Computational design and designability of gene regulatory networks

Nuestro conocimiento de las interacciones moleculares nos ha conducido hoy hacia una perspectiva ingenieril, donde diseños e implementaciones de sistemas artificiales de regulación intentan proporcionar instrucciones fundamentales para la reprogramación celular. Nosotros aquí abordamos el diseño de redes de genes como una forma de profundizar en la comprensión de las regulaciones naturales. También abordamos el problema de la diseñabilidad dada una genoteca de elementos compatibles. Con este fin, aplicamos métodos heuríticos de optimización que implementan rutinas para resolver problemas inversos, así como herramientas de análisis matemático para estudiar la dinámica de la expresión genética. Debido a que la ingeniería de redes de transcripción se ha basado principalmente en el ensamblaje de unos pocos elementos regulatorios usando principios de diseño racional, desarrollamos un marco de diseño computacional para explotar este enfoque. Modelos asociados a genotecas fueron examinados para descubrir el espacio genotípico asociado a un cierto fenotipo. Además, desarrollamos un procedimiento completamente automatizado para diseñar moleculas de ARN no codificante con capacidad regulatoria, basándonos en un modelo fisicoquímico y aprovechando la regulación alostérica. Los circuitos de ARN resultantes implementaban un mecanismo de control post-transcripcional para la expresión de proteínas que podía ser combinado con elementos transcripcionales. También aplicamos los métodos heurísticos para analizar la diseñabilidad de rutas metabólicas. Ciertamente, los métodos de diseño computacional pueden al mismo tiempo aprender de los mecanismos naturales con el fin de explotar sus principios fundamentales. Así, los estudios de estos sistemas nos permiten profundizar en la ingeniería genética. De relevancia, el control integral y las regulaciones incoherentes son estrategias generales que los organismos emplean y que aquí analizamos.Rodrigo Tarrega, G. (2011). Computational design and designability of gene regulatory networks [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/1417

Applied (Meta)-Heuristic in Intelligent Systems

Engineering and business problems are becoming increasingly difficult to solve due to the new economics triggered by big data, artificial intelligence, and the internet of things. Exact algorithms and heuristics are insufficient for solving such large and unstructured problems; instead, metaheuristic algorithms have emerged as the prevailing methods. A generic metaheuristic framework guides the course of search trajectories beyond local optimality, thus overcoming the limitations of traditional computation methods. The application of modern metaheuristics ranges from unmanned aerial and ground surface vehicles, unmanned factories, resource-constrained production, and humanoids to green logistics, renewable energy, circular economy, agricultural technology, environmental protection, finance technology, and the entertainment industry. This Special Issue presents high-quality papers proposing modern metaheuristics in intelligent systems

Maximum entropy models in the analysis of genome-wide data in cancer research

This thesis studies the maximum entropy principle in statistical modelling. Applications are taken from the emerging field of cancer genomics. We start with a short introduction to the biology of cancer in chapter 1. In chapter 2, we discuss general principles of statistical modelling. We discuss in detail the maximum entropy principle in statistical modelling. In particular, we show that many statistical models can be put in a unified framework based on the principle of maximum entropy, which maps them into problems of statistical mechanics. In chapter 3, we consider a particular maximum entropy model, the Ising model, in the context of the inverse Ising problem. We introduce a Bethe–Peierls approximation to the inverse Ising problem. We then also suggest a modification for the mean-field approximation to work at low temperatures. The following chapters apply maximum entropy models to different problems of cancer genomics. A direct application of the inverse Ising problem to gene copy-number data of cancer cells is described in chapter 4. In chapter 5, we extend the concepts of indirect correlations and direct couplings of the inverse Ising problem to investigate the influence of gene copy-numbers on gene expressions in cancer cells. We show that the correlations in gene expression need not be due to regulatory interactions between genes. Instead, correlations in gene expression of cancer cells can be induced by the correlations in their copy-numbers, which is due to the geometrical organisation of the genome. We show that a simple maximum entropy-model can disentangle copy-number-induced correlations and the so-called “bare-correlations” in gene expression, which capture the effect of regulatory interactions alone. Chapter 6 is devoted to cancer classification. We introduce a simple semi-supervised learning algorithm to train a mixture of paramagnetic models with Ising spins to classify cancer mutation profiles. We show that, with the capability of both learning from unlabelled samples and correcting mislabelled samples, this learning algorithm outperforms both the supervised and unsupervised learning algorithms. The two appendices A and B summarise recent studies on sensitivity and resistance of cancer cells to therapy. The results of chapter 3 were published in H. C. Nguyen and J. Berg (2012a). “Bethe– Peierls approximation and the inverse Ising problem”. J. Stat. Mech. P03004; and H. C. Nguyen and J. Berg (2012b). “Mean-field theory for the inverse Ising problem at low temperatures”. Phys. Rev. Lett. 109, p. 50602. Some results of chapter 6 were published as a part of The Clinical Lung Cancer Genome Project (CLCGP) and Network Genomic Medicine (NGM) (2013). “A genomics-based classification of human lung tumors”. Science Transl. Med. 5.209, 209ra153

