This thesis introduces new techniques for finding genes in genomic sequences. Genes are regions of a genome encoding proteins of an organism. Identification of genes in a genome is an important step in the annotation process after a new genome is sequenced. The prediction accuracy of gene finding can be greatly improved by using experimental evidence. This evidence includes homologies between the genome and databases of known proteins, or evolutionary conservation of genomic sequence in different species. <br /><br /> We propose a flexible framework to incorporate several different sources of such evidence into a gene finder based on a hidden Markov model. Various sources of evidence are expressed as partial probabilistic statements about the annotation of positions in the sequence, and these are combined with the hidden Markov model to obtain the final gene prediction. The opportunity to use partial statements allows us to handle missing information transparently and to cope with the heterogeneous character of individual sources of evidence. On the other hand, this feature makes the combination step more difficult. We present a new method for combining partial probabilistic statements and prove that it is an extension of existing methods for combining complete probability statements. We evaluate the performance of our system and its individual components on data from the human and fruit fly genomes. <br /><br /> The use of sequence evolutionary conservation as a source of evidence in gene finding requires efficient and sensitive tools for finding similar regions in very long sequences. We present a method for improving the sensitivity of existing tools for this task by careful modeling of sequence properties. In particular, we build a hidden Markov model representing a typical homology between two protein coding regions and then use this model to optimize a component of a heuristic algorithm called a spaced seed. The seeds that we discover significantly improve the accuracy and running time of similarity search in protein coding regions, and are directly applicable to our gene finder.

In many complex water supply systems, the next generation of water resources planning models will require simultaneous probabilistic streamflow inputs at multiple locations on an interconnected network. To make use of the valuable multicentury records provided by tree-ring data, reconstruction models must be able to produce appropriate multisite inputs. Existing streamflow reconstruction models typically focus on one site at a time, not addressing intersite dependencies and potentially misrepresenting uncertainty. To this end, we develop a model for multisite streamflow reconstruction with the ability to capture intersite correlations. The proposed model is a hierarchical Bayesian nonhomogeneous hidden Markov model (NHMM). A NHMM is fit to contemporary streamflow at each location using lognormal component distributions. Leading principal components of tree rings are used as covariates to model nonstationary transition probabilities and the parameters of the lognormal component distributions. Spatial dependence between sites is captured with a Gaussian elliptical copula. Parameters of the model are estimated in a fully Bayesian framework, in that marginal posterior distributions of all the parameters are obtained. The model is applied to reconstruct flows at 20 sites in the Upper Colorado River Basin (UCRB) from 1473 to 1906. Many previous reconstructions are available for this basin, making it ideal for testing this new method. The results show some improvements over regression-based methods in terms of validation statistics. Key advantages of the Bayesian NHMM over traditional approaches are a dynamic representation of uncertainty and the ability to make long multisite simulations that capture at-site statistics and spatial correlations between sites.

Using a generalized-clique hidden Markov model (HMM) as the starting point for a eukaryotic gene finder, the objective here is to strengthen the signal information at the transitions between coding and non-coding (c/nc) regions. This is done by enlarging the primitive hidden states associated with individual base labeling (as exon, intron, or junk) to substrings of primitive hidden states or footprint states. Moreover, the allowed footprint transitions are restricted to those that include either one c/nc transition or none at all. (This effectively imposes a minimum length on exons and the other regions.) These footprint states allow the c/nc transitions to be seen sooner and have their contributions to the gene-structure identification weighted more heavily – yet contributing as such with a natural weighting determined by the HMM model itself according to the training data – rather than via introducing an artificial gain-parameter tuning on major transitions. The selection of the generalized HMM model is interpolated to highest Markov order on emission probabilities, and to highest Markov order (subsequence length) on the footprint states. The former is accomplished via simple count cutoff rules, the latter via an identification of anomalous base statistics near the major transitions using Shannon entropy. Preliminary indications, from applications to the C. elegans genome, are that the sensitivity/specificity (SN/SP) result for both the individual state and full exon predictions are greatly enhanced using the generalized-clique HMM when compared to the standard HMM. Here the standard HMM is represented by the choice of the smallest size of footprint state in the generalized-clique HMM. Even with these improvements, we observe that both extremely long and short exon and intron segments would go undetected without an explicit model of the duration of state. The key contributions of this effort are the full derivation and experimental confirmation of a rudimentary, yet powerful and competitive gene finding method based on a higher order hidden Markov model. With suitable extensions, this method is expected to provide superior gene finding capability – not only in the context of pre-conditioned data sets as in the evaluations cited but also in the wider context of less preconditioned and/or raw genomic data.

