Project description:Genome-wide DNA Methylation Data from Illumina HumanMethylationEPIC arrays for whole blood samples from 570 healthy individuals. Raw IDAT files are available for a subset of 403 samples on EGA. Raw data (IDAT files) and associated phenotype information are available for all individuals included in this study (n=570) directly from CIBMTR. Data are available under controlled access release upon reasonable request and execution of a data use agreement. Requests should be submitted to CIBMTR at info-request@mcw.edu and include the study reference IB17-04.
Project description:Neuroepigenetics considers genetic sequences and the interplay with environmental influences to elucidate vulnerability risk for various neurological and psychiatric disorders. However, evaluating DNA methylation of brain tissue is challenging owing to the issue of tissue specificity. Consequently, peripheral surrogate tissues were used, resulting in limited progress compared with other epigenetic studies, such as cancer research. Therefore, we developed databases to establish correlations between the brain and peripheral tissues in the same individuals. Four tissues, resected brain tissue, blood, saliva, and buccal mucosa (buccal), were collected from 19 patients (aged 13–73 years) who underwent neurosurgery. Moreover, their genome-wide DNA methylation was assessed using the Infinium HumanMethylationEPIC BeadChip arrays to determine the cross-tissue correlation of each combination. These correlation analyses were conducted with all methylation sites and with variable CpGs, and with when these were adjusted for cellular proportions. For the averaged data for each CpG across individuals, the saliva–brain correlation (r = 0.90) was higher than that for blood–brain (r = 0.87) and buccal–brain (r = 0.88) comparisons. Among individual CpGs, blood had the highest proportion of CpGs correlated to the brain at nominally significant levels (19.0%), followed by saliva (14.4%) and buccal (9.8%). These results were similar to the previous IMAGE-CpG results; however, the correlation analysis between the correlation coefficients of the datasets revealed a relatively low degree of correlation (brain vs. blood: r = 0.27, saliva; r = 0.18, and buccal; r = 0.24). To the best of our knowledge, this is the fourth study in the literature initiating the development of databases for correlations between the brain and peripheral tissues in the same individuals. We present the first database developed from an Asian population, specifically Japanese samples (AMAZE-CpG), which would contribute to interpreting individual epigenetic study results from various Asian populations.
Project description:We report RNA-sequencing data of 283 blood platelet samples, including 228 tumor-educated platelet (TEP) samples collected from patients with six different malignant tumors (non-small cell lung cancer, colorectal cancer, pancreatic cancer, glioblastoma, breast cancer and hepatobiliary carcinomas). In addition, we report RNA-sequencing data of blood platelets isolated from 55 healthy individuals. This dataset highlights the ability of TEP RNA-based 'liquid biopsies' in patients with several types with cancer, including the ability for pan-cancer, multiclass cancer and companion diagnostics.
Project description:Canine mammary gland tumors (CMTs) have been suggested as promising cancer models to human breast cancer due to their many biological and clinical similarities. Here, we collected 222 samples consist of 158 tumor samples and 64 matched normal samples of CMTs. Fresh tissue samples were transferred in to RNAlater, and refrigerated overnight at 4°C and then stored at -80°C. Total RNA was extracted from tissues using RNeasy mini kit. We aligned RNA-Seq raw data from 222 samples to canine reference genome CanFam3.1 using Tophat. We assembled transcript and calculated FPKM values using Cufflinks. All tumor samples were evaluated by histopathological characteristics including histopathological subtype, grade, and lymphatic invasion, and annotated with corresponding sequencing data. The histopathological classification and the histological grading system of CMTs were adopted from those of human breast cancer. In addition, immunohistochemical evaluation was performed in samples for estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. DISCLAIMER: Using this dataset became freely available on Jul 22, 2019. On the other hand, we are now preparing a key paper about comparative analysis of canine and human breast cancer based on this dataset. If you plan to submit a similar paper using this dataset before the main paper is published, please feel free to contact the submitter (swkim@yuhs.ac) to coordinate submission.
