Network-based genomic discovery: application and comparison of Markov random field models

Summary.  As biological knowledge accumulates rapidly, gene networks encoding genomewide gene–gene interactions have been constructed. As an improvement over the standard mixture model that tests all the genes identically and independently distributed a priori , Wei and co-workers have proposed modelling a gene network as a discrete or Gaussian Markov random field (MRF) in a mixture model to analyse genomic data. However, how these methods compare in practical applications is not well understood and this is the aim here. We also propose two novel constraints in prior specifications for the Gaussian MRF model and a fully Bayesian approach to the discrete MRF model. We assess the accuracy of estimating the false discovery rate by posterior probabilities in the context of MRF models. Applications to a chromatin immuno-precipitation–chip data set and simulated data show that the modified Gaussian MRF models have superior performance compared with other models, and both MRF-based mixture models, with reasonable robustness to misspecified gene networks, outperform the standard mixture model.     

Hierarchical Bayesian Approach to a Multi-Site Hidden Markov Model

Multivariate data with a sequential or temporal structure occur in various fields of study. The hidden Markov model (HMM) provides an attractive framework for modeling long-term persistence in areas of pattern recognition through the extension of independent and identically distributed mixture models. Unlike in typical mixture models, the heterogeneity of data is represented by hidden Markov states. This article extends the HMM to a multi-site or multivariate case by taking a hierarchical Bayesian approach. This extension has many advantages over a single-site HMM. For example, it can provide more information for identifying the structure of the HMM than a single-site analysis. We evaluate the proposed approach by exploiting a spatial correlation that depends on the distance between sites.     

Bayesian clustering for continuous-time hidden Markov models

We develop clustering procedures for longitudinal trajectories based on a continuous-time hidden Markov model (CTHMM) and a generalized linear observation model. Specifically, in this article we carry out finite and infinite mixture model-based clustering for a CTHMM and achieve inference using Markov chain Monte Carlo (MCMC). For a finite mixture model with a prior on the number of components, we implement reversible-jump MCMC to facilitate the trans-dimensional move between models with different numbers of clusters. For a Dirichlet process mixture model, we utilize restricted Gibbs sampling split–merge proposals to improve the performance of the MCMC algorithm. We apply our proposed algorithms to simulated data as well as a real-data example, and the results demonstrate the desired performance of the new sampler.     

A New Model for Multivariate Markov Chains

We propose a new model for multivariate Markov chains of order one or higher on the basis of the mixture transition distribution (MTD) model. We call it the MTD‐Probit. The proposed model presents two attractive features: it is completely free of constraints, thereby facilitating the estimation procedure, and it is more precise at estimating the transition probabilities of a multivariate or higher‐order Markov chain than the standard MTD model.     

Alternative Markov Properties for Chain Graphs

Graphical Markov models use graphs to represent possible dependences among statistical variables. Lauritzen, Wermuth, and Frydenberg (LWF) introduced a Markov property for chain graphs (CG): graphs that can be used to represent both structural and associative dependences simultaneously and that include both undirected graphs (UG) and acyclic directed graphs (ADG) as special cases. Here an alternative Markov property (AMP) for CGs is introduced and shown to be the Markov property satisfied by a block-recursive linear system with multivariate normal errors. This model can be decomposed into a collection of conditional normal models, each of which combines the features of multivariate linear regression models and covariance selection models, facilitating the estimation of its parameters. In the general case, necessary and sufficient conditions are given for the equivalence of the LWF and AMP Markov properties of a CG, for the AMP Markov equivalence of two CGs, for the AMP Markov equivalence of a CG to some ADG or decomposable UG, and for other equivalences. For CGs, in some ways the AMP property is a more direct extension of the ADG Markov property than is the LWF property.     