Exploiting Latent Features of Text and Graphs

As the size and scope of online data continues to grow, new machine learning techniques become necessary to best capitalize on the wealth of available information. However, the models that help convert data into knowledge require nontrivial processes to make sense of large collections of text and massive online graphs. In both scenarios, modern machine learning pipelines produce embeddings --- semantically rich vectors of latent features --- to convert human constructs for machine understanding. In this dissertation we focus on information available within biomedical science, including human-written abstracts of scientific papers, as well as machine-generated graphs of biomedical entity relationships. We present the Moliere system, and our method for identifying new discoveries through the use of natural language processing and graph mining algorithms. We propose heuristically-based ranking criteria to augment Moliere, and leverage this ranking to identify a new gene-treatment target for HIV-associated Neurodegenerative Disorders. We additionally focus on the latent features of graphs, and propose a new bipartite graph embedding technique. Using our graph embedding, we advance the state-of-the-art in hypergraph partitioning quality. Having newfound intuition of graph embeddings, we present Agatha, a deep-learning approach to hypothesis generation. This system learns a data-driven ranking criteria derived from the embeddings of our large proposed biomedical semantic graph. To produce human-readable results, we additionally propose CBAG, a technique for conditional biomedical abstract generation

Planning and Scheduling Optimization

Although planning and scheduling optimization have been explored in the literature for many years now, it still remains a hot topic in the current scientific research. The changing market trends, globalization, technical and technological progress, and sustainability considerations make it necessary to deal with new optimization challenges in modern manufacturing, engineering, and healthcare systems. This book provides an overview of the recent advances in different areas connected with operations research models and other applications of intelligent computing techniques used for planning and scheduling optimization. The wide range of theoretical and practical research findings reported in this book confirms that the planning and scheduling problem is a complex issue that is present in different industrial sectors and organizations and opens promising and dynamic perspectives of research and development

The role of visual adaptation in cichlid fish speciation

D. Shane Wright (1) , Ole Seehausen (2), Ton G.G. Groothuis (1), Martine E. Maan (1) (1) University of Groningen; GELIFES; EGDB(2) Department of Fish Ecology & Evolution, EAWAG Centre for Ecology, Evolution and Biogeochemistry, Kastanienbaum AND Institute of Ecology and Evolution, Aquatic Ecology, University of Bern.In less than 15,000 years, Lake Victoria cichlid fishes have radiated into as many as 500 different species. Ecological and sexual sel ection are thought to contribute to this ongoing speciation process, but genetic differentiation remains low. However, recent work in visual pigment genes, opsins, has shown more diversity. Unlike neighboring Lakes Malawi and Tanganyika, Lake Victoria is highly turbid, resulting in a long wavelength shift in the light spectrum with increasing depth, providing an environmental gradient for exploring divergent coevolution in sensory systems and colour signals via sensory drive. Pundamilia pundamila and Pundamilia nyererei are two sympatric species found at rocky islands across southern portions of Lake Victoria, differing in male colouration and the depth they reside. Previous work has shown species differentiation in colour discrimination, corresponding to divergent female preferences for conspecific male colouration. A mechanistic link between colour vision and preference would provide a rapid route to reproductive isolation between divergently adapting populations. This link is tested by experimental manip ulation of colour vision - raising both species and their hybrids under light conditions mimicking shallow and deep habitats. We quantify the expression of retinal opsins and test behaviours important for speciation: mate choice, habitat preference, and fo raging performance