Background: Recent interest in reference-free deconvolution of DNA methylation data has led to several supervised methods, but these methods do not easily permit the interpretation of underlying cell types.
Results: We propose a simple method for reference-free deconvolution that provides both proportions of putative cell types defined by their underlying...
Exposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming in utero. In the present study, we evaluate the epigenome-wide association of arsenic exposure in utero and DNA methylation in placenta (n = 37), umbilical artery (n...
Understanding the precise role of the immune system in cancer has been hindered by the complexity of the immune response and challenges in measuring immune cell types in health and disease in the context of large epidemiologic studies. In this review, we present the rationale to study immunity in cancer...
Exposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming in utero. In the present study, we evaluate the epigenome-wide association of arsenic exposure in utero and DNA methylation in placenta (n=37), umbilical artery (n=45) and human...
Background: Arsenic is an immunotoxicant. Clinical reports observe the reactivation of varicella zoster virus (VZV) in people who have recovered from arsenic poisoning and in patients with acute promyelocytic leukemia that have been treated with arsenic trioxide. Objective: We evaluated the association between arsenic and the seroprevalence of VZV IgG...
We investigated DNA methylomes of pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles. Epigenetic alteration of B-ALLs occurred in two tracks: de novo methylation of small functional compartments and demethylation of large intercompartmental backbones. The deviations were exaggerated in lamina-associated...
BACKGROUND: The impact of cell-composition effects in analysis of DNA methylation data is now widely appreciated. With the availability of a reference data set consisting of DNA methylation measurements on isolated cell types, it is possible to impute cell proportions and adjust for them, but there is increasing interest in...
BACKGROUND: Cell lineage-specific DNA methylation patterns distinguish normal human leukocyte subsets and can be used to detect and quantify these subsets in peripheral blood. We have developed an approach that uses DNA methylation to simultaneously quantify multiple leukocyte subsets, enabling investigation of immune modulations in virtually any blood sample including...
BACKGROUND: A substantial proportion of the general population has low lung function, and lung function is known to decrease as we age. Low lung function is a feature of several pulmonary disorders, such as uncontrolled asthma and chronic obstructive pulmonary disease (COPD). The objective of this study is to investigate...
Epigenetic changes, including aberrant DNA methylation, result in altered gene expression and play an important role in carcinogenesis. Phytochemicals such as sulforaphane (SFN) and 3,3′-diindolylmethane (DIM) are promising chemopreventive agents for the treatment of prostate cancer. Both have been shown to induce re-expression of genes, including tumor suppressor genes silenced...
The potential influence of underlying differences in relative leukocyte distributions in studies involving blood-based profiling of DNA methylation is well recognized and has prompted development of a set of statistical methods for inferring changes in the distribution of white blood cells using DNA methylation signatures. However, the extent to which...
The promise of epigenome-wide association studies (EWAS) and cancer specific somatic changes in improving our understanding of cancer coupled with the decreasing cost and increasing coverage of DNA methylation microarrays, has brought about a surge in the use of these technologies. Here, we aim to provide both a review of...
Background: There is increasing epidemiologic evidence that arsenic exposure in utero, even at low levels found throughout much of the world, is associated with adverse reproductive outcomes and may contribute to long-term health effects. Animal models, in vitro studies, and human cancer data suggest that arsenic may induce epigenetic alterations,...
DNA methylation is a well-recognized epigenetic mechanism that has been the subject of a growing
body of literature typically focused on the identification and study of profiles of DNA methylation and their
association with human diseases and exposures. In recent years, a number of unsupervised clustering algorithms,
both parametric and...