A hierarchical Bayesian model for predicting the functional consequences of amino-acid polymorphisms

Genetic polymorphisms in deoxyribonucleic acid coding regions may have a phenotypic effect on the carrier, e.g. by influencing susceptibility to disease. Detection of deleterious mutations via association studies is hampered by the large number of candidate sites; therefore methods are needed to narrow down the search to the most promising sites. For this, a possible approach is to use structural and sequence-based information of the encoded protein to predict whether a mutation at a particular site is likely to disrupt the functionality of the protein itself. We propose a hierarchical Bayesian multivariate adaptive regression spline (BMARS) model for supervised learning in this context and assess its predictive performance by using data from mutagenesis experiments on lac repressor and lysozyme proteins. In these experiments, about 12 amino-acid substitutions were performed at each native amino-acid position and the effect on protein functionality was assessed. The training data thus consist of repeated observations at each position, which the hierarchical framework is needed to account for. The model is trained on the lac repressor data and tested on the lysozyme mutations and vice versa. In particular, we show that the hierarchical BMARS model, by allowing for the clustered nature of the data, yields lower out-of-sample misclassification rates compared with both a BMARS and a frequen-tist MARS model, a support vector machine classifier and an optimally pruned classification tree.

Learning and detecting activities from movement trajectories using the hierarchical hidden Markov model

Directly modeling the inherent hierarchy and shared structures of human behaviors, we present an application of the hierarchical hidden Markov model (HHMM) for the problem of activity recognition. We argue that to robustly model and recognize complex human activities, it is crucial to exploit both the natural hierarchical decomposition and shared semantics embedded in the movement trajectories. To this end, we propose the use of the HHMM, a rich stochastic model that has been recently extended to handle shared structures, for representing and recognizing a set of complex indoor activities. Furthermore, in the need of real-time recognition, we propose a Rao-Blackwellised particle filter (RBPF) that efficiently computes the filtering distribution at a constant time complexity for each new observation arrival. The main contributions of this paper lie in the application of the shared-structure HHMM, the estimation of the model's parameters at all levels simultaneously, and a construction of an RBPF approximate inference scheme. The experimental results in a real-world environment have confirmed our belief that directly modeling shared structures not only reduces computational cost, but also improves recognition accuracy when compared with the tree HHMM and the flat HMM.

Recognising behaviours of multiple people with hierarchical probabilistic model and statistical data association

Recognising behaviours of multiple people, especially high-level behaviours, is an important task in surveillance systems. When the reliable assignment of people to the set of observations is unavailable, this task becomes complicated. To solve this task, we present an approach, in which the hierarchical hidden Markov model (HHMM) is used for modeling the behaviour of each person and the joint probabilistic data association filters (JPDAF) is applied for data association. The main contributions of this paper lie in the integration of multiple HHMMs for recognising high-level behaviours of multiple people and the construction of the Rao-Blackwellised particle filters (RBPF) for approximate inference. Preliminary experimental results in a real environment show the robustness of our integrated method in behaviour recognition and its advantage over the use of Kalman filter in tracking people.

Polymorphic malware detection using Hierarchical Hidden Markov Model

Binary signatures have been widely used to detect malicious software on the current Internet. However, this approach is unable to achieve the accurate identification of polymorphic malware variants, which can be easily generated by the malware authors using code generation engines. Code generation engines randomly produce varying code sequences but perform the same desired malicious functions. Previous research used flow graph and signature tree to identify polymorphic malware families. The key difficulty of previous research is the generation of precisely defined state machine models from polymorphic variants. This paper proposes a novel approach, using Hierarchical Hidden Markov Model (HHMM), to provide accurate inductive inference of the malware family. This model can capture the features of self-similar and hierarchical structure of polymorphic malware family signature sequences. To demonstrate the effectiveness and efficiency of this approach, we evaluate it with real malware samples. Using more than 15,000 real malware, we find our approach can achieve high true positives, low false positives, and low computational cost.

Discovery of activity structures using the hierarchical hidden Markov model

In building a surveillance system for monitoring people behaviours, it is important to understand the typical patterns of people's movement in the environment. This task is difficult when dealing with high-level behaviours. The flat model such as the hidden Markov model (HMM) is inefficient in differentiating between signatures of such behaviours. This paper examines structure learning for high-level behaviours using the hierarchical hidden Markov model (HHMM).We propose a two-phase learning algorithm in which the parameters of the behaviours at low levels are estimated first and then the structures and parameters of the behaviours at high levels are learned from multi-camera training data. Our algorithm is then evaluated using data from a real environment, demonstrating the robustness of the learned structure in recognising people's behaviour.

