Statistical Methodology Commons^™

A Statistical Framework For The Analysis Of Chip-Seq Data, Pei Fen Kuan, Dongjun Chung, Guangjin Pan, James A. Thomson, Ron Stewart, Sunduz Keles

Sunduz Keles

Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) has revolutionalized experiments for genome-wide profiling of DNA-binding proteins, histone modifications, and nucleosome occupancy. As the cost of sequencing is decreasing, many researchers are switching from microarray-based technologies (ChIP-chip) to ChIP-Seq for genome-wide study of transcriptional regulation. Despite its increasing and well-deserved popularity, there is little work that investigates and accounts for sources of biases in the ChIP-Seq technology. These biases typically arise from both the standard pre-processing protocol and the underlying DNA sequence of the generated data.

We study data from a naked DNA sequencing experiment, which sequences non-cross-linked DNA after deproteinizing and …

Multilevel Functional Principal Component Analysis, Chong-Zhi Di, Ciprian M. Crainiceanu, Brian S. Caffo, Naresh M. Punjabi

Chongzhi Di

The Sleep Heart Health Study (SHHS) is a comprehensive landmark study of sleep and its impacts on health outcomes. A primary metric of the SHHS is the in-home polysomnogram, which includes two electroencephalographic (EEG) channels for each subject, at two visits. The volume and importance of this data presents enormous challenges for analysis. To address these challenges, we introduce multilevel functional principal component analysis (MFPCA), a novel statistical methodology designed to extract core intra- and inter-subject geometric components of multilevel functional data. Though motivated by the SHHS, the proposed methodology is generally applicable, with potential relevance to many modern scientific …

Nonparametric Signal Extraction And Measurement Error In The Analysis Of Electroencephalographic Activity During Sleep, Ciprian M. Crainiceanu, Brian S. Caffo, Chong-Zhi Di, Naresh M. Punjabi

Chongzhi Di

We introduce methods for signal and associated variability estimation based on hierarchical nonparametric smoothing with application to the Sleep Heart Health Study (SHHS). SHHS is the largest electroencephalographic (EEG) collection of sleep-related data, which contains, at each visit, two quasi-continuous EEG signals for each subject. The signal features extracted from EEG data are then used in second level analyses to investigate the relation between health, behavioral, or biometric outcomes and sleep. Using subject specific signals estimated with known variability in a second level regression becomes a nonstandard measurement error problem.We propose and implement methods that take into account cross-sectional and …

Generalized Multilevel Functional Regression, Ciprian M. Crainiceanu, Ana-Maria Staicu, Chong-Zhi Di

Chongzhi Di

We introduce Generalized Multilevel Functional Linear Models (GMFLMs), a novel statistical framework for regression models where exposure has a multilevel functional structure. We show that GMFLMs are, in fact, generalized multilevel mixed models. Thus, GMFLMs can be analyzed using the mixed effects inferential machinery and can be generalized within a well-researched statistical framework. We propose and compare two methods for inference: (1) a two-stage frequentist approach; and (2) a joint Bayesian analysis. Our methods are motivated by and applied to the Sleep Heart Health Study, the largest community cohort study of sleep. However, our methods are general and easy to …