Project description:DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. To identify age-dependent DNA methylation sites, we generated DNA methylation sequencing data for 29 purified normal adjacent human breast epithelia (age range 33-82 years old) using Digital Restriction Enzyme Analysis of Methylation (DREAM). Next, we validated the age-related sites in publicly available DNA methylation (450K array) of 97 normal adjacent TCGA samples. We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39 /427) were outliers for DNA methylation from 6 publicly available DNA methylation datasets (GSE88883, GSE74214, GSE101961, GSE69914(normal), GSE69914(normal-adjacent), TCGA (Firehose Legacy)). We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) then in normal samples (15/228, 5.2%). Additionally, we found significant differences between predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer.
Project description:This dataset consists of miRNA expression in serum of 69 women. This data is the result of remapping raw sequencing FASTQ files being a part of the GSE226445 dataset and the SRA Bioproject PRJNA898621. MicroRNA abundance was quantified by sequencing. Data was analyzed together with plasma samples of those same patients with the aim of assessing the impact of blood processing steps on quantified miRNA abundance. Plasma data belongs to a separate submission (accession will be added when issued). Generation of this dataset was supported by The Gray Foundation grant “Circulating microRNAs for assessment of risk beyond the BRCA genes and early detection of breast cancer in high-risk families” awarded to Dipanjan Chowdhury and Polish National Research Center grant OPUS “Predictive Potential of Circulating MicroRNA Biomarkers in Patients with High Familial or Genetic Risk of Cancer” (2023/49/B/NZ5/03835) awarded to Wojciech Fendler.
Project description:Background: Animal models suggest a role of epigenetic mechanisms, including DNA methylation, in neural tube closure; however, studies characterizing DNA methylation profiles in nervous system tissue from humans with spina bifida are limited, In this study, we assessed DNA methylation profiles in dural tissue of infants with spina bifida, collected at the time of surgical closure of the defect, and examined whether whole blood or buccal swab are appropriate surrogate tissues, as they are more practical to collect in large-scale epidemiological studies, DNA methylation was measured in dural tissue, buccal swab, and whole blood samples collected from 27 unique infants using the Illumina Infinium MethylationEPIC BeadChip array, Results: Correlation analysis for each CpG site comparing DNA methylation from all participants in dural tissue to DNA methylation in whole blood DNA or buccal swab DNA yielded 1,555 statistically significant associations for the whole blood analysis and 920 significant associations for the buccal swab analysis at the Bonferroni threshold of significance, We also performed paired analysis, calculating differences between tissues within each individual and then averaging differences across individuals, After accounting for multiple hypothesis testing using the FDR adjustment, 33% of CpG sites assessed were not significantly differentially methylated between dural tissue and whole blood samples, compared to the 27% of sites not differentially methylated between dural tissue and buccal swab samples, Conclusions: These results suggest that in the absence of dural tissue, both whole blood and buccal swab samples may be considered as surrogates for dural tissue, The study warrants replication in larger groups to validate findings and may assist researchers restricted to more accessible biospecimens (i,e, blood) to further characterize epigenetic contributors to neural tube defect etiology,
Project description:Inter-individual variability in DNA methylation has been hypothesized to contribute to complex phenotypes through epigenetic modulation of gene expression levels. Population epigenetic studies have been examining differences in DNA methylation in a variety of accessible tissues for association with specific diseases or exposures, but relatively little is known about how this inter-individual variation differs between tissues. This study presents an analysis of global DNA methylation differences between matched peripheral blood mononuclear cells and buccal epithelial cells; specifically it examines differential DNA methylation, probe-wise DNA methylation variance, and how methylation relates to a number of demographic factors across the two tissues. We found that peripheral blood mononuclear cells have overall higher DNA methylation than buccal epithelial cells, and regions of the genome that are differently methylated between the tissues tend to have low CpG density. We also discovered that although both tissues show extensive probe-wise variability, the specific regions and magnitude of variability differed between tissues. Finally, we observed that while both buccal epithelial and peripheral mononuclear blood cell DNA methylation was associated with gender, only methylation of the latter was associated with body mass index. The work presented here offers insight into variability of DNA methylation between individuals and across tissues and the suitability of buccal epithelial and peripheral mononuclear cells for the biological questions explored by epigenome-wide association studies in human populations. This cohort consist of genomic DNA extracted from the peripheral blood mononuclear cells and buccal epithelial cells of 25 individuals, bisulphite converted and hybridized to the Illumina GoldenGate Methylation Cancer Panel for genome wide DNA methylation profiling