title: Distinct epigenomic landscapes of pluripotent and lineage-committed human cells

status: Public on Oct 13 2009

city: La Jolla

first: Bing

last: Ren

state: CA

address: 9500 Gilman Drive

country: USA

institute: University of California, San Diego

summary: Human embryonic stem cells share identical genomic sequences with other lineage-committed cells yet possess the remarkable properties of self-renewal and pluripotency.  It has been proposed that epigenetic regulatory mechanisms, involving DNA methylation and various chromatin modifications, are at least partly responsible for the distinct cellular properties between different cell types. Previous studies focusing largely on gene promoters and CpG islands have identified close association between several chromatin modifications and DNA methylation, but revealed a relatively small degree of differences between pluripotent and lineage-committed cells. Here, we examine the association between 11 chromatin modifications and DNA methylation at high resolution throughout the genome in the human embryonic stem cells and primary fetal lung fibroblasts. We observe a new set of relationships between chromatin modifications and DNA methylation occurring outside of the promoter regions. We also find that epigenomic landscapes are drastically different between the ES cells and fibroblasts. In particular, over 40% of the human genome differs in their chromatin structure between the two cell types. Most of the changes come from a dramatic redistribution of the repressive H3K9me3 and H3K27me3 marks, which form large blocks that expand significantly in the fibroblasts relative to ES cells. Additionally, we identified numerous small and punctuated regions outside of   promoters that are associated with many active chromatin modification marks, and show that chromatin dynamics at these potential regulatory sequences are associated with change in DNA methylation between the ES cells and fibroblasts. Our results provide new insights into epigenetic regulatory mechanisms underlying properties of pluripotency and cell fate commitment.

overall_design: ChIP-Seq Analysis of OCT4, KLF4, MYC, TAFII and P300 in hESC H1 cells. 36 cycles of sequencing was done on the Illumina Genome Analyzer or Analyzer II platforms.

first: Ryan

last: Lister

first: Mattia

last: Pelizzola

first: Robert

middle: H

last: Dowen

first: R

middle: D

last: Hawkins

first: Gary

last: Hon

first: Julian

last: Tonti-Filippini

first: Joseph

last: Nery

first: Leonard

last: Lee

first: Zhen

last: Ye

first: Que-Minh

last: Ngo

first: Lee

last: Edsall

first: Jessica

last: Antosiewicz-Bourget

first: Ron

last: Stewart

first: Victor

last: Ruotti

first: A

last: Millar

first: James

last: Thomson

last: Ecker


title: Analysis of gene expression in miR-34a overexpressing K562 cells

status: Public on Jul 13 2009

city: Boston

first: Francisco

last: Navarro

state: MA

address: 200 Longwood Ave

institute: Immune Disease Institute

summary: miR-34a is strongly induced upon TPA-induced megakaryocyte differentiation of K562 cells. To investigate the gene networks regulated by this miRNA during the process of differentiation we performed gene microarray analysis in K562 cells overexpressing miR-34a or a control sequence.

overall_design: K562 cells were transfected by nucleofection (Amaxa) with a miR-34a mimic (Dharmacon) or a control sequence with no homology to human genes. 24 hours post-transfection total RNA was extracted using trizol and hybridized on Affimetrix microarrays for comparing gene expression.

first: Isidore

last: Rigoutsos


title: Chromatin States in Human ES Cells Reveal Key Regulatory Sequences and Genes Involved in Pluripotency and Self-renewal

status: Public on Oct 14 2009

first: Bing

last: Ren

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Human embryonic stem cells (hESCs) are offering a new therapeutic approach because of their unique ability to proliferate indefinitely in vitro and differentiate into multiple cell types. However, our understanding of the molecular mechanisms of pluripotency and self-renewal remain incomplete. To elucidate the key regulatory sequences and genes responsible for these cellular properties, we have determined potential enhancers and insulators in the genome of human ES cells and examined the dynamics of four key chromatin modifications (H3K4me1, H3K4me3, H3K27ac and H3K27me3) at both promoters and enhancers during the differentiation of these cells. We observe that most enhancers gain or lose H3K4me1 and H3K27ac during differentiation in a manner that correlates with expression of their potential target genes.  By contrast, chromatin modifications at promoters remain stable and largely invariant during hESC differentiation, with the exception of a small number of promoters where a dynamic switch between acetylation and methylation at H3K27 marks the transition between activation and silencing of gene expression.  Our results reveal more than 50,000 potential enhancers for early human development, and identify key genes that are involved in differentiation and maintenance of pluripotency in human ES cells.

overall_design: ChIP-Seq Analysis of SOX2 and NANOG in hESC H1 cells. 36 cycles of sequencing was done on the Illumina Genome Analyzer II platform.