A hierarchical PCA-based anomaly detection model

A hierarchical intrusion detection model is proposed to detect both anomaly and misuse attacks. In order to further speed up the training and testing, PCA-based feature extraction algorithm is used to reduce the dimensionality of the data. A PCA-based algorithm is used to filter normal data out in the upper level. The experiment results show that PCA can reduce noise in the original data set and the PCA-based algorithm can reach the desirable performance.

A Bayesian nonparametric model for hierarchical sequence of images

 Scale features are useful for a great number of applications in computer vision. However, it is difficult to tolerate diversities of features in natural scenes by parametric methods. Empirical studies show that object frequencies and segment sizes follow the power law distributions which are well generated by Pitman-Yor (PY) processes. Based on mid-level segments, we propose a hierarchical sequence of images to obtain scale information stored in a hierarchical structure through the hierarchical Pitman-Yor (HPY) model which is expected to tolerate uncertainty of natural images. We also evaluate our representation by the application of segmentation.

Endogenous wage compression and aggregation boundaries in a model of hierarchical human capital

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Parameter recovery for a skew-normal IRT model under a Bayesian approach: hierarchical framework, prior and kernel sensitivity and sample size

Item response theory (IRT) comprises a set of statistical models which are useful in many fields, especially when there is an interest in studying latent variables (or latent traits). Usually such latent traits are assumed to be random variables and a convenient distribution is assigned to them. A very common choice for such a distribution has been the standard normal. Recently, Azevedo et al. [Bayesian inference for a skew-normal IRT model under the centred parameterization, Comput. Stat. Data Anal. 55 (2011), pp. 353-365] proposed a skew-normal distribution under the centred parameterization (SNCP) as had been studied in [R. B. Arellano-Valle and A. Azzalini, The centred parametrization for the multivariate skew-normal distribution, J. Multivariate Anal. 99(7) (2008), pp. 1362-1382], to model the latent trait distribution. This approach allows one to represent any asymmetric behaviour concerning the latent trait distribution. Also, they developed a Metropolis-Hastings within the Gibbs sampling (MHWGS) algorithm based on the density of the SNCP. They showed that the algorithm recovers all parameters properly. Their results indicated that, in the presence of asymmetry, the proposed model and the estimation algorithm perform better than the usual model and estimation methods. Our main goal in this paper is to propose another type of MHWGS algorithm based on a stochastic representation (hierarchical structure) of the SNCP studied in [N. Henze, A probabilistic representation of the skew-normal distribution, Scand. J. Statist. 13 (1986), pp. 271-275]. Our algorithm has only one Metropolis-Hastings step, in opposition to the algorithm developed by Azevedo et al., which has two such steps. This not only makes the implementation easier but also reduces the number of proposal densities to be used, which can be a problem in the implementation of MHWGS algorithms, as can be seen in [R.J. Patz and B.W. Junker, A straightforward approach to Markov Chain Monte Carlo methods for item response models, J. Educ. Behav. Stat. 24(2) (1999), pp. 146-178; R. J. Patz and B. W. Junker, The applications and extensions of MCMC in IRT: Multiple item types, missing data, and rated responses, J. Educ. Behav. Stat. 24(4) (1999), pp. 342-366; A. Gelman, G.O. Roberts, and W.R. Gilks, Efficient Metropolis jumping rules, Bayesian Stat. 5 (1996), pp. 599-607]. Moreover, we consider a modified beta prior (which generalizes the one considered in [3]) and a Jeffreys prior for the asymmetry parameter. Furthermore, we study the sensitivity of such priors as well as the use of different kernel densities for this parameter. Finally, we assess the impact of the number of examinees, number of items and the asymmetry level on the parameter recovery. Results of the simulation study indicated that our approach performed equally as well as that in [3], in terms of parameter recovery, mainly using the Jeffreys prior. Also, they indicated that the asymmetry level has the highest impact on parameter recovery, even though it is relatively small. A real data analysis is considered jointly with the development of model fitting assessment tools. The results are compared with the ones obtained by Azevedo et al. The results indicate that using the hierarchical approach allows us to implement MCMC algorithms more easily, it facilitates diagnosis of the convergence and also it can be very useful to fit more complex skew IRT models.

