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

Load curve data cleansing and imputation via sparsity and low rank

The smart grid vision is to build an intelligent power network with an unprecedented level of situational awareness and controllability over its services and infrastructure. This paper advocates statistical inference methods to robustify power monitoring tasks against the outlier effects owing to faulty readings and malicious attacks, as well as against missing data due to privacy concerns and communication errors. In this context, a novel load cleansing and imputation scheme is developed leveraging the low intrinsic-dimensionality of spatiotemporal load profiles and the sparse nature of "bad data.'' A robust estimator based on principal components pursuit (PCP) is adopted, which effects a twofold sparsity-promoting regularization through an $\ell_1$-norm of the outliers, and the nuclear norm of the nominal load profiles. Upon recasting the non-separable nuclear norm into a form amenable to decentralized optimization, a distributed (D-) PCP algorithm is developed to carry out the imputation and cleansing tasks using networked devices comprising the so-termed advanced metering infrastructure. If D-PCP converges and a qualification inequality is satisfied, the novel distributed estimator provably attains the performance of its centralized PCP counterpart, which has access to all networkwide data. Computer simulations and tests with real load curve data corroborate the convergence and effectiveness of the novel D-PCP algorithm.Comment: 8 figures, submitted to IEEE Transactions on Smart Grid - Special issue on "Optimization methods and algorithms applied to smart grid

Classification of Occluded Objects using Fast Recurrent Processing

Recurrent neural networks are powerful tools for handling incomplete data problems in computer vision, thanks to their significant generative capabilities. However, the computational demand for these algorithms is too high to work in real time, without specialized hardware or software solutions. In this paper, we propose a framework for augmenting recurrent processing capabilities into a feedforward network without sacrificing much from computational efficiency. We assume a mixture model and generate samples of the last hidden layer according to the class decisions of the output layer, modify the hidden layer activity using the samples, and propagate to lower layers. For visual occlusion problem, the iterative procedure emulates feedforward-feedback loop, filling-in the missing hidden layer activity with meaningful representations. The proposed algorithm is tested on a widely used dataset, and shown to achieve 2$\times$ improvement in classification accuracy for occluded objects. When compared to Restricted Boltzmann Machines, our algorithm shows superior performance for occluded object classification.Comment: arXiv admin note: text overlap with arXiv:1409.8576 by other author

Multiple imputation for continuous variables using a Bayesian principal component analysis

We propose a multiple imputation method based on principal component analysis (PCA) to deal with incomplete continuous data. To reflect the uncertainty of the parameters from one imputation to the next, we use a Bayesian treatment of the PCA model. Using a simulation study and real data sets, the method is compared to two classical approaches: multiple imputation based on joint modelling and on fully conditional modelling. Contrary to the others, the proposed method can be easily used on data sets where the number of individuals is less than the number of variables and when the variables are highly correlated. In addition, it provides unbiased point estimates of quantities of interest, such as an expectation, a regression coefficient or a correlation coefficient, with a smaller mean squared error. Furthermore, the widths of the confidence intervals built for the quantities of interest are often smaller whilst ensuring a valid coverage.Comment: 16 page

Multilevel Weighted Support Vector Machine for Classification on Healthcare Data with Missing Values

This work is motivated by the needs of predictive analytics on healthcare data as represented by Electronic Medical Records. Such data is invariably problematic: noisy, with missing entries, with imbalance in classes of interests, leading to serious bias in predictive modeling. Since standard data mining methods often produce poor performance measures, we argue for development of specialized techniques of data-preprocessing and classification. In this paper, we propose a new method to simultaneously classify large datasets and reduce the effects of missing values. It is based on a multilevel framework of the cost-sensitive SVM and the expected maximization imputation method for missing values, which relies on iterated regression analyses. We compare classification results of multilevel SVM-based algorithms on public benchmark datasets with imbalanced classes and missing values as well as real data in health applications, and show that our multilevel SVM-based method produces fast, and more accurate and robust classification results.Comment: arXiv admin note: substantial text overlap with arXiv:1503.0625

Robust training of recurrent neural networks to handle missing data for disease progression modeling

Disease progression modeling (DPM) using longitudinal data is a challenging task in machine learning for healthcare that can provide clinicians with better tools for diagnosis and monitoring of disease. Existing DPM algorithms neglect temporal dependencies among measurements and make parametric assumptions about biomarker trajectories. In addition, they do not model multiple biomarkers jointly and need to align subjects' trajectories. In this paper, recurrent neural networks (RNNs) are utilized to address these issues. However, in many cases, longitudinal cohorts contain incomplete data, which hinders the application of standard RNNs and requires a pre-processing step such as imputation of the missing values. We, therefore, propose a generalized training rule for the most widely used RNN architecture, long short-term memory (LSTM) networks, that can handle missing values in both target and predictor variables. This algorithm is applied for modeling the progression of Alzheimer's disease (AD) using magnetic resonance imaging (MRI) biomarkers. The results show that the proposed LSTM algorithm achieves a lower mean absolute error for prediction of measurements across all considered MRI biomarkers compared to using standard LSTM networks with data imputation or using a regression-based DPM method. Moreover, applying linear discriminant analysis to the biomarkers' values predicted by the proposed algorithm results in a larger area under the receiver operating characteristic curve (AUC) for clinical diagnosis of AD compared to the same alternatives, and the AUC is comparable to state-of-the-art AUCs from a recent cross-sectional medical image classification challenge. This paper shows that built-in handling of missing values in LSTM network training paves the way for application of RNNs in disease progression modeling.Comment: 9 pages, 1 figure, MIDL conferenc