first: Ryan

last: Lister

first: Mattia

last: Pelizzola

last: Dowen

middle: R

middle: A


title: Identification of MicroRNA Expression Patterns and a MicroRNAs/mRNA Regulatory Network in Multiple Myeloma

status: Public on Oct 30 2009

city: MILAN

first: Luca

last: Agnelli

address: Venezian 1

department: Department of Advanced Diagnostics

country: Italy

institute: IRCCS Istituto Nazionale dei Tumori

type:
Non-coding RNA profiling by array
Expression profiling by array
Genome variation profiling by SNP array

summary: To date, little evidence of miRNA expression/deregulation in multiple myeloma (MM) has been reported. To characterize miRNA expression profiling of MM plasma cells (PCs) and integrate miRNA expression data with other molecular features of MM patients, global miRNA expression profiles were generated for PCs isolated from BM biopsies of 38 newly diagnosed MM, 2 plasma cell leukemia patients, and 3 healthy donors; the samples were also profiled for global gene expression, and nineteen of them underwent genome-wide DNA analysis using high-density SNP-microarrays. Differential miRNA expression patterns were mainly identified in association with the major IGH translocations: in particular, t(4;14) showed specific over-expression of let-7e, miR-125a-5p and miR-99b belonging to a cluster at 19q13.33. The occurrence of other lesions, such as 1q gain, 13q and 17p deletions, and hyperdiploidy, was less well characterized by specific miRNA signatures. Genome-wide analysis showed that some allelic imbalances led to the significantly altered expression of miRNAs located in the involved regions, such as let-7b at 22q13.31 loss and miR-142-3p at 17q22 gain. The integrative analysis based on computational target prediction, miRNA and mRNA profiling defined a network of putative functional miRNA-target regulatory relations supported by expression data.

overall_design:
This series of microarray experiments contains the microRNA profiles of purified plasma cells (PCs) obtained from 3 normal donor (N), 38 multiple myeloma (MM) and 2 plasma cell leukemia (PCL) at diagnosis. PCs were purified from bone marrow specimens after red blood cell lysis with 0.86% ammonium chloride using CD138 immunomagnetic microbeads. The purity of the positively selected PCs was assessed by morphology and flow cytometry and was >90% in all cases. 500 nanograms of total RNA was processed in accordance with the manufacturer's protocols (Agilent Technologies) to generate Cy3-labeled RNA which were purified on chromatography columns (Micro Biospin 6, Bio-Rad, Hercules, CA) and hybridized on an Agilent microarray (G4470B) at 55°C for 17 hr in a rotating oven. Images at 5 um resolution were generated using an Agilent scanner G2505B. The Feature Extraction 9.5 software (Agilent Technologies) was used to obtain the raw microarray data. The human miRNAs included in the platform were annotated according to Sanger miRBase Release 12.0. After discarding non-human miRNAs, the data were normalized using the Aroma Light package for Bioconductor. To overcome scaling biases due to background subtraction, the data were converted to obtain positive values throughout the dataset, at a minimum value of 1.

The global gene expression raw data used in this study was originally deposited as GSE13591 and renormalized for this study. The genome wide profile (DNA) analysis was originally deposited as GSE16121.

first: Marta

last: Lionetti

last: Biasiolo

first: Katia

last: Todoerti

first: Laura

last: Mosca

first: Sonia

last: Fabris

first: Gabriele

last: Sales

first: Giorgio

last: Lambertenghi-Deliliers

first: Silvio

last: Bicciato

first: Luigia

last: Lombardi

first: Stefania

last: Bortoluzzi

first: Antonino

last: Neri


title: Comparison of Clinical Staphylococcus aureus Strains Demonstrating Differing Susceptibilities to the Biocide Ethanol

status: Public on Aug 17 2009

city: Normal

first: Arunachalam Muthaiyan

email: amuthai@gmail.com, bjwilkin@ilstu.edu

state: IL

address: Julian Hall

department: Biological Sciences

institute: Illinois State University

summary: Ethanol is utilized widely in medicine for both its antiseptic and disinfectant capabilities. In an effort to understand the effects of ethanol on a very common human pathogen, we have determined the ethanol-stimulon of two well characterized unrelated clinical S. aureus methicillin resistant strains LP9 and MM66 with ethanol minimum inhibitory concentrations (MIC) of 10 and 7% respectively. Using S. aureus microarrays and array data analysis protocols (NIAID's Pathogen Functional Genomics Resource Center) we have characterized the transcriptomes of LP9 and MM66 following 15 min exposure to 10% ethanol. Induction with 10 % ethanol led to the altered regulation of 797 genes in LP9 and 899 genes in MM66. There was an overlap of 600 commonly altered genes in both strains and of these, SAMMD identified 50 genes that are uniquely altered only in the ethanol stimulon compared to the other 93 transcriptomes used for comparison. SAMMD analysis further revealed that 259 of the 600 (43%) commonly Eth-altered genes, overlapped with the stringent response induced with the antibiotic mupirocin. Interestingly the gene SACOL2518 up-regulated 20.4 and 23 fold in LP9 and MM66 respectively has a RelA- and SpoT- like domain. We have also found the MICs and MBCs for both LP9 and MM66 to be affected by the addition of certain amino acids. Genes involved with the heat shock response were also among some of the highest similarly up-regulated genes. Overall, SAMMD found 30% (43 genes) in common between the heat shock and ethanol transcriptomes of LP9 and MM66.    clpB encoding the clpB chaperone was the highest induced gene in both strains.  groES, groEL, hrcA, grpE and dnaK were also some of the highest up-regulated genes in both strains.

overall_design:
S. aureus pangenome microarrays were utilized to determine transcriptome alterations occurring in clinical strains LP9 and MM66 which have dissimilar levels of ethanol susceptibility. Overnight grown S. aureus LP9 and MM66 were inoculated in MHB medium (20 ml) in a 50 ml Erlenmeyer flask and incubated at 37°C, with shaking at 200 rpm. Growth was measured at regular intervals at 625 nm until OD= ~0.5. Based on previous minimum inhibitory concentration studies a 10% final ethanol concentration was added for 15 min of challenge. Total bacterial RNA was isolated as previously described from S. aureus strains LP9 and MM66 grown in Mueller Hinton broth to an OD625nm of 0.5 (37°C, 200 rpm). The RNA samples were then converted to fluorescently-labeled cDNA and hybridized to S. aureus microarrays version 6 (NIAID's Pathogen Functional Genomics Resource Center).

