Modelling state-transition dynamics in resting-state brain signals by the hidden Markov and Gaussian mixture models.
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ABSTRACT:
SUBMITTER: Ezaki T
PROVIDER: S-EPMC9291560 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA key element in the interaction between clinicians and patients with cancer is reassurance giving. Learning about the stochastic nature of reassurances as well as making inferential statements about the influence of covariates such as patient response and time spent on previous reassurances are of particular importance.MethodsWe fit Hidden Markov Models (HMMs) to reassurance type from multiple time series of clinicians' reassurances, decoded from audio files of review consultations between patients with breast cancer and their therapeutic radiographer. Assuming a latent state process driving the observations process, HMMs naturally accommodate serial dependence in the data. Extensions to the baseline model such as including covariates as well as allowing for fixed effects for the different clinicians are straightforward to implement.ResultsWe found that clinicians undergo different states, in which they are more or less inclined to provide a particular type of reassurance. The states are very persistent, however switches occasionally occur. The lengthier the previous reassurance, the more likely the clinician is to stay in the current state.ConclusionsHMMs prove to be a valuable tool and provide important insights for practitioners.Trial registrationTrial Registration number: ClinicalTrials.gov: NCT02599506. Prospectively registered on 11th March 2015.
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Project description:Ecological systems can often be characterised by changes among a finite set of underlying states pertaining to individuals, populations, communities or entire ecosystems through time. Owing to the inherent difficulty of empirical field studies, ecological state dynamics operating at any level of this hierarchy can often be unobservable or 'hidden'. Ecologists must therefore often contend with incomplete or indirect observations that are somehow related to these underlying processes. By formally disentangling state and observation processes based on simple yet powerful mathematical properties that can be used to describe many ecological phenomena, hidden Markov models (HMMs) can facilitate inferences about complex system state dynamics that might otherwise be intractable. However, HMMs have only recently begun to gain traction within the broader ecological community. We provide a gentle introduction to HMMs, establish some common terminology, review the immense scope of HMMs for applied ecological research and provide a tutorial on implementation and interpretation. By illustrating how practitioners can use a simple conceptual template to customise HMMs for their specific systems of interest, revealing methodological links between existing applications, and highlighting some practical considerations and limitations of these approaches, our goal is to help establish HMMs as a fundamental inferential tool for ecologists.
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Project description:The dendritic spines play a crucial role in learning and memory processes, epileptogenesis, drug addiction, and postinjury recovery. The shape of the dendritic spine is a morphological key to understand learning and memory process. The classification of the dendritic spines is based on their shapes but the major questions are how the shapes changes in time, how the synaptic strength changes, and is there a correlation between shapes and synaptic strength? Because the changes of the classes by dendritic spines during activation are time dependent, the forward-directed autoregressive hidden Markov model (ARHMM) can be used to model these changes. It is also more appropriate to use an ARHMM directed backward in time. Thus, the mixture of forward-directed ARHMM and backward-directed ARHMM (MARHMM) is used to model time-dependent data related to the dendritic spines. In this article, we discuss (1) how to choose the initial probability vector and transition and dependence matrices in ARHMM and MARHMM for modeling the dendritic spines changes and (2) how to estimate these matrices. Many descriptors to classify dendritic spines in two-dimensional or/and three-dimensional (3D) are available. Our results from sensitivity analysis show that the classification that comes from 3D descriptors is closer to the truth, and estimated transition and dependence probability matrices are connected with the molecular mechanism of the dendritic spines activation.
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Project description:The shape of extracellularly recorded action potentials is a product of several variables, such as the biophysical and anatomical properties of the neuron and the relative position of the electrode. This allows isolating spikes of different neurons recorded in the same channel into clusters based on waveform features. However, correctly classifying spike waveforms into their underlying neuronal sources remains a challenge. This process, called spike sorting, typically consists of two steps: (1) extracting relevant waveform features (e.g., height, width), and (2) clustering them into non-overlapping groups believed to correspond to different neurons. In this study, we explored the performance of Gaussian mixture models (GMMs) in these two steps. We extracted relevant features using a combination of common techniques (e.g., principal components, wavelets) and GMM fitting parameters (e.g., Gaussian distances). Then, we developed an approach to perform unsupervised clustering using GMMs, estimating cluster properties in a data-driven way. We found the proposed GMM-based framework outperforms previously established methods in simulated and real extracellular recordings. We also discuss potentially better techniques for feature extraction than the widely used principal components. Finally, we provide a friendly graphical user interface to run our algorithm, which allows manual adjustments.
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Project description:In healthcare, the analysis of patients' activities is one of the important factors that offer adequate information to provide better services for managing their illnesses well. Most of the human activity recognition (HAR) systems are completely reliant on recognition module/stage. The inspiration behind the recognition stage is the lack of enhancement in the learning method. In this study, we have proposed the usage of the hidden conditional random fields (HCRFs) for the human activity recognition problem. Moreover, we contend that the existing HCRF model is inadequate by independence assumptions, which may reduce classification accuracy. Therefore, we utilized a new algorithm to relax the assumption, allowing our model to use full-covariance distribution. Also, in this work, we proved that computation wise our method has very much lower complexity against the existing methods. For the experiments, we used four publicly available standard datasets to show the performance. We utilized a 10-fold cross-validation scheme to train, assess, and compare the proposed model with the conditional learning method, hidden Markov model (HMM), and existing HCRF model which can only use diagonal-covariance Gaussian distributions. From the experiments, it is obvious that the proposed model showed a substantial improvement with p value ?0.2 regarding the classification accuracy.
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Project description:The discovery of drug-like molecules that bind pockets in proteins that are not present in crystallographic structures yet exert allosteric control over activity has generated great interest in designing pharmaceuticals that exploit allosteric effects. However, there have only been a small number of successes, so the therapeutic potential of these pockets--called hidden allosteric sites--remains unclear. One challenge for assessing their utility is that rational drug design approaches require foreknowledge of the target site, but most hidden allosteric sites are only discovered when a small molecule is found to stabilize them. We present a means of decoupling the identification of hidden allosteric sites from the discovery of drugs that bind them by drawing on new developments in Markov state modeling that provide unprecedented access to microsecond- to millisecond-timescale fluctuations of a protein's structure. Visualizing these fluctuations allows us to identify potential hidden allosteric sites, which we then test via thiol labeling experiments. Application of these methods reveals multiple hidden allosteric sites in an important antibiotic target--TEM-1 ?-lactamase. This result supports the hypothesis that there are many as yet undiscovered hidden allosteric sites and suggests our methodology can identify such sites, providing a starting point for future drug design efforts. More generally, our results demonstrate the power of using Markov state models to guide experiments.
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Project description:The study of functional brain networks has grown rapidly over the past decade. While most functional connectivity (FC) analyses estimate one static network structure for the entire length of the functional magnetic resonance imaging (fMRI) time series, recently there has been increased interest in studying time-varying changes in FC. Hidden Markov models (HMMs) have proven to be a useful modeling approach for discovering repeating graphs of interacting brain regions (brain states). However, a limitation lies in HMMs assuming that the sojourn time, the number of consecutive time points in a state, is geometrically distributed. This may encourage inaccurate estimation of the time spent in a state before switching to another state. We propose a hidden semi-Markov model (HSMM) approach for inferring time-varying brain networks from fMRI data, which explicitly models the sojourn distribution. Specifically, we propose using HSMMs to find each subject's most probable series of network states and the graphs associated with each state, while properly estimating and modeling the sojourn distribution for each state. We perform a simulation study, as well as an analysis on both task-based fMRI data from an anxiety-inducing experiment and resting-state fMRI data from the Human Connectome Project. Our results demonstrate the importance of model choice when estimating sojourn times and reveal their potential for understanding healthy and diseased brain mechanisms.
| S-EPMC6504179 | biostudies-literature
Project description:Empirical codon models (ECMs) estimated from a large number of globular protein families outperformed mechanistic codon models in their description of the general process of protein evolution. Among other factors, ECMs implicitly model the influence of amino acid properties and multiple nucleotide substitutions (MNS). However, the estimation of ECMs requires large quantities of data, and until recently, only few suitable data sets were available. Here, we take advantage of several new Drosophila species genomes to estimate codon models from genome-wide data. The availability of large numbers of genomes over varying phylogenetic depths in the Drosophila genus allows us to explore various divergence levels. In consequence, we can use these data to determine the appropriate level of divergence for the estimation of ECMs, avoiding overestimation of MNS rates caused by saturation. To account for variation in evolutionary rates along the genome, we develop new empirical codon hidden Markov models (ecHMMs). These models significantly outperform previous ones with respect to maximum likelihood values, suggesting that they provide a better fit to the evolutionary process. Using ECMs and ecHMMs derived from genome-wide data sets, we devise new likelihood ratio tests (LRTs) of positive selection. We found classical LRTs very sensitive to the presence of MNSs, showing high false-positive rates, especially with small phylogenies. The new LRTs are more conservative than the classical ones, having acceptable false-positive rates and reduced power.
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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:BackgroundBioinformatics investigators often gain insights by combining information across multiple and disparate data sets. Merging data from multiple sources frequently results in data sets that are incomplete or contain missing values. Although missing data are ubiquitous, existing implementations of Gaussian mixture models (GMMs) either cannot accommodate missing data, or do so by imposing simplifying assumptions that limit the applicability of the model. In the presence of missing data, a standard ad hoc practice is to perform complete case analysis or imputation prior to model fitting. Both approaches have serious drawbacks, potentially resulting in biased and unstable parameter estimates.ResultsHere we present missingness-aware Gaussian mixture models (MGMM), an R package for fitting GMMs in the presence of missing data. Unlike existing GMM implementations that can accommodate missing data, MGMM places no restrictions on the form of the covariance matrix. Using three case studies on real and simulated 'omics data sets, we demonstrate that, when the underlying data distribution is near-to a GMM, MGMM is more effective at recovering the true cluster assignments than either the existing GMM implementations that accommodate missing data, or fitting a standard GMM after state of the art imputation. Moreover, MGMM provides an accurate assessment of cluster assignment uncertainty, even when the generative distribution is not a GMM.ConclusionCompared to state-of-the-art competitors, MGMM demonstrates a better ability to recover the true cluster assignments for a wide variety of data sets and a large range of missingness rates. MGMM provides the bioinformatics community with a powerful, easy-to-use, and statistically sound tool for performing clustering and density estimation in the presence of missing data. MGMM is publicly available as an R package on CRAN: https://CRAN.R-project.org/package=MGMM .
| S-EPMC9158227 | biostudies-literature