We present a machine learning framework for modeling protein dynamics. Our approach uses L1-regularized, reversible hidden Markov models to understand large protein datasets generated via molecular dynamics simulations. Our model is motivated by three design principles: (1) the requirement of massive scalability; (2) the need to adhere to relevant physical law; and (3) the necessity of providing accessible interpretations, critical for both cellular biology and rational drug design. We present an EM algorithm for learning and introduce a model selection criteria based on the physical notion of convergence in relaxation timescales. We contrast our model with standard methods in biophysics and demonstrate improved robustness. We implement our algorithm on GPUs and apply the method to two large protein simulation datasets generated respectively on the NCSA Bluewaters supercomputer and the Folding@Home distributed computing network. Our analysis identifies the conformational dynamics of the ubiquitin protein critical to cellular signaling, and elucidates the stepwise activation mechanism of the c-Src kinase protein.

A new approach to maximum likelihood learning of discrete graphical models and RBM in particular is introduced. Our method, Perturb and Descend (PD) is inspired by two ideas (I) perturb and MAP method for sampling (II) learning by Contrastive Divergence minimization. In contrast to perturb and MAP, PD leverages training data to learn the models that do not allow efficient MAP estimation. During the learning, to produce a sample from the current model, we start from a training data and descend in the energy landscape of the "perturbed model", for a fixed number of steps, or until a local optima is reached. For RBM, this involves linear calculations and thresholding which can be very fast. Furthermore we show that the amount of perturbation is closely related to the temperature parameter and it can regularize the model by producing robust features resulting in sparse hidden layer activation.

Contrastive divergence (CD) is a promising method of inference in high dimensional distributions with intractable normalizing constants, however, the theoretical foundations justifying its use are somewhat shaky. This document proposes a framework for understanding CD inference, how/when it works, and provides multiple justifications for the CD moment conditions, including framing them as a variational approximation. Algorithms for performing inference are discussed and are applied to social network data using an exponential-family random graph models (ERGM). The framework also provides guidance about how to construct MCMC kernels providing good CD inference, which turn out to be quite different from those used typically to provide fast global mixing.

Developing feature selection algorithms that move beyond a pure correlational to a more causal analysis of observational data is an important problem in the sciences. Several algorithms attempt to do so by discovering the Markov blanket of a target, but they all contain a forward selection step which variables must pass in order to be included in the conditioning set. As a result, these algorithms may not consider all possible conditional multivariate combinations. We improve on this limitation by proposing a backward elimination method that uses a kernel-based conditional dependence measure to identify the Markov blanket in a fully multivariate fashion. The algorithm is easy to implement and compares favorably to other methods on synthetic and real datasets.

This paper proposes an online tree-based Bayesian approach for reinforcement learning. For inference, we employ a generalised context tree model. This defines a distribution on multivariate Gaussian piecewise-linear models, which can be updated in closed form. The tree structure itself is constructed using the cover tree method, which remains efficient in high dimensional spaces. We combine the model with Thompson sampling and approximate dynamic programming to obtain effective exploration policies in unknown environments. The flexibility and computational simplicity of the model render it suitable for many reinforcement learning problems in continuous state spaces. We demonstrate this in an experimental comparison with a Gaussian process model, a linear model and simple least squares policy iteration.

A sequence of random variables is exchangeable if its joint distribution is invariant under variable permutations. We introduce exchangeable variable models (EVMs) as a novel class of probabilistic models whose basic building blocks are partially exchangeable sequences, a generalization of exchangeable sequences. We prove that a family of tractable EVMs is optimal under zero-one loss for a large class of functions, including parity and threshold functions, and strictly subsumes existing tractable independence-based model families. Extensive experiments show that EVMs outperform state of the art classifiers such as SVMs and probabilistic models which are solely based on independence assumptions.

How can we perform efficient inference and learning in directed probabilistic models, in the presence of continuous latent variables with intractable posterior distributions, and large datasets? We introduce a stochastic variational inference and learning algorithm that scales to large datasets and, under some mild differentiability conditions, even works in the intractable case. Our contributions is two-fold. First, we show that a reparameterization of the variational lower bound yields a lower bound estimator that can be straightforwardly optimized using standard stochastic gradient methods. Second, we show that for i.i.d. datasets with continuous latent variables per datapoint, posterior inference can be made especially efficient by fitting an approximate inference model (also called a recognition model) to the intractable posterior using the proposed lower bound estimator. Theoretical advantages are reflected in experimental results.

In recent years, the task of automatically linking pieces of text (anchors) mentioned in a document to Wikipedia articles that represent the meaning of these anchors has received extensive research attention. Typically, link-to-Wikipedia systems try to find a set of Wikipedia articles that are candidates to represent the meaning of the anchor and, later, rank these candidates to select the most appropriate one. In this ranking process the systems rely on context information obtained from the document where the anchor is mentioned and/or from Wikipedia. In this paper we center our attention in the use of Wikipedia links as context information. In particular, we offer a review of several candidate ranking approaches in the state-of-the-art that rely on Wikipedia link information. In addition, we provide a comparative empirical evaluation of the different approaches on five different corpora: the TAC 2010 corpus and four corpora built from actual Wikipedia articles and news items.

This paper introduces a novel mixture model-based approach for simultaneous clustering and optimal segmentation of functional data which are curves presenting regime changes. The proposed model consists in a finite mixture of piecewise polynomial regression models. Each piecewise polynomial regression model is associated with a cluster, and within each cluster, each piecewise polynomial component is associated with a regime (i.e., a segment). We derive two approaches for learning the model parameters. The former is an estimation approach and consists in maximizing the observed-data likelihood via a dedicated expectation-maximization (EM) algorithm. A fuzzy partition of the curves in K clusters is then obtained at convergence by maximizing the posterior cluster probabilities. The latter however is a classification approach and optimizes a specific classification likelihood criterion through a dedicated classification expectation-maximization (CEM) algorithm. The optimal curve segmentation is performed by using dynamic programming. In the classification approach, both the curve clustering and the optimal segmentation are performed simultaneously as the CEM learning proceeds. We show that the classification approach is the probabilistic version that generalizes the deterministic K-means-like algorithm proposed in H\'ebrail et al. (2010). The proposed approach is evaluated using simulated curves and real-world curves. Comparisons with alternatives including regression mixture models and the K-means like algorithm for piecewise regression demonstrate the effectiveness of the proposed approach.

The systematic biases seen in people's probability judgments are typically taken as evidence that people do not reason about probability using the rules of probability theory, but instead use heuristics which sometimes yield reasonable judgments and sometimes systematic biases. This view has had a major impact in economics, law, medicine, and other fields; indeed, the idea that people cannot reason with probabilities has become a widespread truism. We present a simple alternative to this view, where people reason about probability according to probability theory but are subject to random variation or noise in the reasoning process. In this account the effect of noise is cancelled for some probabilistic expressions: analysing data from two experiments we find that, for these expressions, people's probability judgments are strikingly close to those required by probability theory. For other expressions this account produces systematic deviations in probability estimates. These deviations explain four reliable biases in human probabilistic reasoning (conservatism, subadditivity, conjunction and disjunction fallacies). These results suggest that people's probability judgments embody the rules of probability theory, and that biases in those judgments are due to the effects of random noise.