Identifying Virus-Cell Fusion in Two-Channel Fluorescence Microscopy Image Sequences Based on a Layered Probabilistic Approach

Explicit and tractable characterizations of the dynamical behavior of virus particles are pivotal for a thorough understanding of the infection mechanisms of viruses. This thesis deals with the problem of extracting symbolic representations of the dynamical behavior of fluorescent particles from fluorescence microscopy image sequences. The focus is on the behavior of virus particles such as fusion with the cell membrane. A numerical representation is obtained by tracking the particles in the image sequences. We have investigated probabilistic tracking approaches, including approaches based on the Kalman filter as well as based on particle filters. For reasons of efficiency and robustness, we developed a tracking approach based on the probabilistic data association (PDA) algorithm in combination with an ellipsoidal sampling scheme that exploits effectively the image data via parametric appearance models. To track objects in close proximity, we compute the support that each image position provides to each tracked object relative to the support provided to the object's neighbors. After tracking, the problem of mapping the trajectory information computed by the tracking approaches to symbolic representations of the behavior arises. To compute symbolic representations of behaviors related to the fusion of single virus particles with the cell membrane based on their intensity over time, we developed a layered probabilistic approach based on stochastic hybrid systems as well as hidden Markov models (HMMs). We use a maxbelief strategy to efficiently combine both representations. The layered approach describes the intensity, intensity models, and behaviors of single virus particles. We introduce models for the evolution of the intensity and the behavior. To compute estimates for the intensity, intensity models, and behaviors we use a hybrid particle filter and the Viterbi algorithm. The developed approaches have been applied to synthetic images as well as to real microscopy image sequences displaying human immunodeficiency virus (HIV-1) particles. We have performed an extensive quantitative evaluation of the performance and a comparison with several existing approaches. It turned out that our approaches outperform previous ones, thus yielding more accurate and more reliable information about the behavior of virus particles. Moreover, we have successfully applied our tracking approaches to 3D image sequences displaying herpes simplex virus (HSV) replication compartments. We also applied the tracking approaches to image data displaying microtubule tips and analyzed their motion. In addition, our tracking approaches were successfully applied to the 2D and 3D image data of a Particle Tracking Challenge.

This paper describes an automatic text‐ and speaker‐independent language identification method based on hidden Markov models (HMMs) for acoustic features. The hidden Markov modeling is used to represent the phonotactics for each language. Each language has its proper phonotactics.The HMM topology here is a fully structured (ergodic) model wherein any state could transit to all states. Two kinds of HMMs are used: the discrete HMM (DHMM) with the codebook and the continuous density HMM (CHMM). The HMM was trained using both the Baum‐Welch (forward‐backward) algorithm and the Viterbi algorithm. The latter was used for emphasizing the state transition probability.For comparison, experiments also were conducted on the identification using a mixtured Gaussian distribution model with one state. This single‐state Gaussian distribution model gave the same performance as the HMM trained with the Baum‐Welch algorithm. This is because the transition between states which reflects the characteristics of each language does not affect the likelihood scores very much. This problem was addressed by emphasizing the transition probabilities and using the Viterbi algorithm, which resulted in an improvement in the recognition rates. The trigram for optimal state sequence is introduced. Combining it with the HMM produced the best results.

BACKGROUND A hidden Markov model (HMM) is used for exon prediction on DNA of genes Plasmodium falciparum that has a model structure based on exon region structure in coding sequence (CDS). The objective research was to develop a new structure model to predict exon on DNA-genes of Plasmodium falciparum based on CDS structure using the HMM system. METHODS Model design in CDS, between two exon regions can be found one intron region and the model state number is used for its region. Its state number is used by separating start codon from first exon region and stop codon from the last exon region up to 9. The Viterbi algorithm and the backward-forward method for transition as well as emission states are used for training process. Furthermore, Viterbi and Baum-Welch algorithms are used for the testing process. The correlation coefficient (CC) was used as performance indicator, as the ratio of the estimated state in the output and the original state in the input of the model. RESULTS The simulation results has shown that the CC values depend on the given of the backward-forward transition state values randomly. The model with state number 9 showed the highest average of CC values of 0.7289 for Viterbi algorithm, and is 0.7166 for Baum-Welch algorithm. However, the lowest average of CC values has been found for the model with state number five. Its values are 0.6735 by using Viterbi algorithm and 0.6661 by using Baum-Welch algorithm. CONCLUSION The new structure model based on HMM system was valid to predict exon on DNA-genes of Plasmodium falciparum.

