Analysis of Microarray Data using Machine Learning Techniques on Scalable Platforms

Microarray-based gene expression profiling has been emerged as an efficient technique for classification, diagnosis, prognosis, and treatment of cancer disease. Frequent changes in the behavior of this disease, generate a huge volume of data. The data retrieved from microarray cover its veracities, and the changes observed as time changes (velocity). Although, it is a type of high-dimensional data which has very large number of features rather than number of samples. Therefore, the analysis of microarray high-dimensional dataset in a short period is very much essential. It often contains huge number of data, only a fraction of which comprises significantly expressed genes. The identification of the precise and interesting genes which are responsible for the cause of cancer is imperative in microarray data analysis. Most of the existing schemes employ a two phase process such as feature selection/extraction followed by classification. Our investigation starts with the analysis of microarray data using kernel based classifiers followed by feature selection using statistical t-test. In this work, various kernel based classifiers like Extreme learning machine (ELM), Relevance vector machine (RVM), and a new proposed method called kernel fuzzy inference system (KFIS) are implemented. The proposed models are investigated using three microarray datasets like Leukemia, Breast and Ovarian cancer. Finally, the performance of these classifiers are measured and compared with Support vector machine (SVM). From the results, it is revealed that the proposed models are able to classify the datasets efficiently and the performance is comparable to the existing kernel based classifiers. As the data size increases, to handle and process these datasets becomes very bottleneck. Hence, a distributed and a scalable cluster like Hadoop is needed for storing (HDFS) and processing (MapReduce as well as Spark) the datasets in an efficient way. The next contribution in this thesis deals with the implementation of feature selection methods, which are able to process the data in a distributed manner. Various statistical tests like ANOVA, Kruskal-Wallis, and Friedman tests are implemented using MapReduce and Spark frameworks which are executed on the top of Hadoop cluster. The performance of these scalable models are measured and compared with the conventional system. From the results, it is observed that the proposed scalable models are very efficient to process data of larger dimensions (GBs, TBs, etc.), as it is not possible to process with the traditional implementation of those algorithms. After selecting the relevant features, the next contribution of this thesis is the scalable viii implementation of the proximal support vector machine classifier, which is an efficient variant of SVM. The proposed classifier is implemented on the two scalable frameworks like MapReduce and Spark and executed on the Hadoop cluster. The obtained results are compared with the results obtained using conventional system. From the results, it is observed that the scalable cluster is well suited for the Big data. Furthermore, it is concluded that Spark is more efficient than MapReduce due to its an intelligent way of handling the datasets through Resilient distributed dataset (RDD) as well as in-memory processing and conventional system to analyze the Big datasets. Therefore, the next contribution of the thesis is the implementation of various scalable classifiers base on Spark. In this work various classifiers like, Logistic regression (LR), Support vector machine (SVM), Naive Bayes (NB), K-Nearest Neighbor (KNN), Artificial Neural Network (ANN), and Radial basis function network (RBFN) with two variants hybrid and gradient descent learning algorithms are proposed and implemented using Spark framework. The proposed scalable models are executed on Hadoop cluster as well as conventional system and the results are investigated. From the obtained results, it is observed that the execution of the scalable algorithms are very efficient than conventional system for processing the Big datasets. The efficacy of the proposed scalable algorithms to handle Big datasets are investigated and compared with the conventional system (where data are not distributed, kept on standalone machine and processed in a traditional manner). The comparative analysis shows that the scalable algorithms are very efficient to process Big datasets on Hadoop cluster rather than the conventional system

Exploring and Evaluating the Scalability and Efficiency of Apache Spark using Educational Datasets

Research into the combination of data mining and machine learning technology with web-based education systems (known as education data mining, or EDM) is becoming imperative in order to enhance the quality of education by moving beyond traditional methods. With the worldwide growth of the Information Communication Technology (ICT), data are becoming available at a significantly large volume, with high velocity and extensive variety. In this thesis, four popular data mining methods are applied to Apache Spark, using large volumes of datasets from Online Cognitive Learning Systems to explore the scalability and efficiency of Spark. Various volumes of datasets are tested on Spark MLlib with different running configurations and parameter tunings. The thesis convincingly presents useful strategies for allocating computing resources and tuning to take full advantage of the in-memory system of Apache Spark to conduct the tasks of data mining and machine learning. Moreover, it offers insights that education experts and data scientists can use to manage and improve the quality of education, as well as to analyze and discover hidden knowledge in the era of big data

InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms.

Phasing of single nucleotide (SNV), and structural variations into chromosome-wide haplotypes in humans has been challenging, and required either trio sequencing or restricting phasing to population-based haplotypes. Selvaraj et al demonstrated single individual SNV phasing is possible with proximity ligated (HiC) sequencing. Here, we demonstrate HiC can phase structural variants into phased scaffolds of SNVs. Since HiC data is noisy, and SV calling is challenging, we applied a range of supervised classification techniques, including Support Vector Machines and Random Forest, to phase deletions. Our approach was demonstrated on deletion calls and phasings on the NA12878 human genome. We used three NA12878 chromosomes and simulated chromosomes to train model parameters. The remaining NA12878 chromosomes withheld from training were used to evaluate phasing accuracy. Random Forest had the highest accuracy and correctly phased 86% of the deletions with allele-specific read evidence. Allele-specific read evidence was found for 76% of the deletions. HiC provides significant read evidence for accurately phasing 33% of the deletions. Also, eight of eight top ranked deletions phased by only HiC were validated using long range polymerase chain reaction and Sanger. Thus, deletions from a single individual can be accurately phased using a combination of shotgun and proximity ligation sequencing. InPhaDel software is available at: http://l337x911.github.io/inphadel/

Ambient Air Quality Classification by Grey Wolf Optimizer Based Support Vector Machine

With the development of society along with an escalating population, the concerns regarding public health have cropped up. The quality of air becomes primary concern regarding constant increase in the number of vehicles and industrial development. With this concern, several indices have been proposed to indicate the pollutant concentrations. In this paper, we present a mathematical framework to formulate a Cumulative Index (CI) on the basis of an individual concentration of four major pollutants (SO2, NO2, PM2.5, and PM10). Further, a supervised learning algorithm based classifier is proposed. This classifier employs support vector machine (SVM) to classify air quality into two types, that is, good or harmful. The potential inputs for this classifier are the calculated values of CIs. The efficacy of the classifier is tested on the real data of three locations: Kolkata, Delhi, and Bhopal. It is observed that the classifier performs well to classify the quality of air

Systems Analytics and Integration of Big Omics Data

A “genotype"" is essentially an organism's full hereditary information which is obtained from its parents. A ""phenotype"" is an organism's actual observed physical and behavioral properties. These may include traits such as morphology, size, height, eye color, metabolism, etc. One of the pressing challenges in computational and systems biology is genotype-to-phenotype prediction. This is challenging given the amount of data generated by modern Omics technologies. This “Big Data” is so large and complex that traditional data processing applications are not up to the task. Challenges arise in collection, analysis, mining, sharing, transfer, visualization, archiving, and integration of these data. In this Special Issue, there is a focus on the systems-level analysis of Omics data, recent developments in gene ontology annotation, and advances in biological pathways and network biology. The integration of Omics data with clinical and biomedical data using machine learning is explored. This Special Issue covers new methodologies in the context of gene–environment interactions, tissue-specific gene expression, and how external factors or host genetics impact the microbiome

Detecting and comparing non-coding RNAs in the high-throughput era.