Nonparametric Bayesian analysis for multi-site hidden Markov model

The hidden Markov model (HMM) provides an attractive framework for modeling long-term persistence in a variety of applications including pattern recognition. Unlike typical mixture models, hidden Markov states can represent the heterogeneity in data and it can be extended to a multivariate case using a hierarchical Bayesian approach. This article provides a nonparametric Bayesian modeling approach to the multi-site HMM by considering stick-breaking priors for each row of an infinite state transition matrix. This extension has many advantages over a parametric HMM. For example, it can provide more flexible information for identifying the structure of the HMM than parametric HMM analysis, such as the number of states in HMM. We exploit a simulation example and a real dataset to evaluate the proposed approach.     

Mixture Multi-state Markov Regression Model

Although heterogeneity across individuals may be reduced when a two-state process is extended into a multi-state process, the discrepancy between the observed and the predicted for some states may still exist owing to two possibilities, unobserved mixture distribution in the initial state and the effect of measured covariates on subsequent multi-state disease progression. In the present study, we developed a mixture Markov exponential regression model to take account of the above-mentioned heterogeneity across individuals (subject-to-subject variability) with a systematic model selection based on the likelihood ratio test. The model was successfully demonstrated by an empirical example on surveillance of patients with small hepatocellular carcinoma treated by non-surgical methods. The estimated results suggested that the model with the incorporation of unobserved mixture distribution behaves better than the one without. Complete and partial effects regarding risk factors on different subsequent multi-state transitions were identified using a homogeneous Markov model. The combination of both initial mixture distribution and homogeneous Markov exponential regression model makes a significant contribution to reducing heterogeneity across individuals and over time for disease progression.     

Hidden Markov Mixture Autoregressive Models: Stability and Moments

This article introduces a parsimonious structure for mixture of autoregressive models, where the weighting coefficients are determined through latent random variables, as functions of all past observations. These latent variables follow a Markov model. We propose a dynamic programming algorithm for forecasting, which reduces the volume of calculations. We also derive limiting behavior of unconditional first moment of the process and an appropriate upper bound for the limiting value of the variance. Further more, we show convergence and stability of the second moment. Finally, we illustrate the efficacy of the proposed model by simulation.     

Reversible jump and the label switching problem in hidden Markov models

Reversible jump Markov chain Monte Carlo (RJMCMC) algorithms can be efficiently applied in Bayesian inference for hidden Markov models (HMMs), when the number of latent regimes is unknown. As for finite mixture models, when priors are invariant to the relabelling of the regimes, HMMs are unidentifiable in data fitting, because multiple ways to label the regimes can alternate during the MCMC iterations; this is the so-called label switching problem. HMMs with an unknown number of regimes are considered here and the goal of this paper is the comparison, both applied and theoretical, of five methods used for tackling label switching within a RJMCMC algorithm; they are: post-processing, partial reordering, permutation sampling, sampling from a Markov prior and rejection sampling. The five strategies we compare have been proposed mostly in the literature of finite mixture models and only two of them, i.e. rejection sampling and partial reordering, have been presented in RJMCMC algorithms for HMMs. We consider RJMCMC algorithms in which the parameters are updated by Gibbs sampling and the dimension of the model changes in split-and-merge and birth-and-death moves. Finally, an example illustrates and compares the five different methodologies.     

A distance-based diagnostic for trans-dimensional Markov chains

Over the last decade the use of trans-dimensional sampling algorithms has become endemic in the statistical literature. In spite of their application however, there are few reliable methods to assess whether the underlying Markov chains have reached their stationary distribution. In this article we present a distance-based method for the comparison of trans-dimensional Markov chain sample output for a broad class of models. This diagnostic will simultaneously assess deviations between and within chains. Illustration of the analysis of Markov chain sample-paths is presented in simulated examples and in two common modelling situations: a finite mixture analysis and a change-point problem.     

