title: Genistein Cooperates with the Histone Deacetylase Inhibitor Vorinostat to Induce Cell Death in Prostate Cancer Cells (methylation data)

status: Public on Dec 01 2012

city: Atlanta

first: Khanjan

last: Gandhi

state: Georgia

address: 1365-B Clifton Rd NE, Room 4107

institute: Winship Cancer Institute, Emory University.

summary: We have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial-to-mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Using whole-genome expression profiling and whole-genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and a combination treatment, where cell death and cell proliferation was determined.

overall_design: ARCAP-E, ARCAP-M, and normal human PrEC cells were analyzed for genome-wide methylation using the Illumina 27K CpG Methylation BeadChip. ARCAP-E and ARCAP-M cells were treated with DMSO as a negative control, genistein, or 5-aza-deoxycytidine as a positive control for demethylation. PrEC cells, used as a normal human prostate cell line control, were untreated.

first: Cornel

last: Phillip

first: Christopher

middle: K

last: Giardina

first: Yu

last: Lai

first: Omer

last: Kucuk

first: Carlos

last: Moreno


title: Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine (part 3)

city: Urbana

first: Michael

last: Spinella

state: IL

address: 2001 South Lincoln Ave

department: Comparative Biosciences

country: USA

institute: University of Illinois

summary: Human embryonal carcinoma (EC) cells are the stem cells of nonseminoma testicular germ cells tumors (TGCTs) and share remarkable similarities to human embryonic stem (ES) cells. In prior work we found that EC cells are hypersensitive to low nanomolar doses of 5-aza deoxycytidine (5-aza) and that this hypersensitivity partially depended on unusually high levels of the DNA methyltransferase, DNMT3B.  We show here that low-dose 5-aza treatment results in DNA damage and induction of p53 in NT2/D1 cells.  In addition, low-dose 5-aza results in global and gene specific promoter DNA hypomethylation.  Low-dose 5-aza induces a p53 transcriptional signature distinct from that induced with cisplatin in NT2/D1 cells and also uniquely downregulates genes associated with pluripotency including NANOG, SOX2, GDF3 and Myc target genes.  Changes in the p53 and pluripotency signatures with 5-aza were to a large extent dependent on high levels of DNMT3B.  In contrast to the majority of p53 target genes upregulated by 5-aza that did not show DNA hypomethylation, several other genes induced with 5-aza had corresponding decreases in promoter methylation.  These genes include RIN1, SOX15, GPER, and TLR4 and are novel candidate tumors suppressors in TGCTs.  Our studies suggest that the hypersensitivity of NT2/D1 cells to low-dose 5-aza is multifactorial and involves the combined activation of p53 targets, repression of pluripotency genes, and activation of genes repressed by DNA methylation.  Low-dose 5-aza therapy may be a general strategy to treat those tumors that are sustained by cells with embryonic stem-like properties.

overall_design: Genomic DNA obtained from NT2/D1-R1 sh control or NT2/D1-R1 sh DNMT3B knockdown cells treated with vehicle or 10 nM 5-aza deoxycytidine for 3 days.  Four groups in biological triplicate for total of 12 hybridizations on Illumina HumanMethylation27 BeadChip.

middle: J


title: Focal chromosomal aberrations in high-grade cervical intraepithelial neoplasia reveal hsa-miR-375 and EYA2 as drivers in HPV-mediated transformation

status: Public on Dec 31 2012

city: Amsterdam

first: Daoud

last: Sie

address: De Boelelaan 1117

department: Pathology

country: Netherlands

institute: Vrije Universiteit Medical Center

type: Genome variation profiling by high throughput sequencing

summary: Cervical cancer results from the accumulation of (epi)genetic aberrations following persistent infection with high-risk human papillomavirus (HPV). In order to define genetic aberrations associated with cervical carcinogenesis, chromosomal profiles of high-grade cervical intraepithelial neoplasia (CIN) were generated. Common aberrations usually encompass large genomic regions and contain numerous genes, hampering identification of actual driver genes. Consequently, direct evidence of chromosomal alterations actively contributing to cervical carcinogenesis has been lacking so far. By analyzing 60 high-grade CIN with high resolution arrayCGH we identified focal chromosomal aberrations that each harbour only one or a few genes.  In total 74 focal aberrations were identified encoding 305 genes. Analysis of genes located within these focal aberrations, using two independent expression microarray datasets, revealed concurrent altered expression in high-grade CIN and/or cervical carcinomas compared to normal cervical samples for 8 genes: ATP13A3, HES1, OPA1, HRASLS, EYA2, ZMYND8, APOBEC2 and NCR2. Gene silencing of EYA2, located within a focal gain at 20q13, significantly reduced viability and migratory capacity of HPV16-transformed keratinocytes. Interestingly, for hsa-miR-375, located within the most frequently identified focal loss at 2q35, a direct correlation between a (focal) loss and significantly reduced expression was found. Down-regulation of hsa-miR-375 expression during cervical carcinogenesis was confirmed in a second independent series of cervical tissues. Moreover, ectopic expression of hsa-miR-375 in 2 cervical carcinoma cell lines reduced cellular viability.   In conclusion, our data provide a proof of concept that chromosomal aberrations are actively contributing to HPV-induced carcinogenesis and identify EYA2 and hsa-mir-375 as oncogene and tumor suppressor gene, respectively.

overall_design: DNA from microdissected tissues: 60 samples total. 11 high-grade CIN, <5yr preceding hrHPV infection, 43 high-grade CIN >5yr preceding hrHPV infection, 6 CIN3 adjacent to SCC

first: Mariska

last: Bierkens

first: Oscar

last: Krijgsman

first: Saskia

middle: M

last: Wilting

first: Leontien

last: Bosch

first: Annelieke

last: Jaspers

first: Gerrit

middle: A

last: Meijer

first: Chris

first: Peter

last: Snijders

first: Bauke

last: Ylstra

first: Renske

middle: D

last: Steenbergen


title: Analysis of DNA methylation profiles in colorectal cancer cells treated with boswellic acids

city: Dallas

first: Masanobu

last: Takahashi

address: 3500 Gaston Avenue, suite H-250

institute: Baylor University Medical Center

summary: Genome wide DNA methylation profiling of colorectal cancer cell lines treated with acetyl-11-keto-β-boswellic acid (AKBA) or 5-aza-2’-deoxycytidine (DAC). The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in the colorectal cancer cell line SW48. Samples included non-treated, AKBA-treated, and DAC-treated SW48 cells.

overall_design: Bisulphite converted DNA from the 3 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

first: Yan

last: Shen

first: Ajay

last: Goel


title: Mapping of EZH2-WT and EZH2-mTP5 binding sites to human promoter regions

status: Public on Nov 13 2012

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

type: Genome binding/occupancy profiling by genome tiling array

summary:
To gain genome wide information on the association of EZH2 with promoter regions in HeLa cells, DamID experiments and subsequent analysis by promoter arrays (Affymetrix GeneChip Human Promoter 1.0R ) were performed.
The DamID method uses fusions of the bacterial Dam DNA methylase and the protein of interest, to direct the enzymatic activity to the protein’s genomic binding sites, where the DNA is methylated. Methylated DNA is then extracted, enriched and further analysed by microarray. EZH2 is the enzymatic subunit of the Polycomb Repressive Complex 2, which deposits the H3K27me3 mark on chromatin. This mark is associated with low gene expression, either in polycomb repressed regions or, in combination with methylation of H3K4, at poised promoters. An EZH2-T416A mutant (EZH2-mTP5) fails to bind to NIPP1, a factor implied in the regulation of PRC2 binding to a subset of target regions. To obtain a genome wide picture of differential binding of EZH2-WT and the EZH2-mTP5 mutant to promoter regions, the mutant was subjected to DamID/microanalysis as well.

overall_design: DamID of EZH2-WT (2 replicates) and EZH2-mTP5(T416A)(2 replicates) vs. control (Dam without fused protein)(4 samples)

first: Janina

last: Görnemann

first: Aleyde

last: Van Eynde

first: Mathieu

last: Bollen


title: Epigenome analysis of control and neurodevelopmental disorder lymphoblastoid cell lines

city: Los Angeles

first: Kimberly

last: Aldinger

address: 1501 San Pablo St.

department: Zilkha Neurogenetic Institute

institute: University of Southern California

summary: Genome wide DNA methylation profiling of control and neurodevelopmental disorder lymphoblastoid cell lines (LCL). The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in LCLs. Samples included 19 control, 18 Rett syndrome, 17 autism and 6 generalized epilepsy LCL samples. Six technical replicates were also included in the analysis.

overall_design: Bisulphite converted DNA from the 60 samples and 5 technical replicates were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2


title: DNA methylation analysis of pancreatic cancer and non-malignant pancreas cell lines

status: Public on Nov 01 2012

city: Vancouver

first: Kelsie

middle: L

last: Thu

state: British Columbia

address: 675 West 10th Avenue

country: Canada

institute: BC Cancer Research Centre

summary:
Genome wide DNA methylation profiling of 20 PDAC cell lines and an immortalized non-malignant pancreatic duct cell line (HPDE) to facilitate identification of novel tumor suppressor genes using an integrative genomics approach
Genome wide DNA methylation profiling of 20 PDAC cell lines and an immortalized non-malignant pancreatic duct cell line (HPDE) to identify novel tumor suppressor genes

overall_design: Bisulphite converted DNA from the 21 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip


title: The NIH Human Pluripotent Stem Cell Database (Illumina, snp)

status: Public on Oct 31 2012

city: Bethesda

first: Kory

middle: R

last: Johnson

state: MD

address: 10/3B01, 9000 Rockville Pike

department: DIR IT & Bioinformatics

institute: NINDS/NIH

type:
Genome variation profiling by SNP array
SNP genotyping by SNP array

summary: Genotyping was performed on DNA samples matched to the RNA samples included in the NIH Human Pluripotent Stem Cell Database (Series GSE32923). Seventeen undifferentiated human embryonic stem cell lines and 11 human induced pluripotent stem cells were analyzed. Expanded descriptions of methods used are available at: http://stemcelldb.nih.gov.