Annealed Ising model on hierarchical structures: a transfer matrix approach.

Spin systems in the presence of disorder are described by two sets of degrees of freedom, associated with orientational (spin) and disorder variables, which may be characterized by two distinct relaxation times. Disordered spin models have been mostly investigated in the quenched regime, which is the usual situation in solid state physics, and in which the relaxation time of the disorder variables is much larger than the typical measurement times. In this quenched regime, disorder variables are fixed, and only the orientational variables are duly thermalized. Recent studies in the context of lattice statistical models for the phase diagrams of nematic liquid-crystalline systems have stimulated the interest of going beyond the quenched regime. The phase diagrams predicted by these calculations for a simple Maier-Saupe model turn out to be qualitative different from the quenched case if the two sets of degrees of freedom are allowed to reach thermal equilibrium during the experimental time, which is known as the fully annealed regime. In this work, we develop a transfer matrix formalism to investigate annealed disordered Ising models on two hierarchical structures, the diamond hierarchical lattice (DHL) and the Apollonian network (AN). The calculations follow the same steps used for the analysis of simple uniform systems, which amounts to deriving proper recurrence maps for the thermodynamic and magnetic variables in terms of the generations of the construction of the hierarchical structures. In this context, we may consider different kinds of disorder, and different types of ferromagnetic and anti-ferromagnetic interactions. In the present work, we analyze the effects of dilution, which are produced by the removal of some magnetic ions. The system is treated in a “grand canonical" ensemble. The introduction of two extra fields, related to the concentration of two different types of particles, leads to higher-rank transfer matrices as compared with the formalism for the usual uniform models. Preliminary calculations on a DHL indicate that there is a phase transition for a wide range of dilution concentrations. Ising spin systems on the AN are known to be ferromagnetically ordered at all temperatures; in the presence of dilution, however, there are indications of a disordered (paramagnetic) phase at low concentrations of magnetic ions.

Studying Effects of Primary Care Physicians and Patients on the Trade-Off Between Charges for Primary Care and Specialty Care Using a Hierarchical Multivariate Two-Part Model

Objective. To examine effects of primary care physicians (PCPs) and patients on the association between charges for primary care and specialty care in a point-of-service (POS) health plan. Data Source. Claims from 1996 for 3,308 adult male POS plan members, each of whom was assigned to one of the 50 family practitioner-PCPs with the largest POS plan member-loads. Study Design. A hierarchical multivariate two-part model was fitted using a Gibbs sampler to estimate PCPs' effects on patients' annual charges for two types of services, primary care and specialty care, the associations among PCPs' effects, and within-patient associations between charges for the two services. Adjusted Clinical Groups (ACGs) were used to adjust for case-mix. Principal Findings. PCPs with higher case-mix adjusted rates of specialist use were less likely to see their patients at least once during the year (estimated correlation: –.40; 95% CI: –.71, –.008) and provided fewer services to patients that they saw (estimated correlation: –.53; 95% CI: –.77, –.21). Ten of 11 PCPs whose case-mix adjusted effects on primary care charges were significantly less than or greater than zero (p < .05) had estimated, case-mix adjusted effects on specialty care charges that were of opposite sign (but not significantly different than zero). After adjustment for ACG and PCP effects, the within-patient, estimated odds ratio for any use of primary care given any use of specialty care was .57 (95% CI: .45, .73). Conclusions. PCPs and patients contributed independently to a trade-off between utilization of primary care and specialty care. The trade-off appeared to partially offset significant differences in the amount of care provided by PCPs. These findings were possible because we employed a hierarchical multivariate model rather than separate univariate models.

Hierarchical Markov Random Fields Applied to Model Soft Tissue Deformations on Graphics Hardware

Many methodologies dealing with prediction or simulation of soft tissue deformations on medical image data require preprocessing of the data in order to produce a different shape representation that complies with standard methodologies, such as mass–spring networks, finite element method s (FEM). On the other hand, methodologies working directly on the image space normally do not take into account mechanical behavior of tissues and tend to lack physics foundations driving soft tissue deformations. This chapter presents a method to simulate soft tissue deformations based on coupled concepts from image analysis and mechanics theory. The proposed methodology is based on a robust stochastic approach that takes into account material properties retrieved directly from the image, concepts from continuum mechanics and FEM. The optimization framework is solved within a hierarchical Markov random field (HMRF) which is implemented on the graphics processor unit (GPU See Graphics processing unit ).