Contents of raw data files: Channel A = Cy3 dye, Channel B = Cy5 dye.
File names ending with S1,S3 = Cy3 untreated, Cy5 treated.
File names ending with S2,S4 = Cy5 untreated, Cy3 treated:
a.txt,b.txt is S2 file--cy5 for  treated, cy3 untreated
c.txt,d.txt is S4 file--cy5 for  treated, cy3 untreated
e.txt,f.txt is s1 file---cy3 for untreated, cy5 treated
g.txt, h.txt is s3 file---cy3 for untreated, cy5 treated
2.txt, 4.txt is s5 file---cy3 for LP9, cy5 for MM66. No treatment for both.
1.txt, 3.txt is s6 file---cy5 for LP9, Cy3 for MM66. No treatment for both.

The combined replicate results (of Samples GSM434525-GSM434530) representing the final processed data are linked below as supplementary files.

Real-time PCR and physiological experiments were performed to validate the microarray data.

first: Jasmine

middle: M

last: Pando

first: John

last: Rivera

first: Jesus

last: Cuaron

first: Joanne

last: Dupre

first: Yang

last: Song

first: Atul

middle: K

last: Singh

first: Vijayaraj

last: Nagarajan

first: Mohamed

middle: O

last: Elasri

first: Wanqin

last: Yu

first: Brian

middle: J

last: Wilkinson

middle: E

last: Gustafson


title: Human BE(2)-C neuronal responses to WEEV infection

status: Public on Jul 01 2009

city: Ann Arbor

first: David

last: Miller

state: MI

address: 3560B MSRB II, 1150 W. Medical Center Dr.

department: Internal Medicine

institute: University of Michigan

summary:
Human neuronal differentiation alters responsiveness to innate immune stimuli and virus infections.
We used microarrays to examine the transcriptional responses of the human BE(2)-C neuroblastoma cell line to infection with western equine encephalitis virus (WEEV).

overall_design: Cultured BE(2)-C cells were differentiated with 10 uM all-trans retinoic acid (RA) for 3 weeks and infected with WEEV at an MOI=10 for 6 h, and Affymetrix Human Genome Array U133 Plus 2.0 chips were used to analyze transcript levels.


title: Human BE(2)-C neuronal responses to type I IFN stimulation and WEEV infection

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

overall_design: Refer to individual Series


title: Effect of Ovarian Hormone on Gene Expression in Laser Captured Serotonin Neurons from Monkeys

status: Public on May 21 2009

city: Beaverton

first: Arubala

middle: P.

last: Reddy

state: OR

address: 505 NW 185th Ave

department: Oregon National Primate Research Center

institute: Oregon Health and Sciences University

summary:
Ovariectomized monkeys were treated with placebo, estrogen or estrogen plus progesterone for one month. The brain was perfused with RNA Later plus 20% sucrose. Sections through the
dorsal raphe nucleus were immunostained for TPH and then TPH positive neurons were laser captured. The RNA was extracted and hybridized to the Rhesus Affymetrix chip.

overall_design: Each chip represents one monkey. N=2 monkeys per treatment.

first: Cynthia

middle: L

last: Bethea

middle: P


title: Hypoxic endurance exercise in an untrained or six weeks trained state

status: Public on Nov 16 2009

city: Berne 9

first: Martin

last: Flück

state: Bern

address: Bühlstrase 26

department: Department of Anatomy

country: Switzerland

institute: University of Berne

summary: Time course of mRNA after 30 minutes of endurance exercise at simulated altitude of 4000 m in an untrained or six weeks trained state of six subjects.

last: Flueck

first: Silvia

last: Schmutz

first: Hans

last: Hoppeler


title: Corticosteroid Resistant Asthma Is Associated with Classical Activation Of Airway Macrophages and Exposure To LPS

status: Public on Jun 22 2009

city: Denver

first: Clifton

last: Hall

state: CO

address: 1400 Jackson Street

institute: National Jewish

summary:
Background: A subset of asthmatics does not respond to steroid therapy and therefore is at risk for escalation of disease severity. The cause of corticosteroid resistant (CR) asthma is unknown. Gene microarray technologies have the potential to substantiate new hypotheses regarding the etiology of corticosteroid resistance.
Methods: Gene microarray analysis was performed with bronchoalveolar lavage (BAL) cells of CR and corticosteroid sensitive (CS) asthmatics. Increased gene expression was verified with real time PCR and at the protein level by ELISA.
Findings: Microarray analyses demonstrated significantly higher levels (over two-fold increase, p<0.05) of TNF-alpha, IL-1alpha, IL-1beta, IL-6, CXCL1, CXCL2, CXCL3, CXCL8 (IL-8), CCL3, CCL4, CCL20 gene expression in BAL cells of CR than CS asthmatics. These findings, confirmed by RT-PCR in additional BAL samples, were consistent with classical macrophage activation by bacterial products. In contrast, markers of alternatively-activated macrophages, Arginase I and CCL24, were decreased in CR asthmatics. Genes associated with activation of the LPS signaling pathway (EGR1, DUSP2, MAIL, TNFAIP3) were significantly elevated in CR BAL samples (p<0.05). CR asthmatics had significantly higher amounts (1444.0±457.3 pg per mg of total protein) of LPS in BAL fluid than CS asthmatics (270.5±216.0 pg; p<0.05). Prolonged exposure to LPS induced functional steroid resistance to dexamethasone (DEX) in normal monocytes, demonstrated by persistently elevated IL-6 levels in the presence of DEX. Interpretation: Classical macrophage activation and induction of LPS signaling pathways along with high endotoxin levels detected in BAL fluid from CR asthmatics suggest that LPS exposure may contribute to CR asthma.
Keywords: Disease state analysis