overall_design: 17 samples: 17 human ESC (UNDIFFerentiated) lines

first: Barbara

middle: S

last: Mallon

first: Josh

middle: G

last: Chenoweth

first: Rebecca

last: Hamilton

first: Paul

last: Tesar

first: Amarendra

last: Yavatkar

first: Leonard

last: Tyson

first: Yang

middle: C

last: Fann

first: Kye

middle: Y

last: Park

first: Kevin

last: Chen

first: Ronald

last: McKay


title: The NIH Human Pluripotent Stem Cell Database (Illumina, methylation)

summary: Methylation profiling was performed on DNA samples matched to the RNA samples included in the NIH Human Pluripotent Stem Cell Database (Series GSE32923). Nineteen undifferentiated human embryonic stem cell lines and 5 human induced pluripotent stem cells were analyzed. Expanded descriptions of methods used are available at: http://stemcelldb.nih.gov.

overall_design: 24 samples: 19 human ESC (UNDIFFerentiated) and 5 human iPSC (UNDIFFerentiated) lines


title: Genome-wide analysis of mRNA levels in response to a Pin1 knock-down

status: Public on Oct 27 2012

city: Buffalo

first: ROOPA

last: THAPAR

state: NY

address: 700 Ellicott Street

department: Structural Biology

institute: Hauptman Woodward Medical Research Institute

summary: Pin1 is a prolyl isomerase that plays an important role in cancer, Alzheimer's disease, and asthma. To understand how Pin1 levels affect mRNA abundance on a genome-wide scale, we knocked down Pin1 by siRNA and used microarray-based gene expression profiling to identify candidate genes that are significantly up- or down-regulated by Pin1 siRNA. The data provide important information on Pin1-responsive genes. We find that genes that are inherently unstable and have short half-lives are targeted by Pin1.

overall_design: Total RNA was obtained from HeLa cells treated with either control siRNA or an siRNA towards Pin1. There were three replicates each for the control and the siRNA-treated cells. The average signal for the three replicates is reported.

first: Nithya

last: Krishnan

first: Roopa

last: Thapar


title: Ten percent of aberrant cells is sufficient for detection of DNA copy number alterations (part 4)

status: Public on Oct 21 2012

first: Daoud

last: Sie

type: Genome variation profiling by genome tiling array

summary: Array Comparative Genomic Hybridization (aCGH) is a widely used technique to assess chromosomal copy number alterations. Chromosomal content, however, is often not uniform throughout cell populations.  The aim of our present study is to evaluate to what extent aCGH can detect DNA copy number alterations in a heterogeneous cell population. Reported detection limits are a compound of analytical software and laboratory technique whilst systematic evaluation is lacking, despite the importance in diagnostics and research. Detection limits were explored with DNA isolated from a patient with intellectual disability (ID) and from tumor cell line BT474. Both were diluted with increasing amounts of normal DNA to simulate different levels of cellularity. Samples were hybridized on CGH arrays containing 180880 oligonucleotides evenly distributed over the genome (space ~17kb). The ID sample has a single copy number gain of 4Mb and a single copy number loss of 7.5Mb that could both be detected with 10% mosaicism. The tumor cell line BT474 has a dual copy number gain (6 copies in a background of 4 copies) of 46Mb. This corresponds to a single copy number gain in a diploid sample and could be detected with 15% tumor cells. The diagnostic validity of these findings was verified using two clinical mosaic samples with alterations in 20% (40Mb) and 14% (34Mb) of cells. Both alterations could be accurately detected using t-statistics.  In conclusion, single copy number gains and losses, down to 4Mb in as little as 10% of a cell population, can be detected by aCGH.

overall_design: DNA of an ID patient with mosaic aberrations in chromosome 1.

first: Oscar

last: Krijgsman

first: Danielle

last: Israeli

first: Hendrik

middle: F

last: van Essen

middle: P

last: Eijk

first: Michel

last: Berens

first: Clemens

middle: H

last: Mellink

first: Aggie

middle: W

last: Nieuwint

first: Marjan

last: Weiss

first: Renkse

last: Steenbergen

first: Gerrit

last: Meijer

first: Bauke

last: Ylstra


title: FOXP3 binding sites in promoter regions of human Jurkat T cells

status: Public on Nov 26 2012

city: Braunschweig

first: Andreas

last: Jeron

state: Nierdersachsen

address: Inhoffenstraße 7

department: Viral Immunology

country: Germany

institute: Helmholtz Center for Infection Research

summary: The transcription factor (TF) Forkhead Box P3 (FOXP3) is constitutively expressed in high levels in natural occurring CD4+CD25+ regulatory T cells (nTreg) and is not only the most accepted marker for that cell population, but is considered lineage determinative. Chromatin immunoprecipitation (ChIP) of transcription factors in combination with genomic tiling microarray analysis (ChIP-on-Chip) has been shown to be an appropriate tool to identify FOXP3 transcription factor binding sites (TFBS) on a genome-wide scale. In combination with microarray expression analysis the ChIP-on-Chip technique allows to identify direct FOXP3 target genes. ChIP-on-Chip analysis of human FOXP3Δ2 isoform expressed in resting and PMA / ionomycin stimulated Jurkat T cells revealed several thousand putative FOXP3 binding sites and importance of intronic regions for FOXP3 binding. Knowledge of general distribution patterns of FOXP3 TFBS in the human genome under resting and activated conditions  contributes to a better understanding of this TF and its influence on direct target genes with importance for Treg cell phenotype and function.

overall_design: ChIP-DNA from FOXP3(Δ2) expressing Jurkat T cells under resting and PMA / ionomycin stimulated conditions from duplicate experiments was analyzed. FOXP3-specific tiling array data were analyzed in reference to an individual isotype control dataset (J-FOXP3 ChIP'd with FOXP3 antibody vs. J-FOXP3 ChIP'd with isotype control antibody). In total 8 tiling array analyses were performed (2x resting J-FOXP3 with FOXP3-IP, 2x resting J-FOXP3 with isotype-IP, 2x PMA/iono J-FOXP3 with FOXP3-IP, 2x PMA/iono J-FOXP3 with isotype-IP)

first: Wiebke

last: Hansen

first: Jan

last: Buer

first: Robert

last: Geffers

first: Dunja

last: Bruder


title: DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis

status: Public on Oct 29 2012

city: Esplugues de Llobregat

first: Cinzia

last: Lavarino

state: Barcelona

address: Santa Rosa 39-57

department: Oncology

country: Spain

institute: Hospital Sant Joan de Déu

summary: Neuroblastoma pathogenesis has been reported to be closely associated with numerous genetic alterations. However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. In this study, we generated microarray-based DNA methylation profiles of primary neuroblastic tumors. Stringent supervised differential methylation analyses allowed us to identify epigenetic changes characteristic for NB tumors as well as for clinical and biological subtypes of NB. We observed that gene-specific loss of DNA methylation is more prevalent than promoter hypermethylation. Overall, the differentially methylated genes showed that functional pathways affected by hypermethylation are different from those affected by hypomethylation. This study provides a comprehensive view of the global DNA methylation profile of NB tumors.

overall_design: Bisulphite converted DNA from the 25 neuroblastic tumor and 2 non patological tissues (fetal brain and adrenal gland) samples  were hybridised to the Illumina Infinium 27k Human Methylation


title: Analysis of genome-wide methylation of phenotypically discordant monozygotic twins

status: Public on Oct 20 2012

city: Kobe-shi

first: Chihchieh

last: Yu

address: 7-5-1 kusunoki-cho, chuo-ku

country: Japan

institute: Kobe University

summary:
Human intelligence demonstrates one of the highest heritabilities among human quantitative traits. Phenotypically discordant monozygotic twins provide a way to identify loci reponsible for the phenotypical differences.
We performed comprehensive DNA methylation analysis in monozygotic twins manifesting differences in IQ scores. Genes with significantly different methylation status are considered as candidates related to human intelligence.

overall_design: Methylation profiling was conducted using methylated DNA enriched fraction by MethylMiner. Subjects were compared with their co-twins by MAT software and  bed files were generated. Significantly high methyalted regions with MAT score p value < 0.000001 in each twin pairs were extracted as candidates.

first: Mari

last: Furukawa

first: Kazuhiro

last: Kobayashi

first: Chizuru

last: Shikizima

first: Juko

last: Ando

first: Tatsushi

last: Toda


title: Factors underlying variable DNA methylation in a human community cohort

status: Public on Oct 10 2012

first: Michael

middle: S.

last: Kobor

state: BC

address: 950 West 28th Avenue

department: Medical Genetics

institute: Centre for Molecular Medicine and Therapeutics / University of British Columbia

summary: Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression.We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated

overall_design: This cohort consist of genomic DNA extracted from 94 PBMC DNA samples, bisulphite converted and hybridized, along with 5 technical replicates to the Illumina Infinium HumanMethylation27 Beadchip v1.2 for genome wide DNA methylation profiling.

first: Lucia

last: Lam

first: Eldon

last: Emberly

first: Hunter

middle: B

last: Fraser

first: Sarah

last: Neumann

first: Edith

last: Chen

first: Gregory

middle: E

last: Miller


title: Methylation profiling in Ulcerative colitis

status: Public on Sep 27 2012

city: Kiel

first: Zhe

last: Feng

address: Schittenhelmstr. 12

institute: Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany

type: Methylation profiling by genome tiling array

summary: The series was designed to identify the different methylated single CpGs involved in the pathophysiology of ulcerative colitis.

overall_design: A cohort of n=20 monozygotic twins, discordant for ulcerative colitis was selected. Illumina and Nimblegen platforms were used.