In recent years there has been a growing interest in the field of non-coding RNA. This surge is a direct consequence of the discovery of a huge number of new non-coding genes and of the finding that many of these transcripts are involved in key cellular functions. In this context, accurately detecting and comparing RNA sequences has become important. Aligning nucleotide sequences is a key requisite when searching for homologous genes. Accurate alignments reveal evolutionary relationships, conserved regions and more generally any biologically relevant pattern. Comparing RNA molecules is, however, a challenging task. The nucleotide alphabet is simpler and therefore less informative than that of amino-acids. Moreover for many non-coding RNAs, evolution is likely to be mostly constrained at the structural level and not at the sequence level. This results in very poor sequence conservation impeding comparison of these molecules. These difficulties define a context where new methods are urgently needed in order to exploit experimental results to their full potential. This review focuses on the comparative genomics of non-coding RNAs in the context of new sequencing technologies and especially dealing with two extremely important and timely research aspects: the development of new methods to align RNAs and the analysis of high-throughput data

Morphological and genomic shifts in mole-rat 'queens' increase fecundity but reduce skeletal integrity.

In some mammals and many social insects, highly cooperative societies are characterized by reproductive division of labor, in which breeders and nonbreeders become behaviorally and morphologically distinct. While differences in behavior and growth between breeders and nonbreeders have been extensively described, little is known of their molecular underpinnings. Here, we investigate the consequences of breeding for skeletal morphology and gene regulation in highly cooperative Damaraland mole-rats. By experimentally assigning breeding 'queen' status versus nonbreeder status to age-matched littermates, we confirm that queens experience vertebral growth that likely confers advantages to fecundity. However, they also upregulate bone resorption pathways and show reductions in femoral mass, which predicts increased vulnerability to fracture. Together, our results show that, as in eusocial insects, reproductive division of labor in mole-rats leads to gene regulatory rewiring and extensive morphological plasticity. However, in mole-rats, concentrated reproduction is also accompanied by costs to bone strength