overall_design: Patients with a diagnosis of asthma according to American Thoracic Society criteria were selected for evaluation. Asthmatics had a baseline FEV1% predicted of 55% to 85% of predicted, a beta2-adrenergic response of ≥12% of baseline FEV1% predicted and/or a methacholine PC20 value of ≤8 mg/ml. Asthma patients were further subdivided in CR and CS groups, based on their response to steroids. The definition was based on change in FEV1 % predicted over a one-week course of 40 mg/day of oral prednisone. Asthmatic patients were defined as CS if they had an increase in FEV1% predicted of greater than 15% after a one-week course of prednisone, and as CR if less than 12% change in FEV1% predicted was observed. None of the asthmatic subjects recruited for this study had evidence for other types of lung diseases. None of the subjects had received systemic corticosteroid therapy for at least one month prior to bronchoscopy. All subjects provided written informed consent to participate in the study. The study was approved by the Institutional Review Board at National Jewish Medical and Research Center, Denver, CO. Gene array studies of BAL macrophages were performed in 3 CR and 3 CS asthmatics.

first: Elena

last: Goleva

first: Pia

last: Hauk

middle: F

first: Andrew

last: Liu

first: Richard

last: Martin

first: Donald

middle: Y

last: Leung


title: Transcriptome response of Aspergillus fumigatus cultures under different temperatures

status: Public on Jun 16 2009

city: New Haven

first: Swee Yang

last: Low

state: CT

address: 9 Hillhouse Avenue, Mason Laboratory Room 320

department: Environmental Engineering

institute: Yale University

summary:
Microarray analysis was used to compare gene expression of Aspergillus fumigatus under two different sporulation temperatures, 17oC and 32oC, with an emphasis on genes encoding known or putative allergens of the fungus.
The objective of the study was to investigate whether allergenic potencies of A. fumigatus spores produced under different sporulation temperatures would be influenced by temperature-dependent transcriptional regulation of allergenicity genes.

overall_design:
Non-sporulating liquid culture of Aspergillus fumigatus was harvested and divided equally onto two sets of potato dextrose agar plates, one set for incubation at 17oC, the other for incubation at 32oC.
After 48 hours of incubation, RNA was harvested from both sets of sporulating cultures, reverse-transcribed into dye-coupled cDNA and hybridized onto microarrays for analysis of gene expression. For each experiment, extracted RNA from the two cultures were hybridized onto two dye-swap technical replicate arrays. A total of three separate experiments were conducted for biological triplicates, for a total of six hybridizations.

first: Swee

first: Maosheng

last: Yao

first: Jordan

last: Peccia


title: Human BE(2)-C neuronal responses to type I IFN stimulation

summary:
Human neuronal differentiation alters responsiveness to innate immune stimuli and virus infections.
We used microarrays to examine the transcriptional responses of the human BE(2)-C neuroblastoma cell line to retinoic acid-induced differentiation and type I IFN stimulation.

overall_design: Cultured BE(2)-C cells were differentiated with 10 uM all-trans retinoic acid (RA) for 3 weeks, incubated with universal type I IFN (IFNa-A/D) for 6 or 12 h, and Affymetrix Human Genome Array U133 Plus 2.0 chips were used to analyze transcript levels.


title: Dynamic Changes in the Human Methylome During Differentiation

status: Public on Dec 29 2009

city: Singapore

first: Chia-Lin

last: Wei

address: 60 Biopolis Street #02-01

department: Genome Technology & Biology

country: Singapore

institute: Genome Institute of Singapore

type: Methylation profiling by high throughput sequencing

summary: DNA methylation is a critical epigenetic regulator in mammalian development.  Here, we present a whole genome comparative view of DNA methylation using bisulfite sequencing of three cultured cell types representing progressive stages of differentiation: human embryonic stem cells (hESCs), a fibroblastic differentiated derivative of the hESCs, and neonatal fibroblasts.  As a reference, we compared our maps with a methylome map of a fully differentiated adult cell type, mature peripheral blood mononuclear cells (monocytes).  We observed many notable common and cell type-specific features among all cell types.  Promoter hypomethylation (both CG and CA) and higher levels of gene body methylation were positively correlated with transcription in all cell types.  Exons were more highly methylated than introns and sharp transitions of methylation occurred at exon-intron boundaries, suggesting a role for differential methylation in transcript splicing.  Developmental stage was reflected in both the level of global methylation and extent of non-CpG methylation, with hESC highest, fibroblasts intermediate, and monocytes lowest.  Differentiation-associated differential methylation profiles were observed for developmentally regulated genes, including the HOX clusters, other homeobox transcription factors, and pluripotence-associated genes such as POU5F1, TCF3, and KLF4.  Our results highlight the value of high-resolution methylation maps, in conjunction with other systems-level analyses, for investigation of previously undetectable developmental regulatory mechanisms.

