title: Methylation Pattern of Human Dermal Fibroblasts

status: Public on Feb 14 2012

first: Wolfgang

last: Wagner

department: Helmholtz-Institute for Biomedical Engineering

institute: Aachen University Medical School

summary: In this study, we have analyzed DNA methylation changes upon aging of human dermal fibroblasts by using the HumanMethylation27 BeadChip assessing 27,578 unique CpG sites. Cells were isolated from skin samples donated by young (6-23 years) and elderly (60-73 years) patients undergoing surgical interventions. Strikingly, global DNA-methylation profiles of fibroblasts from the same anatomical site clustered closely together indicating that fibroblasts maintain positional memory even after in vitro culture.

overall_design:
Skin samples from younger or elderly donors were treated with dispase (Roche Diagnostics, Mannheim, Germany) for 12 hours to separate the dermis from the epidermis. The dermis was digested with 0,2% collagenase and 1,5% BSA in collagenase buffer (100mM HEPES, 120mM NaCl, 50mM KCl, 1mM CaCl2, 5mM Glucose) for 45 minutes. Dermal remnants were removed by filtering the digest through a 100µm nylon strainer (Falcon, Becton Dickinson [BD], San Jose, USA). The cells were subsequently washed and expanded in standard medium consisting of DMEM (PAA; 1g/L glucose) supplemented with glutamine (PAA), penicillin/sptrepamycin (PAA) and 10% fetal calf serum (Biochrom, Berlin, Germany) in a humidified atmosphere at 5% CO2.
Cells were always replated when grown to 80% confluency. For methylation profiles upon aging we have isolated DNA from the samples of passage 3 of younger and elderly donors. For methylation profiles upon long-term culture we have isolated DNA from the samples of early passage (P3) and late passage (P21)

last: Koch

first: Christoph

last: Suschek

first: Simone

last: Bork

first: Qiong

last: Lin

first: Maria

last: Goergens

first: Sylvia

last: Joussen

first: Norbert

last: Pallua

first: Anthony

last: Ho

last: Zenke


title: DNA methylation screening identifies driver epigenetic events of cancer cell survival.

status: Public on Mar 16 2012

city: Toronto

first: Daniel

last: De Carvalho

state: ON

address: 101 College Street, room 9-302

country: Canada

institute: Ontario Cancer Institute

summary: Genome wide DNA methylation profiling of colon adenocarcinoma cell line HCT116 wild type and with a genetic disruption of DNMT3B and DNMT1 (DKO). The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. For this study, we used two DKO subclones, DKO8 and DKO1, which retain approximately 45% and 5% of the HCT116 wild type global DNA methylation levels, respectively

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

first: Peter

last: Jones


title: TET2 mutations are associated with specific methylation profiles in patients with Chronic Myelomonocytic Leukemia

status: Public on Feb 13 2012

city: Pamplona

first: Xabier

last: Agirre

state: Navarra

address: Pio XII, 55

department: Oncology

country: Spain

institute: CIMA

summary: Chronic myelomonocytic leukemia (CMML) has recently been associated with a high incidence of diverse mutations in genes implicated in epigenetic mechanisms such as TET2 or EZH2. We have performed genome-wide methylation arrays and mutational analysis of TET2, IDH1, IDH2, EZH2 and JAK2 in a group of 24 patients with CMML. 249 genes were differentially methylated between CMML patients and controls. Using Ingenuity pathway analysis enrichment in a gene network centered in PLC, JNK and ERK, a recently described pathway involved in CMML was found, suggesting the potential role of epigenetics in the regulation of these pathways. Mutations of TET2, JAK2 and EZH2 were found in 15 patients (65.2%), 4 patients (16.6%) and 1 patient (4.1%) respectively while no mutations in the IDH1 and IDH2 genes were identified. Interestingly, patients with wild type TET2 clustered separately from patients with TET2 mutations, showed a higher degree of hypermethylation and were associated with the presence of altered karyotypes a known prognostic factor in CMML. Our results demonstrate the presence of aberrant DNA methylation in CMML and identifies TET2 mutant CMML as a biologically distinct disease subtype with a different epigenetic profile.

overall_design: 24 samples of CMML patients, 4 healthy donor Peripheral Blood samples and 4 healthy donor Bone Marror samples

first: Cristina

last: Pérez

first: Nicolas

last: Martínez-Calle

first: José

middle: I

last: Martín-Subero

first: Victor

last: Segura

first: Eric

last: Delabesse

first: Marta

last: Fernandez-Mercado

first: Leire

last: Garate

first: Sara

last: Alvarez

last: Rifón

last: Varea

first: Jacqueline

last: Boultwood

first: James

middle: S

last: Wainscoat

first: Juan

middle: C

last: Cigudosa

first: María

middle: J

last: Calasanz

first: Nicholas

last: Cross

first: Felipe

last: Prósper


title: Genome-wide AID target loci in BL2 cells

status: Public on Feb 01 2012

city: Kyoto

first: Tasuku

last: Honjo

address: Yoshida Konoe-cho, Sakyo-ku

department: Department of Immunology and Genomic Medicine

country: Japan

institute: Kyoto University

type: Genome binding/occupancy profiling by genome tiling array

summary: Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation (SHM) and class-switch recombination (CSR) in activated B cells. AID is also known to target non-immunoglobulin genes and introduce mutations or chromosomal translocations, eventually causing tumors. To identify as-yet-unknown AID targets, we screened early AID-induced DNA breaks using two independent genome-wide approaches. Along with known AID targets, this screen identified a set of novel genes (SNHG3, MALAT1, BCL7A, and CUX1), and confirmed that these new loci accumulated mutations as high as Ig locus after AID activation. Moreover, these genes share three important characteristics with the immunoglobulin gene: translocations in tumors, repetitive sequences and the epigenetic modification of chromatin by H3K4 trimethylation in the vicinity of cleavage sites.

overall_design: BL2 cells expressing JP8Bdel-ER, an AID mutant lacking the C-terminal 16 residues, fused with the hormone-binding domain of the estrogen receptor (ER) were treated with tamoxifen (OHT) for 3 hours to induce AID activation. AID-induced DNA breakage was labeled with biotinilated linker. Comparison of OHT treated vs. non-treated samples.

first: Lucia

last: Kato


title: Tye7 regulates yeast Ty1 retrotransposon sense and antisense transcription in response to adenylic nucleotides stress

status: Public on Feb 10 2012

city: PARIS

first: sophie

last: lemoine

address: 46 rue d'Ulm

department: Biologie

country: France

institute: Ecole Normale Supérieure

summary: We investigated the effects of adenine starvation on the global yeast transcriptome. In this work, global transcription analyses were combined with measurements of intracellular nucleotides pools by HPLC.

overall_design: The bas1delta strain grown with or without adenine was compared to the WT strain grown with or without adenine. For each comparison, we performed 2 technical replicates, swapping dyes.

first: Geraldine

last: Servant

first: Benoit

last: Pinson

first: Aurelie

last: Tchalikian-Cosson

first: Fanny

last: Coulpier

first: Sophie

last: Lemoine

first: Carole

last: Pennetier

first: Anne-Laure

last: Todeschini

first: Helene

last: Fayol

first: Bertrand

last: Daignan-Fornier

first: Lesage

last: Pascale


title: Pediatric age-associated DNA methylation

city: Atlanta

first: Benjamin

middle: G

last: Barwick

state: GA

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

department: Hematology and Medical Oncology

country: USA

institute: Emory University

summary: DNA methylation (DNAm) plays diverse roles in human biology, but this dynamic epigenetic mark remains far from fully characterized. Although earlier studies uncovered loci that undergo age-associated DNAm changes in adults, little is known about such changes during childhood. Despite profound DNAm plasticity during embryogenesis and early development, monozygotic twins show indistinguishable childhood methylation, suggesting DNAm is highly coordinated during the pediatric period. Here we examine the methylation of 27,578 CpG dinucleotides in peripheral blood DNA from 398 boys, aged 3 to 17 years, and find significant age-associated changes in DNAm at 2,078 loci. We report a deficit of such loci on the X chromosome, a preference for specific nucleotides immediately surrounding the interrogated CpG dinucleotide, and a primary association with developmental and immune ontological functions. These pediatric age-associated loci overlap significantly with those previously identified in adults (p < 0.001) but most of the pediatric loci are unique, suggesting many are childhood-specific. Meta-analysis (n = 1080) with two adult studies reveals that the methylation changes in 29.5% of the age-associated pediatric loci follow a linear pattern from childhood into adulthood; however, we also find a three-fold higher rate of change in children compared with adults and that a higher proportion of lifelong changes are more accurately modeled as a function of logarithmic age. We therefore conclude that DNAm changes occur more rapidly during childhood and are imperfectly accounted for by statistical corrections that are linear in age, further suggesting that future DNAm studies are matched closely for age.

overall_design:
Age associated DNA methylation was evaluated at each CpG locus using a fixed-effects linear regression model adjusting for BeadChip as a covariate to account for batch effects. Analysis of variance (ANOVA) was conducted for each CpG locus to assess the age affect at each CpG locus which was subsequently corrected for multiple hypotheses using a Benjamini-Hochberg FDR.

