CSM-427: Coarse Graining in an Evolutionary Algorithm with Recombination, Duplication and Inversion

A generalised form of recombination, wherein an offspring can be formed from any of the genetic material of the parents, is analysed in the context of a two-locus recombinative GA. A complete, exact solution, is derived, showing how the dynamical behaviour is radically different to that of homologous crossover. Inversion is shown to potentially introduce oscillations in the dynamics, while gene duplication leads to an asymmetry between homogeneous and heterogeneous strings. All non-homologous operators lead to allele ?diffusion? along the chromosome. We discuss how inferences from the two-locus results extend to the case of a recombinative GA with selection and more than two loci

CSM-426: Theoretical Analysis of Generalised Recombination

In this paper we propose, model theoretically and study a general notion of recombination for fixed-length strings where homologous crossover, inversion, gene duplication, gene deletion, diploidy and more are just special cases. The analysis of the model reveals similarities and differences between genetic systems based on these operations. It also reveals that the notion of schema emerges naturally from the model?s equations even for the strangest of recombination operations. The study provides a variety of fixed points for the case where recombination is used alone, which generalise Geiringer?s theorem

06061 Abstracts Collection -- Theory of Evolutionary Algorithms

From 05.02.06 to 10.02.06, the Dagstuhl Seminar 06061 ``Theory of Evolutionary Algorithms\u27\u27 was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available

A model for characterising the collective dynamic behaviour of evolutionary algorithms

Exploration and exploitation are considered essential notions in evolutionary algorithms. However, a precise interpretation of what constitutes exploration or exploitation is clearly lacking and so are specific measures for characterising such notions. In this paper, we start addressing this issue by presenting new measures that can be used as indicators of the exploitation behaviour of an algorithm. These work by characterising the extent to which available information guides the search. More precisely, they quantify the dependency of a population's activity on the observed fitness values and genetic material, utilising an empirical model that uses a coarse-grained representation of population dynamics and records information about it. The model uses the k-means clustering algorithm to identify the population's "basins of activity". The exploitation behaviour is then captured by an entropy-based measure based on the model that quantifies the strength of the association between a population's activity distribution and the observed fitness landscape information. In experiments, we analysed the effects of the search operators and their parameter settings on the collective dynamic behaviour of populations. We also analysed the effect of using different problems on algorithm behaviours.We define a behavioural landscape for each problem to identify the appropriate behaviour to achieve good results and point out possible applications for the proposed model

A Model for Characterising the Collective Dynamic Behaviour of Evolutionary Algorithms

Abstract. Exploration and exploitation are considered essential notions in evolutionary algorithms. However, a precise interpretation of what constitutes exploration or exploitation is clearly lacking and so are specific measures for characterising such notions. In this paper, we start addressing this issue by presenting new measures that can be used as indicators of the exploitation behaviour of an algorithm. These work by characterising the extent to which available information guides the search. More precisely, they quantify the dependency of a population's activity on the observed fitness values and genetic material, utilising an empirical model that uses a coarse-grained representation of population dynamics and records information about it. The model uses the k-means clustering algorithm to identify the population's "basins of activity". The exploitation behaviour is then captured by an entropy-based measure based on the model that quantifies the strength of the association between a population's activity distribution and the observed fitness landscape information. In experiments, we analysed the effects of the search operators and their parameter settings on the collective dynamic behaviour of populations. We also analysed the effect of using different problems on algorithm behaviours. We define a behavioural landscape for each problem to identify the appropriate behaviour to achieve good results and point out possible applications for the proposed model

Improving Comparative Genomic Studies:Definitions and Algorithms for Syntenic Blocks

