Biclustering of Gene Expression Data by Correlation-Based Scatter Search

BACKGROUND: The analysis of data generated by microarray technology is very useful to understand how the genetic information becomes functional gene products. Biclustering algorithms can determine a group of genes which are co-expressed under a set of experimental conditions. Recently, new biclustering methods based on metaheuristics have been proposed. Most of them use the Mean Squared Residue as merit function but interesting and relevant patterns from a biological point of view such as shifting and scaling patterns may not be detected using this measure. However, it is important to discover this type of patterns since commonly the genes can present a similar behavior although their expression levels vary in different ranges or magnitudes. METHODS: Scatter Search is an evolutionary technique that is based on the evolution of a small set of solutions which are chosen according to quality and diversity criteria. This paper presents a Scatter Search with the aim of finding biclusters from gene expression data. In this algorithm the proposed fitness function is based on the linear correlation among genes to detect shifting and scaling patterns from genes and an improvement method is included in order to select just positively correlated genes. RESULTS: The proposed algorithm has been tested with three real data sets such as Yeast Cell Cycle dataset, human B-cells lymphoma dataset and Yeast Stress dataset, finding a remarkable number of biclusters with shifting and scaling patterns. In addition, the performance of the proposed method and fitness function are compared to that of CC, OPSM, ISA, BiMax, xMotifs and Samba using Gene the Ontology Database

Internet of Things in urban waste collection

Nowadays, the waste collection management has an important role in urban areas. This paper faces this issue and proposes the application of a metaheuristic for the optimization of a weekly schedule and routing of the waste collection activities in an urban area. Differently to several contributions in literature, fixed periodic routes are not imposed. The results significantly improve the performance of the company involved, both in terms of resources used and costs saving

Preventing premature convergence and proving the optimality in evolutionary algorithms

http://ea2013.inria.fr//proceedings.pdfInternational audienceEvolutionary Algorithms (EA) usually carry out an efficient exploration of the search-space, but get often trapped in local minima and do not prove the optimality of the solution. Interval-based techniques, on the other hand, yield a numerical proof of optimality of the solution. However, they may fail to converge within a reasonable time due to their inability to quickly compute a good approximation of the global minimum and their exponential complexity. The contribution of this paper is a hybrid algorithm called Charibde in which a particular EA, Differential Evolution, cooperates with a Branch and Bound algorithm endowed with interval propagation techniques. It prevents premature convergence toward local optima and outperforms both deterministic and stochastic existing approaches. We demonstrate its efficiency on a benchmark of highly multimodal problems, for which we provide previously unknown global minima and certification of optimality

From metaheuristics to learnheuristics: Applications to logistics, finance, and computing

Un gran nombre de processos de presa de decisions en sectors estratègics com el transport i la producció representen problemes NP-difícils. Sovint, aquests processos es caracteritzen per alts nivells d'incertesa i dinamisme. Les metaheurístiques són mètodes populars per a resoldre problemes d'optimització difícils en temps de càlcul raonables. No obstant això, sovint assumeixen que els inputs, les funcions objectiu, i les restriccions són deterministes i conegudes. Aquests constitueixen supòsits forts que obliguen a treballar amb problemes simplificats. Com a conseqüència, les solucions poden conduir a resultats pobres. Les simheurístiques integren la simulació a les metaheurístiques per resoldre problemes estocàstics d'una manera natural. Anàlogament, les learnheurístiques combinen l'estadística amb les metaheurístiques per fer front a problemes en entorns dinàmics, en què els inputs poden dependre de l'estructura de la solució. En aquest context, les principals contribucions d'aquesta tesi són: el disseny de les learnheurístiques, una classificació dels treballs que combinen l'estadística / l'aprenentatge automàtic i les metaheurístiques, i diverses aplicacions en transport, producció, finances i computació.Un gran número de procesos de toma de decisiones en sectores estratégicos como el transporte y la producción representan problemas NP-difíciles. Frecuentemente, estos problemas se caracterizan por altos niveles de incertidumbre y dinamismo. Las metaheurísticas son métodos populares para resolver problemas difíciles de optimización de manera rápida. Sin embargo, suelen asumir que los inputs, las funciones objetivo y las restricciones son deterministas y se conocen de antemano. Estas fuertes suposiciones conducen a trabajar con problemas simplificados. Como consecuencia, las soluciones obtenidas pueden tener un pobre rendimiento. Las simheurísticas integran simulación en metaheurísticas para resolver problemas estocásticos de una manera natural. De manera similar, las learnheurísticas combinan aprendizaje estadístico y metaheurísticas para abordar problemas en entornos dinámicos, donde los inputs pueden depender de la estructura de la solución. En este contexto, las principales aportaciones de esta tesis son: el diseño de las learnheurísticas, una clasificación de trabajos que combinan estadística / aprendizaje automático y metaheurísticas, y varias aplicaciones en transporte, producción, finanzas y computación.A large number of decision-making processes in strategic sectors such as transport and production involve NP-hard problems, which are frequently characterized by high levels of uncertainty and dynamism. Metaheuristics have become the predominant method for solving challenging optimization problems in reasonable computing times. However, they frequently assume that inputs, objective functions and constraints are deterministic and known in advance. These strong assumptions lead to work on oversimplified problems, and the solutions may demonstrate poor performance when implemented. Simheuristics, in turn, integrate simulation into metaheuristics as a way to naturally solve stochastic problems, and, in a similar fashion, learnheuristics combine statistical learning and metaheuristics to tackle problems in dynamic environments, where inputs may depend on the structure of the solution. The main contributions of this thesis include (i) a design for learnheuristics; (ii) a classification of works that hybridize statistical and machine learning and metaheuristics; and (iii) several applications for the fields of transport, production, finance and computing