overall_design: Examination of 3 cell types DNA methylation profile

first: Guoliang

last: Li

first: Isidore

last: Rigoutsos


title: Expression data from ALL samples for patients included in the Dutch Childhood Oncology Group

status: Public on Jan 26 2009

city: Rotterdam

first: Monique

last: Den Boer

address: POBox 2060

department: Pediatric Oncology

country: Netherlands

institute: Erasmus MC-Sophia Children's Hospital

summary:
Childhood acute lymphoblastic leukemia (ALL) comprises a large group of  genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement  or T-ALL.
About 25% of precursor B-ALL are currently genetically unclassified and have an intermediate prognosis. The present study used genome-wide strategies to reveal new biological insights and advance the prognostic classification of childhood ALL.
A double-loop cross validation was used to construct a classifier based on gene expression in ALL cells from 190 newly diagnosed cases (COALL cohort, GEO GSE13425) with a prediction accuracy of 90%. T-ALL, TEL-AML1-positive, hyperdiploid and E2A-rearranged cases were identified with 100% sensitivity and ≥94% specificity.
The classifier accuracy was confirmed in an independent cohort of 107 cases (87.9%, DCOG cohort, GEO GSE13351).
Keywords: gene expression study for classification of ALL subtypes

overall_design: Bone marrow and peripheral blood samples were collected at diagnosis and frozen. After thawing, RNA was extracted, labelled and hybridized to Affymetrix U133 Plus 2.0 arrays.

last: den Boer


title: Gene Expression Profiling of Scleroderma Skin

status: Public on Jul 15 2008

city: Lebanon

first: Tammara

last: Wood

state: NH

address: WTRB 674

department: Biomedical Data Science

institute: Dartmouth Medical School

summary:
We have analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from 34 subjects:  17 patients with SSc with diffuse scleroderma (dSSc), 7 patients with SSc with limited scleroderma (lSSc), 3 patients with morphea and 6 healthy controls.  In total, 61 skin biopsies were analyzed.  The addition of 14 technical replicates resulted in a total of 75 microarray hybridizations.

The Intrinsic_scleroderma_genes.txt supplementary file lists the 995 genes with the most consistent expression between each forearm-back pair and technical replicates, but with the highest variance across all samples analyzed. An intrinsic gene identifier algorithm was used to select a set of intrinsic scleroderma genes.  A total of 34 experimental groups were defined, each representing the 34 different subjects in our study.  Replicate hybridizations for a given patient were assigned to the same experimental group.   Each gene was analyzed and assigned a score that is inversely related to how intrinsic the gene's expression is across the samples analyzed. The analysis was repeated on randomized data in order to estimate a False Discovery Rate (FDR).   An intrinsic score of 0.3 selected 995 genes with an FDR of 4% (39 ± 7 genes) while retaining reproducible clustering of technical replicates.
Keywords: global gene expression profiling using Agilent Whole Human genome oligo arrays

overall_design: common reference design; we used Universal Human Reference RNA (Stratagene) as our reference for every array; For every hybridization sample RNA was always labeled with Cy3, and reference RNA was always labeled with Cy5; Microarray hybridizations were performed for 61 RNA samples from 34 subjects resulting 61 hybridizations.  Fourteen replicate hybridizations were added, resulting in a total of 75 microarray hybridizations.


title: Histone H3 modifications ChIP on chip

status: Public on Jun 30 2008

city: East Lansing

first: Sookyung

last: Oh

department: Horticulture

institute: Michigan State University

type: Genome binding/occupancy profiling by genome tiling array

summary:
Chromatin modification through the covalent modifications of histones play crucial role on establishment and propagation of gene expression pattern. Here we sought a global view of histone H3 modifications (tri-M-K4/27 and di-M-K27/36) and occupancy in Arabidopsis thaliana using ChIP combined with high-density tiling microarrays. In these analyses, we included vip3 mutant plants as well to gain an insight into role of Paf1C in plants.
Keywords: ChIP on chip

overall_design: Genomic DNAs associated with histone H3 K4 trimethylation (TMK4),  H3 K36 dimethylation (diMK36), H3 K27 dimethylation (diMK27), H3 K27 trimethylation (TMK27), and H3 from wild type (WT) and vip3 mutant plants (vip3) were analyzed using ChIP on chip technology

first: Steven

last: van Nocker

first: Sunchung

last: Park


title: Human pre-invasive and invasive cervical squamous cell carcinomas and normal cervical epithelia

status: Public on Dec 11 2007

first: Rork

last: Kuick

address: University of Michigan, SPH II, 1415 Washington Heights, Room M2533

summary:
10 normal squamous cervical epitheilia samples, 7 high grade squamous intraepithelial lesions, and 21 invasive squamous cell carcinomas of the cervix samples were obtained using laser capture miicrodissection.  Two rounds of T7-based linear RNA amplification using the Arcturus RiboAmp kit were performed for each sample, and assayed using Affymetrix HG_U133A arrays.
Keywords: disease state analysis

overall_design:
10 normal squamous cervical epitheilia samples, 7 high grade squamous intraepithelial lesions, and 21 invasive squamous cell carcinomas of the cervix, each from different patients, were each assayed on single HG_U133A arrays.  Three additional test samples were also assayed.

