Dataset Information

Statistical Learning with Time Series Dependence: An Application to Scoring Sleep in Mice.

ABSTRACT: We develop methodology which combines statistical learning methods with generalized Markov models, thereby enhancing the former to account for time series dependence. Our methodology can accommodate very general and very long-term time dependence structures in an easily estimable and computationally tractable fashion. We apply our methodology to the scoring of sleep behavior in mice. As currently used methods are expensive, invasive, and labor intensive, there is considerable interest in high-throughput automated systems which would allow many mice to be scored cheaply and quickly. Previous efforts have been able to differentiate sleep from wakefulness, but they are unable to differentiate the rare and important state of REM sleep from non-REM sleep. Key difficulties in detecting REM are that (i) REM is much rarer than non-REM and wakefulness, (ii) REM looks similar to non-REM in terms of the observed covariates, (iii) the data are noisy, and (iv) the data contain strong time dependence structures crucial for differentiating REM from non-REM. Our new approach (i) shows improved differentiation of REM from non-REM sleep and (ii) accurately estimates aggregate quantities of sleep in our application to video-based sleep scoring of mice.

SUBMITTER: McShane BB

PROVIDER: S-EPMC3913289 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Statistical Learning with Time Series Dependence: An Application to Scoring Sleep in Mice.

McShane Blakeley B BB Jensen Shane T ST Pack Allan I AI Wyner Abraham J AJ

Journal of the American Statistical Association 20130101 504

We develop methodology which combines statistical learning methods with generalized Markov models, thereby enhancing the former to account for time series dependence. Our methodology can accommodate very general and very long-term time dependence structures in an easily estimable and computationally tractable fashion. We apply our methodology to the scoring of sleep behavior in mice. As currently used methods are expensive, invasive, and labor intensive, there is considerable interest in high-th ...[more]

PMID: 24504359

Similar Datasets

Project description:BackgroundComparing metabolic profiles under different biological perturbations has become a powerful approach to investigating the functioning of cells. The profiles can be taken as single snapshots of a system, but more information is gained if they are measured longitudinally over time. The results are short time series consisting of relatively sparse data that cannot be analyzed effectively with standard time series techniques, such as autocorrelation and frequency domain methods. In this work, we study longitudinal time series profiles of glucose consumption in the yeast Saccharomyces cerevisiae under different temperatures and preconditioning regimens, which we obtained with methods of in vivo nuclear magnetic resonance (NMR) spectroscopy. For the statistical analysis we first fit several nonlinear mixed effect regression models to the longitudinal profiles and then used an ANOVA likelihood ratio method in order to test for significant differences between the profiles.ResultsThe proposed methods are capable of distinguishing metabolic time trends resulting from different treatments and associate significance levels to these differences. Among several nonlinear mixed-effects regression models tested, a three-parameter logistic function represents the data with highest accuracy. ANOVA and likelihood ratio tests suggest that there are significant differences between the glucose consumption rate profiles for cells that had been--or had not been--preconditioned by heat during growth. Furthermore, pair-wise t-tests reveal significant differences in the longitudinal profiles for glucose consumption rates between optimal conditions and heat stress, optimal and recovery conditions, and heat stress and recovery conditions (p-values <0.0001).ConclusionWe have developed a nonlinear mixed effects model that is appropriate for the analysis of sparse metabolic and physiological time profiles. The model permits sound statistical inference procedures, based on ANOVA likelihood ratio tests, for testing the significance of differences between short time course data under different biological perturbations.

Project description:In the recent JAVELIN Bladder 100 phase 3 trial, avelumab plus best supportive care significantly prolonged overall survival relative to best supportive care alone as first-line maintenance therapy following first-line platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). Discovering biomarkers using genomic profiling to understand potential patient heterogeneity is essential to help improve patient care with precision medicine. For the JAVELIN Bladder 100 trial, it is unclear which variable selection methods can most reliably identify biomarkers to inform patient care because the dataset is characterized by high collinearity and low signal. The aim of this paper was to evaluate available selection methods and their ability to discover prognostic and predictive biomarkers in patients with aUC receiving first-line maintenance therapy. A simulation study evaluated the performance of popular variable selection approaches for high-dimensional data, including penalized regression models, random survival forests, and Bayesian variable selection methods. For Bayesian variable selection methods, a modified Bayesian Information Criterion (BIC) thresholding rule was proposed in addition to the traditional BIC thresholding rule. These methods were applied to the JAVELIN Bladder 100 dataset to investigate potential biomarkers associated with survival benefit. Results from the simulations demonstrated the strengths and limitations of the different methods. The variable selection methods demonstrated low false discovery rates under different conditions. However, their performance declined in the presence of high collinearity. Using the JAVELIN Bladder 100 data, we identified some potentially significant biomarkers across multiple models. Several lasso-related methods were able to identify potentially biologically meaningful variables in the trial. Some variable selection methods (such as stochastic search variable selection and random survival forest) may not be well suited to this type of data due to the presence of extreme collinearity and low signal. Future research should explore novel variable selection methods that may be more suitable for identifying prognostic and predictive biomarkers in this population.Trial registration: ClinicalTrials.gov Identifier: NCT02603432.

Dataset Information

Statistical Learning with Time Series Dependence: An Application to Scoring Sleep in Mice.

Publications

Statistical Learning with Time Series Dependence: An Application to Scoring Sleep in Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets