Project description:Confounding due to cellular heterogeneity represents one of the foremost challenges currently facing Epigenome-Wide Association Studies (EWAS). Statistical methods leveraging the tissue-specificity of DNA methylation for deconvoluting the cellular mixture of heterogeneous biospecimens such as whole blood, offer a promising solution. However, their performance depends entirely on the library of DNA methylation markers being used as the basis for deconvolution. The objective of this study was to train and validate an algorithm for the identification of optimal DNA methylation libraries for the deconvolution of adult human whole blood. Purified granulocytes, monocytes, CD4T, CD8T, natural killer cells, and B cells from normal human subjects were purchased from AllCells LLC (Emeryville, CA). DNA extracted from purified leukocyte subtypes were mixed in predetermined proportions to reconstruct two distinct sets of white blood cell (WBC) mixtures, each consisting of six samples. An additional six whole blood (WB) samples from disease-free adult donors with available immune cell profiling data from flow cytometry were purchased from All-Cells LLC and were included in this investigation. All DNA samples were bisulfite modified using the Zymo EZ DNA Methylation kit (Irvine, CA) and profiled for DNA methylation using the Illumina HumanMethylation450 array platform.
Project description:This project contains genome-wide DNA methylation data generated using the HumanMethylation450 BeadChip (Illumina), for 79 rheumatoid arthritis (RA) discordant monozygotic twin pairs. By investigating disease discordant monozygotic twins, DNA methylation can be assessed without the confounding influence of genetic heterogeneity which often affects case-control epigenome-wide association studies of common diseases. Twins were recruited from two cohorts; Arthritis Research UK in Manchester and TwinsUK in London.
Project description:The objective of the study was to utilize DNA methylation to quantify human leukocyte subsets in human blood. This file contains data from an Illumina Infinium HumanMethlation450 for human whole blood samples as well as complex mixtures of DNA from purified human leukocyte subtypes in quantities that mimick human blood under different clinical conditions. Bisulphite converted DNA from the samples were hybridized to an Illumina Infinium HumanMethylation450 beadchip
Project description:Genome-wide DNA methylation profiling of DNA extracted from dried blood spots from preterm and term subjects using longitudinal samples collected at birth and 18 years of age. Infinium HM450 arrays were used to measure methylation at 347,789 autosomal CpGs. DNA was analysed from individuals at birth and 18-years and included 12 preterm and 12 term controls. Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 450K Human Methylation Beadchip
Project description:The contribution of DNA methylation on the evolution of chronic lymphocytic leukemia has not been adequately studied yet. The purpose of this study was to investigate the role of DNA methylation in patients under chemoimmunotherapy. The overtime analysis of DNA methylation was performed on 40 patients in two time points: pre-treatment and after relapse, and 2 samples of memory B cells (MBC), using 450k arrays.
Project description:We have used Illumina Infinium HumanMethylation450 BeadChip array profiling to profile paediatric high grade gliomas and diffuse intrinsic pontine gliomas. The 450K methylation array is being used to separate brain tumour samples on the basis of their methylation profiles which represent the cell of origin the time and place in which tumours arise. Methylation arrays provide data for an integrated molecular diagnosis of brain tumours and define specific molecular subgroups and subtypes of high grade gliomas carrying distinct driver mutations and patterns of somatic alterations. These data form part of an integrated meta-analysis of high grade gliomas in children combining DNA copy number, methylation and high throughput sequencing datasets.
Project description:We have used Illumina Infinium HumanMethylation450 BeadChip array profiling to profile paediatric high grade gliomas within the HERBY clinical trial. The HERBY trial was a phase-II open-label, randomised, multicentre trial evaluating bevacizumab in patients with newly-diagnosed non-brainstem HGG between the ages of 3-18yrs. The 450K methylation array was used to separate brain tumour samples on the basis of their methylation profiles which represent the cell of origin the time and place in which tumours arise. Methylation arrays provide data for an integrated molecular diagnosis of brain tumours and define specific molecular subgroups and subtypes of high grade gliomas carrying distinct driver mutations and patterns of somatic alterations.
Project description:Chronic lymphocytic leukemia (CLL) stereotyped subsets #6 and #8 include cases expressing unmutated B cell receptor immunoglobulin (BcR IG) (U-CLL). Yet, subset #6 (IGHV1-69/IGKV3-20) is less aggressive compared to subset #8 (IGHV4-39/IGKV1(D)-39) which has the highest risk for Richter’s transformation among all CLL. The underlying reasons for this divergent clinical behavior are not fully elucidated. To gain insight into this issue, here we focused on epigenomic signatures and their links with gene expression, particularly investigating genome-wide DNA methylation profiles in subsets #6 and #8 as well as other U-CLL cases not expressing stereotyped BcR IG using the Illumina 450k methylation arrays. Additionally we analysed the methylation profiles of naive and memory B cell subsets from healthy donors and compared them with those of the CLL cases.
Project description:In this study, we used Illumina Infinium HumanMethylation450 Beadchips to compare DNA methylation profiles in blood from 10 pairs of MZ twins and 8 individuals recruited at 0, 3, 6, and 9 months. MZ Group (Group A) contained 10 pairs of MZ twins ranging from 23 to 74 years old, including 8 female and 12 male subjects.Longitudinal study group (Group B) included a pair of MZ (male) twins and 6 unrelated individuals (3 male, 3 female), aged from 24 to 39. Except subject H, all participants in Longitudinal study group (Group B) were recalled every 3 months for 9 months (0, 3, 6, and 9 m). Subject H was studied only at 0, 6, and 9 months. Bisulphite converted DNA from the 60 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip