Sequential regulatory activity prediction across chromosomes with convolutional neural networks.

Models for predicting phenotypic outcomes from genotypes have important applications to understanding genomic function and improving human health. Here, we develop a machine-learning system to predict cell-type-specific epigenetic and transcriptional profiles in large mammalian genomes from DNA sequence alone. By use of convolutional neural networks, this system identifies promoters and distal regulatory elements and synthesizes their content to make effective gene expression predictions. We show that model predictions for the influence of genomic variants on gene expression align well to causal variants underlying eQTLs in human populations and can be useful for generating mechanistic hypotheses to enable fine mapping of disease loci.

Empirical Frequentist Coverage of Deep Learning Uncertainty Quantification Procedures.

Uncertainty quantification for complex deep learning models is increasingly important as these techniques see growing use in high-stakes, real-world settings. Currently, the quality of a model's uncertainty is evaluated using point-prediction metrics, such as the negative log-likelihood (NLL), expected calibration error (ECE) or the Brier score on held-out data. Marginal coverage of prediction intervals or sets, a well-known concept in the statistical literature, is an intuitive alternative to these metrics but has yet to be systematically studied for many popular uncertainty quantification techniques for deep learning models. With marginal coverage and the complementary notion of the width of a prediction interval, downstream users of deployed machine learning models can better understand uncertainty quantification both on a global dataset level and on a per-sample basis. In this study, we provide the first large-scale evaluation of the empirical frequentist coverage properties of well-known uncertainty quantification techniques on a suite of regression and classification tasks. We find that, in general, some methods do achieve desirable coverage properties on in distribution samples, but that coverage is not maintained on out-of-distribution data. Our results demonstrate the failings of current uncertainty quantification techniques as dataset shift increases and reinforce coverage as an important metric in developing models for real-world applications.

Sampling the Variational Posterior with Local Refinement.

Variational inference is an optimization-based method for approximating the posterior distribution of the parameters in Bayesian probabilistic models. A key challenge of variational inference is to approximate the posterior with a distribution that is computationally tractable yet sufficiently expressive. We propose a novel method for generating samples from a highly flexible variational approximation. The method starts with a coarse initial approximation and generates samples by refining it in selected, local regions. This allows the samples to capture dependencies and multi-modality in the posterior, even when these are absent from the initial approximation. We demonstrate theoretically that our method always improves the quality of the approximation (as measured by the evidence lower bound). In experiments, our method consistently outperforms recent variational inference methods in terms of log-likelihood and ELBO across three example tasks: the Eight-Schools example (an inference task in a hierarchical model), training a ResNet-20 (Bayesian inference in a large neural network), and the Mushroom task (posterior sampling in a contextual bandit problem).

Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks.

The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many noncoding variants statistically associated with human disease, nearly all such variants have unknown mechanisms. Here, we address this challenge using an approach based on a recent machine learning advance-deep convolutional neural networks (CNNs). We introduce the open source package Basset to apply CNNs to learn the functional activity of DNA sequences from genomics data. We trained Basset on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrate greater predictive accuracy than previous methods. Basset predictions for the change in accessibility between variant alleles were far greater for Genome-wide association study (GWAS) SNPs that are likely to be causal relative to nearby SNPs in linkage disequilibrium with them. With Basset, a researcher can perform a single sequencing assay in their cell type of interest and simultaneously learn that cell's chromatin accessibility code and annotate every mutation in the genome with its influence on present accessibility and latent potential for accessibility. Thus, Basset offers a powerful computational approach to annotate and interpret the noncoding genome.

Second opinion needed: communicating uncertainty in medical machine learning.

There is great excitement that medical artificial intelligence (AI) based on machine learning (ML) can be used to improve decision making at the patient level in a variety of healthcare settings. However, the quantification and communication of uncertainty for individual predictions is often neglected even though uncertainty estimates could lead to more principled decision-making and enable machine learning models to automatically or semi-automatically abstain on samples for which there is high uncertainty. In this article, we provide an overview of different approaches to uncertainty quantification and abstention for machine learning and highlight how these techniques could improve the safety and reliability of current ML systems being used in healthcare settings. Effective quantification and communication of uncertainty could help to engender trust with healthcare workers, while providing safeguards against known failure modes of current machine learning approaches. As machine learning becomes further integrated into healthcare environments, the ability to say "I'm not sure" or "I don't know" when uncertain is a necessary capability to enable safe clinical deployment.

Unobtrusive Detection of Mild Cognitive Impairment in Older Adults Through Home Monitoring.

The early detection of dementias such as Alzheimer's disease can in some cases reverse, stop, or slow cognitive decline and in general greatly reduce the burden of care. This is of increasing significance as demographic studies are warning of an aging population in North America and worldwide. Various smart homes and systems have been developed to detect cognitive decline through continuous monitoring of high risk individuals. However, the majority of these smart homes and systems use a number of predefined heuristics to detect changes in cognition, which has been demonstrated to focus on the idiosyncratic nuances of the individual subjects, and thus, does not generalize. In this paper, we address this problem by building generalized linear models of home activity of older adults monitored using unobtrusive sensing technologies. We use inhomogenous Poisson processes to model the presence of the recruited older adults within different rooms throughout the day. We employ an information theoretic approach to compare the generalized linear models learned, and we observe significant statistical differences between the cognitively intact and impaired older adults. Using a simple thresholding approach, we were able to detect mild cognitive impairment in older adults with an average area under the ROC curve of 0.716 and an average area under the precision-recall curve of 0.706 using activity models estimated over a time window of 12 weeks.