Computational solutions for addressing heterogeneity in DNA methylation data

DNA methylation, a reversible epigenetic modification, has been implicated with various bi- ological processes including gene regulation. Due to the multitude of datasets available, it is a premier candidate for computational tool development, especially for investigating hetero- geneity within and across samples. We differentiate between three levels of heterogeneity in DNA methylation data: between-group, between-sample, and within-sample heterogeneity. Here, we separately address these three levels and present new computational approaches to quantify and systematically investigate heterogeneity. Epigenome-wide association studies relate a DNA methylation aberration to a phenotype and therefore address between-group heterogeneity. To facilitate such studies, which necessar- ily include data processing, exploratory data analysis, and differential analysis of DNA methy- lation, we extended the R-package RnBeads. We implemented novel methods for calculating the epigenetic age of individuals, novel imputation methods, and differential variability analysis. A use-case of the new features is presented using samples from Ewing sarcoma patients. As an important driver of epigenetic differences between phenotypes, we systematically investigated associations between donor genotypes and DNA methylation states in methylation quantitative trait loci (methQTL). To that end, we developed a novel computational framework –MAGAR– for determining statistically significant associations between genetic and epigenetic variations. We applied the new pipeline to samples obtained from sorted blood cells and complex bowel tissues of healthy individuals and found that tissue-specific and common methQTLs have dis- tinct genomic locations and biological properties. To investigate cell-type-specific DNA methylation profiles, which are the main drivers of within-group heterogeneity, computational deconvolution methods can be used to dissect DNA methylation patterns into latent methylation components. Deconvolution methods require pro- files of high technical quality and the identified components need to be biologically interpreted. We developed a computational pipeline to perform deconvolution of complex DNA methyla- tion data, which implements crucial data processing steps and facilitates result interpretation. We applied the protocol to lung adenocarcinoma samples and found indications of tumor in- filtration by immune cells and associations of the detected components with patient survival. Within-sample heterogeneity (WSH), i.e., heterogeneous DNA methylation patterns at a ge- nomic locus within a biological sample, is often neglected in epigenomic studies. We present the first systematic benchmark of scores quantifying WSH genome-wide using simulated and experimental data. Additionally, we created two novel scores that quantify DNA methyla- tion heterogeneity at single CpG resolution with improved robustness toward technical biases. WSH scores describe different types of WSH in simulated data, quantify differential hetero- geneity, and serve as a reliable estimator of tumor purity. Due to the broad availability of DNA methylation data, the levels of heterogeneity in DNA methylation data can be comprehensively investigated. We contribute novel computational frameworks for analyzing DNA methylation data with respect to different levels of hetero- geneity. We envision that this toolbox will be indispensible for understanding the functional implications of DNA methylation patterns in health and disease.DNA Methylierung ist eine reversible, epigenetische Modifikation, die mit verschiedenen biologischen Prozessen wie beispielsweise der Genregulation in Verbindung steht. Eine Vielzahl von DNA Methylierungsdatensätzen bildet die perfekte Grundlage zur Entwicklung von Softwareanwendungen, insbesondere um Heterogenität innerhalb und zwischen Proben zu beschreiben. Wir unterscheiden drei Ebenen von Heterogenität in DNA Methylierungsdaten: zwischen Gruppen, zwischen Proben und innerhalb einer Probe. Hier betrachten wir die drei Ebenen von Heterogenität in DNA Methylierungsdaten unabhängig voneinander und präsentieren neue Ansätze um die Heterogenität zu beschreiben und zu quantifizieren. Epigenomweite Assoziationsstudien verknüpfen eine DNA Methylierungsveränderung mit einem Phänotypen und beschreiben Heterogenität zwischen Gruppen. Um solche Studien, welche Datenprozessierung, sowie exploratorische und differentielle Datenanalyse beinhalten, zu vereinfachen haben wir die R-basierte Softwareanwendung RnBeads erweitert. Die Erweiterungen beinhalten neue Methoden, um das epigenetische Alter vorherzusagen, neue Schätzungsmethoden für fehlende Datenpunkte und eine differentielle Variabilitätsanalyse. Die Analyse von Ewing-Sarkom Patientendaten wurde als Anwendungsbeispiel für die neu entwickelten Methoden gewählt. Wir untersuchten Assoziationen zwischen Genotypen und DNA Methylierung von einzelnen CpGs, um sogenannte methylation quantitative trait loci (methQTL) zu definieren. Diese stellen einen wichtiger Faktor dar, der epigenetische Unterschiede zwischen Gruppen induziert. Hierzu entwickelten wir ein neues Softwarepaket (MAGAR), um statistisch signifikante Assoziationen zwischen genetischer und epigenetischer Variation zu identifizieren. Wir wendeten diese Pipeline auf Blutzelltypen und komplexe Biopsien von gesunden Individuen an und konnten gemeinsame und gewebespezifische methQTLs in verschiedenen Bereichen des Genoms lokalisieren, die mit unterschiedlichen biologischen Eigenschaften verknüpft sind. Die Hauptursache für Heterogenität innerhalb einer Gruppe sind zelltypspezifische DNA Methylierungsmuster. Um diese genauer zu untersuchen kann Dekonvolutionssoftware die DNA Methylierungsmatrix in unabhängige Variationskomponenten zerlegen. Dekonvolutionsmethoden auf Basis von DNA Methylierung benötigen technisch hochwertige Profile und die identifizierten Komponenten müssen biologisch interpretiert werden. In dieser Arbeit entwickelten wir eine computerbasierte Pipeline zur Durchführung von Dekonvolutionsexperimenten, welche die Datenprozessierung und Interpretation der Resultate beinhaltet. Wir wendeten das entwickelte Protokoll auf Lungenadenokarzinome an und fanden Anzeichen für eine Tumorinfiltration durch Immunzellen, sowie Verbindungen zum Überleben der Patienten. Heterogenität innerhalb einer Probe (within-sample heterogeneity, WSH), d.h. heterogene Methylierungsmuster innerhalb einer Probe an einer genomischen Position, wird in epigenomischen Studien meist vernachlässigt. Wir präsentieren den ersten Vergleich verschiedener, genomweiter WSH Maße auf simulierten und experimentellen Daten. Zusätzlich entwickelten wir zwei neue Maße um WSH für einzelne CpGs zu berechnen, welche eine verbesserte Robustheit gegenüber technischen Faktoren aufweisen. WSH Maße beschreiben verschiedene Arten von WSH, quantifizieren differentielle Heterogenität und sagen Tumorreinheit vorher. Aufgrund der breiten Verfügbarkeit von DNA Methylierungsdaten können die Ebenen der Heterogenität ganzheitlich beschrieben werden. In dieser Arbeit präsentieren wir neue Softwarelösungen zur Analyse von DNA Methylierungsdaten in Bezug auf die verschiedenen Ebenen der Heterogenität. Wir sind davon überzeugt, dass die vorgestellten Softwarewerkzeuge unverzichtbar für das Verständnis von DNA Methylierung im kranken und gesunden Stadium sein werden