SUPPLEMENTARY FILES:
* Matrix_AllSampleDetection.txt: Detection P-values for each sample and each loci
* Matrix_AllSampleSignal.txt: Signal for Probe A and Probe B for each sample and each loci
* Matrix_Non-Normalized_AllSampleBeta.txt: Beta values calculated using GenomeStudio v2010.3 Methylation Module 1.8.5 as Signal of Probe B / (Signal of Probe A + Signal of Probe B + 100)
* Matrix_Normalized_AllSampleBetaPrime.txt: Beta Prime values used for analysis calculated from the Probe B and Probe A signals as Beta Prime = Signal of Probe B / (Signal of Probe A + Signal of Probe A)

first: Reid

last: Alisch

first: Pankaj

last: Chopra

first: Glen

middle: A

last: Satten

first: Karen

middle: N

last: Conneely

first: Stephen

middle: T

last: Warren


title: Distinct chromosomal aberrations in high-grade cervical intraepithelial neoplasia harbouring HPV16 versus HPV31

status: Public on Jan 27 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 genome tiling array

summary: High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behaviour and chromosomal aberrations detected. The current study aimed to investigate whether CIN2/3 harbouring different hrHPV types vary with respect to their chromosomal aberrations, including both number of aberrations and specific chromosomal loci affected.

overall_design: DNA from microdissected CIN2/3 tissues: 43 samples total. 16 HPV16, 3 HPV18, 14 HPV31, 1 HPV33, 4 HPV45, 1 HPV51, 2 HPV52, 2 HPV58.

first: Mariska

last: Bierkens

first: Saskia

middle: M

last: Wilting

first: Wessel

last: van Wieringen

first: Mark

last: van de Wiel

first: Bauke

last: Ylstra

first: Chris

last: Meijer

first: Peter

last: Snijders

first: Renske

middle: D

last: Steenbergen


title: Chromosomal profiles of high-grade cervical intraepithelial neoplasia relate to duration of preceding high-risk human papillomavirus infection

status: Public on Jan 25 2012

summary:
High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behaviour and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence.
Chromosomal profiles were determined of CIN3 of women with a known 5 year history of high-risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≥5 years (CIN3≥5yrPHI). For comparison, 6 CIN3 adjacent to squamous cell carcinomas (CIN3-SCC), the corresponding SCCs, and 6 CIN1 were included.   Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≥5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≥5yrPHI, all except one CIN3-SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≥5yrPHI compared to <5yrPHI was highly significant (p=0.001), suggesting that CIN3≥5yrPHI represent more severe lesions.
A longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short-term risk of cervical cancer.

overall_design: DNA from microdissected tissues: 53 samples total. 11 CIN3<5yrPHI, 24 CIN3>5yrPHI, 6 CIN1, 6CIN3 adjacent to SCC & 6 SCC

first: Folkert

last: van Kemenade

first: Maaike

last: Bleeker

first: Ekatarina

last: Jordanova

first: Marjolein

last: Bekker-Lettink


title: Chronic colitis in Bacteroides Thetaiotaomicron-Monoassociated HLA-B27 Transgenic rats alters expression of receptor and metabolic genes in luminal bacteria.

status: Public on Jan 11 2012

city: Charlottesville

first: Yong

last: Huang

state: VA

address: 1340 Jefferson Park Ave

department: Medicine

institute: University of Viginia

summary:
Background: Inflammatory bowel diseases (IBD) may be caused in part by aberrant immune responses to commensal intestinal microbes including Bacteroides thetaiotaomicron (B.theta).  Healthy, germ-free HLA-B27 transgenic (Tg) rats develop chronic colitis when colonized with complex gut commensal bacteria whereas non-transgenic (nTg) rats remain disease-free.   However, the role of B.theta, a well-characterized anaerobic commensal bacterium, in causing disease in Tg rats is unknown nor is much known about how microbes respond to host inflammation.

Methods: Tg and nTg rats were monoassociated with a human isolate of B.theta. Colonic inflammation was quantified by blinded histological scoring and real-time RT-PCR assays of pro-inflammatory cytokines. Cecal bacterial concentrations were measured by quantitative plating.  Whole genome transcriptional profiling of B.theta recovered from ceca was performed using custom GeneChips and data analyzed using dChip, Significance Analysis of Microarrays, and Gene Set Enrichment Analysis (GSEA) software.

Results: B.theta monoassociated Tg rats had significantly more colonic inflammation and increased colonic levels of pro-inflammatory cytokine mRNAs compared to nTg controls.  Transcriptional profiles of cecal B.theta were significantly different in Tg vs. nTg rats.  GSEA revealed that the Gene Ontology molecular function of receptor activity, which is comprised mainly of genes that encode nutrient binding proteins, was significantly enriched with genes upregulated in B.theta from Tg rats. KEGG canonical pathways of ribosome, oxidative phosphorylation, pyrimidine metabolism, purine metabolism, peptidoglycan biosynthesis, and metabolism were significantly enriched with genes downregulated in B.theta from Tg rats.  Numbers of viable bacteria/gram cecal contents in Tg vs. nTg rats were not significantly different.

Conclusions: B.theta induces mild colitis in HLA-B27 Tg rats, which is associated with changes in the expression of microbial metabolic and nutrient binding pathways, but no difference in concentrations of luminal bacteria. Mechanistic studies of differentially expressed B.theta genes may reveal novel pathways that contribute to IBD.

platform_organism:
Bacteroides thetaiotaomicron
Phocaeicola vulgatus
Parabacteroides distasonis
Methanobrevibacter smithii
Lachnospira eligens
Agathobacter rectalis

overall_design: The fully-sequenced human fecal isolate of B.theta (VPI-5482) was grown on Brain-Heart Infusion (BHI) agar and in BHI broth under strict anaerobic conditions using pre-reduced media. Adult germ-free HLA-B27/b2 microglobulin transgenic rats and adult germ-free non-transgenic littermate were monoassociated with B.theta for six weeks in gnotobiotic isolators at the National Gnotobiotic Rodent Resource Center at UNC Chapel Hill. Bacterial RNA was isolated from rat cecal contents and hybridized on Affymetrix human gut microbiota community GeneChip.

first: Jonathan

last: Hansen

first: Daniel

last: Peterson

first: Laura

last: Goeser

first: Jeffrey

last: Gordon

first: Eugene

middle: B

last: Chang

first: R

last: Sartor


title: Genome wide analysis reveals association of a FTO gene variant with epigenetic changes of several genes in human blood

status: Public on Jan 10 2012

city: Uppsala

first: Markus

last: Sällman Almén

address: Box 593

department: Dept. of Neuroscience

country: Sweden

institute: Uppsala Universitet

summary: FTO gene variants show the strongest association to obesity so far, but the role of the gene in obesity remains unclear. The FTO protein is a demethylation enzyme, which suggests that the link to obesity could be mediated through epigenetic changes. Herein, we determine the genome wide DNA methylation profile in blood from 47 female preadolescents and detect changes in five methylated regions, corresponding to six genes, associated with the FTO risk allele (rs9939609). In addition, we identify 20 differentially methylated regions associated with obesity. Our findings indicate that the effect of the FTO obesity risk allele may be mediated through epigenetic changes. Further, the identified regions might prove valuable biomarkers for the diagnosis and prognosis of obesity and comorbidites, such as cardiovascular disease.

overall_design: Bisulphite converted DNA from 47 girls were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2. Half of the subjects are carriers of the FTO obesity risk allele (AA) and half of the normal allele (TT). In addition, both obese and normal-weigh indiviudals were included.

last: Almén

first: Josefin

last: Jacobsson

first: George

last: Moschonis

first: Christian

last: Benedict

middle: P

last: Chrousos

first: Robert

last: Fredriksson

first: Helgi

last: Schiöth


title: The influence of aging, environmental exposures and local sequence features on the variation of DNA methylation in blood

city: Cincinnati

first: Scott

last: Langevin

state: OH

address: 160 Panzeca Way, ML0056

department: Department of Environmental Health

institute: University of Cincinnati College of Medicine

summary: Genome wide DNA methylation profiling of non-pathologic peripheral blood from subjects with no history of cancer. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in peripheral blood. Samples included 205 normal control peripheral blood samples.

overall_design: Bisulphite converted DNA from the 205 samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2

first: K

last: Kelsey


title: Antibody profiling of smallpox vaccinees with/without a 'take' using custom vaccinia virus proteome microarrays

status: Public on Jan 09 2012

city: Irvine

first: David

middle: Huw

last: Davies

state: CA

address: Med Surge II

institute: University of California Irvine

summary: Successful vaccination against smallpox with conventional vaccinia virus is usually determined by the development of a vesicular skin lesion at the site of vaccinia inoculation, called a ‘take’.    Although previous vaccination is known to be associated with attenuation of the take, the immunology that underlies a no-take in vaccinia-naïve individuals is not well understood.   We hypothesized that antibody profiling of individuals before and after receiving vaccinia would reveal differences between takes and no-takes that may help better understand the phenomenon.   Using vaccinia proteome microarrays and recombinant protein ELISAs we first examined the antibody response in vaccinia-naïve individuals that failed to take after receiving different doses of the replication competent smallpox vaccines, DryVax® and APSV.   Most that received diluted vaccine failed to respond, whereas 4 other no-takes receiving diluted vaccine, and 4 receiving undiluted vaccine, mounted an antibody response.   Interestingly, their antibody profiles were not significantly different from controls that did show a take. However, we did find elevated antibody titers in no-takes prior to receiving DryVax® that was significantly different from takes.   Although the sample size studied was small, we conclude the failure to take in responders correlates with pre-existing immunity of unknown etiology that may attenuate the skin reaction in a way similar to previous smallpox vaccination.

overall_design: Antibody profiling was peformed on sera  from vaccinees receiving smallpox vaccines, either Wyeth DryVax or Aventis Pasteur Vaccine ('WetVax') in NIH-sponsored clinical trials.   These samples comprise 23 vaccinia naïve no-takes, and 50 vaccinia naïve takes and 25 previoulsy vaccinated takes as controls.   Samples from d0 (day of vaccination) and at the peak of the antibody repsonse (d28) were taken from each donor and probed in triplicate against the proteome arrays.

first: Xiaolin

last: Tan

first: Sookhee

last: Chun

first: Jozelyn

last: Pablo

first: Philip

last: Felgner

first: Xiaowu

last: Liang

first: Huw


title: DNA methylation analysis of ovarian cancers and normal peripheral blood lymphocyte DNA by Illumina Infinium platform

status: Public on Jan 01 2012

city: Los Angeles

first: Mihaela

last: Campan

address: 1441 Eastlake Ave

institute: University of Southern California

summary: We performed a genome-scale DNA methylation analysis of 41 ovarian tumors and 10 normal lymphocytic samples. We used the Illumina Infinium HumanMethylation27 Beadchip platform that interrogates the DNA methylation profiles of approximately 27,000 CpGs to identify sensitive markers for ovarian cancer detection. The 41 tumor samples included one mixed (clear cell and endometrioid) tumor, three clear cell carcinomas, four mucinous, four endometrioid, and 32 serous epithelial ovarian carcinomas. The lymphocytic DNA samples were obtained from 10 healthy older women.

overall_design:
DNA obtained from 41 ovarian cancer tissue samples and 10 peripheral blood leukocyte (PBL) samples was bisulfite converted and then hybridized to the Illumina Infinium 27k Human Methylation Beadchip v.1.2
biological replicate: sample WBC6, WBC11
biological replicate: sample WBC8, WBC12

first: Peter

middle: W

last: Laird


title: Methylation data from Down syndrome and non-Down syndrome pediatric acute lymphoblastic leukemia cases and controls

status: Public on Dec 01 2011

city: Houston

first: Hon-chiu

middle: Eastwood

last: Leung

state: TX

address: 1102 Bates Street  Room C1030.09

department: Pediatrics

institute: Baylor College of Medicine

summary:
Methylation profiling can reveal patterns of hypermethlation and hypomethylation associated with distinct biologic subtypes of acute lymphoblastic leukemia (ALL).
We performed methylation profiling of Down syndrome ALL cases and controls to identify unique biologic features of this ALL subgroup.