Machine Learning Approaches in Cardiovascular Imaging.

Cardiovascular imaging technologies continue to increase in their capacity to capture and store large quantities of data. Modern computational methods, developed in the field of machine learning, offer new approaches to leveraging the growing volume of imaging data available for analyses. Machine learning methods can now address data-related problems ranging from simple analytic queries of existing measurement data to the more complex challenges involved in analyzing raw images. To date, machine learning has been used in 2 broad and highly interconnected areas: automation of tasks that might otherwise be performed by a human and generation of clinically important new knowledge. Most cardiovascular imaging studies have focused on task-oriented problems, but more studies involving algorithms aimed at generating new clinical insights are emerging. Continued expansion in the size and dimensionality of cardiovascular imaging databases is driving strong interest in applying powerful deep learning methods, in particular, to analyze these data. Overall, the most effective approaches will require an investment in the resources needed to appropriately prepare such large data sets for analyses. Notwithstanding current technical and logistical challenges, machine learning and especially deep learning methods have much to offer and will substantially impact the future practice and science of cardiovascular imaging.

Patient Prognosis from Vital Sign Time Series: Combining Convolutional Neural Networks with a Dynamical Systems Approach.

In this work, we propose a stacked switching vector-autoregressive (SVAR)-CNN architecture to model the changing dynamics in physiological time series for patient prognosis. The SVAR-layer extracts dynamical features (or modes) from the time-series, which are then fed into the CNN-layer to extract higher-level features representative of transition patterns among the dynamical modes. We evaluate our approach using 8-hours of minute-by-minute mean arterial blood pressure (BP) from over 450 patients in the MIMIC-II database. We modeled the time-series using a third-order SVAR process with 20 modes, resulting in first-level dynamical features of size 20×480 per patient. A fully connected CNN is then used to learn hierarchical features from these inputs, and to predict hospital mortality. The combined CNN/SVAR approach using BP time-series achieved a median and interquartile-range AUC of 0.74 [0.69, 0.75], significantly outperforming CNN-alone (0.54 [0.46, 0.59]), and SVAR-alone with logistic regression (0.69 [0.65, 0.72]). Our results indicate that including an SVAR layer improves the ability of CNNs to classify nonlinear and nonstationary time-series.

Generalized Linear Models of home activity for automatic detection of mild cognitive impairment in older adults.

With a globally aging population, the burden of care of cognitively impaired older adults is becoming increasingly concerning. Instances of Alzheimer's disease and other forms of dementia are becoming ever more frequent. Earlier detection of cognitive impairment offers significant benefits, but remains difficult to do in practice. In this paper, we develop statistical models of the behavior of older adults within their homes using sensor data in order to detect the early onset of cognitive decline. Specifically, we use inhomogenous Poisson processes to model the presence of subjects within different rooms throughout the day in the home using unobtrusive sensing technologies. We compare the distributions learned from cognitively intact and impaired subjects using information theoretic tools and observe statistical differences between the two populations which we believe can be used to help detect the onset of cognitive decline.

Data mining in bone marrow transplant records to identify patients with high odds of survival.

Patients undergoing a bone marrow stem cell transplant (BMT) face various risk factors. Analyzing data from past transplants could enhance the understanding of the factors influencing success. Records up to 120 measurements per transplant procedure from 1751 patients undergoing BMT were collected (Shariati Hospital). Collaborative filtering techniques allowed the processing of highly sparse records with 22.3% missing values. Ten-fold cross-validation was used to evaluate the performance of various classification algorithms trained on predicting the survival status. Modest accuracy levels were obtained in predicting the survival status (AUC = 0.69). More importantly, however, operations that had the highest chances of success were shown to be identifiable with high accuracy, e.g., 92% or 97% when identifying 74 or 31 recipients, respectively. Identifying the patients with the highest chances of survival has direct application in the prioritization of resources and in donor matching. For patients where high-confidence prediction is not achieved, assigning a probability to their survival odds has potential applications in probabilistic decision support systems and in combination with other sources of information.

Towards a single sensor passive solution for automated fall detection.

Falling in the home is one of the major challenges to independent living among older adults. The associated costs, coupled with a rapidly growing elderly population, are placing a burden on healthcare systems worldwide that will swiftly become unbearable. To facilitate expeditious emergency care, we have developed an artificially intelligent camera-based system that automatically detects if a person within the field-of-view has fallen. The system addresses concerns raised in earlier work and the requirements of a widely deployable in-home solution. The presented prototype utilizes a consumer-grade camera modified with a wide-angle lens. Machine learning techniques applied to carefully engineered features allow the system to classify falls at high accuracy while maintaining invariance to lighting, environment and the presence of multiple moving objects. This paper describes the system, outlines the algorithms used and presents empirical validation of its effectiveness.