1. Identification of DNA Methylation-Independent Epigenetic Events Underlying Clear Cell Renal Cell Carcinoma.

    Cancer Research 76(7):1954 (2016) PMID 26759245 PMCID PMC4873378

    Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneo...
  2. An evaluation of processing methods for HumanMethylation450 BeadChip data.

    BMC Genomics 17(1):469 (2016) PMID 27334613 PMCID PMC4918139

    Illumina's HumanMethylation450 arrays provide the most cost-effective means of high-throughput DNA methylation analysis. As with other types of microarray platforms, technical artifacts are a concern, including background fluorescence, dye-bias from the use of two color channels, bias caused by ...
  3. Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history.

    Cancer Epidemiology Biomarkers & Prevention 24(3):512 (2015) PMID 25587051 PMCID PMC4355081

    The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not know...
  4. Identifying differential transcription factor binding in ChIP-seq.

    Frontiers in Genetics 6:169 (2015) PMID 25972895 PMCID PMC4413818

    ChIP seq is a widely used assay to measure genome-wide protein binding. The decrease in costs associated with sequencing has led to a rise in the number of studies that investigate protein binding across treatment conditions or cell lines. In addition to the identification of binding sites, new ...
  5. Ancestral inference in tumors: how much can we know?

    Journal of Theoretical Biology 359:136 (2014) PMID 24907673 PMCID PMC4138290

    A tumor is thought to start from a single cell and genome. Yet genomes in the final tumor are typically heterogeneous. The mystery of this intratumoral heterogeneity (ITH) has not yet been uncovered, but much of this ITH may be secondary to replication errors. Methylation of cytosine bases often...
  6. A panel of three markers hyper- and hypomethylated in urine sediments accurately predicts bladder cancer recurrence.

    Clinical Cancer Research 20(7):1978 (2014) PMID 24691641

    The high risk of recurrence after transurethral resection of bladder tumor of nonmuscle invasive disease requires lifelong treatment and surveillance. Changes in DNA methylation are chemically stable, occur early during tumorigenesis, and can be quantified in bladder tumors and in cells shed int...
  7. Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation.

    PLoS ONE 9(6):e99716 (2014) PMID 24964093 PMCID PMC4070909

    Smoking while pregnant is associated with a myriad of negative health outcomes in the child. Some of the detrimental effects may be due to epigenetic modifications, although few studies have investigated this hypothesis in detail. To characterize site-specific epigenetic modifications conferred ...
  8. Distinct, genome-wide, gene-specific selectivity patterns of four glucocorticoid receptor coregulators.

    Nuclear Receptor Signaling 12:e002 (2014) PMID 25422592 PMCID PMC4242289

    Glucocorticoids are a class of steroid hormones that bind to and activate the glucocorticoid receptor (GR), which then positively or negatively regulates transcription of many genes that govern multiple important physiological pathways such as inflammation and metabolism of glucose, fat and bone...
  9. Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue.

    Nature Communications 5:3365 (2014) PMID 24572595 PMCID PMC3982882

    The genetic regulation of the human epigenome is not fully appreciated. Here we describe the effects of genetic variants on the DNA methylome in human lung based on methylation-quantitative trait loci (meQTL) analyses. We report 34,304 cis- and 585 trans-meQTLs, a genetic-epigenetic interaction ...
  10. Non-specific filtering of beta-distributed data.

    BMC Bioinformatics 15:199 (2014) PMID 24943962 PMCID PMC4230495

    Non-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methy...
  11. Null association between histology of first and second primary malignancies in men with bilateral testicular germ cell tumors.

    American Journal of Epidemiology 178(8):1240 (2013) PMID 23928263 PMCID PMC3792726

    Testicular germ cell tumors (TGCTs), the most common neoplasms of young men, are categorized histologically as either seminomas or nonseminomas/mixed germ cell tumors. These subtypes differ by age at diagnosis and clinical course, but little is known about etiological distinctions. To test the h...
  12. Recommendations for the design and analysis of epigenome-wide association studies.

    Nature Methods 10(10):949 (2013) PMID 24076989

    Epigenome-wide association studies (EWAS) hold promise for the detection of new regulatory mechanisms that may be susceptible to modification by environmental and lifestyle factors affecting susceptibility to disease. Epigenome-wide screening methods cover an increasing number of CpG sites, but ...
  13. Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.

    Human Molecular Genetics 22(13):2748 (2013) PMID 23462292 PMCID PMC3674801

    Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide si...
  14. Integrated transcriptomic and epigenomic analysis of primary human lung epithelial cell differentiation.

    PLoS Genetics 9(6):e1003513 (2013) PMID 23818859 PMCID PMC3688557

    Elucidation of the epigenetic basis for cell-type specific gene regulation is key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how epigenetic changes are integrated with transcriptional activation to determin...
  15. Low-level processing of Illumina Infinium DNA Methylation BeadArrays.

    Nucleic Acids Research 41(7):e90 (2013) PMID 23476028 PMCID PMC3627582

    We propose a novel approach to background correction for Infinium HumanMethylation data to account for technical variation in background fluorescence signal. Our approach capitalizes on a new use for the Infinium I design bead types to measure non-specific fluorescence in the colour channel oppo...
  16. G9a functions as a molecular scaffold for assembly of transcriptional coactivators on a subset of glucocorticoid receptor target genes.

    PNAS 109(48):19673 (2012) PMID 23151507 PMCID PMC3511704

    Histone H3 lysine-9 methyltransferase G9a/EHMT2/KMT1C is a key corepressor of gene expression. However, activation of a limited number of genes by G9a (independent of its catalytic activity) has also been observed, although the precise molecular mechanisms are unknown. By using RNAi in combinati...
  17. Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships.

    Humangenetik 131(10):1565 (2012) PMID 22740325 PMCID PMC3432200

    Changes in epigenetic marks such as DNA methylation and histone acetylation are associated with a broad range of disease traits, including cancer, asthma, metabolic disorders, and various reproductive conditions. It seems plausible that changes in epigenetic state may be induced by environmental...
  18. Particulate matter, DNA methylation in nitric oxide synthase, and childhood respiratory disease.

    Environmental Health Perspectives 120(9):1320 (2012) PMID 22591701 PMCID PMC3440108

    Air pollutants have been associated with childhood asthma and wheeze. Epigenetic regulation of nitric oxide synthase--the gene responsible for nitric oxide production--may be affected by air pollutants and contribute to the pathogenesis of asthma and wheeze. Our goal was to investigate the assoc...
  19. Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression.

    Genome Research 22(7):1197 (2012) PMID 22613842 PMCID PMC3396362

    Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DN...
  20. Carcinogen metabolism genes, red meat and poultry intake, and colorectal cancer risk.

    International Journal of Cancer 130(8):1898 (2012) PMID 21618522 PMCID PMC3883510

    Diets high in red meat are established risk factors for colorectal cancer (CRC). Carcinogenic compounds generated during meat cooking have been implicated as causal agents. We conducted a family-based case-control study to investigate the association between polymorphisms in carcinogen metabolis...