last: Häsler


title: Ahringer FP00001_HPL2_N2_L3_EGS

status: Public on Sep 18 2012

city: Toronto

first: DCC

last: modENCODE

state: Ontario

address: MaRS Centre, South Tower, 101 College Street, Suite 800

institute: Ontario Institute for Cancer Research

summary:
modENCODE_submission_3624
This submission comes from a modENCODE project of Jason Lieb. For full list of modENCODE projects, see http://www.genome.gov/26524648
Project Goal: The focus of our analysis will be elements that specify nucleosome positioning and occupancy, control domains of gene expression, induce repression of the X chromosome, guide mitotic segregation and genome duplication, govern homolog pairing and recombination during meiosis, and organize chromosome positioning within the nucleus. 126 strategically selected targets include key histone modifications, histone variants, RNA polymerase II isoforms, dosage-compensation proteins, centromere components, homolog-pairing facilitators, recombination markers, and nuclear-envelope constituents.
We will integrate information generated with existing knowledge on the biology of the targets, perform ChIP-chip analysis on mutant and RNAi extracts lacking selected target proteins, use extrachromosomal arrays to assess the ability of candidate identified sequence motifs to recruit targets in vivo, identify tissue-specific patterns of selected targets, and create integrated, quantitative models of transcription and whole-chromosome functions.
For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

overall_design: EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: N2; Developmental Stage: L3 Larva; Genotype: wild type; Sex: mixed Male and Hermaphrodite population;  NUMBER OF REPLICATES: 2;  EXPERIMENTAL FACTORS: Developmental Stage L3 Larva; temp (temperature) 20 degree celsius; Antibody FP00001 HPL2 (target is HPL-2); Strain N2

first: Isabel

last: Latorre

first: Paulina

last: Kolasinska-Zwierz

first: Julie

last: Ahringer


title: Expression analysis of TRANSPOSABLE ELEMENT KILLER (TEK) knockdown lines

status: Public on Sep 12 2012

city: Singapore

first: Yifeng

last: Xu

address: 1 Research Link, National University of Singapore

country: Singapore

institute: Temasek Life Sciences Laboratory

summary:
Investigation of the effect of the knockdown of AT-hook motif DNA binding nuclear matrix protein TRANSPOSABLE ELEMENT KILLER (TEK) in the Arabidopsis Landsberg erecta (Ler) background
Transposable elements (TEs) are silenced by epigenetic mechanisms of DNA and histone methylation. The repressive histone modification H3 lysine 9 dimethylation (H3K9me2) is TE-associated epigenetic hallmark, and is necessary for DNA methylation. However the mechanism to direct the repressive epigenetic modification in TEs has remained elusive. Here we show that knockdown of the AT-hook motif DNA binding nuclear matrix protein TRANSPOSABLE ELEMENT KILLER (TEK) in the Arabidopsis Landsberg erecta (Ler) background results in robust activation of various TEs, the repeat-containing floral repressor gene FWA and the TE-containing floral repressor FLOWERING LOCUS C (FLC).

overall_design: A four chip study using two separate wild-type seedling mRNA samples and two separate TEKi seedling mRNA samples

first: Toshiro

last: Ito


title: Ten percent of aberrant cells is sufficient for detection of DNA copy number alterations

first: Daoud

last: Sie

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: CpG Methylation by Illumina Methyl27 Bead Arrays from ENCODE/HAIB

status: Public on Sep 07 2012

city: Stanford

first: ENCODE

last: DCC

state: CA

address: 300 Pasteur Dr

institute: ENCODE DCC

summary:
This data was generated by ENCODE. If you have questions about the data, contact the submitting laboratory directly (Florencia Pauli mailto:fpauli@hudsonalpha.org). If you have questions about the Genome Browser track associated with this data, contact ENCODE (mailto:genome@soe.ucsc.edu).
This track is produced as part of the ENCODE project. The track displays the methylation status of specific CpG dinucleotides in the given cell types as identified by the Illumina Infinium HumanMethylation27 BeadArray platform (http://www.illumina.com/pages.ilmn?ID=243). In general, methylation of CpG sites within a promoter causes silencing of the gene associated with that promoter.
Detailed information for the CpG targets is in an XLS formatted spreadsheet on the Myers' lab protocols website (http://hudsonalpha.org/myers-lab/protocols).

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

overall_design:
Cells were grown according to the approved ENCODE cell culture protocols (http://hgwdev.cse.ucsc.edu/ENCODE/protocols/cell).
Genomic DNA was isolated from each cell line with the QIAGEN DNeasy Blood & Tissue Kit according to the instructions provided by the manufacturer. DNA concentrations and a level of quality of each preparation was determined by fluorescence with the Qubit Fluorometer (Invitrogen).
The Methyl27K platform uses bisulfite treated genomic DNA to assay the methylation status of 27,578 CpG sites within more than 14,000 genes. When genomic DNA is treated with sodium bisulfite, unmethylated cytosine of CpG dinucleotides are converted into uracils; methylated cytosines do not get converted. After bisulfite treatment, the methylation status of a site is assayed by single base-pair extension with a Cy3 or Cy5 labeled nucleotide on oligo-beads specific for the methylated or unmethylated state. A beta value is calculated by Illumina's Bead Studio software for each CpG target. This value represents the intensity value from the methylated bead type divided by the sum of the intensity values from the methylated and unmethylated bead types for any given CpG target.
Bisulfite conversion reaction was done using the Zymo Research EZ-96 DNA Methylation Kit (http://www.zymoresearch.com/epigenetics/dna-methylation/ez-96-dna-methylation-kit). One step of the protocol was modified. During the incubation, a 30 sec 95oC denaturing step every hour was included to increase reaction efficiency as recommended by the Illumina Infinium Human Methylation27 protocol.
The bead arrays were run according to the protocol provided by Illumina (http://www.illumina.com/pagesnrn.ilmn?ID=275).
The intensity data from the BeadArray was processed using Illumina's BeadStudio software with the Methylation Module v3.2. The data was then quality-filtered using p-values.
Any beta value equal to or greater than 0.6 is considered fully methylated. Any beta value equal to or less than 0.2 is considered to be fully unmethylated. Beta values between 0.2 and 0.6 are considered to be partially methylated. Beta-values are quality filtered and spots that fall below the minimum intensity threshold are displayed as "NA".
Score in the bed files is beta value x 1000

first: Richard

last: Myers

first: Devin

last: Absher

first: Florencia

last: Pauli


title: Genotype (CNV and SNP) by Illumina 1MDuo and CBS from ENCODE/HudsonAlpha

summary:
This data was generated by ENCODE. If you have questions about the data, contact the submitting laboratory directly (Florencia Pauli mailto:fpauli@hudsonalpha.org). If you have questions about the Genome Browser track associated with this data, contact ENCODE (mailto:genome@soe.ucsc.edu).
This track is produced as part of the ENCODE project. The track displays copy number variation (CNV) as determined by the Illumina Human 1M-Duo Infinium HD BeadChip assay and circular binary segmentation (CBS). The Human 1M-Duo contains more than 1,100,000 tagSNP markers and a set of ~60,000 additional CNV-targeted markers. The median spacing between markers is 1.5 kb and the mean spacing is 2.4 kb. The B-allele frequency and genotyping single nucleotide polymorphism (SNP) data generated by the experiment are not displayed, but are available for download from the Downloads page.
Where applicable, biological replicates of each cell line are reported separately. Possible uses of the data include correction of copy number in peak-calling for ChIP-seq, transcriptome, DNase hypersensitivity, and methylation determinations.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

overall_design:
Isolation of genomic DNA and hybridization: Cells were grown according to the approved ENCODE cell culture protocols by the Myers lab and by other ENCODE production groups. The production group is reported in the metadata. Genomic DNA was isolated using the DNeasy Blood and Tissue Kit (Qiagen). DNA concentration and quality were determined by fluorescence (Invitrogen Quant-iT dsDNA High Sensitivity Kit and Qubit Fluorometer), and 400 nanograms of each sample were hybridized to Illumina 1M-Duo DNA Analysis BeadChips.
Processing and Analysis: The genotypes from the 1M-Duo Arrays were ascertained with BeadStudio by using default settings and formatting with the A/B genotype designation for each SNP. Primary QC for each sample was a cut-off at a call rate of 0.95.
Copy Number Variation (CNV) analysis was performed with circular binary segmentation (DNAcopy) of the log R ratio values at each probe (Olshen et al., 2004). The parameters used were alpha=0.001, nperm=5000, sd.undo=1. The copy number segments are reported with the mean log R ratio for each chromosomal segment called by CBS. Log ratios of ~-0.2 to -1.5 can be considered heterozygous deletions, < -1.5 homozygous deletions, and > 0.2 amplifications. Primary QC for each sample was SD of < 0.6.


title: Epigenetic analysis of healthy young men following a control and high-fat overfeeding diet

city: Copenhagen N

first: Stine

last: Jacobsen

address: Tagensvej 20, sec. 7652

department: Diabetes and Metabolism

country: Denmark

institute: Rigshospitalet

summary: Genome-wide DNA methylation profiling of healthy young men following a control and high-fat overfeeding diet using Illumina's Infinium 27k Human DNA methylation Beadchip v. 1.2. DNA methylation profiles were obtained for 27,578 CpG sites in human skeletal muscle.

overall_design: Randomized cross-over desgin, where all subjects receieved both treatments (control and high-fat overfeeding diet). Biopsies were obtained from 23 different individuals amounting to 22 samples following the control diet and 22 samples following the high-fat overfeeding diet (paired n=21). Bisulphite converted DNA from the 44 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.

first: Allan

last: Vaag

first: Mario

last: Fraga


title: Lentiviral transduction of CD34+ cells induces genome-wide epigenetic modifications

status: Public on Sep 05 2012

city: Evry

first: NIZAR

last: TOULEIMAT

address: 2 rue Gaston Crémieux

country: France

institute: CEA/Institut de Génomique and Généthon

summary: Human CD34+ cells were cultured shortly in the presence of cytokines then with a gene transfer lentiviral vector (LV) expected to transduce cells but to have otherwise limited biological effects on the cells. At the end of the culture, the population of cells remained largely similar at the phenotypic level but some epigenetic changes were evident. Exposure of CD34+ cells to cytokines caused genome-wide DNA methylation changes. Surprisingly, the LV caused additional and distinct effects. Large-scale genomic DNA methylation analysis showed that balanced methylation changes occurred in about 200 genes following culture of CD34+ cells in the presence of cytokines but 900 genes were modified following addition of the LV, predominantly increasing CpG methylation.  Epigenetic effects resulting from ex vivo culture and from the use of LV may constitute previously unsuspected sources of biological effects in stem cells and may provide new biomarkers to rationally optimize gene and cell therapy protocols.

overall_design: 3 replicates of control unstimulated (Group 1), cytokine stimulated, cytokine strimulated and treated with polybren and cytokine stimulated and transduced with lentiviral vector coding for GFP in the presence of polybren were analysed

first: Yoshiaki

last: Yamagata

first: Véronique

last: Parietti

first: Daniel

last: Stockholm

first: Guillaume

last: Corre

first: Catherine

last: Poinsignon

first: Nizar

last: Touleimat

first: Damien

last: Delafoy

first: Céline

last: Besse

first: Jörg

last: Tost

first: Anne

last: Galy

first: Andras

last: Paldi


title: Ahringer AB1791_H3_N2_L3

first: DCC

last: modENCODE

summary:
modENCODE_submission_3206
This submission comes from a modENCODE project of Jason Lieb. For full list of modENCODE projects, see http://www.genome.gov/26524648
Project Goal: The focus of our analysis will be elements that specify nucleosome positioning and occupancy, control domains of gene expression, induce repression of the X chromosome, guide mitotic segregation and genome duplication, govern homolog pairing and recombination during meiosis, and organize chromosome positioning within the nucleus. 126 strategically selected targets include key histone modifications, histone variants, RNA polymerase II isoforms, dosage-compensation proteins, centromere components, homolog-pairing facilitators, recombination markers, and nuclear-envelope constituents.
We will integrate information generated with existing knowledge on the biology of the targets, perform ChIP-chip analysis on mutant and RNAi extracts lacking selected target proteins, use extrachromosomal arrays to assess the ability of candidate identified sequence motifs to recruit targets in vivo, identify tissue-specific patterns of selected targets, and create integrated, quantitative models of transcription and whole-chromosome functions.
For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

overall_design: EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: N2; Developmental Stage: L3 Larva; Genotype: wild type; Sex: mixed Male and Hermaphrodite population;  NUMBER OF REPLICATES: 2;  EXPERIMENTAL FACTORS: Developmental Stage L3 Larva; temp (temperature) 20 degree celsius; Antibody C. elegans  AB1791 H3 rabbit polyclonal antibody (target is Histone H3); Strain N2

last: Canonge

first: Julie

last: Ahringer


title: Reversal of Aberrant Cancer Methylome and Transcriptome upon Direct Reprogramming of Lung Cancer Cells [Methylation]

status: Public on Sep 01 2012

city: Bad Nauheim

first: Jason

last: Lai

state: Hessen

address: Ludwigstrasse 43

department: Developmental Genetics

institute: Max Planck Institute For Heart and Lung Research

summary: Non-small cell lung cancer cell (NSCLC) lines were reprogrammed with Yamanaka's cocktail and their methylome and transcriptome were studied and characterized.

overall_design: We compared reprogrammed cells to their respective parent (2 NSCLC and 1 human lung fetal fibroblast) and used H1 as a positive control for pluripotency characteristics. The in vitro differentiated cells were also compared to the reprogrammed cells. All samples have biological triplicates except for differentiated cells.


title: atnsrs-study the role of AtNSRs proteins in the regulation of gene expression

status: Public on Oct 01 2012

city: evry

first: Soubigou-Taconnat

last: Ludivine

address: 2 rue gaston crémieux

department: URGV

institute: INRA

summary: blanc-08-01_2012_01_rnapaths_nsr - atnsrs - study the role of AtNSRs proteins in the regulation of gene expression - comparaison between Arabidopsis thaliana Col-0 and Atnsra/b double mutant treated or not with 24h 1µM NAA

overall_design: 12 dye-swap - gene knock out

first: Sandrine

last: Balzergue

first: Ludivine

last: Taconnat

first: Allison-

last: Mallory

first: Marie-Laure

last: Martin-Magniette


title: Androgen receptor function links human sexual dimorphism to DNA methylation

status: Public on Aug 12 2012

city: Ulm

first: Ole

last: Ammerpohl

address: Albert-Einstein-Allee 11

institute: UK Ulm

summary:
To decipher hormonal from chromosomal factors we compared DNA-methylation of 27,568 CpG-loci in genital fibroblasts from 46,XY feminized individuals (AIS) with inactivating androgen receptor mutations to those of normal males.
The results of the following two subset comparisons are linked to the Series record below:
CpG loci differentially methylated (q<0.04) between AIS and male controls (primary human genital fibroblasts): To decipher hormonal from chromosomal factors we compared DNA-methylation of 27,568 CpG-loci in genital fibroblasts from 46,XY feminized individuals (AIS) with inactivating androgen receptor mutations to those of normal males. Cell culture of primary fibroblasts from scrotum/ labia majora from donors with PAIS (n=13), MAIS (n=1) or CAIS (n=13) and 9 controls were analyzed using the HumanMethylation27 Bead Chip. 13 AIS samples and all controls were analyzed in duplicates. Samples with gene call rates <95% as analyzed with BeadStudio software (Illumina, Inc.) and CpGs with detection p-values >0.05 in at least one experiment were excluded from analyses. 54 hybridizations with 25,988 CpGs entered the analysis. Differential methylation analysis (DMA) was performed based on average beta-values were performed using OMICS Explorer (v.2.1(25); Qlucore, Sweden). This file contains CpG loci found differentially methylated (q<0.04) by this approach.
CpG loci characterized by a high varibility in their DNA methylation value in AIS compared to male controls (primary human genital fibroblasts): To decipher hormonal from chromosomal factors we compared DNA-methylation of 27,568 CpG-loci in genital fibroblasts from 46,XY feminized individuals (AIS) with inactivating androgen receptor mutations to those of normal males. Cell culture of primary fibroblasts from scrotum/ labia majora from donors with PAIS (n=13), MAIS (n=1) or CAIS (n=13) and 9 controls were analyzed using the HumanMethylation27 Bead Chip. 13 AIS samples and all controls were analyzed in duplicates. Samples with gene call rates <95% as analyzed with BeadStudio software (Illumina, Inc.) and CpGs with detection p-values >0.05 in at least one experiment were excluded from analyses. 54 hybridizations with 25,988 CpGs entered the analysis. CpG loci with beta-values ranged in control samples up to 0.34 and a difference of the interquartiles between controls and AIS samples above 0.16 were considered as being variably methylated in AIS and are included in this file.

overall_design: Bisulphite converted DNA from the 62 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip

first: Paul-Martin

last: Holterhus


title: Genome wide DNA Methylation analysis of benign and malignant adrenocortical tumors

city: New Haven

first: Annabelle

last: Fonseca

state: CT

address: 300 Cedar Street

department: Department of Surgery

institute: Yale University

summary: Genome wide DNA methylation profiling of normal adrenocortical tissue, adrenocortical adenomas and adrenocortical carcinomas. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles. Samples included 6 normal adrenocortical tissue samples, 27 adenomas and 15 carcinomas.

overall_design: Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

first: Tobias

last: Carling

first: Johan

last: Kugelberg

first: Lee

last: Starker

first: Ute

last: Scholl

first: Murim

last: Choi

first: Per

last: Hellman

first: Göran

last: Åkerström

first: Gunnar

last: Westin

first: Richard

last: Lifton

first: Peyman

last: Björklund


title: Brain transcriptional and epigenetic associations with the autistic phenotype (methylation data)

status: Public on Aug 15 2012

city: Cleveland

first: Matthew

last: Ginsberg

state: OH

address: 9500 Euclid Ave

department: Lerner College of Medicine

institute: Cleveland Clinic Foundation

summary: Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. To uncover important gene dysregulation in autism, we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high-resolution whole genome gene expression and DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.

overall_design: In this set of DNA methylation data, 9 cerebellar autism, 9 cerebellar control, 8 BA19 (occipital cortex) autism, and 8 BA19 control samples were used. Samples are labeled with a B followed by a unique number and letter identifying the subject and brain region, followed by an optional hyphenated number indicating the technical replicates performed on sample 1.

first: Robert

last: Rubin

first: Tatiana

last: Falcone

first: Angela

last: Ting

first: Marvin

last: Natowicz


title: Affymetrix data from Populus nectaries versus leaves

status: Public on Aug 03 2012

city: Wuerzburg

first: Peter

last: Ache

address: Julius von Sachs Platz 2

institute: Julius von Sachs Institut

summary:
To identify the genes encoding the defense proteins and gain a deeper insight into the Ptt nectary transcriptom, poplar DNA microarrays (Affymetrix) were hybridized with RNA of extrafloral nectaries and nectary-free leaf sections
Many plant species grow extrafloral nectaries and produce nectar to attract carnivore arthropods as defenders against herbivores. We studied in Populus how insect feeding feeds back on nectary development and activity. Two nectary types evolved with Populus trichocarpa (Ptr) and P. tremula x P. tremuloides (Ptt) were studied from their ecology down to the genes and molecules.

