Grasping nettles: cellular heterogeneity and other confounders in epigenome-wide association studies

Platform technologies for measurement of CpG methylation at multiple loci across the genome have made ambitious epigenome-wide association studies affordable and practicable. In contrast to genetic studies, which estimate the effects of structural changes in DNA, and transcriptomic studies, which measure genomic outputs, epigenetic studies can access states of regulation of genome function in particular cells and in response to specific stimuli. Although many factors complicate the interpretation of epigenetic variation in human disease, cell-specific methylation patterns and the cellular heterogeneity present in peripheral blood and tissue biopsies are anticipated to cause the most problems. In this review, we suggest that the difficulties may be exaggerated and we explore how cellular heterogeneity may be embraced with appropriate study designs and analytical tools. We further suggest that systematic mapping of the loci influenced by age, sex and genetic polymorphisms will bring important biological insights as well as improved control of epigenome-wide association studies

Planar Object Tracking in the Wild: A Benchmark

Planar object tracking is an actively studied problem in vision-based robotic applications. While several benchmarks have been constructed for evaluating state-of-the-art algorithms, there is a lack of video sequences captured in the wild rather than in constrained laboratory environment. In this paper, we present a carefully designed planar object tracking benchmark containing 210 videos of 30 planar objects sampled in the natural environment. In particular, for each object, we shoot seven videos involving various challenging factors, namely scale change, rotation, perspective distortion, motion blur, occlusion, out-of-view, and unconstrained. The ground truth is carefully annotated semi-manually to ensure the quality. Moreover, eleven state-of-the-art algorithms are evaluated on the benchmark using two evaluation metrics, with detailed analysis provided for the evaluation results. We expect the proposed benchmark to benefit future studies on planar object tracking.Comment: Accepted by ICRA 201

RTeQTL: Real-Time Online Engine for Expression Quantitative Trait Loci Analyses

Our database tool, called Real-Time Engine for Expression Quantitative Trait Loci Analyses (RTeQTL), can efficiently provide eQTL association results that are not available in existing eQTL databases browsers. These functions include (i) single SNP (single-nucleotide polymorphism) and (ii) two-SNP conditional eQTL effects on gene expression regardless of the magnitude of P-values. The database is based on lymphoblastoid cell lines from >900 samples with global gene expression and genome-wide genotyped and imputed SNP data. The detailed result for any pairs of gene and SNPs can be efficiently computed and browsed online, as well as downloaded in batch mode. This is the only tool that can assess the independent effect of a disease- or trait-associated SNP on gene expression conditioning on other SNPs of interest, such as the top eQTL of the same gene. It is also useful to identify eQTLs for candidate genes, which are often missed in existing eQTL browsers, which only store results with genome-wide significant P-value. Additional analyses stratifying by gender can also be easily achieved by this tool. Database URL: http://eqtl.rc.fas.harvard.edu

Autophagy in photodynamic therapy

Macroautophagy (autophagy) is crucial for cell survival during starvation and plays important roles in human diseases. It is a highly conserved intracellular degradation system in eukaryotes for removal and recycling of cytoplasmic components including damaged proteins and organelles to obtain energy. The relationship between cancer and autophagy has been extensively studied in recent years. In cancer and cancer therapy, autophagy acts as a double-edged sword. Photodynamic therapy (PDT) is a kind of tumor therapy applied with a tumor-localizing photosensitizing agent which is followed by activation with the light of a specific wavelength. How much is autophagy involved in photodynamic therapy? The work in this area is still limited.Keywords: Autophagy, Photodynamic therapy, Apoptosis, Cance

Efficient Methods for Analysis of Genome Scale Data.

In my dissertation I develop and evaluate methods for gene-mapping that can extract useful information from large complex datasets with many genetic markers and outcomes measured. The first part of the dissertation describes an extension of the variance components approach to incorporate repeated phenotype measurements and establish a general formula for cost-effectiveness analysis. The second part proposes a discrete-generation framework of the coalescent model that can rapidly simulate large (>100Mb) sequences from a population based on flexible population history and allows recombination rates to vary along the genome. The third part develops a case-control association mapping strategy that uses genetic data to match individuals and accounts for unknown population structure. The fourth part describes a genome-wide genetic map of genetic variants that influence global gene expression integrating data on >50,000 mRNA transcript levels and >400,000 genetic markers. Using this dataset, I perform systematic evaluation of accuracy and power of genotype imputation with respect to different aspects of the phenotypic traits of interest and genetic markers being tested.Ph.D.BiostatisticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/64634/1/lianglim_1.pd