Custom Hidden Markov Models (HMM) for methylmercury detoxification genes merA and merB.
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ORGANISM(S): metagenome
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PROVIDER: S-BSST1154 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Existing methods for the prediction of immunologically active T-cell epitopes are based on the amino acid sequence or structure of pathogen proteins. Additional information regarding the locations of epitopes may be acquired by considering the evolution of viruses in hosts with different immune backgrounds. In particular, immune-dependent evolutionary patterns at sites within or near T-cell epitopes can be used to enhance epitope identification. We have developed a mutation-selection model of T-cell epitope evolution that allows the human leukocyte antigen (HLA) genotype of the host to influence the evolutionary process. This is one of the first examples of the incorporation of environmental parameters into a phylogenetic model and has many other potential applications where the selection pressures exerted on an organism can be related directly to environmental factors. We combine this novel evolutionary model with a hidden Markov model to identify contiguous amino acid positions that appear to evolve under immune pressure in the presence of specific host immune alleles and that therefore represent potential epitopes. This phylogenetic hidden Markov model provides a rigorous probabilistic framework that can be combined with sequence or structural information to improve epitope prediction. As a demonstration, we apply the model to a data set of HIV-1 protein-coding sequences and host HLA genotypes.
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Project description:One major challenge in the emerging field of movement ecology is the inference of behavioural modes from movement patterns. This has been mainly addressed through Hidden Markov models (HMMs). We propose here to evaluate two sets of alternative and state-of-the-art modelling approaches. First, we consider hidden semi-Markov models (HSMMs). They may better represent the behavioural dynamics of foragers since they explicitly model the duration of the behavioural modes. Second, we consider discriminative models which state the inference of behavioural modes as a classification issue, and may take better advantage of multivariate and non linear combinations of movement pattern descriptors. For this work, we use a dataset of >200 trips from human foragers, Peruvian fishermen targeting anchovy. Their movements were recorded through a Vessel Monitoring System (∼1 record per hour), while their behavioural modes (fishing, searching and cruising) were reported by on-board observers. We compare the efficiency of hidden Markov, hidden semi-Markov, and three discriminative models (random forests, artificial neural networks and support vector machines) for inferring the fishermen behavioural modes, using a cross-validation procedure. HSMMs show the highest accuracy (80%), significantly outperforming HMMs and discriminative models. Simulations show that data with higher temporal resolution, HSMMs reach nearly 100% of accuracy. Our results demonstrate to what extent the sequential nature of movement is critical for accurately inferring behavioural modes from a trajectory and we strongly recommend the use of HSMMs for such purpose. In addition, this work opens perspectives on the use of hybrid HSMM-discriminative models, where a discriminative setting for the observation process of HSMMs could greatly improve inference performance.
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Project description:The DNA of most vertebrates is depleted in CpG dinucleotide: a C followed by a G in the 5' to 3' direction. CpGs are the target for DNA methylation, a chemical modification of cytosine (C) heritable during cell division and the most well-characterized epigenetic mechanism. The remaining CpGs tend to cluster in regions referred to as CpG islands (CGI). Knowing CGI locations is important because they mark functionally relevant epigenetic loci in development and disease. For various mammals, including human, a readily available and widely used list of CGI is available from the UCSC Genome Browser. This list was derived using algorithms that search for regions satisfying a definition of CGI proposed by Gardiner-Garden and Frommer more than 20 years ago. Recent findings, enabled by advances in technology that permit direct measurement of epigenetic endpoints at a whole-genome scale, motivate the need to adapt the current CGI definition. In this paper, we propose a procedure, guided by hidden Markov models, that permits an extensible approach to detecting CGI. The main advantage of our approach over others is that it summarizes the evidence for CGI status as probability scores. This provides flexibility in the definition of a CGI and facilitates the creation of CGI lists for other species. The utility of this approach is demonstrated by generating the first CGI lists for invertebrates, and the fact that we can create CGI lists that substantially increases overlap with recently discovered epigenetic marks. A CGI list and the probability scores, as a function of genome location, for each species are available at http://www.rafalab.org.
