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

Improved sequential and batch learning in neural networks using the tangent plane algorithm

The principal aim of this research is to investigate and develop improved sequential and batch learning algorithms based upon the tangent plane algorithm for artificial neural networks. A secondary aim is to apply the newly developed algorithms to multi-category cancer classification problems in the bio-informatics area, which involves the study of dna or protein sequences, macro-molecular structures, and gene expressions

Random Projection in Deep Neural Networks

This work investigates the ways in which deep learning methods can benefit from random projection (RP), a classic linear dimensionality reduction method. We focus on two areas where, as we have found, employing RP techniques can improve deep models: training neural networks on high-dimensional data and initialization of network parameters. Training deep neural networks (DNNs) on sparse, high-dimensional data with no exploitable structure implies a network architecture with an input layer that has a huge number of weights, which often makes training infeasible. We show that this problem can be solved by prepending the network with an input layer whose weights are initialized with an RP matrix. We propose several modifications to the network architecture and training regime that makes it possible to efficiently train DNNs with learnable RP layer on data with as many as tens of millions of input features and training examples. In comparison to the state-of-the-art methods, neural networks with RP layer achieve competitive performance or improve the results on several extremely high-dimensional real-world datasets. The second area where the application of RP techniques can be beneficial for training deep models is weight initialization. Setting the initial weights in DNNs to elements of various RP matrices enabled us to train residual deep networks to higher levels of performance

MACHINE LEARNING APPROACHES FOR BIOMARKER IDENTIFICATION AND SUBGROUP DISCOVERY FOR POST-TRAUMATIC STRESS DISORDER

Post-traumatic stress disorder (PTSD) is a psychiatric disorder caused by environmental and genetic factors resulting from alterations in genetic variation, epigenetic changes and neuroimaging characteristics. There is a pressing need to identify reliable molecular and physiological biomarkers for accurate diagnosis, prognosis, and treatment, as well to deepen the understanding of PTSD pathophysiology. Machine learning methods are widely used to infer patterns from biological data, identify biomarkers, and make predictions. The objective of this research is to apply machine learning methods for the accurate classification of human diseases from genome-scale datasets, focusing primarily on PTSD.The DoD-funded Systems Biology of PTSD Consortium has recruited combat veterans with and without PTSD for measurement of molecular and physiological data from blood or urine samples with the goal of identifying accurate and specific PTSD biomarkers. As a member of the Consortium with access to these PTSD multiple omics datasets, we first completed a project titled Clinical Subgroup-Specific PTSD Classification and Biomarker Discovery. We applied machine learning approaches to these data to build classification models consisting of molecular and clinical features to predict PTSD status. We also identified candidate biomarkers for diagnosis, which improves our understanding of PTSD pathogenesis. In a second project, entitled Multi-Omic PTSD Subgroup Identification and Clinical Characterization, we applied methods for integrating multiple omics datasets to investigate the complex, multivariate nature of the biological systems underlying PTSD. We identified an optimal 2 PTSD subgroups using two different machine learning approaches from 82 PTSD positive samples, and we found that the subgroups exhibited different remitting behavior as inferred from subjects recalled at a later time point. The results from our association, differential expression, and classification analyses demonstrated the distinct clinical and molecular features characterizing these subgroups.Taken together, our work has advanced our understanding of PTSD biomarkers and subgroups through the use of machine learning approaches. Results from our work should strongly contribute to the precise diagnosis and eventual treatment of PTSD, as well as other diseases. Future work will involve continuing to leverage these results to enable precision medicine for PTSD

Protein Superfamily Classification using Computational Intelligence Techniques

The problem of protein superfamily classification is a challenging research area in Bioinformatics and has its major application in drug discovery. If a newly discovered protein which is responsible for the cause of new disease gets correctly classified to its superfamily, then the task of the drug analyst becomes much easier. The analyst can perform molecular docking to find the correct relative orientation of ligand for the protein. The ligand database can be searched for all possible orientations and conformations of the protein belonging to that superfamily paired with the ligand. Thus, the search space is reduced enormously as the protein-ligand pair is searched for a particular protein superfamily. Therefore, correct classification of proteins becomes a very challenging task as it guides the analysts to discover appropriate drugs. In this thesis, Neural Networks (NN), Multiobjective Genetic Algorithm (MOGA),and Support Vector Machine (SVM) are applied to perform the classification task.Adaptive MultiObjective Genetic Algorithm (AMOGA), which is a variation of MOGA is implemented for the structure optimization of Radial Basis Function Network (RBFN). The modification to MOGA is done based on the two key controlling parameters such as probability of crossover and probability of mutation. These values are adaptively varied based upon the performance of the algorithm, i.e., based upon the percentage of the total population present in the best non-domination level. The problem of finding the number of hidden centers remains a critical issue for the design of RBFN. The most optimal RBF network with good generalization ability can be derived from the pareto optimal set. Therefore, every solution of the pareto optimal set gives information regarding the specific samples to be chosen as hidden centers as well as the update weight matrix connecting the hidden and output layer. Principal Component Analysis (PCA) has been used for dimension reduction and significant feature extraction from long feature vector of amino acid sequences.In two-stage approach for protein superfamily classification, feature extraction process is carried in the first stage and design of the classifier has been proposed in the second stage with an overall objective to maximize the performance accuracy of the classifier. In the feature extraction phase, Genetic Algorithm(GA) based wrapper approach is used to select few eigen vectors from the PCA space which are encoded as binary strings in the chromosome. Using PCA-NSGA-II (non-dominated sorting GA), the non-dominated solutions obtained from the pareto front solves the trade-off problem by compromising between the number of eigen vectors selected and the accuracy obtained by the classifier. In the second stage, Recursive Orthogonal Least Square Algorithm (ROLSA) is used for training RBFN. ROLSA selects the optimal number o