An iterated greedy heuristic for a market segmentation problem with multiple attributes

[EN] A real-world customer segmentation problem from a beverage distribution firm is addressed. The firm wants to partition a set of customers, who share geographical and marketing attributes, into segments according to certain requirements: (a) customers allocated to the same segment must have very similar attributes: type of contract, type of store and the average difference of purchase volume; and (b) compact segments are desired. The main reason for creating a partition with these features is because the firm wants to try different product marketing strategies. In this paper, a detailed attribute formulation and an iterated greedy heuristic that iteratively destroys and reconstructs a given partition are proposed. The initial partition is obtained by using a modified k-means algorithm that involves a GRASP philosophy to get the initial configuration of centers. The heuristic includes an improvement method that employs two local search procedures. Computational results and statistical analyses show the effectiveness of the proposed approach and its individual components. The proposed metaheuristic is also observed very competitive, faster, and more robust when compared to existing methods. (C) 2017 Elsevier B.V. All rights reserved.This research has been supported by the Mexican National Council for Science and Technology (CONACYT) through grants CB2005-01-48499Y and CB2011-01-166397, and a scholarship for graduate studies, and by the Universidad Autonoma de Nuevo Leon through its Scientific and Technological Research Support Program (PAICYT), grants CA1478-07, CE012-09, IT511-10, and CE331-15. Ruben Ruiz is partially supported by the Spanish Ministry of Economy and Competitiveness, under the project "SCHEYARD - Optimization of Scheduling Problems in Container Yards" (No. DPI2015-65895-R) financed by FEDER funds. We would like to thank Rafael Frinhani, Richard Fuchshuber, and their corresponding research teams for providing us the source code of their algorithms to carry out the corresponding tests. Furthermore, we are grateful to the editor and the four anonymous reviewers for their careful reading of our manuscript and their constructive comments and suggestions which helped us improve its quality.Huerta-Muñoz, D.; Ríos-Mercado, RZ.; Ruiz García, R. (2017). An iterated greedy heuristic for a market segmentation problem with multiple attributes. European Journal of Operational Research. 261(1):75-87. https://doi.org/10.1016/j.ejor.2017.02.013S7587261

Biclustering sobre datos de expresión génica basado en búsqueda dispersa

Falta palabras claveLos datos de expresión génica, y su particular naturaleza e importancia, motivan no sólo el desarrollo de nuevas técnicas sino la formulación de nuevos problemas como el problema del biclustering. El biclustering es una técnica de aprendizaje no supervisado que agrupa tanto genes como condiciones. Este doble agrupamiento lo diferencia del clustering tradicional sobre este tipo de datos ya que éste sólo agrupa o bien genes o condiciones. La presente tesis presenta un nuevo algoritmo de biclustering que permite el estudio de distintos criterios de búsqueda. Dicho algoritmo utiliza esquema de búsqueda dispersa, o scatter search, que independiza el mecanismo de búsqueda del criterio empleado. Se han estudiado tres criterios de búsqueda diferentes que motivan las tres principales aportaciones de la tesis. En primer lugar se estudia la correlación lineal entre los genes, que se integra como parte de la función objetivo empleada por el algoritmo de biclustering. La correlación lineal permite encontrar biclusters con patrones de desplazamiento y escalado, lo que mejora propuestas anteriores. En segundo lugar, y motivado por el significado biológico de los patrones de activación-inhibición entre genes, se modifica la correlación lineal de manera que se contemplen estos patrones. Por último, se ha tenido en cuenta la información disponible sobre genes en repositorios públicos, como la ontología de genes GO, y se incorpora dicha información como parte del criterio de búsqueda. Se añade un término extra que refleja, por cada bicluster que se evalúe, la calidad de ese grupo de genes según su información almacenada en GO. Se estudian dos posibilidades para dicho término de integración de información biológica, se comparan entre sí y se comprueba que los resultados son mejores cuando se usa información biológica en el algoritmo de biclustering. Las tres aportaciones descritas, junto con una serie de pasos intermedios, han dado lugar a resultados publicados tanto en revistas como en conferencias nacionales e internacionales

