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

Deep Over-sampling Framework for Classifying Imbalanced Data

Class imbalance is a challenging issue in practical classification problems for deep learning models as well as traditional models. Traditionally successful countermeasures such as synthetic over-sampling have had limited success with complex, structured data handled by deep learning models. In this paper, we propose Deep Over-sampling (DOS), a framework for extending the synthetic over-sampling method to exploit the deep feature space acquired by a convolutional neural network (CNN). Its key feature is an explicit, supervised representation learning, for which the training data presents each raw input sample with a synthetic embedding target in the deep feature space, which is sampled from the linear subspace of in-class neighbors. We implement an iterative process of training the CNN and updating the targets, which induces smaller in-class variance among the embeddings, to increase the discriminative power of the deep representation. We present an empirical study using public benchmarks, which shows that the DOS framework not only counteracts class imbalance better than the existing method, but also improves the performance of the CNN in the standard, balanced settings

Discriminative Density-ratio Estimation

The covariate shift is a challenging problem in supervised learning that results from the discrepancy between the training and test distributions. An effective approach which recently drew a considerable attention in the research community is to reweight the training samples to minimize that discrepancy. In specific, many methods are based on developing Density-ratio (DR) estimation techniques that apply to both regression and classification problems. Although these methods work well for regression problems, their performance on classification problems is not satisfactory. This is due to a key observation that these methods focus on matching the sample marginal distributions without paying attention to preserving the separation between classes in the reweighted space. In this paper, we propose a novel method for Discriminative Density-ratio (DDR) estimation that addresses the aforementioned problem and aims at estimating the density-ratio of joint distributions in a class-wise manner. The proposed algorithm is an iterative procedure that alternates between estimating the class information for the test data and estimating new density ratio for each class. To incorporate the estimated class information of the test data, a soft matching technique is proposed. In addition, we employ an effective criterion which adopts mutual information as an indicator to stop the iterative procedure while resulting in a decision boundary that lies in a sparse region. Experiments on synthetic and benchmark datasets demonstrate the superiority of the proposed method in terms of both accuracy and robustness