Comparative genomics aims to understand the structure of genomes and the function of various genomic fragments, by transferring knowledge gained from well studied genomes, to the new object of study. Rapid and inexpensive high-throughput sequencing is making available more and more complete genome sequences. Despite the significant scientific advance, we still lack good models for the evolution of the genomic architecture, therefore analyzing these genomes presents formidable challenges. Early approaches used pairwise comparisons, but today researchers are attempting to leverage the larger potential of multiway comparisons. Current approaches are based on the identification of so called syntenic blocks: blocks of sequence that exhibit conserved features across the genomes under study. Syntenic blocks are in many ways analogous to genesâ -in many cases, the markers are used to constructing them are genes. Like genes they can exist in multiple copies, in which case we could define analogs of orthology and paralogy. However, whereas genes are studied at the sequence level, syntenic blocks are too large for that level of detail - it is their structure and function as a unit that makes them valuable for genome level comparative studies. Syntenic blocks are required for complex computations to scale to the billions of nucleotides present in many genomes; they enable comparisons across broad ranges of genomes because they filter outmuch of the individual variability; they highlight candidate regions for in-depth studies; and they facilitate whole-genome comparisons through visualization tools. The identification of such blocks is the first step in comparative studies, yet its effect on final results has not been well studied, nor has any formalization of syntenic blocks been proposed. Tools for the identification of syntenic blocks yield quite different results, thereby preventing a systematic assessment of the next steps in an analysis. Current tools do not include measurable quality objectives and thus cannot be benchmarked against themselves. Comparisons among tools have also been neglected - what few results are given use superficial measures unrelated to quality or consistency. In this thesis we address two major challenges, and present: (i) a theoretical model as well as an experimental basis for comparing syntenic blocks and thus also for improving the design of tools for the identification of syntenic blocks; (ii) a prototype model that serves as a basis for implementing effective synteny mining tools. We offer an overview of the milestones present in literature, on the development of concepts and tool related to synteny; we illustrate the application of the model and the measures by applying them to syntenic blocks produced by different contemporary tools on publicly available data sets. We have taken the first step towards a formal approach to the construction of syntenic blocks by developing a simple quality criterion based on sound evolutionary principles. Our experiments demonstrate widely divergent results among these tools, throwing into question the robustness of the basic approach in comparative genomics. Our findings highlight the need for a well founded, systematic approach to the decomposition of genomes into syntenic blocks and motivate the second part of the work - starting from the proposed model, we extend the concept with data dependent features and constraints, in order to test the concept on cases of interest

Topological interactions in ring polymers

Ring polymers offer a richness of behaviours that are of broad interest and have deep consequences in many fields of Science. In this Thesis I investigate some general and universal properties, i.e. independent of the chemical nature of the polymers, emerging from systems made of a collection of rings. These will be studied by using methods of equilibrium and non-equilibrium Statistical Mechanics together with Molecular Dynamics and Monte Carlo simulations of coarse-grained models for the systems under investigation. Within these frameworks, important questions regarding the macroscopic behaviour of ring-shaped polymers have yet to find a satisfactory answer. The work presented in this Thesis finds its principal motivations in problems arising in Material Science, the so called \melt" of rings, and in Biology, such as the organisation of mitochondrial DNA in some organisms and the mechanisms governing the electrophoretic separation of DNA samples in gels. There are several theoretical challenges in these fields which represent state-of-the-art scientific research and whose partial answers are provided in the work presented in this Thesis. One of the major achievements of the work presented is the general understanding of the role played by topological properties, i.e. those invariant under smooth deformations of the polymer contour, on the macroscopic behaviour of the investigated systems. Finally, the conclusions drawn from the presented work can have important scientific consequences as they may ultimately lead to a more complete understanding of complicated issues in Biology and to the design of next-generation soft materials

A complex systems approach to education in Switzerland

The insights gained from the study of complex systems in biological, social, and engineered systems enables us not only to observe and understand, but also to actively design systems which will be capable of successfully coping with complex and dynamically changing situations. The methods and mindset required for this approach have been applied to educational systems with their diverse levels of scale and complexity. Based on the general case made by Yaneer Bar-Yam, this paper applies the complex systems approach to the educational system in Switzerland. It confirms that the complex systems approach is valid. Indeed, many recommendations made for the general case have already been implemented in the Swiss education system. To address existing problems and difficulties, further steps are recommended. This paper contributes to the further establishment complex systems approach by shedding light on an area which concerns us all, which is a frequent topic of discussion and dispute among politicians and the public, where billions of dollars have been spent without achieving the desired results, and where it is difficult to directly derive consequences from actions taken. The analysis of the education system's different levels, their complexity and scale will clarify how such a dynamic system should be approached, and how it can be guided towards the desired performance

