Disease progression models are instrumental in predicting individual-level health trajectories and understanding disease dynamics. Existing models are capable of providing either accurate predictions of patients prognoses or clinically interpretable representations of disease pathophysiology, but not both. In this paper, we develop the phased attentive state space (PASS) model of disease progression, a deep probabilistic model that captures complex representations for disease progression while maintaining clinical interpretability. Unlike Markovian state space models which assume memoryless dynamics, PASS uses an attention mechanism to induce "memoryful" state transitions, whereby repeatedly updated attention weights are used to focus on past state realizations that best predict future states. This gives rise to complex, non-stationary state dynamics that remain interpretable through the generated attention weights, which designate the relationships between the realized state variables for individual patients. PASS uses phased LSTM units (with time gates controlled by parametrized oscillations) to generate the attention weights in continuous time, which enables handling irregularly-sampled and potentially missing medical observations. Experiments on data from a realworld cohort of patients show that PASS successfully balances the tradeoff between accuracy and interpretability: it demonstrates superior predictive accuracy and learns insightful individual-level representations of disease progression.
Deep probabilistic models , , Most existing works on deep probabilistic models have focused on developed structured inference algorithms for deep Markov models and their variants @cite_17 @cite_18 @cite_6 @cite_25 . All such models use neural networks to model the transition and emission distributions, but are limited to Markovian dynamics. Other works develop stochastic versions of RNNs for the sake of generative modeling; examples include variational RNNs @cite_12 , SRNN @cite_5 , and STORN @cite_11 . All such models augment stochastic layers to an RNN in order to enrich its output distribution. However, the transition and emission distributions in all these models cannot be decoupled, and hence their latent state representations would not lead to clinically meaningful identification of disease states. To the best of our knowledge, PASS is the first deep probabilistic model that provides both a clinically interpretable latent representation, and interpretable non-Markovian state dynamics.
@cite_18 @cite_11 @cite_6 @cite_5 @cite_25 @cite_12 @cite_17
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We introduce a novel training principle for probabilistic models that is an alternative to maximum likelihood. The proposed Generative Stochastic Networks (GSN) framework is based on learning the transition operator of a Markov chain whose stationary distribution estimates the data distribution. The transition distribution of the Markov chain is conditional on the previous state, generally involving a small move, so this conditional distribution has fewer dominant modes, being unimodal in the limit of small moves. Thus, it is easier to learn because it is easier to approximate its partition function, more like learning to perform supervised function approximation, with gradients that can be obtained by backprop. We provide theorems that generalize recent work on the probabilistic interpretation of denoising autoencoders and obtain along the way an interesting justification for dependency networks and generalized pseudolikelihood, along with a definition of an appropriate joint distribution and sampling mechanism even when the conditionals are not consistent. GSNs can be used with missing inputs and can be used to sample subsets of variables given the rest. We validate these theoretical results with experiments on two image datasets using an architecture that mimics the Deep Boltzmann Machine Gibbs sampler but allows training to proceed with simple backprop, without the need for layerwise pretraining. With the introduction of the variational autoencoder (VAE), probabilistic latent variable models have received renewed attention as powerful generative models. However, their performance in terms of test likelihood and quality of generated samples has been surpassed by autoregressive models without stochastic units. Furthermore, flow-based models have recently been shown to be an attractive alternative that scales well to high-dimensional data. In this paper we close the performance gap by constructing VAE models that can effectively utilize a deep hierarchy of stochastic variables and model complex covariance structures. We introduce the Bidirectional-Inference Variational Autoencoder (BIVA), characterized by a skip-connected generative model and an inference network formed by a bidirectional stochastic inference path. We show that BIVA reaches state-of-the-art test likelihoods, generates sharp and coherent natural images, and uses the hierarchy of latent variables to capture different aspects of the data distribution. We observe that BIVA, in contrast to recent results, can be used for anomaly detection. We attribute this to the hierarchy of latent variables which is able to extract high-level semantic features. Finally, we extend BIVA to semi-supervised classification tasks and show that it performs comparably to state-of-the-art results by generative adversarial networks. Building intelligent systems that are capable of extracting high-level representations from high-dimensional sensory data lies at the core of solving many AI related tasks, including object recognition, speech perception, and language understanding. Theoretical and biological arguments strongly suggest that building such systems requires models with deep architectures that involve many layers of nonlinear processing. The aim of the thesis is to demonstrate that deep generative models that contain many layers of latent variables and millions of parameters can be learned efficiently, and that the learned high-level feature representations can be successfully applied in a wide spectrum of application domains, including visual object recognition, information retrieval, and classification and regression tasks. In addition, similar methods can be used for nonlinear dimensionality reduction. The first part of the thesis focuses on analysis and applications of probabilistic generative models called Deep Belief Networks. We show that these deep hierarchical models can learn useful feature representations from a large supply of unlabeled sensory inputs. The learned high-level representations capture a lot of structure in the input data, which is useful for subsequent problem-specific tasks, such as classification, regression or information retrieval, even though these tasks are unknown when the generative model is being trained. In the second part of the thesis, we introduce a new learning algorithm for a different type of hierarchical probabilistic model, which we call a Deep Boltzmann Machine. Like Deep Belief Networks, Deep Boltzmann Machines have the potential of learning internal representations that become increasingly complex at higher layers, which is a promising way of solving object and speech recognition problems. Unlike Deep Belief Networks and many existing models with deep architectures, the approximate inference procedure, in addition to a fast bottom-up pass, can incorporate top-down feedback. This allows Deep Boltzmann Machines to better propagate uncertainty about ambiguous inputs. The most popular way to use probabilistic models in vision is first to extract some descriptors of small image patches or object parts using well-engineered features, and then to use statistical learning tools to model the dependencies among these features and eventual labels. Learning probabilistic models directly on the raw pixel values has proved to be much more difficult and is typically only used for regularizing discriminative methods. In this work, we use one of the best, pixel-level, generative models of natural images–a gated MRF–as the lowest level of a deep belief network (DBN) that has several hidden layers. We show that the resulting DBN is very good at coping with occlusion when predicting expression categories from face images, and it can produce features that perform comparably to SIFT descriptors for discriminating different types of scene. The generative ability of the model also makes it easy to see what information is captured and what is lost at each level of representation.