The Emergence of Canalization and Evolvability in an Open-Ended, Interactive Evolutionary System

Natural evolution has produced a tremendous diversity of functional organisms. Many believe an essential component of this process was the evolution of evolvability, whereby evolution speeds up its ability to innovate by generating a more adaptive pool of offspring. One hypothesized mechanism for evolvability is developmental canalization, wherein certain dimensions of variation become more likely to be traversed and others are prevented from being explored (e.g. offspring tend to have similarly sized legs, and mutations affect the length of both legs, not each leg individually). While ubiquitous in nature, canalization almost never evolves in computational simulations of evolution. Not only does that deprive us of in silico models in which to study the evolution of evolvability, but it also raises the question of which conditions give rise to this form of evolvability. Answering this question would shed light on why such evolvability emerged naturally and could accelerate engineering efforts to harness evolution to solve important engineering challenges. In this paper we reveal a unique system in which canalization did emerge in computational evolution. We document that genomes entrench certain dimensions of variation that were frequently explored during their evolutionary history. The genetic representation of these organisms also evolved to be highly modular and hierarchical, and we show that these organizational properties correlate with increased fitness. Interestingly, the type of computational evolutionary experiment that produced this evolvability was very different from traditional digital evolution in that there was no objective, suggesting that open-ended, divergent evolutionary processes may be necessary for the evolution of evolvability.Comment: SI can be found at: http://www.evolvingai.org/files/SI_0.zi

Immune System Based Control and Intelligent Agent Design for Power System Applications

The National Academy of Engineering has selected the US Electric Power Grid as the supreme engineering achievement of the 20th century. Yet, this same grid is struggling to keep up with the increasing demand for electricity, its quality and cost. A growing recognition of the need to modernize the grid to meet future challenges has found articulation in the vision of a Smart Grid in using new control strategies that are intelligent, distributed, and adaptive. The objective of this work is to develop smart control systems inspired from the biological Human Immune System to better manage the power grid at the both generation and distribution levels. The work is divided into three main sections. In the first section, we addressed the problem of Automatic Generation Control design. The Clonal Selection theory is successfully applied as an optimization technique to obtain decentralized control gains that minimize a performance index based on Area Control Errors. Then the Immune Network theory is used to design adaptive controllers in order to diminish the excess maneuvering of the units and help the control areas comply with the North American Electric Reliability Corporation\u27s standards set to insure good quality of service and equitable mutual assistance by the interconnected energy balancing areas. The second section of this work addresses the design and deployment of Multi Agent Systems on both terrestrial and shipboard power systems self-healing using a novel approach based on the Immune Multi-Agent System (IMAS). The Immune System is viewed as a highly organized and distributed Multi-Cell System that strives to heal the body by working together and communicating to get rid of the pathogens. In this work both simulation and hardware design and deployment of the MAS are addressed. The third section of this work consists in developing a small scale smart circuit by modifying and upgrading the existing Analog Power Simulator to demonstrate the effectiveness of the developed technologies. We showed how to develop smart Agents hardware along with a wireless communication platform and the electronic switches. After putting together the different designed pieces, the resulting Multi Agent System is integrated into the Power Simulator Hardware. The multi Agent System developed is tested for fault isolation, reconfiguration, and restoration problems by simulating a permanent three phase fault on one of the feeder lines. The experimental results show that the Multi Agent System hardware developed performed effectively and in a timely manner which confirms that this technology is very promising and a very good candidate for Smart Grid control applications

Convergent evolution of modularity in metabolic networks through different community structures

Background: It has been reported that the modularity of metabolic networks of bacteria is closely related to the variability of their living habitats. However, given the dependency of themodularity score on the community structure, it remains unknown whether organisms achieve certain modularity via similar or different community structures. Results: In this work, we studied the relationship between similarities in modularity scores and similarities in community structures of the metabolic networks of 1021 species. Both similarities are then compared against the genetic distances. We revisited the association between modularity and variability of the microbial living environments and extended the analysis to other aspects of their life style such as temperature and oxygen requirements. We also tested both topological and biological intuition of the community structures identified and investigated the extent of their conservation with respect to the taxomony. Conclusions: We find that similar modularities are realized by different community structures. We find that such convergent evolution of modularity is closely associated with the number of (distinct) enzymes in the organismﾒs metabolome, a consequence of different life styles of the species. We find that the order of modularity is the same as the order of the number of the enzymes under the classification based on the temperature preference but not on the oxygen requirement. Besides, inspection of modularity-based communities reveals that these communities are graph-theoretically meaningful yet not reflective of specific biological functions. From an evolutionary perspective, we find that the community structures are conserved only at the level of kingdoms. Our results call for more investigation into the interplay between evolution and modularity: how evolution shapes modularity, and how modularity affects evolution (mainly in terms of fitness and evolvability). Further, our results call for exploring new measures of modularity and network communities that better correspond to functional categorizations

A Hybrid Test Optimization Framework - Coupling Genetic Algorithm with Local Search Technique

