Genetics and Genomics Commons^™

Multiple Testing Correction With Repeated Correlated Outcomes: Applications To Epigenetics, Katie Leap

Masters Theses

Epigenetic changes (specifically DNA methylation) have been associated with adverse health outcomes; however, unlike genetic markers that are fixed over the lifetime of an individual, methylation can change. Given that there are a large number of methylation sites, measuring them repeatedly introduces multiple testing problems beyond those that exist in a static genetic context. Using simulations of epigenetic data, we considered different methods of controlling the false discovery rate. We considered several underlying associations between an exposure and methylation over time.

We found that testing each site with a linear mixed effects model and then controlling the false discovery rate …

Statistical Contributions To Proteomic Research, Jeffrey S. Morris, Keith A. Baggerly, Howard B. Gutstein, Kevin R. Coombes

Jeffrey S. Morris

Proteomic profiling has the potential to impact the diagnosis, prognosis, and treatment of various diseases. A number of different proteomic technologies are available that allow us to look at many proteins at once, and all of them yield complex data that raise significant quantitative challenges. Inadequate attention to these quantitative issues can prevent these studies from achieving their desired goals, and can even lead to invalid results. In this chapter, we describe various ways the involvement of statisticians or other quantitative scientists in the study team can contribute to the success of proteomic research, and we outline some of the …

Hierarchical Hidden Markov Model With Application To Joint Analysis Of Chip-Chip And Chip-Seq Data, Hyungwon Choi, Debashis Ghosh, Zhaohui S. Qin

Debashis Ghosh

Motivation: Identication of transcription factor binding sites (TFBS) is a fundamental problem in understanding the mechanism of gene regulation. The ChIP-chip technology has accelerated this eort by providing a simultaneous genome-wide map of TFBS in a high-throughput fashion. Recently, a sequencing-based ChIP-seq has appeared as a promising alternative that can identify targets with an improved sensitivity/specicity in high resolution. However, studies have suggested that distinct experimental platforms can be complementary in TFBS identication. The availability of data obtained from multiple platforms motivates a meta-analysis for improved identication of candidate motifs.

Results: In this work, we propose a hierarchical hidden Markov …

Discrete Nonparametric Algorithms For Outlier Detection With Genomic Data, Debashis Ghosh

Debashis Ghosh

In high-throughput studies involving genetic data such as from gene expression microarrays, differential expression analysis between two or more experimental conditions has been a very common analytical task. Much of the resulting literature on multiple comparisons has paid relatively little attention to the choice of test statistic. In this article, we focus on the issue of choice of test statistic based on a special pattern of differential expression. The approach here is based on recasting multiple comparisons procedures for assessing outlying expression values. A major complication is that the resulting p-values are discrete; some theoretical properties of sequential testing procedures …