Analysis of microarray and next generation sequencing data for classification and biomarker discovery in relation to complex diseases

PhDThis thesis presents an investigation into gene expression profiling, using microarray and next generation sequencing (NGS) datasets, in relation to multi-category diseases such as cancer. It has been established that if the sequence of a gene is mutated, it can result in the unscheduled production of protein, leading to cancer. However, identifying the molecular signature of different cancers amongst thousands of genes is complex. This thesis investigates tools that can aid the study of gene expression to infer useful information towards personalised medicine. For microarray data analysis, this study proposes two new techniques to increase the accuracy of cancer classification. In the first method, a novel optimisation algorithm, COA-GA, was developed by synchronising the Cuckoo Optimisation Algorithm and the Genetic Algorithm for data clustering in a shuffle setup, to choose the most informative genes for classification purposes. Support Vector Machine (SVM) and Multilayer Perceptron (MLP) artificial neural networks are utilised for the classification step. Results suggest this method can significantly increase classification accuracy compared to other methods. An additional method involving a two-stage gene selection process was developed. In this method, a subset of the most informative genes are first selected by the Minimum Redundancy Maximum Relevance (MRMR) method. In the second stage, optimisation algorithms are used in a wrapper setup with SVM to minimise the selected genes whilst maximising the accuracy of classification. A comparative performance assessment suggests that the proposed algorithm significantly outperforms other methods at selecting fewer genes that are highly relevant to the cancer type, while maintaining a high classification accuracy. In the case of NGS, a state-of-the-art pipeline for the analysis of RNA-Seq data is investigated to discover differentially expressed genes and differential exon usages between normal and AIP positive Drosophila datasets, which are produced in house at Queen Mary, University of London. Functional genomic of differentially expressed genes were examined and found to be relevant to the case study under investigation. Finally, after normalising the RNA-Seq data, machine learning approaches similar to those in microarray was successfully implemented for these datasets

Técnicas big data para el procesamiento de flujos de datos masivos en tiempo real

Programa de Doctorado en Biotecnología, Ingeniería y Tecnología QuímicaLínea de Investigación: Ingeniería, Ciencia de Datos y BioinformáticaClave Programa: DBICódigo Línea: 111Machine learning techniques have become one of the most demanded resources by companies due to the large volume of data that surrounds us in these days. The main objective of these technologies is to solve complex problems in an automated way using data. One of the current perspectives of machine learning is the analysis of continuous flows of data or data streaming. This approach is increasingly requested by enterprises as a result of the large number of information sources producing time-indexed data at high frequency, such as sensors, Internet of Things devices, social networks, etc. However, nowadays, research is more focused on the study of historical data than on data received in streaming. One of the main reasons for this is the enormous challenge that this type of data presents for the modeling of machine learning algorithms. This Doctoral Thesis is presented in the form of a compendium of publications with a total of 10 scientific contributions in International Conferences and journals with high impact index in the Journal Citation Reports (JCR). The research developed during the PhD Program focuses on the study and analysis of real-time or streaming data through the development of new machine learning algorithms. Machine learning algorithms for real-time data consist of a different type of modeling than the traditional one, where the model is updated online to provide accurate responses in the shortest possible time. The main objective of this Doctoral Thesis is the contribution of research value to the scientific community through three new machine learning algorithms. These algorithms are big data techniques and two of them work with online or streaming data. In this way, contributions are made to the development of one of the current trends in Artificial Intelligence. With this purpose, algorithms are developed for descriptive and predictive tasks, i.e., unsupervised and supervised learning, respectively. Their common idea is the discovery of patterns in the data. The first technique developed during the dissertation is a triclustering algorithm to produce three-dimensional data clusters in offline or batch mode. This big data algorithm is called bigTriGen. In a general way, an evolutionary metaheuristic is used to search for groups of data with similar patterns. The model uses genetic operators such as selection, crossover, mutation or evaluation operators at each iteration. The goal of the bigTriGen is to optimize the evaluation function to achieve triclusters of the highest possible quality. It is used as the basis for the second technique implemented during the Doctoral Thesis. The second algorithm focuses on the creation of groups over three-dimensional data received in real-time or in streaming. It is called STriGen. Streaming modeling is carried out starting from an offline or batch model using historical data. As soon as this model is created, it starts receiving data in real-time. The model is updated in an online or streaming manner to adapt to new streaming patterns. In this way, the STriGen is able to detect concept drifts and incorporate them into the model as quickly as possible, thus producing triclusters in real-time and of good quality. The last algorithm developed in this dissertation follows a supervised learning approach for time series forecasting in real-time. It is called StreamWNN. A model is created with historical data based on the k-nearest neighbor or KNN algorithm. Once the model is created, data starts to be received in real-time. The algorithm provides real-time predictions of future data, keeping the model always updated in an incremental way and incorporating streaming patterns identified as novelties. The StreamWNN also identifies anomalous data in real-time allowing this feature to be used as a security measure during its application. The developed algorithms have been evaluated with real data from devices and sensors. These new techniques have demonstrated to be very useful, providing meaningful triclusters and accurate predictions in real time.Universidad Pablo de Olavide de Sevilla. Departamento de Deporte e informátic

Monte Carlo Method with Heuristic Adjustment for Irregularly Shaped Food Product Volume Measurement

Volume measurement plays an important role in the production and processing of food products. Various methods have been proposed to measure the volume of food products with irregular shapes based on 3D reconstruction. However, 3D reconstruction comes with a high-priced computational cost. Furthermore, some of the volume measurement methods based on 3D reconstruction have a low accuracy. Another method for measuring volume of objects uses Monte Carlo method. Monte Carlo method performs volume measurements using random points. Monte Carlo method only requires information regarding whether random points fall inside or outside an object and does not require a 3D reconstruction. This paper proposes volume measurement using a computer vision system for irregularly shaped food products without 3D reconstruction based on Monte Carlo method with heuristic adjustment. Five images of food product were captured using five cameras and processed to produce binary images. Monte Carlo integration with heuristic adjustment was performed to measure the volume based on the information extracted from binary images. The experimental results show that the proposed method provided high accuracy and precision compared to the water displacement method. In addition, the proposed method is more accurate and faster than the space carving method

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

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

WICC 2017 : XIX Workshop de Investigadores en Ciencias de la Computación

Actas del XIX Workshop de Investigadores en Ciencias de la Computación (WICC 2017), realizado en el Instituto Tecnológico de Buenos Aires (ITBA), el 27 y 28 de abril de 2017.Red de Universidades con Carreras en Informática (RedUNCI