A Hidden Markov Factor Analysis Framework for Seizure Detection in Epilepsy Patients

Approximately 1% of the world population suffers from epilepsy. Continuous long-term electroencephalographic (EEG) monitoring is the gold-standard for recording epileptic seizures and assisting in the diagnosis and treatment of patients with epilepsy. Detection of seizure from the recorded EEG is a laborious, time consuming and expensive task. In this study, we propose an automated seizure detection framework to assist electroencephalographers and physicians with identification of seizures in recorded EEG signals. In addition, an automated seizure detection algorithm can be used for treatment through automatic intervention during the seizure activity and on time triggering of the injection of a radiotracer to localize the seizure activity. In this study, we developed and tested a hidden Markov factor analysis (HMFA) framework for automated seizure detection based on different features such as total effective inflow which is calculated based on connectivity measures between different sites of the brain. The algorithm was tested on long-term (2.4-7.66 days) continuous sEEG recordings from three patients and a total of 16 seizures, producing a mean sensitivity of 96.3% across all seizures, a mean specificity of 3.47 false positives per hour, and a mean latency of 3.7 seconds form the actual seizure onset. The latency was negative for a few of the seizures which implies the proposed method detects the seizure prior to its onset. This is an indication that with some extension the proposed method is capable of seizure prediction

Hidden Markov Models for Gene Sequence Classification: Classifying the VSG genes in the Trypanosoma brucei Genome

The article presents an application of Hidden Markov Models (HMMs) for pattern recognition on genome sequences. We apply HMM for identifying genes encoding the Variant Surface Glycoprotein (VSG) in the genomes of Trypanosoma brucei (T. brucei) and other African trypanosomes. These are parasitic protozoa causative agents of sleeping sickness and several diseases in domestic and wild animals. These parasites have a peculiar strategy to evade the host's immune system that consists in periodically changing their predominant cellular surface protein (VSG). The motivation for using patterns recognition methods to identify these genes, instead of traditional homology based ones, is that the levels of sequence identity (amino acid and DNA sequence) amongst these genes is often below of what is considered reliable in these methods. Among pattern recognition approaches, HMM are particularly suitable to tackle this problem because they can handle more naturally the determination of gene edges. We evaluate the performance of the model using different number of states in the Markov model, as well as several performance metrics. The model is applied using public genomic data. Our empirical results show that the VSG genes on T. brucei can be safely identified (high sensitivity and low rate of false positives) using HMM.Comment: Accepted article in July, 2015 in Pattern Analysis and Applications, Springer. The article contains 23 pages, 4 figures, 8 tables and 51 reference

Revealing ensemble state transition patterns in multi-electrode neuronal recordings using hidden Markov models

In order to harness the computational capacity of dissociated cultured neuronal networks, it is necessary to understand neuronal dynamics and connectivity on a mesoscopic scale. To this end, this paper uncovers dynamic spatiotemporal patterns emerging from electrically stimulated neuronal cultures using hidden Markov models (HMMs) to characterize multi-channel spike trains as a progression of patterns of underlying states of neuronal activity. However, experimentation aimed at optimal choice of parameters for such models is essential and results are reported in detail. Results derived from ensemble neuronal data revealed highly repeatable patterns of state transitions in the order of milliseconds in response to probing stimuli

A stochastic model dissects cell states in biological transition processes

Many biological processes, including differentiation, reprogramming, and disease transformations, involve transitions of cells through distinct states. Direct, unbiased investigation of cell states and their transitions is challenging due to several factors, including limitations of single-cell assays. Here we present a stochastic model of cellular transitions that allows underlying single-cell information, including cell-state-specific parameters and rates governing transitions between states, to be estimated from genome-wide, population-averaged time-course data. The key novelty of our approach lies in specifying latent stochastic models at the single-cell level, and then aggregating these models to give a likelihood that links parameters at the single-cell level to observables at the population level. We apply our approach in the context of reprogramming to pluripotency. This yields new insights, including profiles of two intermediate cell states, that are supported by independent single-cell studies. Our model provides a general conceptual framework for the study of cell transitions, including epigenetic transformations

Prediction and Power in Molecular Sensors: Uncertainty and Dissipation When Conditionally Markovian Channels Are Driven by Semi-Markov Environments

Sensors often serve at least two purposes: predicting their input and minimizing dissipated heat. However, determining whether or not a particular sensor is evolved or designed to be accurate and efficient is difficult. This arises partly from the functional constraints being at cross purposes and partly since quantifying the predictive performance of even in silico sensors can require prohibitively long simulations. To circumvent these difficulties, we develop expressions for the predictive accuracy and thermodynamic costs of the broad class of conditionally Markovian sensors subject to unifilar hidden semi-Markov (memoryful) environmental inputs. Predictive metrics include the instantaneous memory and the mutual information between present sensor state and input future, while dissipative metrics include power consumption and the nonpredictive information rate. Success in deriving these formulae relies heavily on identifying the environment's causal states, the input's minimal sufficient statistics for prediction. Using these formulae, we study the simplest nontrivial biological sensor model---that of a Hill molecule, characterized by the number of ligands that bind simultaneously, the sensor's cooperativity. When energetic rewards are proportional to total predictable information, the closest cooperativity that optimizes the total energy budget generally depends on the environment's past hysteretically. In this way, the sensor gains robustness to environmental fluctuations. Given the simplicity of the Hill molecule, such hysteresis will likely be found in more complex predictive sensors as well. That is, adaptations that only locally optimize biochemical parameters for prediction and dissipation can lead to sensors that "remember" the past environment.Comment: 21 pages, 4 figures, http://csc.ucdavis.edu/~cmg/compmech/pubs/piness.ht

The Mathematics of Phylogenomics

The grand challenges in biology today are being shaped by powerful high-throughput technologies that have revealed the genomes of many organisms, global expression patterns of genes and detailed information about variation within populations. We are therefore able to ask, for the first time, fundamental questions about the evolution of genomes, the structure of genes and their regulation, and the connections between genotypes and phenotypes of individuals. The answers to these questions are all predicated on progress in a variety of computational, statistical, and mathematical fields. The rapid growth in the characterization of genomes has led to the advancement of a new discipline called Phylogenomics. This discipline results from the combination of two major fields in the life sciences: Genomics, i.e., the study of the function and structure of genes and genomes; and Molecular Phylogenetics, i.e., the study of the hierarchical evolutionary relationships among organisms and their genomes. The objective of this article is to offer mathematicians a first introduction to this emerging field, and to discuss specific mathematical problems and developments arising from phylogenomics.Comment: 41 pages, 4 figure

Hidden Semi Markov Models for Multiple Observation Sequences: The mhsmm Package for R

This paper describes the R package mhsmm which implements estimation and prediction methods for hidden Markov and semi-Markov models for multiple observation sequences. Such techniques are of interest when observed data is thought to be dependent on some unobserved (or hidden) state. Hidden Markov models only allow a geometrically distributed sojourn time in a given state, while hidden semi-Markov models extend this by allowing an arbitrary sojourn distribution. We demonstrate the software with simulation examples and an application involving the modelling of the ovarian cycle of dairy cows.