Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Methylation profiling by array of pancreatic adenocarcinoma (PDAC) xenografts

ABSTRACT: Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers. the variable MultiOmicsClassification indicates the resulting sample's group. Whole-genome DNA methylation was analyzed using the Illumina Infinium HumanMethylation450 Beadchips. Integragen SA (Evry, France) carried out microarray experiments and hybridized to the BeadChip arrays following the manufacturer’s instructions. Illumina GenomeStudio software was used to extract the beta value DNA methylation score for each locus. We removed data from probes that contained SNPs or overlapped with a repetitive element that was not uniquely aligned to the human genome or regions of insertions and deletions in the human genome. The CpG Island Methylator Phenotype (CIMP) index was determined using methylation Illumina Infinium HumanMethylation450 BeadChips based on previous low throughput work (Toyota, 1999). In brief, all island CpG found to be unmethylated (<20% Beta-value) in all 25 normal pancreatic samples from the ICGC consortium (Nones, 2014) were selected. The CIMP index was calculated independently for each sample as the proportion of methylated (>30% Beta-value) CpGs among the selected normally unmethylated island CpG.

ORGANISM(S): Homo sapiens

SUBMITTER: Nabila Elarouci

PROVIDER: E-MTAB-5008 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on DNA methylation, mRNA expression and microRNA (miRNA) expression in four distinct human brain regions. We show that brain tissues may be readily distinguished based on methylation status or expression profile. We find an abundance of genetic cis regulation mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation. Authorized Access data: Mapping of GEO sample accessions to dbGaP subject/sample IDs is available through dbGaP Authorized Access, see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000249.v1.p1 Because of our interest in genomic regulation of expression and neurological disorders we embarked upon a series of experiments to provide a brain region-specific contextual framework for genetic and epigenetic regulation of gene expression. We obtained frozen brain tissue from the cerebellum, frontal cortex, pons and temporal cortex from 150 subjects (total 600 tissue samples). We undertook four separate assays across this series; first, genome-wide SNP genotyping; second, assay of >27,000 CpG methylation sites in each of the four brain regions; third, mRNA expression profiling of >22,000 transcripts in all four brain regions; and, fourth, miRNA expression profiling of 735 miRNA transcripts. Here we discuss the results of these experiments, particularly in the context of integrated datasets to define expression and CpG methylation quantitative trait loci (eQTL and methQTL) and detailing differences and similarities across brain regions.

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Methylation profiling by array of pancreatic adenocarcinoma (PDAC) xenografts

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