Genetic algorithm-neural network: feature extraction for bioinformatics data.

With the advance of gene expression data in the bioinformatics field, the questions which frequently arise, for both computer and medical scientists, are which genes are significantly involved in discriminating cancer classes and which genes are significant with respect to a specific cancer pathology. Numerous computational analysis models have been developed to identify informative genes from the microarray data, however, the integrity of the reported genes is still uncertain. This is mainly due to the misconception of the objectives of microarray study. Furthermore, the application of various preprocessing techniques in the microarray data has jeopardised the quality of the microarray data. As a result, the integrity of the findings has been compromised by the improper use of techniques and the ill-conceived objectives of the study. This research proposes an innovative hybridised model based on genetic algorithms (GAs) and artificial neural networks (ANNs), to extract the highly differentially expressed genes for a specific cancer pathology. The proposed method can efficiently extract the informative genes from the original data set and this has reduced the gene variability errors incurred by the preprocessing techniques. The novelty of the research comes from two perspectives. Firstly, the research emphasises on extracting informative features from a high dimensional and highly complex data set, rather than to improve classification results. Secondly, the use of ANN to compute the fitness function of GA which is rare in the context of feature extraction. Two benchmark microarray data have been taken to research the prominent genes expressed in the tumour development and the results show that the genes respond to different stages of tumourigenesis (i.e. different fitness precision levels) which may be useful for early malignancy detection. The extraction ability of the proposed model is validated based on the expected results in the synthetic data sets. In addition, two bioassay data have been used to examine the efficiency of the proposed model to extract significant features from the large, imbalanced and multiple data representation bioassay data

Complex Data Imputation by Auto-Encoders and Convolutional Neural Networks—A Case Study on Genome Gap-Filling

Missing data imputation has been a hot topic in the past decade, and many state-of-the-art works have been presented to propose novel, interesting solutions that have been applied in a variety of fields. In the past decade, the successful results achieved by deep learning techniques have opened the way to their application for solving difficult problems where human skill is not able to provide a reliable solution. Not surprisingly, some deep learners, mainly exploiting encoder-decoder architectures, have also been designed and applied to the task of missing data imputation. However, most of the proposed imputation techniques have not been designed to tackle \u201ccomplex data\u201d, that is high dimensional data belonging to datasets with huge cardinality and describing complex problems. Precisely, they often need critical parameters to be manually set or exploit complex architecture and/or training phases that make their computational load impracticable. In this paper, after clustering the state-of-the-art imputation techniques into three broad categories, we briefly review the most representative methods and then describe our data imputation proposals, which exploit deep learning techniques specifically designed to handle complex data. Comparative tests on genome sequences show that our deep learning imputers outperform the state-of-the-art KNN-imputation method when filling gaps in human genome sequences

A Recommendation System for Meta-modeling: A Meta-learning Based Approach

Various meta-modeling techniques have been developed to replace computationally expensive simulation models. The performance of these meta-modeling techniques on different models is varied which makes existing model selection/recommendation approaches (e.g., trial-and-error, ensemble) problematic. To address these research gaps, we propose a general meta-modeling recommendation system using meta-learning which can automate the meta-modeling recommendation process by intelligently adapting the learning bias to problem characterizations. The proposed intelligent recommendation system includes four modules: (1) problem module, (2) meta-feature module which includes a comprehensive set of meta-features to characterize the geometrical properties of problems, (3) meta-learner module which compares the performance of instance-based and model-based learning approaches for optimal framework design, and (4) performance evaluation module which introduces two criteria, Spearman\u27s ranking correlation coefficient and hit ratio, to evaluate the system on the accuracy of model ranking prediction and the precision of the best model recommendation, respectively. To further improve the performance of meta-learning for meta-modeling recommendation, different types of feature reduction techniques, including singular value decomposition, stepwise regression and ReliefF, are studied. Experiments show that our proposed framework is able to achieve 94% correlation on model rankings, and a 91% hit ratio on best model recommendation. Moreover, the computational cost of meta-modeling recommendation is significantly reduced from an order of minutes to seconds compared to traditional trial-and-error and ensemble process. The proposed framework can significantly advance the research in meta-modeling recommendation, and can be applied for data-driven system modeling