overall_design: 3 samples of leaves and 3 of nectaries from P. tremula tremuloides field-culture


title: DNA methylation alterations and transcriptional gene silencing induced by IDH1 R132H mutation [Illumina]

status: Public on Aug 14 2012

city: Atlanta

first: Benjamin

last: Barwick

state: GA

address: 1365 Clifton Rd. NE WCI-C 4th Floor Benches 36-37

department: Hematology and Medical Oncology

institute: Emory University

summary: The cytosolic NADP+-dependent isocitrate dehydrogenase IDH1 is frequently mutated in human cancers. Recent studies have shown that IDH1 mutant primary glioblastomas (GBM) and acute myeloid leukemias (AML) display robust association with CpG island methylator phenotype (CIMP).  Such observations bring into question whether IDH1 mutations directly contribute to the development of CIMP or if the hypermethylation phenotype precedes acquisition of IDH1 mutations.  To reveal the effects of IDH1 mutations on DNA methylation and gene expression, we introduced the most frequently observed IDH1 mutation, R132H, into a human cancer cell line through gene targeting.  We profiled changes in methylation at over 27,000 CpG dinucleotides spanning 14,475 unique gene regions and characterized genome-wide gene expression alterations resulting from IDH1R132H knockin.  We observed consistent changes in both DNA methylation and gene expression when comparing two independent IDH1R132H knockin clones to their wild-type parent, and report hypermethylation of over 2,000 loci, the majority of which contained preexisting methylation in IDH1WT parental cells. These loci exhibit the same trend in primary TCGA glioblastoma tumors with mutant IDH1 as compared to those with wild-type IDH1 and have significant overlap with genes hypermethylated in glioma-CIMP+ tumors. Furthermore, we identify specific DNA methylation and gene expression alterations which correlate with IDH1 mutations in our cell-line model as well as primary glioblastomas, including hypermethylation and transcriptional silencing of RBP1.  The presented data provide insight on epigenetic alterations induced by IDH1 mutations and support a contributory role for IDH1 mutants in regulation of DNA methylation and gene expression in human cancer cells.

overall_design: Comparison of IDH1 R132H and wild-type HCT116 cells as well as HOG cells overexpressing either wild-type IDH1 or IDH1 R132H

first: Christopher

last: Duncan

first: Paula

last: Vertino

first: Hai

last: Yan


title: An integrated genomic and expression analysis of 7q deletion in SMZL (Illumina Infinium Human Methylation 27 array)

status: Public on Aug 30 2012

city: Cambridge

first: Alan

middle: J

last: Watkins

address: Addenbrooke's Hospital

country: United Kingdom

institute: University of Cambridge

summary: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterised by 7q32 deletion, but the target genes of this deletion remain unknown. In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrative transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed (P <0.05) in SMZL relative to other lymphomas. Genomic sequencing of these miRNA and IRF5, a strong candidate gene, did not show any evidence of somatic mutation in SMZL.

overall_design: For methylation arrays. Epigenetic methylation analysis was performed using the Infinium Human Methylation 27 array (Illumina, San Diego, California, USA). The array contained 27,568 CpG islands within the proximal promoter regions of transcription start sites of 14,475 RefSeq genes, including 12,883 well annotated genes (NCBI CCDS database: Build 36). The methylation array was carried out in 12 SMZL (6 cases with 7q deletion), 6 follicular lymphomas (FL) and 6 mantle cell lymphomas (MCL) as per the manufacturer’s instructions. Briefly, 2μg genomic DNA extracted from frozen tissues with >70% tumour cells was bisulphite modified using the EZ DNA Methylation Kit (Zymo Research Corporation). Bisulphite modified DNA was then amplified using the MSM master mix (Illumina) and incubated at 37oC for 22 hours. Amplified DNA was then fragmented and hybridised to BeadChips in an Illumina Hybridisation Oven at 48oC for 18 hours. Following hybridisation, single base extension of hybridised DNA using hapten labelled bases was performed. Staining was then developed using immunochemical stains catalysed by the haptens, and the arrays washed. The chips were scanned using the BeadArray™ Reader (Illumina) and the BeadScan™ software (Illumina) using the Infinium Methylation Scan setting. The scanned data was then analysed in GenomeStudio™ (Illumina) using the Methylation analysis module.

first: Rifat

last: Hamoudi

first: Naiyan

last: Zeng

first: Qingguo

first: Yuanxue

last: Huang

first: Hongxiang

last: Liu

first: Jianzhong

last: Zhang

first: Esteban

last: Braggio

first: Rafael

last: Fonseca

first: Laurence

last: de Leval

last: Isaacson

first: Andrew

last: Wotherspoon

first: Ellen

last: McPhail

first: Ahmet

last: Dogan

first: Ming

middle: Q

last: Du


title: Neonatal DNA methylation profile in humans is specified by a complex interplay between intrauterine environmental/ genetic factors subject to tissue-specific influence

status: Public on Jul 18 2012

city: Parkville

first: Richard

last: Saffery

state: Victoria

address: Flemington Rd

department: Cancer, Disease and Developmental Epigenetics

country: Australia

institute: Murdoch Children's Research Institute

summary: Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic, shared and non-shared environmental factors to phenotypic variability. Using DNA methylation profiling of ~20,000 CpG sites as a phenotype, we have examined discordance levels in multiple tissues in neonatal twins. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. This was largely independent of distance from transcriptional start site in promoters without CpG islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of non-shared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic and other complex diseases. Finally, comparison of our data with that of several older twins, revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyse DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.

overall_design: Data from cord blood mononuclear cells (CBMCs), human umbilical vascular endothelial cells (HUVECs) and placenta from 22 MZ and 11 DZ pairs with one replicate sample

first: Lavinia

last: Gordon

first: Eric

last: Joo

first: Joseph

last: Powell

first: Miina

last: Ollikainen

first: Boris

last: Novakovic

first: Xin

last: Li

first: Roberta

last: Andronikos

first: Mark

middle: N

last: Cruickshank

first: Karen

last: Conneely

first: Alicia

middle: K

last: Smith

first: Reid

last: Alisch

first: Ruth

last: Morley

first: John

last: Carlin

first: Peter

middle: M

last: Visscher

first: Jeffery

last: Craig


title: DNA methylation analyses of urothelial carcinoma reveal distinct epigenetic subtypes and an association between gene copy number and methylation status

status: Public on Aug 31 2012

city: Lund

first: Mattias

last: Aine

address: Klinikgatan 28

country: Sweden

institute: Lund University

summary: We assessed DNA methylation and copy number status of 27,000 CpGs in 149 urothelial carcinomas and integrated the findings with gene expression and mutation data. Methylation was associated with gene expression for 1,332 CpGs, of which 26% showed positive correlation with expression, i.e., high methylation and high gene expression levels. These positively correlated CpGs were part of specific transcription factor binding sites, such as sites for MYC and CREBP1, or located in gene bodies. Furthermore, we found genes with copy number gains, low expression and high methylation levels, revealing an association between methylation and copy number levels. This phenomenon was typically observed for developmental genes, such as HOX genes and tumor suppressor genes. In contrast, we also identified genes with copy number gains, high expression and low methylation levels. This was for instance observed for some keratin genes. Tumor cases could be grouped into four subgroups, termed epitypes, by their DNA methylation profiles. One epitype was influenced by the presence of infiltrating immune cells, two epitypes were mainly composed of non-muscle invasive tumors, and the remaining epitype of muscle invasive tumors. The polycomb complex protein EZH2 that blocks differentiation in embryonic stem cells showed increased expression both at the mRNA and protein levels in the muscle invasive epitype, together with methylation of polycomb target genes and HOX genes. Our data highlights HOX gene silencing and EZH2 expression as mechanisms to promote a more undifferentiated and aggressive state in UC.

overall_design:
The study was conducted on genomic DNA from 150 primary fresh-frozen urothelial carcinoma tumors selected to have equal representation of stages Ta, T1 and T2>. The design also included four fully methylated and four unmethylated hybridization controls as well as 7 Normal urothelium samples. One tumor sample (UC_0556_1) was included as a technical replicate in each of four bisulfite treatment batches. The samples were bisulfite treated and hybridized to Illumina Human Methylation27 Bead Chip arrays according to manufacturers instructions at the SCIBLU Genomics Centre at Lund University, Sweden.

Note: Illumina methylation data set comprises total of 168 samples (raw data), but 156 samples (processed data), derived from primary urothelial carcinoma samples.  See README.txt for details of the 12 samples not included in the final, processed data.

first: Gottfrid

last: Sjödahl

first: Martin

last: Lauss

first: David

last: Lindgren

last: Höglund


title: Identification of Developing Xylem-Specific Promoters from Poplar by Using tissue type-Specific Whole Genome Transcriptome Analysis.

status: Public on Jul 07 2012

city: Yongin

first: Jae-Heung

last: Ko

state: Gyeonggi

address: 1 Seocheon-dong, Giheung-gu

department: Plant & Environmental Resources

country: South Korea

institute: Kyung Hee University

summary: Lignocellulosic feedstock (i.e., wood) is gaining popularity as a source of fermentable sugars for liquid fuel production. To improve the quantity and quality of woody biomass, the developing xylem (DX) cell-specific genetic modification is desired. Bioinformatic analyses followed by the validation of cell type-specific transcriptomes led to the identification of 37 transcripts specifically expressed in DX. After further confirmation of DX-specific expression, we selected four genes (DX5, DX8, DX11 and DX15) to demonstrate the feasibility of our strategy. The promoter regions of selected DX genes were isolated and produced stable transformants of poplar by using transcriptional promoter:β-glucuronidase (GUS) fusion constructs. The GUS expression patterns of DX5 and ANAC073 (orthologous gene of Arabidopsis) revealed that these promoters were active in xylem cells in poplar at early seedling growth, and showed strongest expression in the developing xylem cells in the wood formation/development at later growth stages of poplar. DX specific and strong expression patterns of all the other DX promoters (DX8, DX11 and DX15) tested suggests that these promoters may be useful to control transgene expression in the DX cells of woody plants with the aim of the feedstock improvement.

overall_design: In order to identify specifically and strongly expressed genes from DX cells of woody plant, we generated the tissue/cell type-specific transcriptomes from poplar stem by using whole genome GeneChip technology (Affymetrix).

first: Kyung-Hwan

last: Han


title: Oligo array for CNV calling AUTS2 project [Agilent]

status: Public on Jul 12 2012

city: Amsterdam

first: Els

last: Voorhoeve

address: De Boelelaan 1117

department: Clinical Genetics

institute: VU medical center

summary: Phenotypic and genotypic description of AUTS2 deletion patients found by Array analysis in an international cohort of intellectual disability (ID) and multiple congenital malformations (MCA).

