Inferring hidden Markov models from noisy time sequences: a method to alleviate degeneracy in molecular dynamics

We present a new method for inferring hidden Markov models from noisy time sequences without the necessity of assuming a model architecture, thus allowing for the detection of degenerate states. This is based on the statistical prediction techniques developed by Crutchfield et al., and generates so called causal state models, equivalent to hidden Markov models. This method is applicable to any continuous data which clusters around discrete values and exhibits multiple transitions between these values such as tethered particle motion data or Fluorescence Resonance Energy Transfer (FRET) spectra. The algorithms developed have been shown to perform well on simulated data, demonstrating the ability to recover the model used to generate the data under high noise, sparse data conditions and the ability to infer the existence of degenerate states. They have also been applied to new experimental FRET data of Holliday Junction dynamics, extracting the expected two state model and providing values for the transition rates in good agreement with previous results and with results obtained using existing maximum likelihood based methods.Comment: 19 pages, 9 figure

The Computational Structure of Spike Trains

Neurons perform computations, and convey the results of those computations through the statistical structure of their output spike trains. Here we present a practical method, grounded in the information-theoretic analysis of prediction, for inferring a minimal representation of that structure and for characterizing its complexity. Starting from spike trains, our approach finds their causal state models (CSMs), the minimal hidden Markov models or stochastic automata capable of generating statistically identical time series. We then use these CSMs to objectively quantify both the generalizable structure and the idiosyncratic randomness of the spike train. Specifically, we show that the expected algorithmic information content (the information needed to describe the spike train exactly) can be split into three parts describing (1) the time-invariant structure (complexity) of the minimal spike-generating process, which describes the spike train statistically; (2) the randomness (internal entropy rate) of the minimal spike-generating process; and (3) a residual pure noise term not described by the minimal spike-generating process. We use CSMs to approximate each of these quantities. The CSMs are inferred nonparametrically from the data, making only mild regularity assumptions, via the causal state splitting reconstruction algorithm. The methods presented here complement more traditional spike train analyses by describing not only spiking probability and spike train entropy, but also the complexity of a spike train's structure. We demonstrate our approach using both simulated spike trains and experimental data recorded in rat barrel cortex during vibrissa stimulation.Comment: Somewhat different format from journal version but same conten

Structure and Randomness of Continuous-Time Discrete-Event Processes

Loosely speaking, the Shannon entropy rate is used to gauge a stochastic process' intrinsic randomness; the statistical complexity gives the cost of predicting the process. We calculate, for the first time, the entropy rate and statistical complexity of stochastic processes generated by finite unifilar hidden semi-Markov models---memoryful, state-dependent versions of renewal processes. Calculating these quantities requires introducing novel mathematical objects ({\epsilon}-machines of hidden semi-Markov processes) and new information-theoretic methods to stochastic processes.Comment: 10 pages, 2 figures; http://csc.ucdavis.edu/~cmg/compmech/pubs/ctdep.ht

Causal Effect Inference with Deep Latent-Variable Models

Learning individual-level causal effects from observational data, such as inferring the most effective medication for a specific patient, is a problem of growing importance for policy makers. The most important aspect of inferring causal effects from observational data is the handling of confounders, factors that affect both an intervention and its outcome. A carefully designed observational study attempts to measure all important confounders. However, even if one does not have direct access to all confounders, there may exist noisy and uncertain measurement of proxies for confounders. We build on recent advances in latent variable modeling to simultaneously estimate the unknown latent space summarizing the confounders and the causal effect. Our method is based on Variational Autoencoders (VAE) which follow the causal structure of inference with proxies. We show our method is significantly more robust than existing methods, and matches the state-of-the-art on previous benchmarks focused on individual treatment effects.Comment: Published as a conference paper at NIPS 201

Reductions of Hidden Information Sources

In all but special circumstances, measurements of time-dependent processes reflect internal structures and correlations only indirectly. Building predictive models of such hidden information sources requires discovering, in some way, the internal states and mechanisms. Unfortunately, there are often many possible models that are observationally equivalent. Here we show that the situation is not as arbitrary as one would think. We show that generators of hidden stochastic processes can be reduced to a minimal form and compare this reduced representation to that provided by computational mechanics--the epsilon-machine. On the way to developing deeper, measure-theoretic foundations for the latter, we introduce a new two-step reduction process. The first step (internal-event reduction) produces the smallest observationally equivalent sigma-algebra and the second (internal-state reduction) removes sigma-algebra components that are redundant for optimal prediction. For several classes of stochastic dynamical systems these reductions produce representations that are equivalent to epsilon-machines.Comment: 12 pages, 4 figures; 30 citations; Updates at http://www.santafe.edu/~cm

The Origins of Computational Mechanics: A Brief Intellectual History and Several Clarifications

The principle goal of computational mechanics is to define pattern and structure so that the organization of complex systems can be detected and quantified. Computational mechanics developed from efforts in the 1970s and early 1980s to identify strange attractors as the mechanism driving weak fluid turbulence via the method of reconstructing attractor geometry from measurement time series and in the mid-1980s to estimate equations of motion directly from complex time series. In providing a mathematical and operational definition of structure it addressed weaknesses of these early approaches to discovering patterns in natural systems. Since then, computational mechanics has led to a range of results from theoretical physics and nonlinear mathematics to diverse applications---from closed-form analysis of Markov and non-Markov stochastic processes that are ergodic or nonergodic and their measures of information and intrinsic computation to complex materials and deterministic chaos and intelligence in Maxwellian demons to quantum compression of classical processes and the evolution of computation and language. This brief review clarifies several misunderstandings and addresses concerns recently raised regarding early works in the field (1980s). We show that misguided evaluations of the contributions of computational mechanics are groundless and stem from a lack of familiarity with its basic goals and from a failure to consider its historical context. For all practical purposes, its modern methods and results largely supersede the early works. This not only renders recent criticism moot and shows the solid ground on which computational mechanics stands but, most importantly, shows the significant progress achieved over three decades and points to the many intriguing and outstanding challenges in understanding the computational nature of complex dynamic systems.Comment: 11 pages, 123 citations; http://csc.ucdavis.edu/~cmg/compmech/pubs/cmr.ht