A wide range of researchers record physiological signals over time. These signals contain dynamic information about important biological processes, a deeper understanding of which is essential for advancing preventions, diagnoses and treatments of disease. The complex nature of physiological time series signals, which are inher- ently nonstationary and where biological interest often lies in oscillatory patterns, presents challenges for their analysis. These challenges are exacerbated in modern studies, where researchers often record a large number of signals simultaneously. Simultaneous analyses of such data that take into account cross-signal relations is essential to obtaining a comprehensive understanding of complex biological pathways. Researchers' ability to fully utilize the information contained in these data is currently hindered by a dearth of formal statistical methods for the spectral analysis of high-dimensional nonstationary time series under modern study designs. The broad goal of this research is to develop a framework of scalable methods for the adaptive spectral analysis of non- stationary high-dimensional time series. The framework will introduce a novel spectral domain factor structure to overcome the high-dimensionality of the data and will be formulated in a Bayesian framework that can ?exibly adapt to the dynamics of the data. Speci?c aims will establish three aspects within this framework: (1) estimation and inference for a high-dimensional time-varying power spectrum, (2) analysis of associations between high- dimensional time-varying power spectra and biological covariates, and (3) using high-dimensional time-varying spectra to predict future events. For each aspect, we will formulate a novel model and explore its properties, create a sampling scheme for estimation and inference using advanced Monte Carlo techniques, develop user friendly software, and compare empirical performance to that of existing approaches in simulation and validation studies. The framework will be used to analyze data from three studies: an observational study of signals col- lected across systemic physiological systems in critical care patients, a study of nocturnal high-density EEG, and a study of physiological systems involved in regulating locomotion.

Public Health Relevance

The proposed work will present the ?rst comprehensive set of formal statistical methods for the spectral analysis of collections of high-dimensional nonstationary time series from modern studies. These methods can provide a powerful tool for unlocking previously inaccessible dynamic physiological information, which can lay the foundation for advances in the prevention, diagnosis and treatment of a wide range of diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM113243-05
Application #
9593830
Study Section
Biostatistical Methods and Research Design Study Section (BMRD)
Program Officer
Brazhnik, Paul
Project Start
2014-08-10
Project End
2021-05-31
Budget Start
2018-08-01
Budget End
2019-05-31
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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