overall_design: Arrays were hybridized and analysed using manufacturer's  protocols on DNA from patients with ID/MCA

first: Ellen

last: van Binsbergen

first: Gea

last: Beunders


title: DNA methylation alterations in response to pesticide exposure in vitro

status: Public on Jun 14 2012

city: Chicago

first: xiao

last: zhang

address: 680 N. Lake Shore Drive

institute: Northwestern University

summary: Genome wide DNA methylation profiling of DNA from K562 cells treated with three commonly used pesticides and control (EtOH). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 27,000 CpGs in DNA samples.

overall_design: Bisulphite converted DNA from the samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip. 7 pesticides were used.

first: Lifang

last: Hou

first: Xiao

last: Zhang


title: Identification of novel DNA copy number aberrations associated to GIST

status: Public on Jul 01 2012

city: Porto

first: Rune

last: Matthiesen

address: Rua Dr. Roberto Frias s/n

country: Portugal

institute: IPATIMUP

summary: aCGH data of paraffin embedded gastrointestinal stromal tumors versus blood reference

first: Rui

last: Reis


title: Illumina SNP-array data for 2 ETV6/RUNX1-positive Acute Lymphoblastic Leukemia samples and corresponding normal samples

status: Public on Jul 03 2012

first: Henrik

last: Lilljebjörn

address: Lund University Hospital

department: Dept of Clinical Genetics

summary: Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL.

overall_design: Illumina SNP-array genotyping was performed according to the manufacturer's directions on DNA extracted from 2 leukemic bone marrow samples and two corresponding normal blood samples. The genotype data from the arrays were used for quality assesment of genotype data from high throughput sequencing.

first: Thoas

last: Fioretos


title: Transcriptome profiling data for secondary vascular tissue regeneration in Populus tomentosa

status: Public on Jul 26 2012

city: Beijing

first: Jing

address: Room 224, Old Building of Life Sciences, No.5 Yiheyuan Road, Haidian District,

department: College of Life Sciences

country: China

institute: Peking University

summary:
Regeneration is a common strategy for plants to repair their damaged body plans after attack from other organisms or physical assaults. Trees with bark girdling on a large scale will grow new bark within one month and this bark regeneration after girdling system has been proven to be an efficient method to study secondary vascular development as well as plant tissue regeneration in vivo.
We herein show the molecular features of differentiating xylem cell fate switch process during secondary vascular tissue (SVT) regeneration in Populus. Based on our data, we propose a working model to illustrate the molecular dynamics underlying xylem cell fate switch process during SVT regeneration, which is significant to understand the pattern formation during the SVTs regeneration and also would shed light on the mechanisms of tissue regeneration in plants.

overall_design:
Specific regenerated tissues of Populus at different stages were isolated by tangential cryo-sectioning. Total RNA from cryo-sections representing different regenerating tissues was extracted for Affymetrix Poplar Whole Genome Array hybridization. Five samples (two replicates for each sample) were used for gene expression analysis: differentiating xylem (diX, Stage 0), dedifferentiating xylem cells (deX, Stage I), regenerated phloem (rPh, Stage II), differentiating regenerated cambium (diC, Stage II) and regenerated cambium (rC, Stage III). In addition, one pooled genomic DNA sample from cryo-sections of differentiating xylem from two trees  was isolated for DNA hybridization to produce a new CDF file that was used to mask out some potentially cross-hybridizing probesets from the standard Affymetrix Poplar Genome Array.
Supplementary file: poplar.cdf

first: Ge

last: Gao

first: Xinqiang

last: He

first: Keming

last: Cui


title: Genetic Aberrations Relate Early and Advanced Stage Ovarian Cancer and are Associated with Survival

status: Public on Aug 22 2012

first: Daoud

last: Sie

department: Pathology

institute: Vrije Universiteit Medical Center

summary:
BACKGROUND:
Because of the distinct clinical presentation of early and advanced stage ovarian cancer, we aim to clarify whether these disease entities are solely separated by time of diagnosis or whether they arise from distinct molecular events.
METHODS:
Sixteen early and sixteen advanced stage ovarian carcinomas, matched for histological subtype and differentiation grade, were included. Genomic aberrations were compared for each early and advanced stage ovarian cancer by array comparative genomic hybridization. To study how the aberrations correlate to the clinical characteristics of the tumors we clustered tumors based on the genomic aberrations.
RESULTS:
The genomic aberration patterns in advanced stage cancer equalled those in early stage, but were more frequent in advanced stage (p = 0.012). Unsupervised clustering based on genomic aberrations yielded two clusters that significantly discriminated early from advanced stage (p = 0.001), and that did differ significantly in survival (p = 0.002). These clusters however did give a more accurate prognosis than histological subtype or differentiation grade.
CONCLUSION:
This study indicates that advanced stage ovarian cancer either progresses from early stage or from a common precursor lesion but that they do not arise from distinct carcinogenic molecular events. Furthermore, we show that array comparative genomic hybridization has the potential to identify clinically distinct patients.

first: A

last: Zaal

first: W

last: Peyrot

first: E

last: Berns

first: M

last: van der Burg

first: J

last: Veerbeek

last: Trimbos

first: I

last: Cadron

first: P

last: van Diest

last: van Wieringen

first: O

last: Krijgsman

first: G

middle: A

last: Meijer

last: Piek

last: Timmers

last: Vergote

first: R

last: Verheijen

first: B

last: Ylstra

last: Zweemer


title: Cellular aging can be monitored by DNA-methylation changes at specific CpG sites

status: Public on May 22 2012

city: Aachen

first: Wolfgang

last: Wagner

address: Pauwelsstrasse 20

department: Helmholtz Institute for Biomedical Engineering

institute: RWTH Aachen University

summary: Long-term culture associated changes need to be considered for quality control of cell preparations – especially in cellular therapy. Here we describe a simple method to track cellular aging based on continuous DNA-methylation changes at six specific CpG sites. This epigenetic signature can be used as a biomarker for various cell types to predict the state of cellular aging with regard to the number of passages or days of in vitro culture.

overall_design: 8 samples of human dermal fibroblasts.  4 samples of mesenchymal stem cells (MSC) from human adipose tissue.

first: Carmen

last: Koch

first: Sylvia

last: Joussen

first: Anne

last: Schellenberg

first: Qiong

last: Lin

first: Martin

last: Zenke


title: Transcript expression data from Populus euphratica leaves subjected to infection by Marssonina pathogen

city: Haidian

first: Dong-hui

last: YAN

state: Beijing

address: 1#, Dong Xiao Fu

institute: Chinese Academy of Forestry

summary:
Gene expression profiles of Populus deltoides induced by fungal pathogenic Marssonina brunneain iduring time-course infection.
We used Affymetrix poplar genome genechip microarrays to analyze the full transcript expression underlying time-course infection and identified significantly differently expressed genes during the infection process.

overall_design: 2-year-old seedlings of P. deltoides grown were innoculated with the suspension of the pathogenic spores throught leaves spraying. Collecting the samples at interval time of  2 days and one week. Affymetrix poplar genechip was hired to investigate the full transcripts changed of the poplar response to the pathogen attack during the time.

last: Yan


title: Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and their Differentiated Derivatives [Illumina Infinium 27K DNA Methylation]

status: Public on May 14 2012

city: La Jolla

first: Kristopher

middle: L.

last: Nazor

address: 10550 North Torrey Pines Road

department: Regenerative Medicine

institute: The Scripps Research Institute

summary: Human pluripotent stem cells (hPSCs) are potential sources of cells for modeling disease and development, drug discovery, and regenerative medicine. However, it is important to identify factors that may impact the utility of hPSCs for these applications. In an unbiased analysis of 205 hPSC and 130 somatic samples, we identified hPSC-specific epigenetic and transcriptional aberrations in genes subject to X chromosome inactivation (XCI) and genomic imprinting, which were not corrected during directed differentiation. We also found that specific tissue types were distinguished by unique patterns of DNA hypomethylation, which were recapitulated by DNA demethylation during in vitro directed differentiation. Our results suggest that verification of baseline epigenetic status is critical for hPSC-based disease models in which the observed phenotype depends on proper XCI or imprinting, and that tissue-specific DNA methylation patterns can be accurately modeled during directed differentiation of hPSCs, even in the presence of variations in XCI or imprinting.

overall_design: To obtain a comprehensive view of hPSC-specific epigenomic patterns, we collected 136 hESC and 69 hiPSC samples representing more than 100 cell lines for analysis.  In order to establish expected variation in human tissues, we collected 80 high-quality and well-replicated samples representing 17 distinct tissue types from multiple individuals. Finally, we selected 50 additional samples from primary cell lines of diverse origin to control for any aberrations that may arise as a general, non-hPSC-specific, consequence of in vitro manipulation. With these samples, we performed genome-wide DNA methylation and mRNA expression profiling using the Illumina Infinium 27K and 450K DNA Methylation BeadChips as well as the Illumina HT12v3 Gene Expression BeadArray.

middle: L

first: Gulsah

last: Altun

first: Candace

last: Lynch

first: Ha

last: Tran

first: Julie

middle: V

last: Harness

first: Ileana

last: Slavin

first: Ibon

last: Garitaonandia

first: Franz-Josef

last: Müller

first: Yu-Chieh

last: Wang

first: Francesca

middle: S

last: Boscolo

first: Eyitayo

last: Fakunle

first: Sunray

last: Lee

first: Hyun

last: Park

first: Marina

last: Martynova

first: Tsaiwei

last: Ole

first: Darryl

middle: D

last: D'Lima

first: Ruslan

last: Semechkin

first: Mana

last: Parast

first: Vasiliy

last: Galat

first: Andrew

last: Laslett

first: Uli

last: Schmidt

first: Hans

last: Keirstead

first: Jeanne

last: Loring

first: Louise

last: Laurent


title: Genome-wide DNA methylation profiling of CpG islands in breast cancer

status: Public on Apr 30 2012

city: Birmingham

first: Farida

last: Latif

address: Vincent Drive

department: Medical and Molecular Genetics, School of Clinical and Experimental Medicine

institute: University of Birmingham

summary: Epigenetic profiling of tumor DNAs may reveal important new theranostic targets to improve prognosis and treatment of advanced cancer patients. In this study, we performed a genome-wide profile of DNA methylation patterns in sporadic breast tumors by using the HumanMethylation27 BeadChips to assess relationships between DNA methylation changes and patient tumor characteristics. The arrays identified 264 hypermethylated loci/genes present in breast cancer genomes

overall_design: This study has used the Illumina HumanMethylation27 BeadChip to assess methylation levels of 39 sporadic ductal carcinomas and 4 additional sporadic ductal carcinoma samples. Four normal breast tissue DNA samples were used as controls that were sourced from the same patient as the 4 additional tumour samples.