Semantic Biclustering

Tato disertační práce se zaměřuje na problém hledání interpretovatelných a prediktivních vzorů, které jsou vyjádřeny formou dvojshluků, se specializací na biologická data. Prezentované metody jsou souhrnně označovány jako sémantické dvojshlukování, jedná se o podobor dolování dat. Termín sémantické dvojshlukování je použit z toho důvodu, že zohledňuje proces hledání koherentních podmnožin řádků a sloupců, tedy dvojshluků, v 2-dimensionální binární matici a zárove ň bere také v potaz sémantický význam prvků v těchto dvojshlucích. Ačkoliv byla práce motivována biologicky orientovanými daty, vyvinuté algoritmy jsou obecně aplikovatelné v jakémkoli jiném výzkumném oboru. Je nutné pouze dodržet požadavek na formát vstupních dat. Disertační práce představuje dva originální a v tomto ohledu i základní přístupy pro hledání sémantických dvojshluků, jako je Bicluster enrichment analysis a Rule a tree learning. Jelikož tyto metody nevyužívají vlastní hierarchické uspořádání termů v daných ontologiích, obecně je běh těchto algoritmů dlouhý čin může docházet k indukci hypotéz s redundantními termy. Z toho důvodu byl vytvořen nový operátor zjemnění. Tento operátor byl včleněn do dobře známého algoritmu CN2, kde zavádí dvě redukční procedury: Redundant Generalization a Redundant Non-potential. Obě procedury pomáhají dramaticky prořezat prohledávaný prostor pravidel a tím umožňují urychlit proces indukce pravidel v porovnání s tradičním operátorem zjemnění tak, jak je původně prezentován v CN2. Celý algoritmus spolu s redukčními metodami je publikován ve formě R balííčku, který jsme nazvali sem1R. Abychom ukázali i možnost praktického užití metody sémantického dvojshlukování na reálných biologických problémech, v disertační práci dále popisujeme a specificky upravujeme algoritmus sem1R pro dv+ úlohy. Zaprvé, studujeme praktickou aplikaci algoritmu sem1R v analýze E-3 ubikvitin ligázy v trávicí soustavě s ohledem na potenciál regenerace tkáně. Zadruhé, kromě objevování dvojshluků v dat ech genové exprese, adaptujeme algoritmus sem1R pro hledání potenciálne patogenních genetických variant v kohortě pacientů.This thesis focuses on the problem of finding interpretable and predic tive patterns, which are expressed in the form of biclusters, with an orientation to biological data. The presented methods are collectively called semantic biclustering, as a subfield of data mining. The term semantic biclustering is used here because it reflects both a process of finding coherent subsets of rows and columns in a 2-dimensional binary matrix and simultaneously takes into account a mutual semantic meaning of elements in such biclusters. In spite of focusing on applications of algorithms in biological data, the developed algorithms are generally applicable to any other research field, there are only limitations on the format of the input data. The thesis introduces two novel, and in that context basic, approaches for finding semantic biclusters, as Bicluster enrichment analysis and Rule and tree learning. Since these methods do not exploit the native hierarchical order of terms of input ontologies, the run-time of algorithms is relatively long in general or an induced hypothesis might have terms that are redundant. For this reason, a new refinement operator has been invented. The refinement operator was incorporated into the well-known CN2 algorithm and uses two reduction procedures: Redundant Generalization and Redundant Non-potential, both of which help to dramatically prune the rule space and consequently, speed-up the entire process of rule induction in comparison with the traditional refinement operator as is presented in CN2. The reduction procedures were published as an R package that we called sem1R. To show a possible practical usage of semantic biclustering in real biological problems, the thesis also describes and specifically adapts the algorithm for two real biological problems. Firstly, we studied a practical application of sem1R algorithm in an analysis of E-3 ubiquitin ligase in the gastrointestinal tract with respect to tissue regeneration potential. Secondly, besides discovering biclusters in gene expression data, we adapted the sem1R algorithm for a different task, concretely for finding potentially pathogenic genetic variants in a cohort of patients