Currently, the most popular algorithm for hidden Markov model (HMM) decoding is the Viterbi algorithm with beam search to reduce search space. However, it is a difficult problem in determining a beam width beforehand. To address this problem, we propose a novel approach on search space reduction. Following the definition of HMM, we first detect the possible change points between HMM states sequentially, then use the change points to locate a subspace for searching. Using a combined forward and backward scheme, we can detect two boundaries consisting of change points to enclose the subspace. The Viterbi algorithm or any other search algorithms can then be applied in the subspace. The experiments on a speaker verification task show that the proposed algorithm is about 4 times faster than a full search algorithm while the accuracy is almost the same. On the same decoding speed, the proposed algorithm provides a better accuracy than a beam-search approach. For an HMM with S states, the upper bound of speedup comparing to the full search approach is approximately S/3.

We present a nonparametric regression method for denoising 3-D image sequences acquired via fluorescence microscopy. The proposed method exploits the redundancy of the 3-D+time information to improve the signal-to-noise ratio of images corrupted by Poisson-Gaussian noise. A variance stabilization transform is first applied to the image-data to remove the dependence between the mean and variance of intensity values. This preprocessing requires the knowledge of parameters related to the acquisition system, also estimated in our approach. In a second step, we propose an original statistical patch-based framework for noise reduction and preservation of space-time discontinuities. In our study, discontinuities are related to small moving spots with high velocity observed in fluorescence video-microscopy. The idea is to minimize an objective nonlocal energy functional involving spatio-temporal image patches. The minimizer has a simple form and is defined as the weighted average of input data taken in spatially-varying neighborhoods. The size of each neighborhood is optimized to improve the performance of the pointwise estimator. The performance of the algorithm (which requires no motion estimation) is then evaluated on both synthetic and real image sequences using qualitative and quantitative criteria.

In order to further enhance the performance of syntax parsing, for the shortcomings of hidden Markov model (HMM) in the parameter optimization, an improved syntax parsing method based on adaptive genetic annealing and HMM was presented. First, an adaptive hybrid genetic annealing algorithm was adopted to optimize HMM initial parameters. Second, the improved HMM was trained by Baum Welch algorithm, and then a modified Viterbi algorithm was used to recognize various types of phrases at the same layer, finally a hierarchical analysis algorithm and Viterbi algorithm were combined together to solve hierarchy and recursion in the sentence. In the adaptive genetic annealing HMM algorithm, genetic operators and parameters of simulated annealing (SA) were first respectively improved, subpopulations were classified according to the adaptive crossover and mutation probability of GA in order to realize the multi-group parallel search and information exchange, which could avoid premature and accelerate convergence, then SA was taken as a GA operator to strengthen the local search capability. Compared with several new approaches, Fβ = 1 value is averagely increased by 3%. The experiment results prove that this method is very effective for syntactic parsing.

Computational cancer phylogenetics can play an important role in delineating possible tumor progression pathways and identifying molecular subtypes and mechanisms of action. We previously developed a pipeline for constructing tumor phylogenies from recurring cell types computationally inferred from whole genome copy number data. The accuracy and detail of these tumor phylogenies, however, depends on the identification of accurate and high-resolution molecular markers of progression, i.e., reproducible regions of copy number variation that can be used to robustly differentiate different subtypes and stages of progression. Here we present a new method for the problem using hidden Markov models (HMMs) to derive robust, high resolution progression markers from sets of tumor samples. We demonstrate our method on a publicly available array comparative genome hybridization (aCGH) dataset (NCBI GEO GSE16672, Navin et al., 2010) from sectioned primary ductal breast tumors. Our method uses an HMM, a class of probabilistic models, to classify sets of aCGH data into a partitioning of samples into normal (diploid) or amplified at each copy number probe. It differs from other similar HMM methods primarily in seeking a parsimonious set of combinations of amplification states able to explain all aCGH profiles simultaneously in order to identify robust markers of progression across samples. The model learns frequencies with which different combinations of amplifications are observed across the samples by modeling individual probes as Gaussian random variables with either normal or tetraploid means, with data more consistent with tetraploid being classified as amplified and those more consistent with diploid classified as normal. To handle a combinatorial explosion in combinations of amplification states with increasing numbers of samples, the method introduces a Gibbs sampling algorithm to learn a parsimonious model of the most frequently occurring combinations of amplification states. We applied our methods to a previously constructed set of inferred cell types derived from the Navin et al. data (Tolliver et al., 2010) and to a comparison set of 9 random samples from the raw aCGH data. We validated our model relative to manual labeling of amplicons on the same data. In both experiments, the HMM method was able to pick up significantly larger numbers of robustly amplified segments per chromosome than did prior methods or manual analysis. The resulting segments can be directly fed into downstream analysis routines for phylogeny inference or other predictions. In future work, the HMM method may be improved by fine-tuning the underlying model for copy number variation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3964. doi:1538-7445.AM2012-3964