first: Victoria

last: Hill

first: Christopher

last: Ricketts


title: Epigenome analysis of genomic DNA isolated from whole blood of non-diabetic control and type-2 diabetic individuals

status: Public on Apr 23 2012

city: Brussels

first: Michael

last: Volkmar

address: 808 route de Lennik

department: Faculty of Medicine, C.P. 614

institute: Free University of Brussels (U.L.B.)

summary: DNA methylation profiling of whole blood using Illumina's Infinium HumanMethylation27 Beadchip array. The dataset encompasses profiles of 12 non-diabetic control blood donors and 12 type-2 diabetic (T2D) individuals.

overall_design: Bisulfite converted DNA from 24 blood samples were hybridised to the Illumina Infinium HumanMethylation27 Beadchip

first: Emilie

last: Calonne

first: Miriam

last: Cnop

first: François

last: Fuks


title: Illumina and Affymetrix SNP-array data for 2 ETV6/RUNX1-positive Acute Lymphoblastic Leukemia samples and corresponding normal samples

first: Henrik

last: Lilljebjörn

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Analysis of copy number changes and complex rearrangements in patients with congenital abnormalities

status: Public on May 11 2012

city: Utrecht

first: Wigard

last: Kloosterman

address: Universiteitsweg 100

institute: University Medical Center Utrecht

type:
SNP genotyping by SNP array
Genome variation profiling by SNP array

summary: Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyzed the genomes of ten patients with congenital disease that were preselected to carry complex chromosomal rearrangements (CCRs) with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint-junctions indicates that break-repair involves non-homologous or microhomology mediated end-joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred bp and several Mb. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template-switching. Our work provides detailed insight in the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements.

overall_design: We analyzed five patient-parent trios with Illumina BeadChip arrays to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients.

middle: P

first: Ellen

last: van Binsbergen

first: Karen

last: Duran

first: Masoumeh

last: Tavakoli-Yaraki

first: Ivo

last: Renkens

first: Kerstin

last: Hansson

first: Markus

last: van Roosmalen

first: Lucia

last: Ballarati

first: Lidia

last: Larizza

first: Thomas

last: Haaf

first: Ruben

last: van 't Slot

first: Martin

last: Poot

first: Victor

last: Guryev

first: Eberhard

last: Passarge

first: Björn

last: Menten

first: Elly

middle: F

last: Ippel

first: Arie

last: van Haeringen

first: Claudia

last: Ruivenkamp

first: Sarah

last: Vergult

first: Daniela

last: Giardino

first: Ron

last: Hochstenbach

first: Edwin

last: Cuppen


title: DNA methylation profiling of male human pancreatic islets identifies loci for type 2 diabetes

first: Michael

last: Volkmar

summary:
Little is known about the contribution of the epigenome to the pathophysiology of type 2 diabetes (T2D). Here we have used genome-wide DNA methylation profiling to obtain the first comprehensive DNA methylation data set for human T2D pancreatic islets. Therefore, we analyzed the methylation profile of 27,578 CpG sites affiliated to more than 14,000 genes in 16 samples of pancreatic islets, 11 normal and 5 type 2-diabetic.
Keywords: DNA methylation

Keywords: Methylation profiling by array

overall_design: We measured the methylation status of the 27,578 CpG sites (Human Methylation27 DNA BeadChip array) in genomic DNA obtained from pnacreatic islets of 11 non-diabetic and 5 type-2-diabetic male human donors to identify genes that are differentially methylated in T2D.

first: Emilie

last: Calonne

last: Dedeurwaerder

first: François

last: Fuks


title: SNP array profiling of childhood adrenocortical tumours reveals distinct pathways of tumourigenesis and highlights candidate driver genes

status: Public on Apr 02 2012

city: Paris

first: Eric

last: Letouzé

address: 15 rue de l'école de médecine

institute: Ligue Contre Le Cancer


title: The HDAC inhibitor panobinostat (LBH589) inhibits Acute Lymphoblastic leukemia (ALL) in vitro and in vivo in a new characterized human ALL mice model (Illumina)

status: Public on Apr 18 2012

city: Pamplona

first: Xabier

last: Agirre

state: Navarra

address: Pio XII, 55

department: Oncology

institute: CIMA

summary: Histone deacetylases (HDACs) have been identified as therapeutic targets due to regulatory function in DNA structure and organization. We have analyzed the role of the LBH589, a novel pan inhibitor of class I and II HDACs, in Acute Lymphoblastic Leukemia.  In vitro, LBH589 was shown to induce a dose dependent antiproliferative and apoptotic effect which was associated with an increase in the acetylation of H3 and H4 histone acetylation which was uniformly in every genetic subgroup of ALL. In vivo administration of LBH589 in BALB/c-RAG2-/-γc-/- mice in which T and B-cell leukemic cell lines were injected induced a significant reduction in tumor growth (TOM-1, p<0.01 and MOLT-4 p<0.05). Leukemic cells from patients were employed to establish a xenograft model of human leukemia in BALB/c-RAG2-/-γc-/- mice and further transplanted in consecutive generations of mice. Treatment of these xenografts with LBH589 induced an increase in the acetylation of H3 and H4 and prolonged the survival of mice in comparison with the animals treated with Vincristine and Dexametasone (p<0.05) and this effect was significantly higher when LBH589 was combined with Vincristine and Dexametasone (p<0.001). Our results that the use of LBH589 in combination with standard chemotherapy represents an attractive option for treatment of patients with ALL.

overall_design: Two primary samples of ALL (one ALL-B and one ALL-T) and two samples of each leukemia after passages in immunodeficient mice.

first: Amaia

last: Vilas-Zornoza

first: Gloria

last: Abizanda

first: Cristina

last: Moreno

last: Segura

first: Alba

last: Rodriguez

first: Edurne

last: San José-Eneriz

first: María

first: Jose

last: García de Jalón

first: José

last: Rifón

first: Juan

middle: C

last: Cigudosa

last: Martinez-Climent

last: Román-Gómez

last: Calasanz

first: Felipe

last: Prósper


title: Expression analysis of picloram responsive genes preceding cell elongation in Arabidopsis hypocotyls.

status: Public on Apr 13 2012

city: Hanover

first: Kathleen

last: Greenham

state: NH

address: 78 College St

institute: Dartmouth College

summary: In this study we profile expression of target genes downstream of auxin signaling in Arabidopsis hypocotyls elongating in response to auxin. The synthetic auxin picloram is used in order to take advantage of the picloram-resistant auxin receptor mutant afb5-5, which fails to elongate in response to picloram.

overall_design:
A 4-plex chip was used for analyzing the transcriptome in hypocotyls dissected from wild-type seedlings following a 30min and 2hr picloram or solvent control treatment.  Three biological replicate samples were analyzed, each containing roughly 400 hypocotyls.
A 12-plex chip was used for analyzing mRNA from hypocotyls dissected from wild-type and afb5-5 (SALK_110643) mutant seedlings following a 2hr picloram or solvent control treatment.  Three biological replicates were analyzed, each containing roughly 700 hypocotyls.

first: Elisabeth

last: Chapman

last: Castillejo

first: Ryan

last: Sartor

first: Mark

last: Estelle


title: Identity by descent mapping of founder mutations in cancer using high-resolution tumor SNP data

status: Public on Mar 23 2012

last: Letouzé

summary:
We present a computational tool, FounderTracker, for discovering founder mutations in cancer, based on the detection of significantly conserved haplotypes in tumor SNP profiles. We demonstrate the relevance of the approach by identifying founder mutations in two different cancers, and we show with simulated data that FounderTracker can detect rare founder mutations with high power and negligible false discovery rate. FounderTracker is a powerful tool for discovering novel founder mutations that may explain part of the "missing" heritability in cancer.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series.


title: Aberrant promoter methylation and expression of UTF1 during cervix carcinogenesis

status: Public on Mar 21 2012

city: LIEGE

first: Samuel

last: GUENIN

address: CHU Sart Tilman, B23+4

department: GIGA CANCER

institute: Université de Liège

summary:
Promoter methylation profiles are proposed as potential prognosis and/or diagnosis biomarkers in cervical cancer. Up to now, little is known about the promoter methylation profile and expression pattern of stem cell (SC) markers during tumor development. In this study, we were interested to identify SC genes methylation profiles during cervical carcinogenesis. A genome-wide promoter methylation screening revealed a strong hypermethylation of Undifferentiated cell Transcription Factor 1 (UTF1) promoter in cervical cancer in comparison with normal ectocervix. By direct bisulfite pyrosequencing of DNA isolated from liquid-based cytological samples, we showed that UTF1 promoter methylation increases with lesion severity, the highest level of methylation being found in carcinoma. This hypermethylation was associated with increased UTF1 mRNA and protein expression. By using quantitative RT-PCR and Western Blot, we showed that both UTF1 mRNA and protein are present in epithelial cancer cell lines, even in the absence of its two main described regulators Oct4A and Sox2. Moreover, by immunofluorescence, we confirmed the nuclear localisation of UTF1 in cell lines. Surprisingly, direct bisulfite pyrosequencing revealed that the inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine was associated with decreased UTF1 gene methylation and expression in two cervical cancer cell lines of the four tested. These findings strongly suggest that UTF1 promoter methylation profile might be a useful biomarker for cervical cancer diagnosis and raise the questions of its role during epithelial carcinogenesis and of the mechanisms regulating its expression.