The log-transformed probe-set values and the results of the statistical analysis for each probe-set, and the associated README file, are included as Supplementary files.

first: Yali

last: Zhai

first: Bin

first: Ichiro

last: Ota

first: Stephen

last: Weiss

first: Cornelia

last: Trimble

first: Eric

last: Fearon

first: Kathleen

last: Cho


title: Trancriptome Kinetics of Arsenic-induced Adaptive Response in Zebrafish Liver.

status: Public on Aug 02 2006

first: Siew Hong

last: Lam

address: 14 Science Drive 4

institute: National University of Singapore

summary:
In this study, we performed microarray-based expression profiling on liver of zebrafish exposed to 60 mg/L (192?M) arsenic
[As(V)] for 8-96 h, to identify global transcriptional programs and biological networks involved in arsenic-induced adaptive responses in
vivo. We identified temporal differentially-expressed gene sets which we have grouped into early, late and all-time arsenic-responsive gene
sets.
Keywords: compound treatment design

overall_design: We analyzed 12 arrays for arsenic treated zebrafish liver and 12 arrays for control liver.

first: Yan

last: Tong

first: Sinnakarupan

last: Mathavan

first: Zhiyuan

last: Gong


title: Sexually dimorphic gene expression in the hypothalamus, pituitary gland and cortex by SAGE

status: Public on Jan 14 2006

city: Hershey

first: Yuichiro

last: Nishida

state: PA

address: 500 University Drive

department: Department of Anatomy and Physiology

institute: Penn State College of Medicine

summary:
C57BL6 mice (12-15 weeks old) were obtained from Charles River Laboratories (St. Constant, Québec). They were housed in an air-conditioned room (19-25Åé) with controlled lighting from 07:15 to 19:15 h and were given free access to laboratory chow (Lab Rodent Diet No. 5002, Ren’s Feed and Suppliers, Ontario) and water. The hypothalamus, pituitary gland and parietal cortex of 51 male and 51 randomly estrous cycling female mice were pooled and used for expression profiling. After vertebral cervical dislocation under isoflurane anesthesia, the brain and pituitary gland were removed from the skull and the three organs were immediately dissected, snap-frozen in liquid nitrogen and stored at -80Åé until further analysis.
Keywords: other

first: Mayumi

last: Yoshioka

first: Jonny

last: St-Amand


title: Expression data from different stages of plasma cell neoplasm

status: Public on Apr 01 2007

city: Scottsdale

first: Rafael

last: Fonseca

state: AZ

address: 13400 E Shea Blvd

department: Hematology-Oncology

institute: Mayo Clinic

summary:
Multiple myeloma is a relatively common B-cell malignancy that is currently incurable. Certain recurrent genetic abnormalities characteristics of different genetic subtypes have been described. Hyperdiploid myeloma characterized by recurrent trisomies is the most common genetic subtypes. However little is know about it's biology. Another common genetic abnormality is chromosome 13 deletion which is also associated with inferior prognosis. This abnormality is already present at the pre-malignant MGUS stage and is clonally selected with disease progression. Although it is biologically and clinically important the molecular consequence of chromosome 13 deletion is unknown.
Keywords: disease subtype analysis

overall_design: Hyperdiploid myeloma was identified using FISH. The gene expression profile of hyperdiploid MM is compared to that of non-hyperdiploid myeloma to identify differentially expressed genes. Molecular heterogeneity within H-MM is analyzed using unsupervised techniques. The distinctive subgroups identified are also tested in MGUS/SMM and NH-MM. The clinical relevance of these subtypes of hyperdiploid myeloma is then analyzed by correlating with relevant clinical information. Chromosome 13 deleted and undeleted MM are identified by FISH and their gene expression profile compared to identify molecular signature.


title: Endurance exercise in an untrained or six weeks trained state

status: Public on Sep 30 2005

city: Bern

first: Silvia

last: Schmutz

institute: University of Bern

summary:
Time course of mRNA after 30 minutes of endurance exercise in an untrained (1) or six weeks trained state (2) of six subjects (Hoxxx)

Ho980: 	(1) GSM47111, GSM47112, GSM47113, GSM47114, (2) GSM47115, GSM47116, GSM47125, GSM47126

Ho983:  (1) GSM47129, GSM47131, GSM47135, GSM47136, (2) GSM47139, GSM47142, GSM47144, GSM47145

Ho985:  (1) GSM47146, GSM47147, GSM47148, GSM47149, (2) GSM47155, GSM47159, GSM47160, GSM47161

Ho995: (1) GSM47162, GSM47163, GSM47164, GSM47165, (2) GSM47166, GSM47167, GSM47168, GSM47169

Ho997:  (1) GSM47170, GSM47171, GSM47172, GSM47173, (2) GSM47174, GSM47175, GSM47176, GSM47177

Ho999:  (1) GSM47178, GSM47179, GSM47180, GSM47181, (2) GSM47182, GSM47185, GSM47195, GSM47196
Keywords: time-course