overall_design: Ficoll-enriched, cryopreserved bone marrow aspirate samples were obtained from patients with B-precursor ALL at diagnosis and in remission

first: Karen

middle: R

last: Rabin

first: Eastwood


title: Heat stress reveals heritable changes in mRNA profile in 4-cell stage embryos of the nematode Caenorhabditis elegans.

status: Public on Dec 31 2011

city: Cambridge

first: Daniel

last: Schott

state: MA

address: 16 Divinity Avenue

department: Molecular and Cellular Biology

institute: Harvard University

summary: For centuries, scientists have wondered whether the responses of animals and plants to environmental change can be transmitted to subsequent generations.  Lately, there been much interest in the inheritance of information that is not encoded by differences in DNA sequence.  Here we show that transient, mild heat stress results in a heritable change in the messenger RNA profile of early-stage C. elegans embryos.  After heat stress is removed for one generation, abundances of most, but not all, mRNAs have relaxed to the unstressed state.

overall_design: Our approach was to culture worms at 20°C, then split the culture into 20°C control and 25°C treatment, followed by return of the 25°C culture to 20°C. Specifically, we compared mRNA abundances in 4-cell stage embryos collected from mothers kept at 20°C, with embryos whose mothers were also reared at 20°C but whose grandparents had been reared at 25°C.  Two strains and two generations under a treatment and under a control condition were analyzed by microarray with three separately collected 50-embryo replicates for each combination, for a total of 24 samples.

middle: H

first: Itai

last: Yanai

first: Craig

last: Hunter


title: Comparison of male and female floral organs

status: Public on Dec 29 2011

city: Monticello

first: Joshua

last: Adams

state: AR

address: PO Box 3468

department: Forest Resources

institute: University of Arkansas-Monticello

summary: We conducted micro-array analysis to quantify the global transcriptome variations in floral organs of a male and female tree allowing for identification of sex-linked transcripts. We used RNA samples from male floral buds in August and female floral buds in Spetemeber. Bud scale were removed. While the sampling time differed, the developmental stage of the floral organs was similar between the male and female.

overall_design: Five independent samples of floral bud tissues with bud scales removes were collected from the upper crown  of a sexually mature male tree and female tree. RNA was extracted from tissues and hybridized on Affymetrix Genechip Poplar Genome Array.

first: Chuan-Yu

last: Hsu

first: Grier

last: Page

first: Cetin

last: Yuceer


title: Time-course bud expression data from Populus deltoides

summary: We conducted micro-array analysis to quantify the global transcriptome variations in floral buds through the course of the year allowing for identification of changing developmental signals. We used RNA samples from floral buds, with bud scale removed,  in the upper crown of a sexually mature Populus deltoides tree 2 hours after sunrise.

overall_design: Three independent samples of floral bud tissues with bud scales removes were collected from the upper crown of a single sexually mature male tree. RNA was extracted from tissues and hybridized on Affymetrix Genechip Poplar Genome Array.


title: Global methylation analysis of psoriatic (involved and uninvolved) and control skin

status: Public on Nov 11 2011

city: St. Louis

first: Elisha

last: Roberson

state: MO

address: 660 South Euclid Ave., CB 8045

department: Internal Medicine & Genetics

institute: Washington University in St. Louis

summary: Psoriasis is a chronic inflammatory immune-mediated disorder affecting the skin and other organs including joints. Over 1,300 transcripts are altered in psoriatic involved skin compared to normal skin. Global epigenetic profiles of psoriatic skin have not been described. Here we describe the first genome-wide study of altered CpG methylation in psoriatic skin. We determined the methylation levels at 27,578 CpG sites in skin samples from individuals with psoriasis (12 involved, 8 uninvolved) and 10 unaffected individuals. CpG methylation of involved skin differed from normal skin at 1,108 sites. Twelve mapped to the epidermal differentiation complex, upstream or within genes that are highly up-regulated in psoriasis. Hierarchical clustering of 50 of the top differentially methylated (DM) sites separated psoriatic from normal skin samples. CpG sites where methylation was correlated with gene expression are reported. Sites with inverse correlations between methylation and nearby gene expression include those of KYNU, OAS2, S100A12, and SERPINB3, whose strong transcriptional up-regulation are important discriminators of psoriasis. We observed intrinsic epigenetic differences in uninvolved skin. Pyrosequencing of bisulfite-treated DNA from skin biopsies at three DM loci confirmed earlier findings and revealed a reversion of methylation levels towards the non-psoriatic state after one month of anti-TNF-a therapy.

overall_design:
Control n=8 (NN), psoriasis involved n = 19 (PP), psoriasis uninvolved n=8 (PN). Hybridized to Illumina Human 27k methylation array.
Paired samples are as follows:
PN1 and PP1
PN2 and PP2
PN3 and PP3
PN4 and PP4
PN5 and PP5
PN6 and PP6
PN7 and PP7
PN8 and PP8

first: Ying

last: Liu

first: Catriona

last: Ryan

first: Cailin

middle: E

last: Joyce

first: Shengui

last: Duan

first: Li

last: Cao

first: Ann

last: Martin

first: Wilson

last: Liao

first: Alan

last: Menter

first: Anne

last: Bowcock


title: CO1 network analysis in poplar

summary: We conducted microarray experiments by comparing constitutive constructs with appropriate controls, followed by the identification of downstream targets of Pro35S:CO1

overall_design: Four samples of mature leaf tissues were collected from four independent lines of 35S:CO1 and pBI101. RNA was extracted from tissues and hybridized on Affymetrix Genechip Poplar Genome Array.


title: CO2 network analysis in poplar

summary: We conducted microarray experiments by comparing constitutive constructs with appropriate controls, followed by the identification of downstream targets of Pro35S:CO2.

overall_design: Four samples of mature leaf tissues were collected from four independent lines of 35S:CO2 and pBI101. RNA was extracted from tissues and hybridized on Affymetrix Genechip Poplar Genome Array.


title: CO1 and CO2 network analysis in poplar

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

overall_design: Refer to individual Series


title: Genome-wide Methylation Profiling Identifies Candidate DNA Methylation Drivers of Acquired Cisplatin Resistance in Ovarian Cancer.

status: Public on Dec 20 2011

city: London

first: Wei

last: Dai

address: Du Cane Road

department: Sugery and Cancer

country: United Kingdom

institute: Imperial College London

summary: Multiple DNA methylation changes have been associated with the acquisition of drug resistance; however it remains uncertain how many of these changes may represent critical DNA methylation drivers of chemoresistance. Using genome-wide DNA methylation profiling across 27,578 CpG sites on Illumina HumanMethylation27 bead array we identified loci at 4092 genes becoming hypermethylated in the chemoresistant A2780/cp70 ovarian tumour cell line compared to the parental sensitive A2780 line. Hypermethylation at CpG islands (CGI) is often associated with transcriptional silencing, however only 245 of these hypermethylated genes become down-regulated in A2780/cp70 as measured by microarray expression profiling. Treatment with the demethylating agent Decitabine induces re-sensitisation to cisplatin and resulted in re-expression of 41 of the down-regulated genes in cisplatin-resistant cells at the time point when re-sensitisation occurs. 13 of the 41 genes were consistently hypermethylated in two further independent cisplatin-resistant A2780 cell derivatives. Nine out of the 13 genes (ARHGDIB, ARMCX2, COL1A, FLNA, FLNC, MEST, MLH1, NTS, PSMB9) acquired methylation at CpG sites in ovarian tumours at relapse following chemotherapy or chemoresistant cell lines derived at the time of patient relapse. Furthermore, 5/13 candidate genes acquired methylation in drug-resistant in vivo-derived ovarian cancer sustaining (side population) cells. Therefore, this small set of genes are potential key drivers of chemoresistance and should be further evaluated as predictive biomarkers, both to existing chemotherapies, but also to epigenetic therapies used to modulate drug resistance.

overall_design: Array-based methylation profiling was performed using the Infinium HumanMethylation27 BeadChip in two cisplatin sensitive cell lines and three cisplatin resistant cell lines derived in vitro, four pairs of cisplatin sensitive and resistant cell lines derived in vivo, 7 pairs of tumour tissues obtained from patients before chemotherapy and at disease relapse, 2 pairs of IGROV1 SP and NSP cells. The reproducibility of the Infinium HumanMethylation27 BeadChips was evaluated using biological and technical replicates of matched chemosensitive/chemoresistant ovarian cancer cell lines PEO1/PEO4. Differential methylation cutoff was estimated from two biological replicates by bootstrap resampling.

first: Constanze

last: Zeller

first: Nicola

middle: L

last: Steele

first: Afshan

last: Siddiq

first: Andrew

last: Walley

first: Sian

last: Rizzo

first: Ate

last: ven der Zee

first: Jane

last: Plumb

first: Robert

last: Brown


title: Somatic copy number variants in monozygotic twins and elderly single-born individuals

status: Public on Dec 16 2011

city: Huntsville

first: Devin

last: Absher

state: AL

address: 601 Genome Way

institute: HudsonAlpha Institute for Biotechnology

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

summary: We perfomed copy number analysis of young and old monozygotic twin pairs and young and old single-born individuals to identify somatic copy number changes that occur with age in blood DNA.

overall_design: DNA from peripheral blood was run on Illumina genotyping arrays and the R and B-allele-frequency data were used to identify somatic copy number events. The young Samples were omited because all young twins lacked CNVs in the >1 megabase range.

first: Jan

last: Dumanski


title: Expression profiles of barley chromosome addition lines of common wheat

status: Public on Dec 08 2011

city: Yokohama

first: Jianwei

last: Tang

state: Kanagawa

address: 641-12 Maioka-cho, Totsuka-ku

department: Kihara Institute for Biological Research

institute: Yokohama City University

summary: Barley contains a much higher content of bioactive substances than wheat. In order to investigate the effect of genome interaction between barley and wheat on phytosterol content, we used a series of barley chromosome addition lines of common wheat. The wheat 38k-microarray was utilized for screening of genes with expression levels specifically increased by an additive effect or synergistic action between wheat and barley chromosomes. We determined the overall expression pattern of genes related to phytosterol biosynthesis in wheat and in each addition line. Together with determining the phytosterol levels of wheat, barley and each addition line, we assess the critical genes in the phytosterol pathway that can be expressed to promote phytosterol levels.

