The Cancer Genome Atlas (TCGA) provides a high-quality resource of molecular data on a large variety of human cancers. Corces et al. used a recently modified assay to profile chromatin accessibility to determine the accessible chromatin landscape in 410 TCGA samples from 23 cancer types (see the Perspective by Taipale). When the data were integrated with other omics data available for the same tumor samples, inherited risk loci for cancer predisposition were revealed, transcription factors and enhancers driving molecular subtypes of cancer with patient survival differences were identified, and noncoding mutations associated with clinical prognosis were discovered. Science, this issue p. eaav1898; see also p. 401 Cancer is one of the leading causes of death worldwide. Although the 2% of the human genome that encodes proteins has been extensively studied, much remains to be learned about the noncoding genome and gene regulation in cancer. Genes are turned on and off in the proper cell types and cell states by transcription factor (TF) proteins acting on DNA regulatory elements that are scattered over the vast noncoding genome and exert long-range influences. The Cancer Genome Atlas (TCGA) is a global consortium that aims to accelerate the understanding of the molecular basis of cancer. TCGA has systematically collected DNA mutation, methylation, RNA expression, and other comprehensive datasets from primary human cancer tissue. TCGA has served as an invaluable resource for the identification of genomic aberrations, altered transcriptional networks, and cancer subtypes. Nonetheless, the gene regulatory landscapes of these tumors have largely been inferred through indirect means. A hallmark of active DNA regulatory elements is chromatin accessibility. Eukaryotic genomes are compacted in chromatin, a complex of DNA and proteins, and only the active regulatory elements are accessible by the cell's machinery such as TFs. ATAC-seq enables the genome-wide profiling of TF binding events that orchestrate gene expression programs and give a cell its identity. We generated high-quality ATAC-seq data in 410 tumor samples from TCGA, identifying diverse regulatory landscapes across 23 cancer types. These chromatin accessibility profiles identify cancer- and tissue-specific DNA regulatory elements that enable classification of tumor subtypes with newly recognized prognostic importance. We identify distinct TF activities in cancer based on differences in the inferred patterns of TF-DNA interaction and gene expression. Genome-wide correlation of gene expression and chromatin accessibility predicts tens of thousands of putative interactions between distal regulatory elements and gene promoters, including key oncogenes and targets in cancer immunotherapy, such as MYC, SRC, BCL2, and PDL1.

Machine learning logistic regressions is a widely popular method to model credit modeling. There are excellent and efficient packages in R, that can perform these types of analysis. Typically you will first create different machine learning visualizations before you perform the machine learning logistic regression analysis. This article is the second step of a credit modeling analysis, where I recently published the first step in this article. Now it is time to load the dataset and do some data management.

The wide implementation of electronic health record (EHR) systems facilitates the collection of large-scale health data from real clinical settings. Despite the significant increase in adoption of EHR systems, this data remains largely unexplored, but presents a rich data source for knowledge discovery from patient health histories in tasks such as understanding disease correlations and predicting health outcomes. However, the heterogeneity, sparsity, noise, and bias in this data present many complex challenges. This complexity makes it difficult to translate potentially relevant information into machine learning algorithms. In this paper, we propose a computational framework, Patient2Vec, to learn an interpretable deep representation of longitudinal EHR data which is personalized for each patient. To evaluate this approach, we apply it to the prediction of future hospitalizations using real EHR data and compare its predictive performance with baseline methods. Patient2Vec produces a vector space with meaningful structure and it achieves an AUC around 0.799 outperforming baseline methods. In the end, the learned feature importance can be visualized and interpreted at both the individual and population levels to bring clinical insights.

Learning from an imbalanced dataset is a tricky proposition. Because these datasets are biased towards one class, most existing classifiers tend not to perform well on minority class examples. Conventional classifiers usually aim to optimize the overall accuracy without considering the relative distribution of each class. This article presents a superensemble classifier, to tackle and improve predictions in imbalanced classification problems, that maps Hellinger distance decision trees (HDDT) into radial basis function network (RBFN) framework. Regularity conditions for universal consistency and the idea of parameter optimization of the proposed model are provided. The proposed distribution-free model can be applied for feature selection cum imbalanced classification problems. We have also provided enough numerical evidence using various real-life data sets to assess the performance of the proposed model. Its effectiveness and competitiveness with respect to different state-of-the-art models are shown.

