Applications Of Machine Learning In Biology And Medicine

Machine learning as a field is defined to be the set of computational algorithms that improve their performance by assimilating data. As such, the field as a whole has found applications in many diverse disciplines from robotics and communication in engineering to economics and finance, and also biology and medicine. It should not come as a surprise that many popular methods in use today have completely different origins. Despite this heterogeneity, different methods can be divided into standard tasks, such as supervised, unsupervised, semi-supervised and reinforcement learning. Although machine learning as a field can be formalized as methods trying to solve certain standard tasks, applying these tasks on datasets from different fields comes with certain caveats, and sometimes is fraught with challenges. In this thesis, we develop general procedures and novel solutions, dealing with practical problems that arise when modeling biological and medical data. Cost sensitive learning is an important area of research in machine learning which addresses the widespread and practical problem of dealing with different costs during the learning and deployment of classification algorithms. In many applications such as credit fraud detection, network intrusion and specifically medical diagnosis domains, prior class distributions are highly skewed, which makes the training examples very much unbalanced. Combining this with uneven misclassification costs renders standard machine learning approaches useless in learning an acceptable decision function. We experimentally show the benefits and shortcomings of various methods that convert cost blind learning algorithms to cost sensitive ones. Using the results and best practices found for cost sensitive learning, we design and develop a machine learning approach to ontology mapping. Next, we present a novel approach to deal with uncertainty in classification when costs are unknown or otherwise hard to assign. Support Vector Machines (SVM) are considered to be among the most successful approaches for classification. However prediction of instances near the decision boundary depends more on the specific parameter selection or noise in data, rather than a clear difference in features. In many applications such as medical diagnosis, these regions should be labeled as uncertain rather than assigned to any particular class. Furthermore, instances may belong to novel disease subtypes that are not from any previously known class. In such applications, declining to make a prediction could be beneficial when more powerful but expensive tests are available. We develop a novel approach for optimal selection of the threshold and show its successful application on three biological and medical datasets. The last part of this thesis provides novel solutions for handling high dimensional data. Although high-dimensional data is ubiquitously found in many disciplines, current life science research almost always involves high-dimensional genomics/proteomics data. The ``omics\u27\u27 data provide a wealth of information and have changed the research landscape in biology and medicine. However, these data are plagued with noise, redundancy and collinearity, which makes the discovery process very difficult and costly. Any method that can accurately detect irrelevant and noisy variables in omics data would be highly valuable. We present Robust Feature Selection (RFS), a randomized feature selection approach dedicated to low-sample high-dimensional data. RFS combines an embedded feature selection method with a randomization procedure for stability. Recent advances in sparse recovery and estimation methods have provided efficient and asymptotically consistent feature selection algorithms. However, these methods lack finite sample error control due to instability. Furthermore, the chances of correct recovery diminish with more collinearity among features. To overcome these difficulties, RFS uses a randomization procedure to provide an accurate and stable feature selection method. We thoroughly evaluate RFS by comparing it to a number of popular univariate and multivariate feature selection methods and show marked prediction accuracy improvement of a diagnostic signature, while preserving a good stability

Scalable Machine Learning Methods for Massive Biomedical Data Analysis.

Modern data acquisition techniques have enabled biomedical researchers to collect and analyze datasets of substantial size and complexity. The massive size of these datasets allows us to comprehensively study the biological system of interest at an unprecedented level of detail, which may lead to the discovery of clinically relevant biomarkers. Nonetheless, the dimensionality of these datasets presents critical computational and statistical challenges, as traditional statistical methods break down when the number of predictors dominates the number of observations, a setting frequently encountered in biomedical data analysis. This difficulty is compounded by the fact that biological data tend to be noisy and often possess complex correlation patterns among the predictors. The central goal of this dissertation is to develop a computationally tractable machine learning framework that allows us to extract scientifically meaningful information from these massive and highly complex biomedical datasets. We motivate the scope of our study by considering two important problems with clinical relevance: (1) uncertainty analysis for biomedical image registration, and (2) psychiatric disease prediction based on functional connectomes, which are high dimensional correlation maps generated from resting state functional MRI.PhDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111354/1/takanori_1.pd

Feature selection for microarray gene expression data using simulated annealing guided by the multivariate joint entropy