first: Christoph

last: Däpp

first: Matthias

last: Wittwer

first: Michael

last: Vogt

first: Hans

last: Hoppeler

first: Martin

last: Flück


title: A network-based analysis of systemic inflammation in humans

status: Public on Sep 14 2005

first: Wenzhong Xiao

address: 55 Fruit Street, GRV 1302

department: Department of Surgery

institute: Massachusetts General Hospital

summary:
Oligonucleotide and complementary DNA microarrays are being used to subclassify histologically similar tumours, monitor disease progress, and individualize treatment regimens. However, extracting new biological insight from high-throughput genomic studies of human diseases is a challenge, limited by difficulties in recognizing and evaluating relevant biological processes from huge quantities of experimental data. Here we present a structured network knowledge-base approach to analyse genome-wide transcriptional responses in the context of known functional interrelationships among proteins, small molecules and phenotypes. This approach was used to analyse changes in blood leukocyte gene expression patterns in human subjects receiving an inflammatory stimulus (bacterial endotoxin). We explore the known genome-wide interaction network to identify significant functional modules perturbed in response to this stimulus. Our analysis reveals that the human blood leukocyte response to acute systemic inflammation includes the transient dysregulation of leukocyte bioenergetics and modulation of translational machinery. These findings provide insight into the regulation of global leukocyte activities as they relate to innate immune system tolerance and increased susceptibility to infection in humans.
Keywords: Gene expression profiling of human blood leukocytes in response to in vivo endotoxin administration.

overall_design: Healthy male and female subjects were intravenously administered either endotoxin or only vehicle (control).  Arterial blood samples were collected before infusion (0 hours) and at post infusion times of 2, 4, 6, 9, and 24 hours. Blood leukocytes were isolated and analyzed using Affymetrix GeneChip arrays.

first: S

last: Calvano

first: W

last: Xiao

first: D

last: Richards

first: R

last: Felciano

first: H

middle: V

last: Baker

last: Chen

first: B

last: Brownstein

first: J

last: Cobb

last: Tschoeke

first: C

last: Miller-Graziano

first: L

last: Moldawer

first: M

middle: N

last: Mindrinos

middle: W

last: Davis

middle: G

last: Tompkins

last: Lowery


title: Effect of glutamine concentration on hepatoma cell line

status: Public on Apr 16 2003

city: Cambridge

first: R.

middle: Michael

last: Raab

address: 77 Massachusetts Avenue

department: Chemical Engineering

institute: Massachusetts Institute of Technology

summary:
A mouse hepatoma cell line (Hepa1-6 cells, ATCC) was grown in T-25 tissue culture flasks (Corning) at 37ºC in 5% CO2 under two conditions. The first condition was the control, which contained DMEM medium (Gibco BRL) with 25 mM glucose, 4 mM glutamine, 1% penicillin-streptomycin (Sigma), and 10% CPSR-3 (Sigma). The second condition was identical to the first, however the glutamine concentration was altered periodically.

Once the cells had grown to confluency, the experiment began at 9:30 PM by exchanging the medium in all flasks. The control flasks received the same medium, containing 4 mM glutamine, while the experimental flasks received identical medium with no glutamine. Twenty-four hours later, the medium was exchanged again, however this time all flasks received medium containing 4 mM glutamine. The first medium exchange was repeated at 48 hours into the experiment, while the second was repeated at 72 hours into the experiment. Hence the glutamine concentration of the experimental flasks oscillated between 0 mM and 4 mM glutamine over 96 hours, while the glutamine concentration of the control flasks remained constant at 4 mM glutamine. At regular intervals, the flasks were sampled. Total RNA was isolated, medium samples were retained, and isotopic measurements were performed from flasks fed different labelled compounds. All samples taken during the experiment were analyzed.

The total RNA harvested was labeled and hybridized to DNA microarrays to measure the abundance of transcripts present. Total RNA control samples were labeled using Cy3 dCTP (Perkin-Elmer), and total RNA experimental samples were labeled using Cy5 dCTP (Perkin-Elmer) during reverse transcription. For reverse transcription 10 ug of total RNA was aliquoted into a 6 uL volume. If concentration of the RNA was necessary, this was conducted using a speed vacufuge (Eppendorf) at 60ºC for 10 minutes. The RNA sample was then mixed with 2 uL of 10X Cy-labeled dCTP, 2 uL of 100 mM DTT (Invitrogen), 4 uL of 5X First Strand Buffer (Invitrogen), 2 uL of a dNTP mixture containing 5 mM dGTP, dATP, dTTP and 2 mM dCTP (Invitrogen), 2 uL of 0.5 mg/ mL oligo-dT18-20 (Invitrogen), and 2 uL of Superscript II reverse transcriptase (Invitrogen). This reaction mixture was incubated at 42ºC for approximately two hours. Following the reverse transcription reaction, the RNA template was degraded by addition of 2 uL of 1 N NaOH and incubation at 65 ºC for 10 minutes. The alkaline conditions were then neutralized by addition of 2 uL of 1 N HCl. Samples from identical time points that were to be compared on DNA microarrays were then mixed. The combined sample was cleaned to remove extra primers and nucleotides using a QIAquick Nucleotide Removal kit as described by the manufacturer's instructions. Once cleaned, the sample was concentrated using a speed vacufuge (Eppendorf) for 20 minutes at 65ºC. Following concentration, the sample was resuspended in 32 uL of prewarmed hybridization buffer (Clontech Laboratories), 1 uL was
removed for quantitation, and hybridized to prepared oligonucleotide microarrays. Hybridization occurred overnight at 55 ºC using Corning hybridization chambers. The following day the arrays were washed in Glass Hybridization Wash Solution (Clontech Laboratories), and then in 1X SSC, and finally 0.1X SSC. Each wash step was conducted for 20 minutes under high agitation. The arrays were dried by centrifugation and scanned using GenePix 4000B scanner (Axon Instruments). The resulting data was downloaded and formatted in Excel (Microsoft), and then analyzed using Matlab (The MathWorks, Inc.).

