Genome-wide plasma cell-free DNA methylation profiling in pancreatic cancer patients using MeDIP-seq
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2000
ORGANISM(S): Homo sapiens
SUBMITTER: Pengxiao Li
PROVIDER: E-MTAB-9678 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:As a non-invasive blood testing, the detection of cell-free DNA (cfDNA) methylation in plasma is raising increasing interest due to its diagnostic and biology applications. Although extensively used in cfDNA methylation analysis, bisulfite sequencing is less cost-effective. Through enriching methylated cfDNA fragments with MeDIP followed by deep sequencing, we aimed to characterize cfDNA methylome in cancer patients. In this study, we investigated the cfDNA methylation patterns in lung cancer patients by MeDIP-seq. MEDIPS package was used for the identification of differentially methylated regions (DMRs) between patients and normal ones. Overall, we identified 330 differentially methylated regions (DMRs) in gene promoter regions, 33 hypermethylation and 297 hypomethylation respectively, by comparing lung cancer patients and healthy individuals as controls. The 33 hypermethylation regions represent 32 genes. Some of the genes had been previously reported to be associated with lung cancers, such as GAS7, AQP10, HLF, CHRNA9 and HOPX. Taken together, our study provided an alternative method of cfDNA methylation analysis in lung cancer patients with potential clinical applications.
2019-03-31 | E-MTAB-7163 | biostudies-arrayexpress
Project description:DNA methylation is critical for development and is strongly associated with gene regulation. Variation in the DNA methylome between closely related species may reveal unique functional adaptation. We have implemented a novel inter-primate DNA methylation genome-wide analysis between human, chimpanzee and rhesus macaque to identify human species-specific Differentially Methylated Regions (human s-DMRs) in orthologous loci. We analysed the peripheral blood cell DNA methylomes of these primates and identified 22,758 hypomethylated and 15,858 hypermethylated human s-DMRs. These s-DMRs are globally enriched within weak promoter, enhancer and transcribed regions via comparison with ChromHMM segmentation. Human s-DMRs, (both hypo- and hypermethylated) are found to be more prevalent in CpG Island shores than within the islands themselves (?2 P = 1.80 x 10-32). Examining human-specific Transcription Factor Binding Site motif change within CpG islands, we show gain and loss, in hypomethylated and hypermethylated s-DMRs, respectively, of CTCF motifs. Epigenetically the most divergent human-specific locus was the immunological Leukotriene B4 receptor (LTB4R, aka BLT1 receptor), due to collocating hypomethylated s-DMRs within the promoter CpG island and shore, as well as inverse increased gene body methylation. This gene is vital in host immune responses and associated with the pathogenesis of a wide range of human inflammatory diseases. This finding was supported by additional neutrophil-only DNA methylome and lymphoblastoid H3K4me3 chromatin comparative data. Functional investigation of the consequences of these epigenetic differences identified this receptor to have increased expression, and have a higher response to the LTB4 ligand in human versus rhesus macaque peripheral blood mononuclear cells. This result further emphasises the exclusive nature of the human immunological system, its divergent adaptation even from closely related primates, and the power of comparative epigenomics to identify and understand human uniqueness. DNA methylome analysis of pooled Human, Chimpanzee and Macaque
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Project description:Purpose: Generate genome-wide methylation profiles of non-small cell lung carcinomas (NSCLC) and their matching lung tissues for detection of hypermethylated and hypomethylated regions present in the tumors. Methods: MethylCapture followed by next-generation sequencing (Illumina GAIIx) of 7 nsclc tumor samples and paired lung tissues in replicated, plus one cell line, 2 fully artificially methylated and 2 fully artificially unmethylated controls. Normalization of methylation reads based on CpG coupling factor–method. Relative methylation scores (rms) in 500bp non-overlapping windows. 90th percentile of rpm (reads per million) values for all 500bp genome-wide windows, with rpm <1.33 were considered. Distributions of 10bp bins rms values within each 500bp genomic region were compared using both one-sided Student’s t-test and one-sided Wilcoxon rank-sum test. Testing was done separately for hypo- and hypermethylation and p-value threshold of 10-18. Results: MethylCap-seq data revealed strong positive correlation between replicate experiments and between paired tumor/lung samples. 14472 differentially methylated regions (DMR) with non-overlapping 500 bp windows were found. 57 DMRs were present in all NSCLC tumors. 287 were unique for squamous-cell carcinomas and 26 unique for adenocarcinomas. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. Conclusion: We provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC. The DMRs can be in further studies to develop sensitive biological markers for NSCLC, which may enable non-invasive diagnosis and early detection of the disease, and potentially allow histological classification. MethylCap-seq of 7 nsclc tumor samples and paired lung tissues, plus 2 fully methylated and 2 fully unmethylated controls.
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