Quality of test cases is determined by their ability to uncover as many errors as possible in the software code. In our approach, we applied Hybrid Genetic Algorithm (HGA) for improving the quality of test cases. This improvement can be achieved by analyzing both mutation score and path coverage of each test case. Our approach selects effective test cases that have higher mutation score and path coverage from a near infinite number of test cases. Hence, the final test set size is reduced which in turn reduces the total time needed in testing activity. In our proposed framework, we included two improvement heuristics, namely RemoveTop and LocalBest, to achieve near global optimal solution. Finally, we compared the efficiency of the test cases generated by our approach against the existing test case optimization approaches such as Simple Genetic Algorithm (SGA) and Bacteriologic Algorithm (BA) and concluded that our approach generates better quality test cases

Genome-scale metabolic modelling of an extremophile microbial community

Dissertação de mestrado em BioinformaticsBiomining offers an ecological alternative to the standard mining practices by using ex tremophiles that can endure elevated temperatures and low pH values. Several studies have been performed using Acidithiobacillus caldus SM-1 and Acidimicrobium ferrooxidans DSM 10331, suggesting that these bacteria in a community offer several advantages in bioleaching environ ments. Genome-Scale Metabolic (GSM) models simulate the organisms’ metabolism through constraint based approaches. Therefore, the reconstruction of GSM models for A. caldus and A. ferroox idans and their integration into a community will offer, besides valuable insights into their metabolism, a unique perspective on the potential interaction mechanisms between the two organisms within the community. In this work, we developed manually curated GSM models for A. caldus with 416 genes, 846 reactions and 646 metabolites, and A. ferrooxidans with 408 genes, 817 reactions and 640 metabolites. Both models were reconstructed using the user-friendly software merlin. We performed the functional annotation of both organisms’ genomes to identify their metabolic characteristics, which allowed generating a draft of the metabolic network. Manual curation efforts through literature, genomic information, phylogenetically close organisms and biological databases allowed refining the metabolic network. Furthermore, the models were validated using Cobrapy and Mewpy which allowed analysing flux distribution and interactions in different environmental conditions, and the results were compared with the literature and experimental data. Lastly, the community model was built using the organisms’ validated GSM models. In silico phenotypic simulations of the community model revealed that A. caldus exchanged lipid-production related compounds whilst A. ferrooxidans donated hydrogen sulfide assisting the former with its more complex sulfur metabolism. Moreover, the results suggest a more significant influence of A. ferrooxidans in the community’s growth rate whilst A. caldus assists A. ferrooxidans in biomass production. These models can serve as a starting point to study and model the community’s behaviour in several bioleaching conditions.A biomineração oferece uma alternativa ecológica às práticas de mineração comuns através do uso de extremófilos que são capazes suportar elevadas temperaturas e baixos valores de pH. Vários estudos foram realizados usando os microrganismos Acidithiobacillus caldus SM-1 e Acidimicrobium ferrooxidans DSM 10331 em comunidade, sugerindo várias vantagens em ambientes de biolixiviação. Os modelos metabólicos à escala genómica permitem a modelação do metabolismo através de abordagens baseadas em restrições. Portanto, a construção de uma comunidade com contendo o modelo da A. caldus e outro da A. ferrooxidans poderá oferecer novas perspetivas sobre os seus respetivos metabolismos, assim como sobre os mecanismos de interação entre os dois organismos dentro da comunidade. Neste trabalho, foram reconstruídos dois modelos metabólicos à escala genómica com um elevado nível de curação manual utilizando a ferramenta merlin. O modelo da A. caldus conta com 416 genes e 846 reações enquanto que o da A. ferrooxidans possuí 408 genes e 817 reações. Os modelos foram funcionalmente anotados a fim de identificar as características metabólicas dos organismos, gerando um esboço da rede metabólica. Esta rede metabólica foi depois curada manualmente a fim de a refinar. Para isto foi usado informação presente na literatura, dados genómicos, organismos filogeneticamente próximos e bases de dados biológicas. Posteriormente, os modelos foram validados através de uma análise da distribuição de fluxo com diferentes condições ambientais e os resultados foram comparados com a literatura e dados experimentais. Por fim, o modelo da comunidade foi construído usando os modelos validados dos dois organismos. Simulações fenotípicas in silico do modelo da comunidade revelaram uma troca de compostos relacionados com produção de lípidios por parte da A. caldus, enquanto A. ferrooxidans doou sulfato de hidrogénio, auxiliando o primeiro no seu metabolismo de enxofre mais complexo. Por fim, os resultados sugerem uma maior influência de A. ferrooxidans na taxa de crescimento da comunidade enquanto que A. caldus auxilia o primeiro na produção de biomassa