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Project description:BackgroundRiboswitches are a type of noncoding RNA that regulate gene expression by switching from one structural conformation to another on ligand binding. The various classes of riboswitches discovered so far are differentiated by the ligand, which on binding induces a conformational switch. Every class of riboswitch is characterized by an aptamer domain, which provides the site for ligand binding, and an expression platform that undergoes conformational change on ligand binding. The sequence and structure of the aptamer domain is highly conserved in riboswitches belonging to the same class. We propose a method for fast and accurate identification of riboswitches using profile Hidden Markov Models (pHMM). Our method exploits the high degree of sequence conservation that characterizes the aptamer domain.ResultsOur method can detect riboswitches in genomic databases rapidly and accurately. Its sensitivity is comparable to the method based on the Covariance Model (CM). For six out of ten riboswitch classes, our method detects more than 99.5% of the candidates identified by the much slower CM method while being several hundred times faster. For three riboswitch classes, our method detects 97-99% of the candidates relative to the CM method. Our method works very well for those classes of riboswitches that are characterized by distinct and conserved sequence motifs.ConclusionRiboswitches play a crucial role in controlling the expression of several prokaryotic genes involved in metabolism and transport processes. As more and more new classes of riboswitches are being discovered, it is important to understand the patterns of their intra and inter genomic distribution. Understanding such patterns will enable us to better understand the evolutionary history of these genetic regulatory elements. However, a complete picture of the distribution pattern of riboswitches will emerge only after accurate identification of riboswitches across genomes. We believe that the riboswitch detection method developed in this paper will aid in that process. The significant advantage in terms of speed, of our pHMM-based approach over the method based on CM allows us to scan entire databases (rather than 5'UTRs only) in a relatively short period of time in order to accurately identify riboswitch candidates.
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Project description:Adaptive introgression-the flow of adaptive genetic variation between species or populations-has attracted significant interest in recent years and it has been implicated in a number of cases of adaptation, from pesticide resistance and immunity, to local adaptation. Despite this, methods for identification of adaptive introgression from population genomic data are lacking. Here, we present Ancestry_HMM-S, a hidden Markov model-based method for identifying genes undergoing adaptive introgression and quantifying the strength of selection acting on them. Through extensive validation, we show that this method performs well on moderately sized data sets for realistic population and selection parameters. We apply Ancestry_HMM-S to a data set of an admixed Drosophila melanogaster population from South Africa and we identify 17 loci which show signatures of adaptive introgression, four of which have previously been shown to confer resistance to insecticides. Ancestry_HMM-S provides a powerful method for inferring adaptive introgression in data sets that are typically collected when studying admixed populations. This method will enable powerful insights into the genetic consequences of admixture across diverse populations. Ancestry_HMM-S can be downloaded from https://github.com/jesvedberg/Ancestry_HMM-S/.
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Project description:BackgroundA computational method (called p53HMM) is presented that utilizes Profile Hidden Markov Models (PHMMs) to estimate the relative binding affinities of putative p53 response elements (REs), both p53 single-sites and cluster-sites. These models incorporate a novel "Corresponded Baum-Welch" training algorithm that provides increased predictive power by exploiting the redundancy of information found in the repeated, palindromic p53-binding motif. The predictive accuracy of these new models are compared against other predictive models, including position specific score matrices (PSSMs, or weight matrices). We also present a new dynamic acceptance threshold, dependent upon a putative binding site's distance from the Transcription Start Site (TSS) and its estimated binding affinity. This new criteria for classifying putative p53-binding sites increases predictive accuracy by reducing the false positive rate.ResultsTraining a Profile Hidden Markov Model with corresponding positions matching a combined-palindromic p53-binding motif creates the best p53-RE predictive model. The p53HMM algorithm is available on-line: (http://tools.csb.ias.edu).ConclusionUsing Profile Hidden Markov Models with training methods that exploit the redundant information of the homotetramer p53 binding site provides better predictive models than weight matrices (PSSMs). These methods may also boost performance when applied to other transcription factor binding sites.
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Project description:Protein families are often represented by profile hidden Markov models (pHMMs). Homology between two distant protein families can be determined by comparing the pHMMs. Here we explored the idea of building a phylogeny of protein families using the distance matrix of their pHMMs. We developed a new software and web server (pHMM-tree) to allow four major types of inputs: (i) multiple pHMM files, (ii) multiple aligned protein sequence files, (iii) mixture of pHMM and aligned sequence files and (iv) unaligned protein sequences in a single file. The output will be a pHMM phylogeny of different protein families delineating their relationships. We have applied pHMM-tree to build phylogenies for CAZyme (carbohydrate active enzyme) classes and Pfam clans, which attested its usefulness in the phylogenetic representation of the evolutionary relationship among distant protein families.This software is implemented in C/C?++?and is available at http://cys.bios.niu.edu/pHMM-Tree/source/.zhanghan@nankai.edu.cn or yyin@niu.edu.Supplementary data are available at Bioinformatics online.
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