<p>Genes coding for alpha-helical transmembrane proteins constitute roughly 25% of the total number of genes in a typical organism. As these proteins are vital parts of many biological processes, an improved understanding of them is important for achieving a better understanding of the mechanisms that constitute life.</p><p>All proteins consist of an amino acid sequence that fold into a three-dimensional structure in order to perform its biological function. The work presented in this thesis is directed towards improving the understanding of the relationship between sequence and structure for alpha-helical transmembrane proteins. Specifically, five original methods for predicting the topology of alpha-helical transmembrane proteins have been developed: PRO-TMHMM, PRODIV-TMHMM, OCTOPUS, Toppred III and SCAMPI. </p><p>A general conclusion from these studies is that approaches that use multiple sequence information achive the best prediction accuracy. Further, the properties of reentrant regions have been studied, both with respect to sequence and structure. One result of this study is an improved definition of the topological grammar of transmembrane proteins, which is used in OCTOPUS and shown to further improve topology prediction. Finally, Z-coordinates, an alternative system for representation of topological information for transmembrane proteins that is based on distance to the membrane center has been introduced, and a method for predicting Z-coordinates from amino acid sequence, Z-PRED, has been developed.</p>

Genes coding for alpha-helical transmembrane proteins constitute roughly 25% of the total number of genes in a typical organism. As these proteins are vital parts of many biological processes, an improved understanding of them is important for achieving a better understanding of the mechanisms that constitute life. All proteins consist of an amino acid sequence that fold into a three-dimensional structure in order to perform its biological function. The work presented in this thesis is directed towards improving the understanding of the relationship between sequence and structure for alpha-helical transmembrane proteins. Specifically, five original methods for predicting the topology of alpha-helical transmembrane proteins have been developed: PRO-TMHMM, PRODIV-TMHMM, OCTOPUS, Toppred III and SCAMPI. A general conclusion from these studies is that approaches that use multiple sequence information achive the best prediction accuracy. Further, the properties of reentrant regions have been studied, both with respect to sequence and structure. One result of this study is an improved definition of the topological grammar of transmembrane proteins, which is used in OCTOPUS and shown to further improve topology prediction. Finally, Z-coordinates, an alternative system for representation of topological information for transmembrane proteins that is based on distance to the membrane center has been introduced, and a method for predicting Z-coordinates from amino acid sequence, Z-PRED, has been developed.

This paper presents a method for pedestrian activity classification and gait analysis based on the microelectromechanical-systems inertial measurement unit (IMU). The work targets two groups of applications, including the following: 1) human activity classification and 2) joint human activity and gait-phase classification. In the latter case, the gait phase is defined as a substate of a specific gait cycle, i.e., the states of the body between the stance and swing phases. We model the pedestrian motion with a continuous hidden Markov model (HMM) in which the output density functions are assumed to be Gaussian mixture models. For the joint activity and gait-phase classification, motivated by the cyclical nature of the IMU measurements, each individual activity is modeled by a "circular HMM." For both the proposed classification methods, proper feature vectors are extracted from the IMU measurements. In this paper, we report the results of conducted experiments where the IMU was mounted on the humans' chests. This permits the potential application of the current study in camera-aided inertial navigation for positioning and personal assistance for future research works. Five classes of activity, including walking, running, going upstairs, going downstairs, and standing, are considered in the experiments. The performance of the proposed methods is illustrated in various ways, and as an objective measure, the confusion matrix is computed and reported. The achieved relative figure of merits using the collected data validates the reliability of the proposed methods for the desired applications. / <p>QC 20130114</p>

No description available.

This thesis introduces new techniques for finding genes in genomic sequences. Genes are regions of a genome encoding proteins of an organism. Identification of genes in a genome is an important step in the annotation process after a new genome is sequenced. The prediction accuracy of gene finding can be greatly improved by using experimental evidence. This evidence includes homologies between the genome and databases of known proteins, or evolutionary conservation of genomic sequence in different species. <br /><br /> We propose a flexible framework to incorporate several different sources of such evidence into a gene finder based on a hidden Markov model. Various sources of evidence are expressed as partial probabilistic statements about the annotation of positions in the sequence, and these are combined with the hidden Markov model to obtain the final gene prediction. The opportunity to use partial statements allows us to handle missing information transparently and to cope with the heterogeneous character of individual sources of evidence. On the other hand, this feature makes the combination step more difficult. We present a new method for combining partial probabilistic statements and prove that it is an extension of existing methods for combining complete probability statements. We evaluate the performance of our system and its individual components on data from the human and fruit fly genomes. <br /><br /> The use of sequence evolutionary conservation as a source of evidence in gene finding requires efficient and sensitive tools for finding similar regions in very long sequences. We present a method for improving the sensitivity of existing tools for this task by careful modeling of sequence properties. In particular, we build a hidden Markov model representing a typical homology between two protein coding regions and then use this model to optimize a component of a heuristic algorithm called a spaced seed. The seeds that we discover significantly improve the accuracy and running time of similarity search in protein coding regions, and are directly applicable to our gene finder.

In this thesis, a Mandarin toponym speech recognition system is developed using MFCC, LPC and HMM under Red Hat Linux 9.0. The system is based on monosyllable HMM's to select the initial toponym candidates, and its final classification result can be obtained by further pitch identification mechanisms. For speaker-dependent case, a 90% correct rate can be achieved approximately and the recognition process can be accomplished within 1.5 seconds on the average.

No description available.