overall_design: Gene expression levels of each barley chromosome addition line of common wheat were compared to that of common wheat. Total RNA samples were isolated from the 2-week-old seedling leaves. The experiments were replicated three times for each addition line using independent samples.

first: Tang

last: Jianwei


title: Drosophila brain microRNA expression with age: miRNA profiling

status: Public on Dec 23 2011

city: Philadelphia

first: Bonini

last: Nancy

state: PA

address: 415 S University Ave

institute: University of Pennsylvania

summary: microRNA expression profiles in fly brains with age

overall_design: microRNA expression profiles in fly brains, 3d, 30d and 60d

first: Michael

last: Fitzen

last: Liu


title: Dysfunction of mitotic cell division at shoot apices triggered severe growth abortion in interspecific hybrids between tetraploid wheat and Aegilops tauschii Coss.

status: Public on Nov 01 2011

city: Kobe

first: Shigeo

last: Takumi

state: Hyogo

address: Rokkodai 1-1, Nada

department: Graduate School of Agricultural Science

institute: Kobe University

summary: Common wheat is an allohexaploid species, derived through endoreduplication of an inter-specific triploid hybrid produced from a cross between cultivated tetraploid wheat and the wild diploid relative Aegilops tauschii Coss. Hybrid incompatibilities, including hybrid necrosis, have been observed in triploid wheat hybrids. A limited number of Ae. tauschii accessions show hybrid lethality in triploid hybrids crossed with tetraploid wheat due to developmental arrest at the early seedling stage, which is termed severe growth abortion (SGA). Despite the potential severity of this condition, the genetic mechanisms underlying SGA are not well understood. We conducted comparative analyses of gene expression profiles in crown tissues to characterize developmental arrest in triploid hybrids displaying SGA. A number of defense-related genes were highly up-regulated, whereas many transcription factor genes, such as the KNOTTED1-type homeobox gene, which function in shoot apical meristem (SAM) and leaf primordia, were down-regulated in the crown tissues of SGA plants. Transcript accumulation levels of cell cycle-related genes were also markedly reduced in SGA plants, and no histone H4-expressing cells were observed in the SAM of SGA hybrid plants. Our findings demonstrate that SGA shows unique features among other types of abnormal growth phenotypes, such as type II and III necrosis.

overall_design: Expression patterns were compared between the two triploid  hybrids showing the wild-type phenotype (as a reference) and severe growth abortion. Total RNA samples were isolated from the 3-week-old crown tissues. Two independent experiments were conducted in each exprement.

first: Hitoshi

last: Hatano

first: Nobuyuki

last: Mizuno


title: Changes in DNA methylation In cultered WI-38 cells over passages

status: Public on Oct 31 2011

city: Jerusalem

first: Amir

last: Eden

address: Givat Ram

department: Cell & Developmental Biology

country: Israel

institute: Hebrew University

summary: We used Illumina infinium methylation array analysis to document spontaneous DNA methylation changes in human fibroblasts growing in long term culture. Starting with a culture derived from a single cell we compared the methylation profile of late passage clones with that of the initial culture, allowing unambiguous identification of methylation changes.

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

first: Shulamit

last: Ron-Bigger

last: Bocker

first: Dan

last: Michlin

first: Sara

last: Isaac

first: Frank

last: Lyko


title: Replicative senescence of mesenchymal stem cells causes DNA methylation changes which correlate with repressive histone marks

status: Public on Oct 28 2011

city: Aachen

first: Martin

last: Zenke

state: NRW

address: Universitatsklinikum Aachen, RWTH

department: Cell Biology

country: Germany

institute: Institute for Biomedical Engineering

summary: Cells in culture undergo replicative senescence. In this study, we analyzed functional, genetic and epigenetic sequels of long‐term culture in human mesenchymal stem cells (MSC). Already within early passages the fibroblastoid colony‐ forming unit (CFU‐f) frequency and the differentiation potential of MSC declined significantly. Relevant chromosomal aberrations were not detected by karyotyping and SNP‐microarrays. Subsequently, we have compared DNA‐methylation profiles with the Infinium HumanMethylation27 Bead Array and the profiles differed markedly in MSC derived from adipose tissue and bone marrow. Notably, all MSC revealed highly consistent senescence‐associated modifications at specific CpG sites. These DNA‐methylation changes correlated with histone marks of previously published data sets, such as trimethylation of H3K9, H3K27 and EZH2 targets. Taken together, culture expansion of MSC has profound functional implications ‐ these are hardly reflected by genomic instability but they are associated with highly reproducible DNA‐methylation changes which correlate with repressive histone marks. Therefore replicative senescence seems to be epigenetically controlled.

overall_design: 8 samples of mesenchymal stem cells (MSC) from human adipose tissue

first: Anne

last: Schellenberg

first: Qiong

last: Lin

first: Herdit

last: Schüler

first: Carmen

last: Koch

first: Sylvia

last: Joussen

first: Bernd

last: Denecke

first: Gudrun

last: Bokermann

first: Norbert

last: Pallua

first: Christoph

middle: V

last: Suschek

first: Wolfgang

last: Wagner


title: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: blood controls

city: Providence

first: Graham

last: Poage

state: RI

address: 70 Ship St

institute: Brown University

summary: Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas (HNSCCs). The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples.

overall_design: Bisulphite-converted DNA from the 213 control blood samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

first: G

first: K

last: Kelsey


title: Methylation profiling of enchondromas with and without IDH1 mutations

status: Public on Nov 05 2011

city: Leiden

first: Twinkal

middle: Chandubhai

last: Pansuriya

state: Zuid-Holland

address: Albinusdreef 2

institute: LUMC

type: Methylation profiling by genome tiling array

summary: Ollier disease and Maffucci syndrome are non-hereditary skeletal disorderscharacterized by multiple enchondromas (Ollier disease) combined with spindle cellhemangiomas (Maffucci syndrome). Somatic heterozygous IDH1 (R132C and R132H) orIDH2 (R172S) mutations were found in 87% of enchondromas, benign cartilage tumors,as well as in 70% of spindle cell hemangiomas, benign vascular lesions. In total, 35 of 43(81%) patients with Ollier disease and 10 of 13 (77%) patients with Maffucci syndromecarried IDH1 (98%) or rarely IDH2 (2%) mutations in their tumors. Fourteen patientswith multiple tumors at different anatomic locations displayed identical mutations inseparate lesions. Since in other tumor types the presence of an IDH1 mutation is strongly associated withhypermethylation 26, 27, we assessed whether there was a difference in methylation patternof enchondromas with (n = 8) and without (n = 4) IDH1 mutations detactable at Sangersequencing. Methylation and expressionprofiling showed that IDH1 mutations in cartilage tumors are associated withhypermethylation and downregulation of the expression of several genes.

overall_design: Total 12 samples which includes 8 enchondromas with IDH1 mutation (4 Ollier enchondromas, 2 Maffucci enchondromas and 2 solitary enchondromas) and 4 enchondromas (1 Ollier enchondroma, 3 solitary enchondromas) without IDH1 or IDH2 mutations were used. Of these 4 enchondromas without IDH1 mutation, one had R132G IDH1 mutated cells present in the subpopulation, below the threshold level of Sanger sequencing. Bisulfite treatment was performed using EZ DNA Methylation™ Kit (ZymoResearch, Orange, CA). Bisulphite converted DNA was then hybridized to IlluminaHumanMethylation27 BeadChip (Illumina Inc., San Diego, CA) by followingmanufacturer’s instructions. Infinium Unsupervised clustering analysis was performed 25 using the Ward’s clustering algorithm based on Euclidian distance. The 2000 most variable CpG sites (excluding those on the X and Y chromosomes) were used in the clustering analysis.

middle: C

first: Judith

middle: v

last: Bovée

first: Pio

last: d’ Adamo


title: Epigenome analysis of saliva samples from alcohol users

city: Atlanta

first: Jingyu

last: Liu

address: 55 Park Pl

institute: Georgia State University

summary: Genome wide DNA methylation profiling of saliva DNA from 197 alcohol dependent subjects. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in saliva samples.

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

first: Kent

last: Hutchison


title: DNA Methylation Profiling of Melanoma Cell Lines

status: Public on Oct 25 2011

city: Herston

first: Derek

middle: John

last: Nancarrow

state: Queensland

address: 300 Herston Road

department: Genetics & Population Health

country: Australia

institute: Queensland Institute of Medical Research

summary: Epigenetic regulation of tumor suppressor genes (TSGs) has been shown to play a central role in melanomagenesis. Integrating gene expression and methylation array analysis we identified novel candidate TSGs frequently methylated in melanoma. We validated the methylation status of the most promising TSGs using the highly sensitive, specific and comprehensive Sequenom Epityper assay in a large panel of melanoma cell lines and resected melanomas, and compared the findings with that from cultured melanocytes. We found transcript levels of UCHL1, COL1A2, THBS1 and TNFRSF10D were inversely correlated with promoter methylation. The effect of this methylation on expression was confirmed at the protein level. Identification of these candidate TSGs and how their silencing is related to melanoma development will increase our understanding of the etiology of this cancer and may provide tools for its early diagnosis.

overall_design: Analysed samples consisted of 11 melanoma cell lines and 1 neonatal foreskin melanocyte pool as a reference. Melanoma cell lines overlap with members of the DNA copy number analysis series GSE9003 and expression profiling series GSE7127 . The matching copy number data GEO samples IDs are noted in characteristics: Matching CN Sample ID and characteristics: Matching expn Sample ID columns respectively.

first: Vanessa

middle: F

last: Bonazzi

middle: J

first: Mitchell

middle: S

last: Stark

first: Ralf

last: Moser

first: Glen

last: Boyle

first: Lauren

middle: G

last: Aoude

first: Christopher

last: Schmidt

first: Nicholas

middle: K

last: Hayward


title: Progression of Neuroblastoma Tumor

city: Gaithersburg

first: Peter

last: Johansson

state: Maryland

address: 8717 Grovemont Circle

department: Pediatric Oncology Branch

institute: National Cancer Institute

summary: Previous studies have reported that metastatic tumor cells acquire genomic aberrations compared to those present in the primary due to an unstable genome. However, it is not clear if all malignancies follow a similar pattern. Neuroblastoma is the most common extra-cranial solid tumor of childhood. To examine how the neuroblastoma genome changes during tumor progression, we investigated chromosomal structural alterations across three tumors from a patient with hisg-risk neuroblastoma. The tumors included the primary tumor, one metastatis collected at diagnosis before any treatment, and a second metastatis collected during post mortem investigation. The recapitulated chromosomal structural alterations demonstrated that all three tumors had extensive chromosomal alterations involving virtually every chromosome. All tumors were aneuploid and shared many chromosomal alterations often seen in neuroblastoma. Despite some tumor to tumor structural variability, approximately 81-91% of the altered regions were shared among the three tumor genomes with primary tumor and pre-treamment metastatis being the most similar.