In this work a new way to calculate the multivariate joint entropy is presented. This measure is the basis for a fast information-theoretic based evaluation of gene relevance in a Microarray Gene Expression data context. Its low complexity is based on the reuse of previous computations to calculate current feature relevance. The mu-TAFS algorithm --named as such to differentiate it from previous TAFS algorithms-- implements a simulated annealing technique specially designed for feature subset selection. The algorithm is applied to the maximization of gene subset relevance in several public-domain microarray data sets. The experimental results show a notoriously high classification performance and low size subsets formed by biologically meaningful genes.Postprint (published version

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

A theoretical and methodological framework for machine learning in survival analysis: Enabling transparent and accessible predictive modelling on right-censored time-to-event data

Survival analysis is an important field of Statistics concerned with mak- ing time-to-event predictions with ‘censored’ data. Machine learning, specifically supervised learning, is the field of Statistics concerned with using state-of-the-art algorithms in order to make predictions on unseen data. This thesis looks at unifying these two fields as current research into the two is still disjoint, with ‘classical survival’ on one side and su- pervised learning (primarily classification and regression) on the other. This PhD aims to improve the quality of machine learning research in survival analysis by focusing on transparency, accessibility, and predic- tive performance in model building and evaluation. This is achieved by examining historic and current proposals and implementations for models and measures (both classical and machine learning) in survival analysis and making novel contributions. In particular this includes: i) a survey of survival models including a crit- ical and technical survey of almost all supervised learning model classes currently utilised in survival, as well as novel adaptations; ii) a survey of evaluation measures for survival models, including key definitions, proofs and theorems for survival scoring rules that had previously been missing from the literature; iii) introduction and formalisation of composition and reduction in survival analysis, with a view on increasing transparency of modelling strategies and improving predictive performance; iv) imple- mentation of several R software packages, in particular mlr3proba for machine learning in survival analysis; and v) the first large-scale bench- mark experiment on right-censored time-to-event data with 24 survival models and 66 datasets. Survival analysis has many important applications in medical statistics, engineering and finance, and as such requires the same level of rigour as other machine learning fields such as regression and classification; this thesis aims to make this clear by describing a framework from prediction and evaluation to implementation

Data-Adaptive Kernel Support Vector Machine

In this thesis, we propose the data-adaptive kernel Support Vector Machine (SVM), a new method with a data-driven scaling kernel function based on real data sets. This two-stage approach of kernel function scaling can enhance the accuracy of a support vector machine, especially when the data are imbalanced. Followed by the standard SVM procedure in the first stage, the proposed method locally adapts the kernel function to data locations based on the skewness of the class outcomes. In the second stage, the decision rule is constructed with the data-adaptive kernel function and is used as the classifier. This process enlarges the magnification effect directly on the Riemannian manifold within the feature space rather than the input space. The proposed data-adaptive kernel SVM technique is applied in the binary classification, and is extended to the multi-class situations when imbalance is a main concern. We conduct extensive simulation studies to assess the performance of the proposed methods, and the prostate cancer image study is employed as an illustration. The data-adaptive kernel is further applied in feature selection process. We propose the data-adaptive kernel-penalized SVM, a new method of simultaneous feature selection and classification by penalizing data-adaptive kernels in SVMs. Instead of penalizing the standard cost function of SVMs in the usual way, the penalty will be directly added to the dual objective function that contains the data-adaptive kernel. Classification results with sparse features selected can be obtained simultaneously. Different penalty terms in the data-adaptive kernel-penalized SVM will be compared. The oracle property of the estimator is examined. We conduct extensive simulation studies to assess the performance of all the proposed methods, and employ the method on a breast cancer data set as an illustration. The data-adaptive kernel is further applied in feature selection process. We propose the data-adaptive kernel-penalized SVM, a new method of simultaneous feature selection and classification by penalizing data-adaptive kernels in SVMs. Instead of penalizing the standard cost function of SVMs in the usual way, the penalty will be directly added to the dual objective function that contains the data-adaptive kernel. Classification results with sparse features selected can be obtained simultaneously. Different penalty terms in the data-adaptive kernel-penalized SVM will be compared. The oracle property of the estimator is examined. We conduct extensive simulation studies to assess the performance of all the proposed methods, and employ the method on a breast cancer data set as an illustration