We present a new algorithm for the nonrigid registration of three-dimensional magnetic resonance (MR) intraoperative image sequences showing brain shift. The algorithm tracks key surfaces of objects (cortical surface and the lateral ventricles) in the image sequence using a deformable surface matching algorithm. The volumetric deformation field of the objects is then inferred from the displacements at the boundary surfaces using a linear elastic biomechanical finite-element model. Two experiments on synthetic image sequences are presented, as well as an initial experiment on intraoperative MR images showing brain shift. The results of the registration algorithm show a good correlation of the internal brain structures after deformation, and a good capability of measuring surface as well as subsurface shift. We measured distances between landmarks in the deformed initial image and the corresponding landmarks in the target scan. Cortical surface shifts of up to 10 mm and subsurface shifts of up to 6 mm were recovered with an accuracy of 1 mm or less and 3 mm or less respectively.

This paper introduces two unsupervised learning methods for analyzing functional magnetic resonance imaging (fMRI) data based on hidden Markov model (HMM). HMM approach is focused on capturing the first-order statistical evolution among the samples of a voxel time series, and it can provide a complimentary perspective of the BOLD signals. Two-state HMM is created for each voxel, and the model parameters are estimated from the voxel time series and the stimulus paradigm. Two different activation detection methods are presented in this paper. The first method is based on the likelihood and likelihood-ratio test, in which an additional Gaussian model is used to enhance the contrast of the HMM likelihood map. The second method is based on certain distance measures between the two state distributions, in which the most likely HMM state sequence is estimated through the Viterbi algorithm. The distance between the on-state and off-state distributions is measured either through a t-test, or using the Kullback-Leibler distance (KLD). Experimental results on both normal subject and brain tumor subject are presented. HMM approach appears to be more robust in detecting the supplemental active voxels comparing with SPM, especially for brain tumor subject.

This paper proposes a novel cooperative anomaly detection system that uses mobile sensing and delay tolerant network (DTN) technologies. As an example application, the anomaly detection system in which vehicles detect dangerous states of the road that could cause traffic accidents and/or traffic jams is considered. Assuming that the predicted road states by the anomaly detection include some prediction errors, a hidden Markov model (HMM) is introduced for representing the spatial relationship among the road states. The EM algorithm is employed to estimate the HMM parameters such that the Viterbi algorithm is applied to a target predicted road sequence. In addition, the reliable road states shared with other vehicles by the DTN technology are combined with the locally predicted sequence to perform trellis pruning in the Viterbi algorithm as the cooperative data processing, which further improves the accuracy of road state estimation.

Using IDE usage data to analyze the behavior of software developers in the field, during the course of their daily work, can lend support to (or dispute) laboratory studies of devel- opers. This paper describes a technique that leverages Hidden Markov Models (HMMs) as a means of mining high-level developer behavior from low-level IDE interaction traces of many developers in the field. HMMs use dual stochastic processes to model higher-level hidden behavior using observable input sequences of events. We propose an interactive approach of mining interpretable HMMs, based on guiding a human expert in building a high quality HMM in an iterative, one state at a time, manner. The final result is a model that is both representative of the field data and captures the field phenomena of interest. We apply our HMM construction approach to study debugging behavior, using a large IDE interaction dataset collected from nearly 200 developers at ABB, Inc. Our results highlight the different modes and constituent actions in debugging, exhibited by the developers in our dataset.