overall_design: Three samples from one patient with high-risk neuroblastoma. Primary tumor plus two metastatic tumors. One of metastasis sampled at diagnosis, before any treatment, and second metastasis taken at autopsy.

first: Jun

last: Wei

first: Javed

last: Khan

first: Young

last: Song


title: Clonal Selection Drives Genetic Divergence of Metastatic Medulloblastoma [Illumina Infinium HumanMethylation27 Beadchip v1.2]

status: Public on Dec 13 2011

city: HEIDELBERG

first: Paul

middle: A.

last: Northcott

address: Im Neuenheimer Feld 280

institute: German Cancer Research Center (DKFZ)

summary: Medulloblastoma, the most common malignant pediatric brain tumour, disseminates by shedding cells into the cerebrospinal fluid, which then re-implant to cover the surface of the brain and spinal cord.  Metastases are a very poor prognostic sign at presentation and are usually lethal at recurrence.  Mechanisms driving dissemination have been described in the bulk primary tumour, with the underlying assumption that primary tumour and metastases are biologically similar.  Here we show that in both mouse and human medulloblastoma, multiple metastases from a single animal are extremely similar, but are genetically highly divergent from the primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted sub-clone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize.  Failure to account for the bicompartmental nature of primary and metastatic medulloblastoma represents a major barrier to the development of effective targeted therapies.

overall_design: DNA methylation analysis of 15 pediatric medulloblastoma samples consisting of 6 primary-metastatic pairs and 4 normal cerebella samples profiled in Illumina Infinium HumanMethylation27 Beadchip v1.2

first: Adrian

middle: M

last: Dubuc

first: Xiaochong

last: Wu

first: Michael

middle: D

last: Taylor


title: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: normal head and neck tissue

first: Graham

last: Poage

summary: Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas. The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples.

overall_design: Bisulphite-converted DNA from the 18 normal head and neck samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

first: G

first: K

middle: T

last: Kelsey


title: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: HNSCC

overall_design: Bisulphite-converted DNA from the 91 head and neck squamous cell carcinoma samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.


title: Epigenetic portraits of human breast cancers (methylation data 2)

status: Public on Oct 19 2011

city: Toronto

first: Benjamin

last: Haibe-Kains

state: Ontario

address: 610 University Avenue

department: Princess Margaret Research

institute: Princess Margaret Cancer Centre

summary: Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Here we used the Infinium Methylation Platform to profile at single-CpG resolution (over 14,000 genes interrogated) the methylomes of 119 breast tumours. It emerges that many genes whose expression is linked to the ER status are epigenetically controlled (or/ we show that the two major phenotypes of breast cancers determined by ER status are widely involving epigenetic regulatory mechanisms), offering the prospect of a novel approach to treating ER-positive tumours. We have distinguished methylation-profile-based tumour clusters, some coinciding with known “expression subtypes” but also new entities that may provide a meaningful basis for refining breast tumour typology. We show that methylation patterns may reflect the cellular origins of tumours. Having highlighted an unexpectedly strong epigenetic component in the regulation of key immune pathways, we show that a set of immune genes have high prognostic value in specific tumour categories. By laying the ground for better understanding of breast cancer heterogeneity and improved tumour taxonomy, the precise epigenetic portraits drawn here should contribute to better management of breast cancer patients.

overall_design: 125 gene expression profiling of breast tissues (117 tumors + 8 normal). Study of epigenetic variation (methylation) linked to gene expression. No replicate, no reference sample.

first: Sarah

last: Dedeurwaerder

first: Christine

last: Desmedt

first: Emilie

last: Calonne

first: Sandeep

last: Singhal

first: Judith

last: Luciani

first: Pascale

last: Putmans

first: Françoise

last: Lallemand

first: Denis

last: Larsimont

first: Jérôme

last: Toussaint

first: Sandy

last: Haussy

last: Rothé

first: Ghizlane

last: Rouas

first: Otto

last: Metzger

first: Michel

last: Georges

first: Christos

last: Sotiriou

first: François

last: Fuks


title: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer

first: Graham

last: Poage

overall_design: Refer to individual Series


title: Maintenance of hESCs in mesenchymal stem cell-conditioned media augments hematopoietic specification

status: Public on Oct 03 2011

city: Oviedo

first: Agustin

last: Fernandez

email: affernandez@hca.es, agusff@gmail.com

state: Asturias

address: Avenida de Roma s/n

department: IUOPA

institute: Oviedo University-HUCA

summary: The realization of human embryonic stem cells (hESC) as a model for human developmental hematopoiesis and potential cell replacement strategies relies on an improved understanding of the extrinsic and intrinsic factors regulating hematopoietic-specific hESC differentiation. Mesenchymal stem cells (hMSCs) are multipotent cells of mesodermal origin that form part of hematopoietic stem cell niches and have an important role in the regulation of hematopoiesis through production of secreted factors and/or cell-to-cell interactions. We have previously shown that hESCs may be successfully maintained feeder-free using hMSC-conditioned media (MSC-CM). Here, we hypothesized that hESCs maintained in MSC-CM may be more prone to differentiation towards hematopoietic lineage than hESCs grown in standard human foreskin fibroblast (HFF)-conditioned media (HFF-CM). We report that specification into hemogenic progenitors and subsequent hematopoietic differentiation and clonogenic progenitor capacity is robustly enhanced in hESC lines maintained in MSC-CM. Interestingly, co-culture of hESCs on hMSCs fully abrogates hematopoietic specification of hESCs suggesting that the improved hematopoietic differentiation is mediated by MSC-secreted factors rather than by MSC-hESC physical interactions. To investigate the molecular mechanism involved in this process, we analyzed global (LINE-1) methylation and genome-wide promoter DNA methylation. Human ESCs grown in MSC-CM showed a decrease of 20% in global DNA methylation and a promoter DNA methylation signature consisting in 45 genes commonly hypomethylated and 102 genes frequently hypermethylated. Our data indicate that maintenance of hESCs in MSC-CM robustly augments hematopoietic specification and that the process seems mediated by MSC-secreted factors conferring a DNA methylation signature to undifferentiated hESCs which may influence further predisposition towards hematopoietic specification.

overall_design: Total DNA isolated by standard procedures from human embryonic stem cells (hESC) cultured in different conditioned media

first: Verónica

last: Ramos-Mejía

last: Ayllón

first: Pedro

last: Real

first: Clara

last: Bueno

first: Laura

last: Sánchez

first: Gertrudis

last: Ligero

first: Mario

last: Fraga

first: Pablo

last: Menendez


title: Epigenetic portraits of human breast cancers (HCT116 cell line data)

first: Benjamin

last: Haibe-Kains

overall_design: 6 methylation profiling of HCT116 cell lines. Study of epigenetic variation (methylation) linked to gene expression. No replicate, no reference sample.

first: Sarah

last: Dedeurwaerder

first: Christine

last: Desmedt

first: Emilie

last: Calonne

first: Sandeep

last: Singhal

first: Judith

last: Luciani

first: Pascale

last: Putmans

first: Françoise

last: Lallemand

first: Denis

last: Larsimont

last: Toussaint

last: Haussy


title: Epigenetic portraits of human breast cancers (methylation data)

overall_design: 123 gene expression profiling breast cancer patients. Study of epigenetic variation (methylation) linked to gene expression. No replicate, no reference sample.

first: Jérôme

first: Sandy

last: Rothé

first: Ghizlane

last: Rouas

first: Otto

last: Metzger

first: Michel

last: Georges

first: Christos

last: Sotiriou

first: François

last: Fuks


title: Epigenetic portraits of human breast cancers (various cell lines methylation data)

last: Haibe-Kains

overall_design: Gene expression profiling  cell lines. Study of epigenetic variation (methylation) linked to gene expression. No replicate, no reference sample.


title: affy_rnai_cadpoplars: Transcriptome analysis of RNAi-CAD transgenic poplars

status: Public on Sep 30 2011

city: evry

first: stephanie

last: huguet

address: 2 rue gaston cremieux

institute: inra

summary: affy_rnai_cadpoplar - affy_rnai_cadpoplars - This experiment aims to characterize global gene expression in young xylem of transgenic RNAi-CAD poplars in comparison to WT poplars. Cinnamyl Alcohol Dehydrogenase (CAD) is the final enzyme involved in the monolignol biosynthesis pathway. Transgenic poplars were produced using RNAi strategy (pHellsgate 8 vector, Helliwell and Waterhouse, 2003) and exhibited the expected phenotype (red xylem, reduced CAD activity).Biological question (15 lines max):This experiment aims to characterize global gene expression in young xylem of transgenic RNAi-CAD poplars in comparison to WT poplars. Cinnamyl AlcoholDehydrogenase (CAD) is the final enzyme involved in the monolignol biosynthesispathway.Transgenic poplars were produced using RNAi strategy (pHellsgate 8 vector, Helliwell and Waterhouse, 2003) and exhibited the expectedphenotype (red xylem, reduced CAD activity). -RNAi-CAD transgenic poplars were produced using hairpin RNAi strategy (pHellsgate 8 vector, Helliwell and Waterhouse, 2003). For this transcriptome anaylsis, 2 independent transgenic lines (named pHG8-CAD2 and pHG8-CAD19) from the same transformation procedure were used as biological repeats. Four-month-old poplar plants were inclined at 30° in the greenhouse and sampled after 26 days. Young differentiating xylem originating from the lower side of stems - opposite wood - (ODX) was sampled on each individual tree by scrapping slightly the debarked stem with a scalpel. Samples were immediately flash frozen in liquid nitrogen, ground with mortar and pestle, and total RNAs were extracted from fine ground powder using the QIAGEN miRNeasy kit according to the manufacturer. One Affymetrix slide corresponds to a pool of RNA samples from 2-4 individual trees (WT, RNAi-CAD transgenic lines 2 and 19). Total number of slides = 2 genotypes (WT/RNAi line) x 1 tissue x 2 biological replicates = 4 slides were done.