*Mouallif M and Guenin S contributed equally to this work

overall_design: Bisulfite converted DNA from the 9 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

first: Mustapha

last: Mouallif*

last: Guenin*

first: Xavier

last: Lampe

first: Nathalie

last: Krusy

first: Katty

last: Delbecque

first: Frederic

last: Kridelka

first: François

last: Fuks

last: Ennaji

first: Philippe

last: Delvenne


title: SNP data from 13 childhood adrenocortical tumours from Brazilian patients and 6 matched normal samples

first: Eric

summary: SNP array data from 13 Brazilian childhood adrenocortical tumors (ACTs) were analyzed to detect recurrent copy number changes and highlight potential candidate driver genes.

overall_design: 13 childhood ACT were analyzed with Illumina HumanCNV370-Duo v1.0 chips. Paired normal blood samples from 6 patients were analyzed with Illumina HumanCNV370-Quad v3.0 chips.

first: Roberto

last: Rosati

first: Mabrouka

last: Doghman

first: Jean-Christophe

last: Mas

first: Gerard

last: Zambetti

first: Bonald

last: Figueiredo

first: Enzo

last: Lalli


title: North American Brain Expression Consortium: DNA Methylation

status: Public on May 09 2012

city: Bethesda

first: J Raphael

last: Gibbs

address: 35 Convent Drive, Bldg 35/1A1015, MSC3707

department: Computational Biology Core

institute: National Institutue on Aging, NIH

summary:
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 and mRNA expression 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

overall_design: 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 and frontal cortex from 318 subjects (total 724 tissue samples).

first: Jesse

middle: R

first: Dena

middle: G

last: Hernandez

first: Allisa

last: Dillman

first: Bryan

last: Traynor

first: Michael

last: Nalls

first: Sampath

last: Arepalli

first: Marcel

last: van der Brug

first: Juan

last: Troncoso

first: Robert

last: Johnson

first: Richard

last: O'Brien

first: H

last: Zielke

first: Alan

last: Zonderman

first: Luigi

last: Ferrucci

first: Dan

last: Longo

last: Walker

last: Cookson

first: Andrew

last: Singleton


title: Epigenome analysis of cord blood samples from newborns

status: Public on Mar 29 2012

city: Philadelphia

first: Nahid

last: Turan

state: PA

address: 3307 North Broad Street, AHB

department: Fels Institute

institute: Temple University School of Medicine

summary: Genome wide DNA methylation profiling of cord blood samples from 48 newborns. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs.

overall_design: Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

first: Carmen

last: Sapienza


title: The effect of periconceptional micronutrient supplementation on offspring DNA methylation

status: Public on Mar 15 2012

city: Cambridge

first: Julien

last: Bauer

state: Cambridgeshire

address: Tennis court road

institute: Cambridge University

summary: The effect of pre and periconceptional multiple micronutrient supplementation on methylation of CpG loci within CpG islands associated with 14,000 genes across the human genome has been investigated in the offspring of a cohort of Gambian women participating in a controlled double blinded trial. Methylation levels in placebo and micronutrient supplemented cohorts were compared in genomic DNA from cord blood (35 placebo and 21 micronutrient supplemented) and in circulating blood samples (14 placebo and 9 micronutrient supplemented) drawn from the same cohort at 9 months old. A small number of differentially methylated CpG loci were identified in cord blood (14 in males and 21 in females) and a larger number in the 9 month infant comparison (108 in males and 106 in females). Seven differentially methylated loci in males and 8 in females persisted from cord to infant. These findings indicate that micronutrient supplementation pre-conception or early in embryonic development is potentially associated with programming of gene activity at birth, which is maintained into early infanthood. Strikingly, the loci affected by micronutrient supplementation differed between males and females, with no shared changes in cord blood and only 5 shared changes at 9 months. Additionally, a large number of CpG loci showed variation in methylation level when comparing 9-month samples to cord blood samples. These postnatal changes were more consistent between sexes, with 85% of female alterations being found as a subset of male changes in the placebo cohort and 62% of the female changes shared with males in the supplemented cohort. Taken together, the results suggest that there is a core developmental program shared between the sexes that is unaffected by nutrient supplementation, but that there are also sex-specific developmental changes which are altered under conditions of micronutrient supplementation and deficiency.

overall_design: Bisulphite converted DNA from 59 cord (36 placebo and 23 treated) and 25 infant peripheral blood (15 placebo and 10 treated) samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2.  (For further analysis, five were excluded during quality control leaving 56 cord (35 placebo and 21 treated) and 23 infant peripheral blood (14 placebo and 9 treated) samples. Full data set of 84 samples were submitted to GEO)

first: Batbayar

last: Khulan

first: Wendy

last: Cooper

first: Ben

last: Skinner

first: Stephen

last: Owens

last: Prentice

first: Gusztav

last: Belteki

first: Miguel

last: Constância

first: David

middle: B

last: Dunger

first: Nabeel

last: Affara


title: Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression

city: Los Angeles

first: Ite

last: Laird-Offringa

address: 1441 Eastlake Avenue, Suite 6420

department: Biochemistry

institute: University of Southern California

summary: Lung cancer is the leading cause of cancer death worldwide and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung samples, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung.  By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent downregulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and downregulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell-cell and cell-matrix interactions, was recently shown to be a tumor-suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by providing new candidate DNA methylation biomarkers for early detection, identifying novel molecular alterations potentially involved in lung adenocarcinoma development/progression, and describing an epigenetic subgroup of lung adenocarcinoma associated with KRAS mutation.

overall_design: 59 lung adenocarcinoma and 59 adjacent non-tumor lung tissue were macrodissected, bisulfite treated and analyzed on the Illumina Infinium HumanMethylation27K BeadChip

first: Suhaida

last: Selamat


title: Epigenome analysis of white blood cells from healthy women with and without BRCA1 mutation.

status: Public on Feb 20 2012

city: London

first: Joanna

last: Zhuang

address: 74 Huntley Street

institute: UCL

summary: The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in white blood cells from women with and without BRCA1 mutation. Whole blood samples were drawn from 30 BRCA1 mutation carriers (15 women with breast cancer and 15 healthy women with mean age 57.2) and 30 females without BRCA1 mutation (15 breast cancers and 15 healthy with mean age 57.1). All samples were collected between 2001 and 2008. The samples were drawn from women attending the General Faculty Hospital in Prague and the complete coding sequence, intron-exon junctions and large rearrangements for BRCA1 and BRCA2 genes were tested.

overall_design: Bisulphite converted DNA from the 60 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

last: Teschendorff

first: Martin

last: Widschwendter


title: Population-specificity of human DNA methylation

status: Public on Jan 30 2012

city: Vancouver

first: Michael

middle: S.

last: Kobor

address: 950 West 28th Avenue

department: Medical Genetics

institute: Centre for Molecular Medicine and Therapeutics / University of British Columbia

summary: Ethnic differences in human DNA methylation have been shown for a number of CpG sites, but the genome-wide patterns and extent of these differences are unknown. In addition, whether the genetic control of polymorphic DNA methylation is population-specific has not been investigated. Here we measure DNA methylation near the transcription start sites of over 14,000 genes in 180 cell lines derived from one African and one European population. We find population-specific patterns of DNA methylation at over a third of all genes. Furthermore, although the methylation at over a thousand CpG sites is heritable, these heritabilities are also distinctly different between populations, suggesting extensive divergence in the genetic control of DNA methylation. In support of this, genetic mapping of DNA methylation reveals that there is also little overlap in genetic associations between populations. This population-specificity is supported by the patterns of DNA methylation in several hundred brain samples, suggesting it holds in vivo and across tissues. These results suggest that DNA methylation is highly divergent between populations, and that this divergence may be due in large part to complex epistasis or gene x environment interactions.

overall_design: Genomic DNA from 180 lymphoblastoid cell lines were bisulphite converted and hybridized, along with 8 additional technical replicates, to the Illumina Infinium HumanMethylation27 Beadchip v1.2 for genome-wide DNA methylation profiling. The cell lines were derived from two HapMap populations: 'CEPH (Utah residents with ancestry from northern and western Europe)' (CEU) and 'Yoruba in Ibadan, Nigeria' (YRI).

first: Hunter

last: Fraser

first: Lucia

last: Lam

first: Sarah

last: Neumann


title: Epigenome analysis of placenta samples from newborns

first: Nahid

last: Turan

summary: Genome wide DNA methylation profiling of placenta samples from 48 newborns. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs.

first: Carmen

last: Sapienza


title: Genome-scale DNA methylation profiling of lung adenocarcinoma: validation using Ontario Tumor Bank samples

summary: The independent population of lung adenocarcinoma and adjacent non-tumor lung used for verification of the EDRN/Canary Foundation study

overall_design: 28 lung adenocarcinoma and 27 adjacent non-tumor lung fresh frozen tissues were macrodissected, bisulfite treated and analyzed on the Illumina Infinium HumanMethylation27K BeadChip

first: S

first: A

middle: I


title: Epigenome analysis of endometrium tissue from women with metastatic endometrial cancer.

summary: The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in endometrium tissues from women with metastatic endometrial cancer. Endometrium tissue samples were drawn from 18 metastatic endometrial cancers. The metastatic endometrial cancer tissue samples were from women (mean age 67.1) who were diagnosed with metastatic endometrial cancer.

overall_design: Bisulphite converted DNA from the 18 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

first: Andrew


title: Epigenome analysis of breast tissue from women with and without breast cancer.

summary: The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in breast tissues from women with and without breast cancer. Breast tissue samples were drawn from 114 breast cancers and 23 non-neoplastic breast tissues. The breast cancer tissue samples were from women (mean age 59.4) who were diagnosed with breast cancer.  Among the cancers, 33 were at stage 1 and 81 at stage 2/3/4; 34, 59, and 19 were grade 1, 2, and 3 respectively;and 91 were invasive ductal carcinoma breast cancers. The 23 non-neoplastic samples are from healthy woman (mean age 47.6).

overall_design: Bisulphite converted DNA from the 137 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2