In silico evolution of diauxic growth

The glucose effect is a well known phenomenon whereby cells, when presented with two different nutrients, show a diauxic growth pattern, i.e. an episode of exponential growth followed by a lag phase of reduced growth followed by a second phase of exponential growth. Diauxic growth is usually thought of as a an adaptation to maximise biomass production in an environment offering two or more carbon sources. While diauxic growth has been studied widely both experimentally and theoretically, the hypothesis that diauxic growth is a strategy to increase overall growth has remained an unconfirmed conjecture. Here, we present a minimal mathematical model of a bacterial nutrient uptake system and metabolism. We subject this model to artificial evolution to test under which conditions diauxic growth evolves. As a result, we find that, indeed, sequential uptake of nutrients emerges if there is competition for nutrients and the metabolism/uptake system is capacity limited. However, we also find that diauxic growth is a secondary effect of this system and that the speed-up of nutrient uptake is a much larger effect. Notably, this speed-up of nutrient uptake coincides with an overall reduction of efficiency. Our two main conclusions are: (i) Cells competing for the same nutrients evolve rapid but inefficient growth dynamics. (ii) In the deterministic models we use here no substantial lag-phase evolves. This suggests that the lag-phase is a consequence of stochastic gene expression

Network-based identification of driver pathways in clonal systems

Highly ethanol-tolerant bacteria for the production of biofuels, bacterial pathogenes which are resistant to antibiotics and cancer cells are examples of phenotypes that are of importance to society and are currently being studied. In order to better understand these phenotypes and their underlying genotype-phenotype relationships it is now commonplace to investigate DNA and expression profiles using next generation sequencing (NGS) and microarray techniques. These techniques generate large amounts of omics data which result in lists of genes that have mutations or expression profiles which potentially contribute to the phenotype. These lists often include a multitude of genes and are troublesome to verify manually as performing literature studies and wet-lab experiments for a large number of genes is very time and resources consuming. Therefore, (computational) methods are required which can narrow these gene lists down by removing generally abundant false positives from these lists and can ideally provide additional information on the relationships between the selected genes. Other high-throughput techniques such as yeast two-hybrid (Y2H), ChIP-Seq and Chip-Chip but also a myriad of small-scale experiments and predictive computational methods have generated a treasure of interactomics data over the last decade, most of which is now publicly available. By combining this data into a biological interaction network, which contains all molecular pathways that an organisms can utilize and thus is the equivalent of the blueprint of an organisms, it is possible to integrate the omics data obtained from experiments with these biological interaction networks. Biological interaction networks are key to the computational methods presented in this thesis as they enables methods to account for important relations between genes (and gene products). Doing so it is possible to not only identify interesting genes but also to uncover molecular processes important to the phenotype. As the best way to analyze omics data from an interesting phenotype varies widely based on the experimental setup and the available data, multiple methods were developed and applied in the context of this thesis: In a first approach, an existing method (PheNetic) was applied to a consortium of three bacterial species that together are able to efficiently degrade a herbicide but none of the species are able to efficiently degrade the herbicide on their own. For each of the species expression data (RNA-seq) was generated for the consortium and the species in isolation. PheNetic identified molecular pathways which were differentially expressed and likely contribute to a cross-feeding mechanism between the species in the consortium. Having obtained proof-of-concept, PheNetic was adapted to cope with experimental evolution datasets in which, in addition to expression data, genomics data was also available. Two publicly available datasets were analyzed: Amikacin resistance in E. coli and coexisting ecotypes in E.coli. The results allowed to elicit well-known and newly found molecular pathways involved in these phenotypes. Experimental evolution sometimes generates datasets consisting of mutator phenotypes which have high mutation rates. These datasets are hard to analyze due to the large amount of noise (most mutations have no effect on the phenotype). To this end IAMBEE was developed. IAMBEE is able to analyze genomic datasets from evolution experiments even if they contain mutator phenotypes. IAMBEE was tested using an E. coli evolution experiment in which cells were exposed to increasing concentrations of ethanol. The results were validated in the wet-lab. In addition to methods for analysis of causal mutations and mechanisms in bacteria, a method for the identification of causal molecular pathways in cancer was developed. As bacteria and cancerous cells are both clonal, they can be treated similar in this context. The big differences are the amount of data available (many more samples are available in cancer) and the fact that cancer is a complex and heterogenic phenotype. Therefore we developed SSA-ME, which makes use of the concept that a causal molecular pathway has at most one mutation in a cancerous cell (mutual exclusivity). However, enforcing this criterion is computationally hard. SSA-ME is designed to cope with this problem and search for mutual exclusive patterns in relatively large datasets. SSA-ME was tested on cancer data from the TCGA PAN-cancer dataset. From the results we could, in addition to already known molecular pathways and mutated genes, predict the involvement of few rarely mutated genes.nrpages: 246status: publishe

Multi-species integrative biclustering

We describe an algorithm, multi-species cMonkey, for the simultaneous biclustering of heterogeneous multiple-species data collections and apply the algorithm to a group of bacteria containing Bacillus subtilis, Bacillus anthracis, and Listeria monocytogenes. The algorithm reveals evolutionary insights into the surprisingly high degree of conservation of regulatory modules across these three species and allows data and insights from well-studied organisms to complement the analysis of related but less well studied organisms