Robust estimation for order of hidden Markov models based on density power divergences

In this paper, we study the robust estimation for the order of hidden Markov model (HMM) based on a penalized minimum density power divergence estimator, which is obtained by utilizing the finite mixture marginal distribution of HMM. For this task, we adopt the locally conic parametrization method used in [D. Dacunha-Castelle and E. Gassiate, Testing in locally conic models and application to mixture models. ESAIM Probab. Stat. (1997), pp. 285–317; D. Dacunha-Castelle and E. Gassiate, Testing the order of a model using locally conic parametrization: population mixtures and stationary arma processes, Ann. Statist. 27 (1999), pp. 1178–1209; T. Lee and S. Lee, Robust and consistent estimation of the order of finite mixture models based on the minimizing a density power divergence estimator, Metrika 68 (2008), pp. 365–390] to avoid the difficulties that arise in handling mixture marginal models, such as the non-identifiability of the parameter space and the singularity problem with the asymptotic variance. We verify that the estimated order is consistent and simulation results are provided for illustration.     

Sparse Markov Chains for Sequence Data

Finite memory sources and variable‐length Markov chains have recently gained popularity in data compression and mining, in particular, for applications in bioinformatics and language modelling. Here, we consider denser data compression and prediction with a family of sparse Bayesian predictive models for Markov chains in finite state spaces. Our approach lumps transition probabilities into classes composed of invariant probabilities, such that the resulting models need not have a hierarchical structure as in context tree‐based approaches. This can lead to a substantially higher rate of data compression, and such non‐hierarchical sparse models can be motivated for instance by data dependence structures existing in the bioinformatics context. We describe a Bayesian inference algorithm for learning sparse Markov models through clustering of transition probabilities. Experiments with DNA sequence and protein data show that our approach is competitive in both prediction and classification when compared with several alternative methods on the basis of variable memory length.     

Markov Chain Markov Field dynamics: Models and statistics

This study deals with time dynamics of Markov fields defined on a finite set of sites with state space <$>E<$>, focussing on Markov Chain Markov Field (MCMF) evolution. Such a model is characterized by two families of potentials: the instantaneous interaction potentials, and the time delay potentials. Four models are specified: auto-exponential dynamics (<$>E = {\of R}^+<$>), auto-normal dynamics (<$>E = {\of R}<$>), auto-Poissonian dynamics (<$>E = {\of N}<$>) and auto-logistic dynamics ( E qualitative and finite). Sufficient conditions ensuring ergodicity and strong law of large numbers are given by using a Lyapunov criterion of stability, and the conditional pseudo-likelihood statistics are summarized. We discuss the identification procedure of the two Markovian graphs and look for validation tests using martingale central limit theorems. An application to meteorological data illustrates such a modelling.     

Empirical Performance and Asset Pricing in Hidden Markov Models

Abstract

To improve the empirical performance of the Black-Scholes model, many alternative models have been proposed to address leptokurtic feature, volatility smile, and volatility clustering effects of the asset return distributions. However, analytical tractability remains a problem for most alternative models. In this article, we study a class of hidden Markov models including Markov switching models and stochastic volatility models, that can incorporate leptokurtic feature, volatility clustering effects, as well as provide analytical solutions to option pricing. We show that these models can generate long memory phenomena when the transition probabilities depend on the time scale. We also provide an explicit analytic formula for the arbitrage-free price of the European options under these models. The issues of statistical estimation and errors in option pricing are also discussed in the Markov switching models.     

Fitting Gaussian Markov Random Fields to Gaussian Fields

This paper discusses the following task often encountered in building Bayesian spatial models: construct a homogeneous Gaussian Markov random field (GMRF) on a lattice with correlation properties either as present in some observed data, or consistent with prior knowledge. The Markov property is essential in designing computationally efficient Markov chain Monte Carlo algorithms to analyse such models. We argue that we can restate both tasks as that of fitting a GMRF to a prescribed stationary Gaussian field on a lattice when both local and global properties are important. We demonstrate that using the KullbackLeibler discrepancy often fails for this task, giving severely undesirable behaviour of the correlation function for lags outside the neighbourhood. We propose a new criterion that resolves this difficulty, and demonstrate that GMRFs with small neighbourhoods can approximate Gaussian fields surprisingly well even with long correlation lengths. Finally, we discuss implications of our findings for likelihood based inference for general Markov random fields when global properties are also important.     