Ranking to Learn and Learning to Rank: On the Role of Ranking in Pattern Recognition Applications

The last decade has seen a revolution in the theory and application of machine learning and pattern recognition. Through these advancements, variable ranking has emerged as an active and growing research area and it is now beginning to be applied to many new problems. The rationale behind this fact is that many pattern recognition problems are by nature ranking problems. The main objective of a ranking algorithm is to sort objects according to some criteria, so that, the most relevant items will appear early in the produced result list. Ranking methods can be analyzed from two different methodological perspectives: ranking to learn and learning to rank. The former aims at studying methods and techniques to sort objects for improving the accuracy of a machine learning model. Enhancing a model performance can be challenging at times. For example, in pattern classification tasks, different data representations can complicate and hide the different explanatory factors of variation behind the data. In particular, hand-crafted features contain many cues that are either redundant or irrelevant, which turn out to reduce the overall accuracy of the classifier. In such a case feature selection is used, that, by producing ranked lists of features, helps to filter out the unwanted information. Moreover, in real-time systems (e.g., visual trackers) ranking approaches are used as optimization procedures which improve the robustness of the system that deals with the high variability of the image streams that change over time. The other way around, learning to rank is necessary in the construction of ranking models for information retrieval, biometric authentication, re-identification, and recommender systems. In this context, the ranking model's purpose is to sort objects according to their degrees of relevance, importance, or preference as defined in the specific application.Comment: European PhD Thesis. arXiv admin note: text overlap with arXiv:1601.06615, arXiv:1505.06821, arXiv:1704.02665 by other author

Ranking to Learn and Learning to Rank: On the Role of Ranking in Pattern Recognition Applications

The last decade has seen a revolution in the theory and application of machine learning and pattern recognition. Through these advancements, variable ranking has emerged as an active and growing research area and it is now beginning to be applied to many new problems. The rationale behind this fact is that many pattern recognition problems are by nature ranking problems. The main objective of a ranking algorithm is to sort objects according to some criteria, so that, the most relevant items will appear early in the produced result list. Ranking methods can be analyzed from two different methodological perspectives: ranking to learn and learning to rank. The former aims at studying methods and techniques to sort objects for improving the accuracy of a machine learning model. Enhancing a model performance can be challenging at times. For example, in pattern classification tasks, different data representations can complicate and hide the different explanatory factors of variation behind the data. In particular, hand-crafted features contain many cues that are either redundant or irrelevant, which turn out to reduce the overall accuracy of the classifier. In such a case feature selection is used, that, by producing ranked lists of features, helps to filter out the unwanted information. Moreover, in real-time systems (e.g., visual trackers) ranking approaches are used as optimization procedures which improve the robustness of the system that deals with the high variability of the image streams that change over time. The other way around, learning to rank is necessary in the construction of ranking models for information retrieval, biometric authentication, re-identification, and recommender systems. In this context, the ranking model's purpose is to sort objects according to their degrees of relevance, importance, or preference as defined in the specific application.Comment: European PhD Thesis. arXiv admin note: text overlap with arXiv:1601.06615, arXiv:1505.06821, arXiv:1704.02665 by other author