Single ion channel signal of cell membrane is a stochastic ionic currents in the order of picoampere (pA). Because of the weakness of the signal, the background noise always dominates in the patch-clamp recordings. The threshold detector is traditionally used to eliminate noise and restore the single channel signal. However, this method cannot work satisfactorily when signal-to-noise ratio is lower. An approach based on hidden Markov model (HMM) is used to reconstruct ionic single-channel currents and estimate model parameters under white background noise. Firstly, ionic single-channel currents were depicted and analyzed by HMM. Then, an iterative algorithm of Baum-Welch was introduced to train HMM and estimate the model parameters. Finally, the ideal channel currents were reconstructed by Viterbi algorithm. Compared HMM with the threshold detection by computer simulating under different transition probabilities and signal-to-noise ratios, and the results have shown that the method performs effectively under the low signal-to-noise ratio (SNR<;5.0) and has fast model parameter convergence, high restoration precision and strong noise robustness.

In a communication using texts input, viseme (visual phonemes) is derived from a group of phonemes having similar visual appearances. Hidden Markov model (HMM) has been a popular mathematical approach for sequence classification such as speech recognition. For speech emotion recognition, a HMM is trained for each emotion and an unknown sample is classified according to the model which illustrate the derived feature sequence best. Viterbi algorithm, HMM is used for guessing the most possible state sequence of observable states. In this work, first stage, we defined system of an Indonesian viseme set and the associated mouth shapes, namely system of text input segmentation. The second stage, we defined a choice of one of affection type as input in the system. The last stage, we experimentally using Trigram HMMs for generating the viseme sequence to be used for synchronized mouth shape and lip movements. The whole system is interconnected in a sequence. The final system produced a viseme sequence for natural speech of Indonesian sentences with affection. We show through various experiments that the proposed, the results in about 82,19% relative improvement in classification accuracy.

The exponential growth and proliferation of wireless devices for different wireless applications have led to the emergence of cognitive radio network (CRN) for optimal utilization of scarce spectrum resources. However, these resources have grossly been under-utilized due to the inaccurate spectrum predictions. Existing spectrum occupancy and prediction techniques which rely on 2-state hidden Markov model (HMM) results in false alarm or missed detection caused by noisy or incomplete observable effects. In this paper, a 3-state HMM spectrum occupancy and prediction technique in CRNs is proposed. The transmission, emission and initial state probabilities of the proposed 3-state HMM parameters were derived based on the three canonical problems associated with HMM. The evaluation, decoding and learning problems were solved using Forward algorithm, Viterbi algorithm and the Baum-Welch algorithm, respectively. The performance of the proposed 3-state HMM spectrum prediction technique was evaluated using prediction accuracy, probability of detection and spectrum utilization efficiency. The simulation results obtained revealed that the 3-state HMM outperformed the 2-state HMM spectrum prediction technique by 24.1% in prediction accuracy.

Staphylococcus aureus is a common bacterial etiology of serious infectious diseases. S. aureus can invade various types of non-professional phagocytes to produce host cell death. We show here that shortly after invasion of HeLa cells S. aureus transit to autophagosomes was characterized by double membranes and co-localization with LC3. S. aureus were not able to replicate and produce cell death in autophagy-deficient atg5-/- mouse embryonic fibroblasts. S. aureus-containing autophagosomes do not acidify nor do they acquire lysosome-associated membrane protein-2, indicating that S. aureus inhibits autophagosome maturation and fusion with lysosomes. Eventually, S. aureus escape from autophagosomes into the cytoplasm, which results in caspase-independent host cell death. S. aureus strains deficient for agr, a global regulator of S. aureus virulence, were not targeted by autophagy and did not produce host-cell death. Autophagy induction by rapamycin restored both replication and cytotoxicity of agr-deficient S. aureus strains, indicating that an agr-regulated factor(s) is required for autophagy-mediated cytotoxicity. The results of this study suggest that rapid induction of autophagy is essential for S. aureus replication, escape into the cytoplasm, and host cell killing.