Statistical properties of microbial phenotypes and colony growth

Cells are the fundamental units of which all life forms are composed. To understand the elementary organization of life, it is therefore meaningful to start the investigation on the single cell level.Modern microscopy permits the examination of both subcellular processes and collective microbial behavior. In this microscopic regime, fluctuations are of eminent importance. As this noise is an inherent property of such systems, life evolved robust systems, which work effectively in spite of severe fluctuations. Moreover, life also makes use of these fluctuations for its benefit. For modeling purposes in this field of research, concepts from statistical mechanics and from the analysis of stochastic processes can be applied to account for the fluctuations. This work is roughly divided into two parts, which also address the background, concepts and literature of the corresponding topics. The first part is concerned with the modeling of intracellular processes, for which noise is important. In this context two publications, which arose from collaborations with experimental biophysicists, are discussed: In gene therapy external genetic material is injected into cells to remedy deficient behavior. To characterize this process, fluorophore encoding plasmids were administered to eukaryotic cells by means of two chemical transfection methods. The distribution of expression levels is explained by several strongly stochastic steps during transfection and subsequent quasi-deterministic gene expression. The second collaboration addresses the switching kinetics between different phenotypes in bacteria. In the case at hand, the emergence of "competence" in B. subtilis is studied. This ability (to take up genetic material from the extracellular medium) is strongly regulated by a network of interacting genes. While the different phenotypes are associated with stable fixed points of non-linear differential equations, switching between phenotypes relies on fluctuations in the small number of mRNA molecules. The second part of this work elaborates on collective, stochastic growth of many cells in an expanding colony. The corresponding manuscript analyzes a theoretical model with methods from statistical mechanics. Microbial colony growth is sometimes seen as a model system for range expansion or colonization processes. Inspired by experiments, a stochastic surface growth process, in the form of a generalized Eden model, is set up and analyzed. The model explicitly takes into account selection between two strains, irreversible mutations, and the roughness of the propagating colony front. The asymmetric character of mutations implies the existence of an absorbing state, where only the mutant strain is at the front of the expanding population. Hence, the model combines two interesting branches of non-equilibrium statistical mechanics: phase transitions to absorbing states and dynamic surface roughening. As usual for these processes, one can define critical exponents, which describe the divergence of observables near the phase transition, and admit organization of models into universality classes. It turns out that the coupling between roughening dynamics and population dynamics induces qualitative different behavior. As a consequence, the model cannot be assigned to any universality class currently known

Role of complement genetic variants in inflammatory diseases by an interactive database and protein structure modelling

The rare diseases atypical haemolytic uraemic syndrome (aHUS) and C3 glomerulopathy (C3G) are associated with dysregulation of complement activation. It is unclear which genes most frequently predispose to aHUS or C3G. Accordingly, a six- centre analysis of 610 rare genetic variants in 13 mostly complement genes from >3500 patients with aHUS and C3G was performed. A new interactive Database of Complement Gene Variants was developed to extract allele frequencies for these 13 genes using the Exome Aggregation Consortium server as the reference genome. For aHUS, significantly more protein-altering rare variation was found in the five genes CFH, CFI, CD46, C3 and DGKE than in ExAC. For C3G, an association was only found for rare variants in C3 and the N-terminal C3b-binding or C-terminal non-surface-associated regions of factor H (FH). FH is the major regulator of C3b and its Tyr402His polymorphism is an age-related macular degeneration risk-factor. To better understand FH complement binding, the solution structures of both allotypes were studied. Starting from known FH short complement regulator domains and glycan structures, small angle X-ray scattering data were fitted using Monte Carlo methods to determine atomistic structures for monomeric FH. The analysis of 29,715 physically realistic but randomised FH conformations resulted in 100 similar best-fit FH structures for each allotype. Two distinct molecular structures resulted; an extended N-terminal domain arrangement with a folded-back C-terminus, or an extended C-terminus and folded-back N-terminus. To clarify FH functional roles in host protection, crystal structures for the FH complexes with C3b and C3dg revealed that the extended N-terminal conformation accounted for C3b fluid phase regulation, the extended C-terminal conformation accounted for C3d binding, and both conformations accounted for bivalent FH binding to the host cell-surface. Finally, statistical analyses indicated that the structural location of rare variants in complement may predict the occurrences of aHUS or C3G