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 PLOS Computational Biology , 2007, DOI: 10.1371/journal.pcbi.0030216 Abstract: The discovery and analysis of cis-regulatory modules (CRMs) in metazoan genomes is crucial for understanding the transcriptional control of development and many other biological processes. Cross-species sequence comparison holds much promise for improving computational prediction of CRMs, for elucidating their binding site composition, and for understanding how they evolve. Current methods for analyzing orthologous CRMs from multiple species rely upon sequence alignments produced by off-the-shelf alignment algorithms, which do not exploit the presence of binding sites in the sequences. We present here a unified probabilistic framework, called MORPH, that integrates the alignment task with binding site predictions, allowing more robust CRM analysis in two species. The framework sums over all possible alignments of two sequences, thus accounting for alignment ambiguities in a natural way. We perform extensive tests on orthologous CRMs from two moderately diverged species Drosophila melanogaster and D. mojavensis, to demonstrate the advantages of the new approach. We show that it can overcome certain computational artifacts of traditional alignment tools and provide a different, likely more accurate, picture of cis-regulatory evolution than that obtained from existing methods. The burgeoning field of cis-regulatory evolution, which is amply supported by the availability of many related genomes, is currently thwarted by the lack of accurate alignments of regulatory regions. Our work will fill in this void and enable more reliable analysis of CRM evolution.
 Journal of Biomedical Science and Engineering (JBiSE) , 2010, DOI: 10.4236/jbise.2010.36086 Abstract: The research hotspot in post-genomic era is from sequence to function. Building genetic regulatory network (GRN) can help to understand the regulatory mechanism between genes and the function of organisms. Probabilistic GRN has been paid more attention recently. This paper discusses the Hidden Markov Model (HMM) approach served as a tool to build GRN. Different genes with similar expression levels are considered as different states during training HMM. The probable regulatory genes of target genes can be found out through the resulting states transition matrix and the determinate regulatory functions can be predicted using nonlinear regression algorithm. The experiments on artificial and real-life datasets show the effectiveness of HMM in building GRN.
 Maria A. Avino-Diaz Mathematics , 2006, Abstract: In this paper we study homomorphisms of Probabilistic Regulatory Gene Networks(PRN) introduced in arXiv:math.DS/0603289 v1 13 Mar 2006. The model PRN is a natural generalization of the Probabilistic Boolean Networks (PBN), introduced by I. Shmulevich, E. Dougherty, and W. Zhang in 2001, that has been using to describe genetic networks and has therapeutic applications. In this paper, our main objectives are to apply the concept of homomorphism and $\epsilon$-homomorphism of probabilistic regulatory networks to the dynamic of the networks. The meaning of $\epsilon$ is that these homomorphic networks have similar distributions and the distance between the distributions is upper bounded by $\epsilon$. Additionally, we prove that the class of PRN together with the homomorphisms form a category with products and coproducts. Projections are special homomorphisms, and they always induce invariant subnetworks that contain all the cycles and steady states in the network. Here, it is proved that the $\epsilon$-homomorphism for $0<\epsilon<1$ produce simultaneous Markov Chains in both networks, that permit to introduce the concept of $\epsilon$-isomorphism of Markov Chains, and similar networks.
 Statistics , 2007, DOI: 10.1214/07-AOAS103 Abstract: Cis-regulatory modules (CRMs) composed of multiple transcription factor binding sites (TFBSs) control gene expression in eukaryotic genomes. Comparative genomic studies have shown that these regulatory elements are more conserved across species due to evolutionary constraints. We propose a statistical method to combine module structure and cross-species orthology in de novo motif discovery. We use a hidden Markov model (HMM) to capture the module structure in each species and couple these HMMs through multiple-species alignment. Evolutionary models are incorporated to consider correlated structures among aligned sequence positions across different species. Based on our model, we develop a Markov chain Monte Carlo approach, MultiModule, to discover CRMs and their component motifs simultaneously in groups of orthologous sequences from multiple species. Our method is tested on both simulated and biological data sets in mammals and Drosophila, where significant improvement over other motif and module discovery methods is observed.