Approximating hidden Gaussian Markov random fields

Summary.  Gaussian Markov random-field (GMRF) models are frequently used in a wide variety of applications. In most cases parts of the GMRF are observed through mutually independent data; hence the full conditional of the GMRF, a hidden GMRF (HGMRF), is of interest. We are concerned with the case where the likelihood is non-Gaussian, leading to non-Gaussian HGMRF models. Several researchers have constructed block sampling Markov chain Monte Carlo schemes based on approximations of the HGMRF by a GMRF, using a second-order expansion of the log-density at or near the mode. This is possible as the GMRF approximation can be sampled exactly with a known normalizing constant. The Markov property of the GMRF approximation yields computational efficiency.The main contribution in the paper is to go beyond the GMRF approximation and to construct a class of non-Gaussian approximations which adapt automatically to the particular HGMRF that is under study. The accuracy can be tuned by intuitive parameters to nearly any precision. These non-Gaussian approximations share the same computational complexity as those which are based on GMRFs and can be sampled exactly with computable normalizing constants. We apply our approximations in spatial disease mapping and model-based geostatistical models with different likelihoods, obtain procedures for block updating and construct Metropolized independence samplers.     

Statistical Inference for Partially Hidden Markov Models

ABSTRACT

In this article we introduce a new missing data model, based on a standard parametric Hidden Markov Model (HMM), for which information on the latent Markov chain is given since this one reaches a fixed state (and until it leaves this state). We study, under mild conditions, the consistency and asymptotic normality of the maximum likelihood estimator. We point out also that the underlying Markov chain does not need to be ergodic, and that identifiability of the model is not tractable in a simple way (unlike standard HMMs), but can be studied using various technical arguments.     

ML, PL, QL in Markov Chain Models

Abstract.  In many spatial and spatial-temporal models, and more generally in models with complex dependencies, it may be too difficult to carry out full maximum-likelihood (ML) analysis. Remedies include the use of pseudo-likelihood (PL) and quasi-likelihood (QL) (also called the composite likelihood). The present paper studies the ML, PL and QL methods for general Markov chain models, partly motivated by the desire to understand the precise behaviour of the PL and QL methods in settings where this can be analysed. We present limiting normality results and compare performances in different settings. For Markov chain models, the PL and QL methods can be seen as maximum penalized likelihood methods. We find that QL is typically preferable to PL, and that it loses very little to ML, while sometimes earning in model robustness. It has also appeal and potential as a modelling tool. Our methods are illustrated for consonant-vowel transitions in poetry and for analysis of DNA sequence evolution-type models.     

Markov Random Fields with Higher-order Interactions

Discrete-state Markov random fields on regular arrays have played a significant role in spatial statistics and image analysis. For example, they are used to represent objects against background in computer vision and pixel-based classification of a region into different crop types in remote sensing. Convenience has generally favoured formulations that involve only pairwise interactions. Such models are in themselves unrealistic and, although they often perform surprisingly well in tasks such as the restoration of degraded images, they are unsatisfactory for many other purposes. In this paper, we consider particular forms of Markov random fields that involve higher-order interactions and therefore are better able to represent the large-scale properties of typical spatial scenes. Interpretations of the parameters are given and realizations from a variety of models are produced via Markov chain Monte Carlo. Potential applications are illustrated in two examples. The first concerns Bayesian image analysis and confirms that pairwise-interaction priors may perform very poorly for image functionals such as number of objects, even when restoration apparently works well. The second example describes a model for a geological dataset and obtains maximum-likelihood parameter estimates using Markov chain Monte Carlo. Despite the complexity of the formulation, realizations of the estimated model suggest that the representation is quite realistic.     

Parameter Estimation in Pair-hidden Markov Models

Abstract.  This paper deals with parameter estimation in pair-hidden Markov models. We first provide a rigorous formalism for these models and discuss possible definitions of likelihoods. The model is biologically motivated and therefore naturally leads to restrictions on the parameter space. Existence of two different information divergence rates is established and a divergence property is shown under additional assumptions. This yields consistency for the parameter in parametrization schemes for which the divergence property holds. Simulations illustrate different cases which are not covered by our results.