Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Ensemble feature learning of genomic data using support vector machine

© 2016 Anaissi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The identification of a subset of genes having the ability to capture the necessary information to distinguish classes of patients is crucial in bioinformatics applications. Ensemble and bagging methods have been shown to work effectively in the process of gene selection and classification. Testament to that is random forest which combines random decision trees with bagging to improve overall feature selection and classification accuracy. Surprisingly, the adoption of these methods in support vector machines has only recently received attention but mostly on classification not gene selection. This paper introduces an ensemble SVM-Recursive Feature Elimination (ESVM-RFE) for gene selection that follows the concepts of ensemble and bagging used in random forest but adopts the backward elimination strategy which is the rationale of RFE algorithm. The rationale behind this is, building ensemble SVM models using randomly drawn bootstrap samples from the training set, will produce different feature rankings which will be subsequently aggregated as one feature ranking. As a result, the decision for elimination of features is based upon the ranking of multiple SVM models instead of choosing one particular model. Moreover, this approach will address the problem of imbalanced datasets by constructing a nearly balanced bootstrap sample. Our experiments show that ESVM-RFE for gene selection substantially increased the classification performance on five microarray datasets compared to state-of-the-art methods. Experiments on the childhood leukaemia dataset show that an average 9% better accuracy is achieved by ESVM-RFE over SVM-RFE, and 5% over random forest based approach. The selected genes by the ESVM-RFE algorithm were further explored with Singular Value Decomposition (SVD) which reveals significant clusters with the selected data

Feature selection of imbalanced gene expression microarray data

Gene expression data is a very complex data set characterised by abundant numbers of features but with a low number of observations. However, only a small number of these features are relevant to an outcome of interest. With this kind of data set, feature selection becomes a real prerequisite. This paper proposes a methodology for feature selection for an imbalanced leukaemia gene expression data based on random forest algorithm. It presents the importance of feature selection in terms of reducing the number of features, enhancing the quality of machine learning and providing better understanding for biologists in diagnosis and prediction. Algorithms are presented to show the methodology and strategy for feature selection taking care to avoid over fitting. Moreover, experiments are done using imbalanced Leukaemia gene expression data and special measurement is used to evaluate the quality of feature selection and performance of classification. © 2011 IEEE

Class prediction for high-dimensional class-imbalanced data

<p>Abstract</p> <p>Background</p> <p>The goal of class prediction studies is to develop rules to accurately predict the class membership of new samples. The rules are derived using the values of the variables available for each subject: the main characteristic of high-dimensional data is that the number of variables greatly exceeds the number of samples. Frequently the classifiers are developed using class-imbalanced data, i.e., data sets where the number of samples in each class is not equal. Standard classification methods used on class-imbalanced data often produce classifiers that do not accurately predict the minority class; the prediction is biased towards the majority class. In this paper we investigate if the high-dimensionality poses additional challenges when dealing with class-imbalanced prediction. We evaluate the performance of six types of classifiers on class-imbalanced data, using simulated data and a publicly available data set from a breast cancer gene-expression microarray study. We also investigate the effectiveness of some strategies that are available to overcome the effect of class imbalance.</p> <p>Results</p> <p>Our results show that the evaluated classifiers are highly sensitive to class imbalance and that variable selection introduces an additional bias towards classification into the majority class. Most new samples are assigned to the majority class from the training set, unless the difference between the classes is very large. As a consequence, the class-specific predictive accuracies differ considerably. When the class imbalance is not too severe, down-sizing and asymmetric bagging embedding variable selection work well, while over-sampling does not. Variable normalization can further worsen the performance of the classifiers.</p> <p>Conclusions</p> <p>Our results show that matching the prevalence of the classes in training and test set does not guarantee good performance of classifiers and that the problems related to classification with class-imbalanced data are exacerbated when dealing with high-dimensional data. Researchers using class-imbalanced data should be careful in assessing the predictive accuracy of the classifiers and, unless the class imbalance is mild, they should always use an appropriate method for dealing with the class imbalance problem.</p

Filter-wrapper combination and embedded feature selection for gene expression data

Biomedical and bioinformatics datasets are generally large in terms of their number of features - and include redundant and irrelevant features, which affect the effectiveness and efficiency of classification of these datasets. Several different features selection methods have been utilised in various fields, including bioinformatics, to reduce the number of features. This study utilised Filter-Wrapper combination and embedded (LASSO) feature selection methods on both high and low dimensional datasets before classification was performed. The results illustrate that the combination of filter and wrapper feature selection to create a hybrid form of feature selection provides better performance than using filter only. In addition, LASSO performed better on high dimensional data

Learning from high-dimensional and class-imbalanced datasets using random forests

Class imbalance and high dimensionality are two major issues in several real-life applications, e.g., in the fields of bioinformatics, text mining and image classification. However, while both issues have been extensively studied in the machine learning community, they have mostly been treated separately, and little research has been thus far conducted on which approaches might be best suited to deal with datasets that are class-imbalanced and high-dimensional at the same time (i.e., with a large number of features). This work attempts to give a contribution to this challenging research area by studying the effectiveness of hybrid learning strategies that involve the integration of feature selection techniques, to reduce the data dimensionality, with proper methods that cope with the adverse effects of class imbalance (in particular, data balancing and cost-sensitive methods are considered). Extensive experiments have been carried out across datasets from different domains, leveraging a well-known classifier, the Random Forest, which has proven to be effective in high-dimensional spaces and has also been successfully applied to imbalanced tasks. Our results give evidence of the benefits of such a hybrid approach, when compared to using only feature selection or imbalance learning methods alone

Supervised Methods for Biomarker Detection from Microarray Experiments

Biomarkers are valuable indicators of the state of a biological system. Microarray technology has been extensively used to identify biomarkers and build computational predictive models for disease prognosis, drug sensitivity and toxicity evaluations. Activation biomarkers can be used to understand the underlying signaling cascades, mechanisms of action and biological cross talk. Biomarker detection from microarray data requires several considerations both from the biological and computational points of view. In this chapter, we describe the main methodology used in biomarkers discovery and predictive modeling and we address some of the related challenges. Moreover, we discuss biomarker validation and give some insights into multiomics strategies for biomarker detection.Non peer reviewe

A Survey of Feature Selection Strategies for DNA Microarray Classification

Classification tasks are difficult and challenging in the bioinformatics field, that used to predict or diagnose patients at an early stage of disease by utilizing DNA microarray technology. However, crucial characteristics of DNA microarray technology are a large number of features and small sample sizes, which means the technology confronts a "dimensional curse" in its classification tasks because of the high computational execution needed and the discovery of biomarkers difficult. To reduce the dimensionality of features to find the significant features that can employ feature selection algorithms and not affect the performance of classification tasks. Feature selection helps decrease computational time by removing irrelevant and redundant features from the data. The study aims to briefly survey popular feature selection methods for classifying DNA microarray technology, such as filters, wrappers, embedded, and hybrid approaches. Furthermore, this study describes the steps of the feature selection process used to accomplish classification tasks and their relationships to other components such as datasets, cross-validation, and classifier algorithms. In the case study, we chose four different methods of feature selection on two-DNA microarray datasets to evaluate and discuss their performances, namely classification accuracy, stability, and the subset size of selected features. Keywords: Brief survey; DNA microarray data; feature selection; filter methods; wrapper methods; embedded methods; and hybrid methods. DOI: 10.7176/CEIS/14-2-01 Publication date:March 31st 202

Stability and Accuracy of Feature Selection Methods on Datasets of Varying Data Complexity

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