Multi-Objective Optimization in Metabolomics/Computational Intelligence

The development of reliable computational models for detecting non-linear patterns encased in throughput datasets and characterizing them into phenotypic classes has been of particular interest and comprises dynamic studies in metabolomics and other disciplines that are encompassed within the omics science. Some of the clinical conditions that have been associated with these studies include metabotypes in cancer, in ammatory bowel disease (IBD), asthma, diabetes, traumatic brain injury (TBI), metabolic syndrome, and Parkinson's disease, just to mention a few. The traction in this domain is attributable to the advancements in the procedures involved in 1H NMR-linked datasets acquisition, which have fuelled the generation of a wide abundance of datasets. Throughput datasets generated by modern 1H NMR spectrometers are often characterized with features that are uninformative, redundant and inherently correlated. This renders it di cult for conventional multivariate analysis techniques to e ciently capture important signals and patterns. Therefore, the work covered in this research thesis provides novel alternative techniques to address the limitations of current analytical pipelines. This work delineates 13 variants of population-based nature inspired metaheuristic optimization algorithms which were further developed in this thesis as wrapper-based feature selection optimizers. The optimizers were then evaluated and benchmarked against each other through numerical experiments. Large-scale 1H NMR-linked datasets emerging from three disease studies were employed for the evaluations. The rst is a study in patients diagnosed with Malan syndrome; an autosomal dominant inherited disorder marked by a distinctive facial appearance, learning disabilities, and gigantism culminating in tall stature and macrocephaly, also referred to as cerebral gigantism. Another study involved Niemann-Pick Type C1 (NP-C1), a rare progressive neurodegenerative condition marked by intracellular accrual of cholesterol and complex lipids including sphingolipids and phospholipids in the endosomal/lysosomal system. The third study involved sore throat investigation in human (also known as `pharyngitis'); an acute infection of the upper respiratory tract that a ects the respiratory mucosa of the throat. In all three cases, samples from pathologically-con rmed cohorts with corresponding controls were acquired, and metabolomics investigations were performed using 1H NMR technique. Thereafter, computational optimizations were conducted on all three high-dimensional datasets that were generated from the disease studies outlined, so that key biomarkers and most e cient optimizers were identi ed in each study. The clinical and biochemical signi cance of the results arising from this work were discussed and highlighted

Analysing functional genomics data using novel ensemble, consensus and data fusion techniques

Motivation: A rapid technological development in the biosciences and in computer science in the last decade has enabled the analysis of high-dimensional biological datasets on standard desktop computers. However, in spite of these technical advances, common properties of the new high-throughput experimental data, like small sample sizes in relation to the number of features, high noise levels and outliers, also pose novel challenges. Ensemble and consensus machine learning techniques and data integration methods can alleviate these issues, but often provide overly complex models which lack generalization capability and interpretability. The goal of this thesis was therefore to develop new approaches to combine algorithms and large-scale biological datasets, including novel approaches to integrate analysis types from different domains (e.g. statistics, topological network analysis, machine learning and text mining), to exploit their synergies in a manner that provides compact and interpretable models for inferring new biological knowledge. Main results: The main contributions of the doctoral project are new ensemble, consensus and cross-domain bioinformatics algorithms, and new analysis pipelines combining these techniques within a general framework. This framework is designed to enable the integrative analysis of both large- scale gene and protein expression data (including the tools ArrayMining, Top-scoring pathway pairs and RNAnalyze) and general gene and protein sets (including the tools TopoGSA , EnrichNet and PathExpand), by combining algorithms for different statistical learning tasks (feature selection, classification and clustering) in a modular fashion. Ensemble and consensus analysis techniques employed within the modules are redesigned such that the compactness and interpretability of the resulting models is optimized in addition to the predictive accuracy and robustness. The framework was applied to real-word biomedical problems, with a focus on cancer biology, providing the following main results: (1) The identification of a novel tumour marker gene in collaboration with the Nottingham Queens Medical Centre, facilitating the distinction between two clinically important breast cancer subtypes (framework tool: ArrayMining) (2) The prediction of novel candidate disease genes for Alzheimer’s disease and pancreatic cancer using an integrative analysis of cellular pathway definitions and protein interaction data (framework tool: PathExpand, collaboration with the Spanish National Cancer Centre) (3) The prioritization of associations between disease-related processes and other cellular pathways using a new rule-based classification method integrating gene expression data and pathway definitions (framework tool: Top-scoring pathway pairs) (4) The discovery of topological similarities between differentially expressed genes in cancers and cellular pathway definitions mapped to a molecular interaction network (framework tool: TopoGSA, collaboration with the Spanish National Cancer Centre) In summary, the framework combines the synergies of multiple cross-domain analysis techniques within a single easy-to-use software and has provided new biological insights in a wide variety of practical settings