulatory activity in terms of ligands' concentrations is obtained for Wegscheider cases.Comment: 20 pages, 13 figure

Universality classes of interaction structures for NK fitness landscapes

Kauffman's NK-model is a paradigmatic example of a class of stochastic models of genotypic fitness landscapes that aim to capture generic features of epistatic interactions in multilocus systems. Genotypes are represented as sequences of $L$ binary loci. The fitness assigned to a genotype is a sum of contributions, each of which is a random function defined on a subset of $k \le L$ loci. These subsets or neighborhoods determine the genetic interactions of the model. Whereas earlier work on the NK model suggested that most of its properties are robust with regard to the choice of neighborhoods, recent work has revealed an important and sometimes counter-intuitive influence of the interaction structure on the properties of NK fitness landscapes. Here we review these developments and present new results concerning the number of local fitness maxima and the statistics of selectively accessible (that is, fitness-monotonic) mutational pathways. In particular, we develop a unified framework for computing the exponential growth rate of the expected number of local fitness maxima as a function of $L$, and identify two different universality classes of interaction structures that display different asymptotics of this quantity for large $k$. Moreover, we show that the probability that the fitness landscape can be traversed along an accessible path decreases exponentially in $L$ for a large class of interaction structures that we characterize as locally bounded. Finally, we discuss the impact of the NK interaction structures on the dynamics of evolution using adaptive walk models.Comment: 61 pages, 9 figure