overall_design: 4 arrays - poplar; normal vs rnai mutant comparaison

first: Stephanie

last: Huguet

first: Annabelle

last: Dejardin

first: Sandrine

last: Balzergue

first: Marie-Laure

last: Martin-Magniette


title: Copy number profiling of ovarian cancer ascitic effusion

city: Pieve Emanuele

first: Charlotte

middle: K Y

last: Ng

state: MI

address: Via Rita Montalcini 4

department: Biomedical Sciences

country: Italy

institute: Humanitas University

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

summary: The PEO/PEA series of ovarian cancer cell lines was established in 1988 from samples in this dataset.

overall_design: Copy number profiling of ascitic effusion of PE cell lines on Illumina Infinium Human1M-Duo v3 BeadChips

first: Susanna

last: Cooke

first: James

last: Brenton


title: Promoter methylation in HNSCC tumor cell lines is significantly different from primary tumors and xenografts

status: Public on Oct 01 2011

city: Baltimore

first: Michael

last: Ochs

state: MD

address: 550 North Broadway, Ste 1103

department: Oncology Biostatistics

institute: Johns Hopkins University

summary: This study focused on global methylation changes between tumors, normal mucosa, primary tumor xenografts, and cell lines in order to determine epigenetic changes in cell cultures and xenografts derived from primary tumors.

overall_design: 1 fully methylated control cell line, 1 fully demethylated control cell line, 5 HNSCC cell lines, 2 normal cell lines, 7 normal mucosa, 3 primary HNSCC tumors, 3 xenografts of primary tumors

first: Patrick

last: Hennessey

first: Joseph

middle: A

last: Califano


title: Clonal evolution through loss of chromosomes and subsequent polyploidization in chondrosarcoma

status: Public on Sep 26 2011

city: Lund

first: Karolin

middle: H

last: Nord

address: BMC C13

department: Dept of Clinical Genetics

institute: Lund University

summary: Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP) array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events.

overall_design: Tumor DNA was hybridized onto Illumina Human Omni-Quad v1.0 BeadChip or Human CNV370-Quad v3.0 BeadChip (Illumina, San Diego, CA, USA), following standard protocols supplied by the manufacturer. Data were extracted from the GenomeStudio software (Illumina), and subsequently normalized and segmented using thresholded quantile normalization (tQN) and BAFsegmentation, respectively (Staaf et al. Normalization of array-CGH data: influence of copy number imbalances. BMC Genomics 2007, 8:382; Staaf et al. Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays. Genome Biol 2008, 9:R136). Base pair positions are indicated according to the NCBI build 36 (hg18).

first: Linda

last: Olsson

first: Kajsa

last: Paulsson

first: Judith

last: Bovée


title: Promoter methylation data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases

status: Public on Sep 23 2011

city: Stony Brook

first: Laura

middle: E.

last: Hogan

state: New York

department: Department of Pediatrics

institute: Stony Brook University

summary: Relapse samples have high methylation level than dianosis samples

overall_design: Promoter mehtylation level was measured and compared between relapse and diagnosis samples

middle: E

first: Jinhua

last: Wang

first: William

middle: L

last: Carroll


title: A promoter DNA demethylation landscape of human hematopoietic differentiation

status: Public on Sep 15 2011

first: Agustin

last: Fernandez

summary: Global mechanisms defining the gene expression programs specific for hematopoiesis are still not fully understood.  Here, we show that promoter DNA demethylation is associated the activation of hematopoietic-specific genes.  Using genome-wide promoter methylation arrays, we identified 694 hematopoietic-specific genes repressed by promoter DNA methylation in human ESCs and whose loss of methylation in hematopoietic can be associated with gene expression.  The association between promoter methylation and gene expression was studied for many hematopoietic-specific genes including CD45, CD34, CD28, CD19, the T cell receptor (TCR), the MHC class II gene HLA-DR, perforin 1, and the phosphoinositide 3-kinase (PI3K) and results indicated that DNA demethylation was not always sufficient for gene activation.  Promoter demethylation occurred either early during embryonic development or later on during hematopoietic differentiation.  Analysis of the genome-wide promoter methylation status of induced pluripotent stem cells (iPSCs) generated from somatic CD34+ HSPCs and differentiated derivatives from CD34+ HSPCs confirmed the role of DNA methylation in regulating the expression of genes of the hemato-immune system, and indicated that promoter methylation of these genes may be associated to stemness.  Together, these data suggest that promoter DNA demethylation might play a role in the tissue/cell-specific genome-wide gene regulation within the hematopoietic compartment.

overall_design: Total DNA isolated by standard procedures from different primary samples corresponding to healthy patients and several cell lines.

first: Vincenzo

last: Calvanese

first: Rocío

last: Urdinguio

first: Beatriz

last: Suárez-Alvarez

first: Cristina

last: Mangas

first: Vicente

last: Pérez-García

first: Clara

last: Bueno

first: Rosa

last: Montes

first: Verónica

last: Ramos-Mejía

first: Pablo

last: Martínez-Camblor

first: Cecilia

last: Ferrero

first: Yassen

last: Assenov

first: Christoph

last: Bock

last: Menendez

first: Ana

middle: C

last: Carrera

first: Carlos

last: Lopez-Larrea

first: Mario

last: Fraga


title: Transcriptome response to embolism in stems of P. trichocarpa

city: Boston

first: Francesca

last: Secchi

state: MA

address: 1300 Centre St

institute: Arnold Arboretum of Harvard University

summary:
Embolism and the refilling of xylem vessels are intrinsic to the ability of plants to handle the transport of water under tension.  While the formation of an embolized vessel is an abiotic process, refilling against the pressure gradient requires biological activity to provide both the energy and the water needed to restore xylem transport capacity.
We used microarrays to analyze the global transcriptome response of xylem parenchyma cells after embolism formation or infiltration of xylem tissue with sucrose solution.

overall_design: Plants subjected to artificial embolism treatment (ET), to sucrose infiltration treatment (ST), and controls (C) were selected for RNA extraction and hybridization on Affymetrix microarrays. Embolism was artificially induced through air-injection into the stems of the ET plants, while ST plants were exposed to osmotic stress by adding sucrose to the growing solution. Woody stems were respectively collected 90 minutes following the injection and after 90 minutes of exposure to sucrose.

first: Matthew

last: Gilbert

first: Maciej

last: Zwieniecki


title: Prognostic DNA Methylation Patterns in Cytogenetically Normal Acute Myeloid Leukemia are predefined by Stem Cell Chromatin Marks [methylation]

status: Public on Sep 21 2011

city: Stockholm

first: Stefan

last: Deneberg

department: Internal medicine/Huddinge

institute: Karolinska Institutet

summary: Cytogenetically normal acute myeloid leukemia (CN-AML) comprise between forty and fifty percent of all adult acute myeloid leukemia (AML) cases. In this clinically diverse group molecular aberrations such as FLT3ITD, NPM1 and CEBPA mutations recently have added to the prognostic accuracy. Aberrant DNA methylation is a hallmark of cancer including AML. We investigated in total 89 CN-AML samples in a test and a validation cohort for genome-wide promoter DNA methylation with Illumina Methylation Bead arrays and compared them to normal myeloid precursors and global gene expression. IDH and NPM1 mutations were associated with different methylation patterns (p=0.0004 and 0.04, respectively). Genome-wide methylation levels were elevated in IDH mutated samples (p=0.006). We observed a negative impact of DNA methylation on transcription. Genes targeted by Polycomb group (PcG) proteins and genes associated with bivalent histone marks in stem cells showed increased aberrant methylation in AML (p<0.0001). Furthermore, high methylation levels of PcG target genes were independently associated with better progression free (OR 0.47, p=0.01) and overall survival (OR 0.36, p=0.001). In summary, genome wide methylation patterns show preferential methylation of PcG targets with prognostic impact in CN-AML.

overall_design: Genome wide methylation pattern study of cytogenetically normal AML

first: Sören

last: Lehmann


title: MYC binding in human B cells (P493-6) and ESC (H9)

status: Public on Sep 19 2011

first: Hongkai

last: Ji

address: 615 North Wolfe Street, Rm E3638

department: Department of Biostatistics

institute: Johns Hopkins Bloomberg School of Public Health

summary: Myc plays important roles in cancer and stem cell biology including reprogramming adult cells to pluripotent stem cells. We have indentified a core set of Myc target genes in human B-cells and embryonic stem cells by genome wide ChIP-on-chip and transcriptional profiling.

overall_design: A total of 8 chromatin immunoprecipitation (ChIP) samples were generated from P493-6 cells (5 using 1 of 2 MYC antibodies and 3 using anti rabbit IgG. A total of 6 ChIP samples were generated from undifferentiated H9 hES cells (3 using anti c-Myc and 3 using anti rabbit IgG.

first: Karen

last: Zeller

first: Chi

middle: V

last: Dang


title: Community network analysis of complex microbial biofilms reveals characteristic microbial assemblages in health and disease

status: Public on Sep 17 2011

city: Cambridge

first: Jorge

last: Frias-Lopez

address: 245 First street

institute: Forsyth Institute

summary: This study compared the subgingival microbiota of subjects with periodontitis  to those with periodontal health using the Human Oral Microbe Identification Microarray (HOMIM).

overall_design: The microbial profiles of subgingival plaque from healthy and periodontitis subjects was compared using community network analysis.

first: Bruce

last: Paster

middle: P

last: Colombo


title: Genome-wide methylation analysis detects genes specific to breast cancer hormone receptor status and risk of recurrence

status: Public on Sep 09 2011

first: leslie

last: cope

address: 550 N. Broadway

institute: leslie cope

summary: To better understand the biology of hormone receptor-positive and negative breast cancer and to identify methylated gene markers of disease progression, we performed a genome-wide methylation array analysis on 103 primary invasive breast cancers and 21 normal breast samples using the Illumina Infinium HumanMethylation27 array that queried 27,578 CpG loci. Estrogen and/or progesterone receptor-positive tumors displayed more hypermethylated loci than ER-negative tumors. However, the hypermethylated loci in ER-negative tumors were clustered closer to the transcriptional start site compared to ER-positive tumors. An ER-classifier set of CpG loci was identified, which independently partitioned primary tumors into ER-subtypes. Forty (32 novel, 8 previously known) CpG loci showed differential methylation specific to either ER-positive or ER-negative tumors.  Each of the 40 ER-subtype-specific loci was validated in silico using an independent, publicly available methylome dataset from The Cancer Genome Atlas (TCGA).  In addition, we identified 100 methylated CpG loci that were significantly associated with disease progression; the majority of these loci were informative particularly in ER-negative breast cancer. Overall, the set was highly enriched in homeobox containing genes. This pilot study demonstrates the robustness of the breast cancer methylome and illustrates its potential to stratify and reveal biological differences between ER-subtypes of breast cancer. Further, it defines candidate ER-specific markers and identifies potential markers predictive of outcome within ER subgroups.