 EURASIP Journal on Advances in Signal Processing , 2007, DOI: 10.1155/2008/675787 Abstract: This paper introduces a novel methodology that combines the multiresolution feature of the discrete wavelet transform (DWT) with the local interactions of the facial structures expressed through the structural hidden Markov model (SHMM). A range of wavelet filters such as Haar, biorthogonal 9/7, and Coiflet, as well as Gabor, have been implemented in order to search for the best performance. SHMMs perform a thorough probabilistic analysis of any sequential pattern by revealing both its inner and outer structures simultaneously. Unlike traditional HMMs, the SHMMs do not perform the state conditional independence of the visible observation sequence assumption. This is achieved via the concept of local structures introduced by the SHMMs. Therefore, the long-range dependency problem inherent to traditional HMMs has been drastically reduced. SHMMs have not previously been applied to the problem of face identification. The results reported in this application have shown that SHMM outperforms the traditional hidden Markov model with a 73% increase in accuracy.
 Computer Science , 2013, Abstract: In this paper, we study statistical classification accuracy of two different Markov field environments for pixelwise image segmentation, considering the labels of the image as hidden states and solving the estimation of such labels as a solution of the MAP equation. The emission distribution is assumed the same in all models, and the difference lays in the Markovian prior hypothesis made over the labeling random field. The a priori labeling knowledge will be modeled with a) a second order anisotropic Markov Mesh and b) a classical isotropic Potts model. Under such models, we will consider three different segmentation procedures, 2D Path Constrained Viterbi training for the Hidden Markov Mesh, a Graph Cut based segmentation for the first order isotropic Potts model, and ICM (Iterated Conditional Modes) for the second order isotropic Potts model. We provide a unified view of all three methods, and investigate goodness of fit for classification, studying the influence of parameter estimation, computational gain, and extent of automation in the statistical measures Overall Accuracy, Relative Improvement and Kappa coefficient, allowing robust and accurate statistical analysis on synthetic and real-life experimental data coming from the field of Dental Diagnostic Radiography. All algorithms, using the learned parameters, generate good segmentations with little interaction when the images have a clear multimodal histogram. Suboptimal learning proves to be frail in the case of non-distinctive modes, which limits the complexity of usable models, and hence the achievable error rate as well. All Matlab code written is provided in a toolbox available for download from our website, following the Reproducible Research Paradigm.
 Statistics , 2014, Abstract: We obtain a perfect sampling characterization of weak ergodicity for backward products of finite stochastic matrices, and equivalently, simultaneous tail triviality of the corresponding nonhomogeneous Markov chains. Applying these ideas to hidden Markov models, we show how to sample exactly from the finite-dimensional conditional distributions of the signal process given infinitely many observations, using an algorithm which requires only an almost surely finite number of observations to actually be accessed. A notion of "successful" coupling is introduced and its occurrence is characterized in terms of conditional ergodicity properties of the hidden Markov model and related to the stability of nonlinear filters.
 Computer Science , 2013, Abstract: This paper studies the connection between probabilistic conditional independence in uncertain reasoning and data dependency in relational databases. As a demonstration of the usefulness of this preliminary investigation, an alternate proof is presented for refuting the conjecture suggested by Pearl and Paz that probabilistic conditional independencies have a complete axiomatization.
 Peter Spreij Mathematics , 2001, DOI: 10.1016/S0167-7152(03)00011-7 Abstract: In this paper we study various properties of finite stochastic systems or hidden Markov chains as they are alternatively called. We discuss their construction following different approaches and we also derive recursive filtering formulas for the different systems that we consider. The key tool is a simple lemma on conditional expectations.
 Computer Science , 2015, DOI: 10.1007/978-3-319-11191-9_31 Abstract: Hidden Markov Models (HMMs) are learning methods for pattern recognition. The probabilistic HMMs have been one of the most used techniques based on the Bayesian model. First-order probabilistic HMMs were adapted to the theory of belief functions such that Bayesian probabilities were replaced with mass functions. In this paper, we present a second-order Hidden Markov Model using belief functions. Previous works in belief HMMs have been focused on the first-order HMMs. We extend them to the second-order model.
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