We introduce a semiparametric approach to neighbor-based classification. We build off the recently proposed Boundary Trees algorithm by Mathy et al. (2015) which enables fast neighbor-based classification, regression and retrieval in large datasets. While boundary trees use an Euclidean measure of similarity, the Differentiable Boundary Tree algorithm by Zoran et al. (2017) was introduced to learn low-dimensional representations of complex input data, on which semantic similarity can be calculated to train boundary trees. As is pointed out by its authors, the differentiable boundary tree approach contains a few limitations that prevents it from scaling to large datasets. In this paper, we introduce Differentiable Boundary Sets, an algorithm that overcomes the computational issues of the differentiable boundary tree scheme and also improves its classification accuracy and data representability. Our algorithm is efficiently implementable with existing tools and offers a significant reduction in training time. We test and compare the algorithms on the well known MNIST handwritten digits dataset and the newer Fashion-MNIST dataset by Xiao et al. (2017).

Noname manuscript No. (will be inserted by the editor) Abstract Ensemble techniques are powerful approaches that combine several weak learners to build a stronger one. As a meta-learning framework, ensemble techniques can easily be applied to many machine learning methods. Inspired by ensemble techniques, in this paper we propose an ensemble loss functions applied to a simple regressor. We then propose a half-quadratic learning algorithm in order to find the parameter of the regressor and the optimal weights associated with each loss function. Moreover, we show that our proposed loss function is robust in noisy environments. For a particular class of loss functions, we show that our proposed ensemble loss function is Bayes consistent and robust. Experimental evaluations on several data sets demonstrate that the our proposed ensemble loss function significantly improves the performance of a simple regressor in comparison with state-of-the-art methods. Keywords Loss function · Ensemble methods · Bayes Consistent Loss function · Robustness 1 Introduction Loss functions are fundamental components of machine learning systems and are used to train the parameters of the learner model.

In this paper we investigate panel regression models with interactive fixed effects. We propose two new estimation methods that are based on minimizing convex objective functions. The first method minimizes the sum of squared residuals with a nuclear (trace) norm regularization. The second method minimizes the nuclear norm of the residuals. We establish the consistency of the two resulting estimators. Those estimators have a very important computational advantage compared to the existing least squares (LS) estimator, in that they are defined as minimizers of a convex objective function. In addition, the nuclear norm penalization helps to resolve a potential identification problem for interactive fixed effect models, in particular when the regressors are low-rank and the number of the factors is unknown. We also show how to construct estimators that are asymptotically equivalent to the least squares (LS) estimator in Bai (2009) and Moon and Weidner (2017) by using our nuclear norm regularized or minimized estimators as initial values for a finite number of LS minimizing iteration steps. This iteration avoids any non-convex minimization, while the original LS estimation problem is generally non-convex, and can have multiple local minima.

An important task in structural design is to quantify the structural performance of an object under the external forces it may experience during its use. The problem proves to be computationally very challenging as the external forces' contact locations and magnitudes may exhibit significant variations. We present an efficient analysis approach to determine the most critical force contact location in such problems with force location uncertainty. Given an input 3D model and regions on its boundary where arbitrary normal forces may make contact, our algorithm predicts the worst-case force configuration responsible for creating the highest stress within the object. Our approach uses a computationally tractable experimental design method to select number of sample force locations based on geometry only, without inspecting the stress response that requires computationally expensive finite-element analysis. Then, we construct a simple regression model on these samples and corresponding maximum stresses. Combined with a simple ranking based post-processing step, our method provides a practical solution to worst-case structural analysis problem. The results indicate that our approach achieves significant improvements over the existing work and brute force approaches. We demonstrate that further speed- up can be obtained when small amount of an error tolerance in maximum stress is allowed.

The normalized sequence of moments characterizes the law of any finite-dimensional random variable. We prove an analogous result for path-valued random variables, that is stochastic processes, by using the normalized sequence of signature moments. We use this to define a metric for laws of stochastic processes. This metric can be efficiently estimated from finite samples, even if the stochastic processes themselves evolve in high-dimensional state spaces. As an application, we provide a non-parametric two-sample hypothesis test for laws of stochastic processes.

Learning of RBMs using standard algorithms such as CD(k) involves gradient descent on negative log-likelihood. One of the terms in the gradient, which is expectation of visible and hidden units is intractable and is obtained through an MCMC estimate. In this work we show that the Hessian of the log-likelihood can be written in terms of covariances of hidden and visible units and hence all elements of the Hessian can also be estimated using the same MCMC samples with minimal extra computational costs. Since inverting the Hessian may be computationally expensive, we propose an algorithm that uses inverse of the diagonal approximation of the Hessian. This essentially results in parameter-specific adaptive learning rates for the gradient descent process. We show that this algorithm improves the efficiency of learning RBMs compared to state-of-art methods. Specifically we show that using the inverse of diagonal approximation of Hessian in the stochastic DC (difference of convex functions) program approach results in very efficient learning of RBMs. We use different evaluation metrics to test the probability distribution learnt by the RBM along with the traditional criterion of average test and train log-likelihood.