overall_design: Frozen breast cancer tissues that were excised from patients with Stage 1-3 disease prior to treatment (n=103) were retrieved from Surgical Pathology at Johns Hopkins Hospital (Baltimore, Maryland) and confirmed to contain > 50% epithelial cells.  Normal breast organoids were prepared by enzymatic digestion of reduction mammoplasty specimens (n=15; median patient age = 52 years, range 47 to 71).  Normal ducts from breast tissue > 2 cm away from the tumor (n=6) were isolated from cryosections using laser-capture micro-dissection (PALM MicroBeam, Carl Zeiss Microimaging, North America).  To determine the differences in breast cancer biology/behavior between ER subtypes, we characterized methylation patterns at 8376 selected CpG loci according to ER status.  These loci met two criteria: 1) showed the most variation across primary tumors (SD >0.100) and 2) had probe detection p-values <0.0001.  To develop an epigenomic signature that predicts outcome in patients with breast cancer, we conducted differential methylation analysis on primary tumors from recurrent versus non-recurrent breast cancers.  We used a subgroup of 82 well-annotated, invasive breast tumors derived from the discovery set of 103 tumors that included 44 ER-positive (7 recurrences) and 38 ER-negative (11 recurrences) breast cancers and independently queried the ER-positive and ER-negative tumor groups

first: Mary-Jo

last: Fackler

first: Christopher

last: Umbricht

first: Danielle

last: Williams

first: Pedram

last: Argani

first: Leigh-Ann

last: Cruz

first: Vanessa

middle: F

last: Merino

first: Wei

middle: W

last: Teo

first: Zhe

last: Zhang

first: Peng

last: Huang

first: Kala

last: Visvananthan

first: Jeffrey

last: Marks

first: Stephen

last: Ethier

first: Joe

last: Gray

first: Antonio

last: Wolff

first: Leslie

last: Cope

first: Saraswati

last: Sukumar


title: Epigenetic Impact of Long-Term Shiftwork:  Poly Evidence from Cricadian Genes and Whole-Genome Methylation Analyses

status: Public on Sep 03 2011

city: New Haven

first: Alan

last: Fu

state: CT

address: 60 College St.

institute: Yale University

summary: Analysis of genomic methylation differences between day workers and shift workers.  We hypothesized that there would be differences in methylation patterns between day workers and shift workers, and that some of these differences may explain the association between long-term shift work and breast cancer.  The array provides methylation data on more than 27,000 CpG sites spread across the genome.

overall_design: Bisulfite-converted DNA from 10 day workers and 10 shift workers were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

first: Yong

last: Zhu

first: Richard

middle: G

last: Stevens

first: Aaron

last: Hoffman

first: Anne

last: Tjonneland

first: Ulla

middle: B

last: Vogel

first: Tongshang

last: Zheng

first: Johnni

last: Hansen


title: Methylation analysis of samples from a phase II clinical trial of decitatbine in combination with carboplatin in patients with recurrent, platinum resistant epithelial ovarian cancer

status: Public on Sep 02 2011

city: Bloomington

first: Kenneth

last: Nephew

state: IN

institute: Indiana University

summary: Genome wide DNA methylation profiling of blood and biopsy samples from recurrent, platinum resistant epithelial ovarian cancer patients before and after treatment of decitabine in combination with carboplatin. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in PBMC (14 paired samples), tumor (8 paired samples) and ascites (6 paired samples).

overall_design: Bisulphite converted DNA from 56 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

first: Fang

last: Fang

first: Daniela

last: Matei


title: Effect of AICAr and SAICAr accumulation on global transcription in the ade3 mutant

status: Public on Sep 01 2011

city: PARIS

first: sophie

last: lemoine

address: 46 rue d'Ulm

department: Biologie

institute: Ecole Normale Supérieure

summary: We investigated the effects of AICAr and SAICAr accumulation on the global transcriptome of yeast, comparing the ade3 mutant to the WT strain.

overall_design: The ade3 mutant strain (Y4143) was compared to the WT strain (Y2946). For each comparison, we made 2 technical replicates, swapping dyes.

first: Benoit

last: Pinson

first: Fanny

last: Coulpier

first: Sophie

last: Lemoine

first: Bertrand

last: Daignan-Fornier


title: Role of Ado1p in the transcriptional response associated with AICAr supplementation

summary: We investigated the role of Ado1p associated with AICAr supplementation on the global transcriptome of Y3188.

overall_design: The Y3188 strain was grown with or without AICAr. For each comparison, we made 2 biological replicates, swapping dyes.


title: Embryos of wheat seeds: Temperature effect

status: Public on Sep 08 2011

city: Tsukuba

first: Shingo

last: Nakamura

state: Ibaraki

address: Kannondai 2-1-18

institute: National Institute of Crop Science

summary: Transcriptional profiling of wheat embryos of developing seed comparing seeds grown at low temperature:13˚C with seeds grown at high temperature:25˚C during seed development using wheat 2 cultivars: Norin61 (N61) and Shiroganekomugi (SK). Goal was to determine the effects of temperature on global gene expression.

overall_design: Two-condition experiment, Low(13˚C) vs. high (25˚C) temperatures during seed development. Time course experiments along with  days after anthesis (DAA).


title: Effect of 5-amino-4-imidazolecarboxamide ribotide (AICAr) supplementation on global transcription

summary: We investigated the effects of AICAr supplementation on the global transcriptome of Y2950.

overall_design: The Y2950 strain was grown with or without AICAr. For each comparison, we made 2 biological replicates, swapping dyes.


title: Correlation between maternal age and newborn DNA methylation

city: Memphis

first: Ronald

last: Adkins

state: TN

address: 50 N Dunlap, 308 West Patient Tower

department: Pediatrics

institute: Univ TN Health Science Center

summary: Background: Changes in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, particularly cancer. Additionally, the offspring of older parents are at significantly increased risk of cancer, diabetes, and neurodevelopmental disorders. Only a proportion of these increased risks among the children of older parents can be attributed to nondisjunction and chromosomal rearrangements. Results: Using a genome-wide survey of 27,578 CpG dinucleotides in a cohort of 168 newborns, we examined the relationship between DNA methylation in newborns and a variety of parental and newborn traits. We found that methylation levels of 144 CpGs belonging to 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. Among these genes, processes related to cancer were over-represented, as were functions related to neurological regulation, glucose/carbohydrate metabolism, nucleocytoplasmic transport, and transcriptional regulation. CpGs exhibiting gender differences in methylation were overwhelmingly located on the X chromosome, although a small subset of autosomal CpGs were found in genes previously shown to exhibit gender-specific differences in methylation levels. Conclusions: These results indicate that there are differences in CpG methylation levels at birth that are related to parental age and that could influence disease risk in childhood and throughout life.

overall_design: 168 newborn umbilical cord buffy coat samples run singly as a cross-sectional study, not case-control.


title: Response of Candida albicans towards a novel antifungal benzimidazole derivative

status: Public on Jul 15 2011

city: Stuttgart

first: Steffen

last: Rupp

address: Nobelstr. 12

department: MBT

institute: Fraunhofer IGB

summary: Fungal infections are a serious health problem in the clinic especially in the immunocompromised patient. Disease ranges from widespread superficial vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses only a limited arsenal of antimycotica are available, including azoles, polyenes, echinocandines and amphothericin B. Due to emerging resistance to standard therapy and significant side effects for some antimycotica there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities we screened compound libraries, including combinatorial libraries as well as more than 30 000 pure compounds derived from organic synthesis for antimycotic activity. In total more than 100 000 compounds were screened using an innovative AS (activity-selectivity) assay analyzing both the antifungal activity and the compatability with human cells at the same time. One promising hit, a Benzimidazol-2-yl-alkylamine derivative, was developed in a series of lead compounds showing potent antifungal activity. ((1S)-1-[1-(3-chlorobenzyl)-1H-benzimidazol-2-yl]-2-methylpropyl-amine) (EMC120B12) showed the highest antifungal activity and best compatability with human cells in several cell culture models and against a number of different yeasts and clinical isolates. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol-pathway.

overall_design: In total, three biological replicates were performed. All experiments were performed as dye swaps. Thus, in total six arrays have been hybridzed. Hybridization experiments included an untreated reference sample and a sample of cells treated with ((1S)-1-[1-(3-chlorobenzyl)-1H-benzimidazol-2-yl]-2-methylpropyl-amine) (EMC120B12). The array included one technical replicate of each probe.

first: Anke

last: Burger-Kentischer

first: Doris

last: Finkelmeier

first: Jörg

last: Bauer

first: Holger

last: Eickhoff

first: Gerald

last: Kleymann

first: Karin

last: Lemuth

first: Petra

last: Keller

first: Walid

last: Rayyan

first: Klaus

last: Schröppel

first: Karl-Heinz

last: Wiesmüller


title: Genome-wide analysis of autosomal sex differences in human DNA methylome

status: Public on Aug 22 2011

first: Rosanna

last: Weksberg

address: 555 University Ave.

department: Genetics and Genome Biology

institute: The Hospital for Sick Children

summary:
Sex difference had been implicated in pathophysiology and prognosis of common diseases, such as acute lymphoblastic leukemia and coronary heart disease. It is well known that the disease phenotype is shaped by the interaction between the environment, genome, and epigenome. The environmental and the genetic components were extensively studied in the past. Unlike the formers, the role of epigenetics has only been recently investigated. To date, little has been known about differences in epigenetic makeup between the two sexes. Here we present a genome-wide study of sex-specific differences in DNA methylation in healthy individuals.
We compared the methylation status of ~26,000 CpGs in the promoter of ~14,000 genes between age-matched males (n=12) and females (n=12). We identified 19 CpGs in 18 genes to have significant sex-specific methylation differences. Our finding was validated by a recent publication of Liu et al. 2010 where they found  similar results (ie. 11 of their 12 CpGs overlapped with ours) using the same microarray platform. However, with further investigation we showed that the probes with sex-specific methylation differences displayed cross-reactive targets on the sex chromosomes. This data indicates that autosomal sex-specific methylation detected  in this study and by Lui et al, 2010 using the Illumina array platform, is the result of  technical artifacts or non-specificity of those microarray probes. Overall, our findings suggest that there is no sex-specific DNA methylation difference in human beyond the sex chromosomes using the Illumina Methylation 27 microarray.

