Motivation: Histone modifications are among the most important factors that control gene regulation. Computational methods that predict gene expression from histone modification signals are highly desirable for understanding their combinatorial effects in gene regulation. This knowledge can help in developing 'epigenetic drugs' for diseases like cancer. Previous studies for quantifying the relationship between histone modifications and gene expression levels either failed to capture combinatorial effects or relied on multiple methods that separate predictions and combinatorial analysis. This paper develops a unified discriminative framework using a deep convolutional neural network to classify gene expression using histone modification data as input. Our system, called DeepChrome, allows automatic extraction of complex interactions among important features. To simultaneously visualize the combinatorial interactions among histone modifications, we propose a novel optimization-based technique that generates feature pattern maps from the learnt deep model. This provides an intuitive description of underlying epigenetic mechanisms that regulate genes. Results: We show that DeepChrome outperforms state-of-the-art models like Support Vector Machines and Random Forests for gene expression classification task on 56 different cell-types from REMC database. The output of our visualization technique not only validates the previous observations but also allows novel insights about combinatorial interactions among histone modification marks, some of which have recently been observed by experimental studies.
@cite_20 applied Support Vector Machine (SVM) models on worm datasets ( @cite_23 ) and reformulated the task as gene expression classification and prediction. The authors divided regions flanking transcription start site (TSS) and transcription termination site (TTS) into 100 base-pair (bp) bins and used the histone modification signal in each bin as a feature for the SVM. To incorporate information from all positions or bins, they trained different models for different bins that resulted in 160 models for 160 bins. They validated the existence of the quantitive relationship between histone modifications and gene expression by such bin-specific modeling. Furthermore, using a separate linear regression model, the paper inferred pair-wise interactions between different histone modifications using binary combinatorial terms. Since it is infeasible to consider all possible higher order interaction terms through polynomial regression, Bayesian networks were then used for modeling such relationships. However, Bayesian networks do not take into consideration local neighboring bin information and their highly connected output network is difficult to interpret.
@cite_23 @cite_20
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The Support Vector Machine (SVM) of Vapnik (1998) has become widely established as one of the leading approaches to pattern recognition and machine learning. It expresses predictions in terms of a linear combination of kernel functions centred on a subset of the training data, known as support vectors. Despite its widespread success, the SVM suffers from some important limitations, one of the most significant being that it makes point predictions rather than generating predictive distributions. Recently Tipping (1999) has formulated the Relevance Vector Machine (RVM), a probabilistic model whose functional form is equivalent to the SVM. It achieves comparable recognition accuracy to the SVM, yet provides a full predictive distribution, and also requires substantially fewer kernel functions. The original treatment of the RVM relied on the use of type II maximum likelihood (the evidence framework') to provide point estimates of the hyperparameters which govern model sparsity. In this paper we show how the RVM can be formulated and solved within a completely Bayesian paradigm through the use of variational inference, thereby giving a posterior distribution over both parameters and hyperparameters. We demonstrate the practicality and performance of the variational RVM using both synthetic and real world examples. a b s t r a c t Linear Proximal Support Vector Machines (LPSVMs), like decision trees, classic SVM, etc. are originally not equipped to handle drifting data streams that exhibit high and varying degrees of class imbalance. For online classification of data streams with imbalanced class distribution, we propose a dynamic class imbalance learning (DCIL) approach to incremental LPSVM (IncLPSVM) modeling. In doing so, we simplify a computationally non-renewable weighted LPSVM to several core matrices multiplying two simple weight coefficients. When data addition and or retirement occurs, the proposed DCIL-IncLPSVM 1 accommodates newly presented class imbalance by a simple matrix and coefficient updating, meanwhile ensures no discriminative information lost throughout the learning process. Experiments on benchmark datasets indicate that the proposed DCIL-IncLPSVM outperforms classic IncSVM and IncLPSVM in terms of F -measure and G-mean metrics. Moreover, our application to online face membership authentication shows that the proposed DCIL-IncLPSVM remains effective in the presence of highly dynamic class imbalance, which usually poses serious problems to previous approaches. We introduce a semi-supervised support vector machine (S3VM) method. Given a training set of labeled data and a working set of unlabeled data, S3VM constructs a support vector machine using both the training and working sets. We use S3VM to solve the transduction problem using overall risk minimization (ORM) posed by Vapnik. The transduction problem is to estimate the value of a classification function at the given points in the working set. This contrasts with the standard inductive learning problem of estimating the classification function at all possible values and then using the fixed function to deduce the classes of the working set data. We propose a general S3VM model that minimizes both the misclassification error and the function capacity based on all the available data. We show how the S3VM model for 1-norm linear support vector machines can be converted to a mixed-integer program and then solved exactly using integer programming. Results of S3VM and the standard 1-norm support vector machine approach are compared on ten data sets. Our computational results support the statistical learning theory results showing that incorporating working data improves generalization when insufficient training information is available. In every case, S3VM either improved or showed no significant difference in generalization compared to the traditional approach. Structured output support vector machine (SVM) based tracking algorithms have shown favorable performance recently. Nonetheless, the time-consuming candidate sampling and complex optimization limit their real-time applications. In this paper, we propose a novel large margin object tracking method which absorbs the strong discriminative ability from structured output SVM and speeds up by the correlation filter algorithm significantly. Secondly, a multimodal target detection technique is proposed to improve the target localization precision and prevent model drift introduced by similar objects or background noise. Thirdly, we exploit the feedback from high-confidence tracking results to avoid the model corruption problem. We implement two versions of the proposed tracker with the representations from both conventional hand-crafted and deep convolution neural networks (CNNs) based features to validate the strong compatibility of the algorithm. The experimental results demonstrate that the proposed tracker performs superiorly against several state-of-the-art algorithms on the challenging benchmark sequences while runs at speed in excess of 80 frames per second.