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

An Incremental Construction of Deep Neuro Fuzzy System for Continual Learning of Non-stationary Data Streams

Existing FNNs are mostly developed under a shallow network configuration having lower generalization power than those of deep structures. This paper proposes a novel self-organizing deep FNN, namely DEVFNN. Fuzzy rules can be automatically extracted from data streams or removed if they play limited role during their lifespan. The structure of the network can be deepened on demand by stacking additional layers using a drift detection method which not only detects the covariate drift, variations of input space, but also accurately identifies the real drift, dynamic changes of both feature space and target space. DEVFNN is developed under the stacked generalization principle via the feature augmentation concept where a recently developed algorithm, namely gClass, drives the hidden layer. It is equipped by an automatic feature selection method which controls activation and deactivation of input attributes to induce varying subsets of input features. A deep network simplification procedure is put forward using the concept of hidden layer merging to prevent uncontrollable growth of dimensionality of input space due to the nature of feature augmentation approach in building a deep network structure. DEVFNN works in the sample-wise fashion and is compatible for data stream applications. The efficacy of DEVFNN has been thoroughly evaluated using seven datasets with non-stationary properties under the prequential test-then-train protocol. It has been compared with four popular continual learning algorithms and its shallow counterpart where DEVFNN demonstrates improvement of classification accuracy. Moreover, it is also shown that the concept drift detection method is an effective tool to control the depth of network structure while the hidden layer merging scenario is capable of simplifying the network complexity of a deep network with negligible compromise of generalization performance.Comment: This paper has been published in IEEE Transactions on Fuzzy System

DanQ: a hybrid convolutional and recurrent deep neural network for quantifying the function of DNA sequences.

Modeling the properties and functions of DNA sequences is an important, but challenging task in the broad field of genomics. This task is particularly difficult for non-coding DNA, the vast majority of which is still poorly understood in terms of function. A powerful predictive model for the function of non-coding DNA can have enormous benefit for both basic science and translational research because over 98% of the human genome is non-coding and 93% of disease-associated variants lie in these regions. To address this need, we propose DanQ, a novel hybrid convolutional and bi-directional long short-term memory recurrent neural network framework for predicting non-coding function de novo from sequence. In the DanQ model, the convolution layer captures regulatory motifs, while the recurrent layer captures long-term dependencies between the motifs in order to learn a regulatory 'grammar' to improve predictions. DanQ improves considerably upon other models across several metrics. For some regulatory markers, DanQ can achieve over a 50% relative improvement in the area under the precision-recall curve metric compared to related models. We have made the source code available at the github repository http://github.com/uci-cbcl/DanQ