overall_design: Genome-wide DNA methylation data of sodium-bisulfite converted-genomic DNA obtained from whole blood lymphocytes of 12 healthy males compared to that of 12 age-matched healthy females

first: Yi-an

last: Chen


title: Expression data of male and female floral bud with Populus tomentosa during their development process.

status: Public on Jul 01 2011

city: beijing

first: ye

middle: mei

last: xia

address: qinghua eastern road 35#

department: faculty of biology

country: China

institute: beijing forestru university

summary: Poplar GeneChip was employed to detect genes expressed during the whole floral developmental process, in order to improve understanding of poplar flower development, since current knowledge on flower development was mainly from model plant Arabidopsis.

overall_design: Male and female floral buds of Populus tomentosa were selected at successive stages of the whole development process for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain genes contributed to floral development, but not the dynamic expression changes. To that end, equal amount of floral buds RNA per gender from different stages were mixed for the detection of expressed genes.

first: Xinmin

last: An

first: Meixia

last: Ye


title: Genome-wide transcript profiling associated with metabolic regulation of Poplar N storage and cycling

city: college park

first: rongshuang

last: lin

address: Plant Sci building

department: Plant sci

institute: Univ Maryland

summary: Previous research has shown that glutamine and sucrose treatment of excised poplar stems induces bark storage protein (BSP) gene expression. The objective of this research is to identify changes in gene expression associated with metabolic regulation of nitrogen storage and cycling and use this information to identify potential regulatory genes. Significant, differentially expressed genes were identified in excised poplar stems incubated in solutions of glutamine, sucrose, glycine, glutamine+glucose, and glutamine+sucrose compared to incubation in a water control.

overall_design: Poplar shoots with approximately 10 nodes were excised from greenhouse stock plants that were grown in LD photoperiods. The basal leaves were removed to leave only the 5 apical leaves. The basal ends of the 5-leaved shoots were pre-incubated by placing in water for 24 h in a growth chamber (20 °C, 16-light/8-h dark). Following a 24 h pre-incubation, the excised stems were then transferred to 25 mM aqueous solutions of glutamine, glucose, sucrose, glycine, glutamine+glucose or glutamine+sucrose as well as a water control and incubated for either 48 or 72 h. Solutions were replenished at 24 h intervals to maintain an approximate volume of 0.5 L. After 48 h and 72 h of incubation in the respective solutions, bark tissue was collected from each treatment and immediately frozen in liquid nitrogen. For each treatment, 3 biological replicates were collected with 5 excised stems per biological replicate. Bark from 2 pre-treatments consisting of 3 biological replicates was also collected. Bark of the 'pre1' was collected immediately after excising from the stock plants and 'pre2' bark was collected after the 24 h pre-incubation period.

first: Rongshuang

last: Lin

first: Gary

last: Coleman

first: Ganesh

last: Sriram

first: Jianhua

last: Zhu


title: Ploidy influences the cellular responses of gross chromosomal rearrangements in Saccharomyces cerevisiae

status: Public on Jun 17 2011

first: sophie

last: lemoine

summary: We investigated the effects of the ploidy on cellular response in strains carrying various types of gross chromosomal rearrangements.

overall_design: Fourteen mutated strains (6 haploid strains and 8 diploid strains) were compared to their associated parental strain (haploid or diploid parental strain). For each comparison, 2 microarray experiments implying biological replicates were performed.

first: Paul

last: Jung

first: Emilie

last: Fritsch

first: Corinne

last: Blugeon

first: Jean-Luc

last: Souciet

first: Serge

last: Potier

first: Sophie

last: Lemoine

first: Joseph

last: Schacherer

first: Jacky

last: de Montigny


title: Epigenetic Vestiges of Early Developmental Adversity: Child Stress Exposure and Adolescent DNA Methylation

status: Public on May 30 2011

city: Vancouver

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: Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents’ infancy and preschool periods. Microarray technology applied to 28,000 cytosine–guanine dinucleotide sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children’s early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children’s gender. To the authors’ knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents’ genomic DNA.

overall_design:
Genomic DNA was extracted from 109 Buccal DNA samples, bisulphite converted and hybridized, along with 4 technical replicates to the Illumina Infinium HumanMethylation27 Beadchip v1.2 for genome wide DNA methylation profiling.
Processed signal intensity data and Detection Pvalues for individual replicates of Samples 006 (reps a,b), 099 (reps a,b,c), 106 (reps a,b) reported in the supplementary file "processed_individual reps.txt."

first: Marilyn

middle: J

last: Essex

first: W

last: Boyce

first: Clyde

last: Hertzman

first: Lucia

last: Lam

first: Jeffrey

middle: M

last: Armstrong

first: Sarah

last: Neumann

middle: S


title: Methylation screening of reciprocal genome-wide UPDs identifies novel human specific imprinted genes

status: Public on May 26 2011

city: Setagaya

first: Kazuhiko

last: Nakabayashi

state: Tokyo

department: Department of Maternal-Fetal Biology

institute: National Research Institute for Child Health and Development

summary: Utilizing reciprocal genome-wide uniparental disomy samples presenting with Beckwith-Wiedemann and Silver-Russell syndrome-like phenotypes, we have analyzed ~0.1% of CpG dinucleotides present in the human genome for imprinted differentially methylated regions (DMRs) using the Illumina Infinium HumanMethylation27 BeadChip microarray. This approach identified 15 imprinted DMRs associated with previously characterized imprinted domains, and confirmed the maternal methylation of the RB1 DMR. In addition, we discovered two novel DMRs: a maternally methylated region overlapping the FAM50B promoter CpG island, which results in paternal expression of this retrotransposon, and a paternally methylated region located between maternally expressed ZNF597 and NAT15 genes.

overall_design: We analyzed reciprocal genome-wide uniparental disomy samples (one maternal UPD and three paternal UPD samples) and  six different normal somatic tissues derived from the three germinal layers (lymphocytes, buccal cells, placenta, brain, muscle, and fat) .

first: David

last: Monk


title: Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells (methylation data)

status: Public on Jun 16 2011

city: Ghent

first: Leander

last: Van Neste

address: Coupure Links 653

department: Molecular Biotechnology

country: Belgium

institute: Ghent University

summary: he ability to induce pluripotent stem cells from committed, somatic human cells provides tremendous potential for regenerative medicine. However, there is a defined neoplastic potential inherent to such reprogramming that must be understood and may provide a model for understanding key events in tumorigenesis. Using genome-wide assays, we identify cancer-related epigenetic abnormalities that arise early during reprogramming and persist in induced pluripotent stem cell (iPS) clones. These include hundreds of abnormal gene silencing events, patterns of aberrant responses to epigenetic-modifying drugs resembling those for cancer cells, and presence in iPS and partially reprogrammed cells of cancer-specific gene promoter DNA methylation alterations. Our findings suggest that by studying the process of induced reprogramming, we may gain significant insight into the origins of epigenetic gene silencing associated with human tumorigenesis, and add to means of assessing iPS for safety.

overall_design: Methylation was analyzed using Illumina's 27k Infinium platform for direct detection of methylation after bisulfite conversion. The overall methylation status was determined for several iPS lines and the pool cells from which they are derived. These methylation levels can be compared directly to those of cultured stem cells, differentiated cells and cancer cell lines.

first: Joyce

last: Ohm

first: Stephen

last: Baylin


title: Global DNA methylation profiling of CD4+ T cells from patients with systemic lupus erythematosus

status: Public on Jun 10 2011

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary: Systemic lupus erythematosus (SLE) is a chronic-relapsing autoimmune disease of incompletely understood etiology. Recent evidence strongly supports an epigenetic contribution to the pathogenesis of lupus. To understand the extent and nature of dysregulated DNA methylation in lupus T cells, we performed a genome-wide DNA methylation study in CD4+ T cells from 12 lupus patients and 12 normal healthy controls. Cytosine methylation was quantified in 27,578 CG pairs located within the promoter regions of 14,495 genes.  We identified 236 hypomethylated and 105 hypermethylated CG sites in lupus CD4+ T cells compared to normal controls, consistent with a global hypomethylation in lupus T cells. Further analysis identified hypomethylation in genes involved in connective tissue development including CD9, MMP9, and PDGFRA. Hypermethylated genes highlight “response to nutrients” ontology such as folate biosynthesis, suggesting a link between environmental factor and lupus and emphasizing the role of folate in DNA methylation.  In addition, the transcription factor RUNX3 was hypermethylated in lupus CD4+ T cells. Protein-protein interaction maps identified a transcription factor, HNF4a, as a regulatory hub affecting a number of differentially methylated genes. Functional annotations such as apoptosis is also overrepresented. Further, our data indicate that the methylation status of certain genes predicts disease activity in lupus patients. This work provides a foundation to begin identifying novel pathogenic pathways in lupus T cells and developing novel epigenetic biomarkers for disease activity in lupus.

overall_design: We employed microarray-based technologies to perform a genome-wide DNA methylation assay and quantify CD4+ T cell DNA methylation levels at 27,578 CG sites spanning 14,495 genes of 11 lupus patients and 12 healthy controls.

first: Matlock

last: Jeffries

first: Yuhong

last: Tang

first: Joan

middle: T

last: Merrill

first: Jonathan

middle: D

last: Wren

first: Amr

last: Sawalha


title: Effect of AICAR monophosphate and AICAr riboside accumulation on global transcription

status: Public on Jul 11 2011

first: sophie

last: lemoine

summary:
AICAR monophosphate (5-Aminoimidazole-4-carboxamide ribonucleotide) is a metabolic intermediate of the de novo purine synthesis pathway presenting highly promising metabolic and antiproliferative properties. Yeast mutants accumulating AICAR are auxotroph for histidine. A  screening for suppressors of this phenotype identified recessive and dominant mutants that result in lowering intracellular AICAR concentration. The recessive mutants affect adenosine kinase which is shown here to catalyze the phosphorylation of AICAR riboside in yeast. The dominant mutants strongly enhance the capacity of the alkaline phosphatase Pho13p to dephosphorylate succinyl-AICAR monophosphate into the non-toxic riboside form. By combining these mutants to transcriptomic and metabolomic analyses, we establish that in yeast both toxic and physiological responses to AICAR are linked to the concentration of the monophosphate form, while the nucleoside moiety has no effect even at high concentration. Finally, we establish that (S)AICAR concentration varies under physiological conditions, thus modulating transcriptional regulation of purine pathway genes.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series