The arrays used for hybridization were prepared using GAPS glass slides (Corning), and a Virtek arrayer (Bio-Rad). These arrays contained 17,280 features, printed from a synthesized oligonucleotide mouse library (Operon). Briefly, the library was resuspended in 3X SSC, centrifuged, and loaded into the arrayer. Arrays were printed using 32 pins (Telechem), at approximately 50% humidity. Once printed, the probes were crosslinked to the glass slides using a UV Stratalinker (Stratagene). The slides were then blocked for 15 minutes in a 250 mL mixture containing 15.7 g/ L succinic anhydride, 239 mL 1-methyl-2-pyrrolidinone, and 10.7 mL of 1 M boric acid, pH 8.0. They were cleaned by rinsing in 250 mL of milli-Q water (X2), followed by 250 mL of 95% ethanol. They were finally dried using filtered air and stored in the dark at room temperature.
Keywords = mouse, liver, hepatoma, cell culture, glutamine, carbon metabolism
Keywords: time-course

last: Wong

first: Isidore

last: Rigoutsos

last: Kelleher

first: G

last: Stephanopoulos


title: A Gene Expression Signature to Predict Metastasis and Survival in Non-small Cell Lung Cancer

status: Public on Jun 07 2006

city: Taipei

first: Sung-Liang

last: Yu

address: Jen Ai Road Section1

department: Clinical Laboratory Sciences and Medical Biotechnology

country: Taiwan

institute: National Taiwan University

summary:
Background: Current histopathological methods are inadequate for predicting outcome and recurrence in patients with non-small cell lung carcinoma (NSCLC) after surgery. In this study, we investigated the use of gene expression signatures to predict outcome and metastasis in lung cancer patients. Methods: Gene expression was studied by microarray and the real-time reverse transcriptase polymerase chain reaction (RT-PCR) in normal and lung tumor tissue of 188 NSCLC patients who underwent surgical resection. The 5 cancer-related genes and 1 reference gene expression levels measureed by real-time RT-PCR were used in a prospectively defined algorithm to determine the risk for each patient. Finally, we used an independent cohort to verify the 5 gene-based predictive model derived from decision tree analysis. Results: The 5 gene-based decision tree model was able to predict the prognosis. The recurrence rate at 36 months was 53% in the low-risk group versus 83% in the high-risk group (P=0.002). The 5 gene-based model could also predict overall survival (P<0.001). In multivariate analysis, the decision tree model predicted that high-low dichotomy and stage were both significant for recurrence. In addition, it could also predict metastasis and survival of NSCLC patients within the stage I-II subgroups. A similar result was found using an independent cohort of NSCLC patients. The high-risk patients had a significantly poorer overall survival than the low-risk patients (P=0.005). We also found distinct gene signatures which could distinguish between NSCLC, and normal tissue and histology subtypes. Conclusions: A gene expression signature can predict metastasis and survival of NSCLC patients.
Keywords: Survival and metastasis analysis

overall_design: In this study, we investigated the use of gene expression signatures to predict outcome and metastasis in lung cancer patients. Lung cancer tissue specimens from 125 patients who underwent surgical resection of their primary NSCLC at the Taichung Veterans General Hospital in Taiwan between December 1999 and December 2003 were included in this study. Specimens were stored frozen. Of these patients, 60 had adenocarcinoma, 52 squamous cell carcinoma, and 13 other types, all histologically defined.

first: Hsuan-Yu

first: Chun-Houh

first: Gee-Chen

last: Chang

first: Chih-Yi

first: Ang

last: Yuan

first: Chiou-Ling

last: Cheng

first: Chien-Hsun

last: Wang

first: Harn-Jing

last: Terng

first: Shu-Fang

last: Kao

first: Wei-J

first: Jian-Wei

first: Pan-Chyr

last: Yang


title: Liver Genomic Responses to Ciguatoxin (P-CTX-1)

status: Public on May 08 2008

city: Charleston

first: Frances

last: Van Dolah

state: SC

address: 219 Fort Johnson Rd

institute: Marine Biotoxins Program, NOAA Center for Coastal Environmental Health and Biomolecular Research

summary:
Ciguatoxins (CTX) are polyether neurotoxins responsible for ciguatera, the most common fish-borne food poisoning in humans.  This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1).  At 1 h post exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure.  Early gene expression was likely influenced prominently by an acute 4 °C decline in core body temperature by 1 h, which resolved by 8 h following exposure.  Cytochrome P450s were of particular interest due to their role in xenobiotic metabolism.  Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression.  Many Cyps underwent an initial down-regulation at 1 h but were quickly and strongly up-regulated at 4 and 24 h post exposure.  In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice.
Keywords: biotoxin, time course

overall_design: Individual C57/BL6 mice (n=3) exposed to 0.26 ng/g P-CTX-1 ip for 1, 4, or 24 h were compared to pooled time-matched controls (n=3).  The triplicate arrays at each time point included a dye swap.

first: Jeanine

middle: S

last: Morey

first: James

middle: C

last: Ryan


title: Hepatic Transcriptional Profiling of Hatchling Chicks and Market-age Broiler Chickens during Fasting and Re-feeding

status: Public on Apr 01 2008

city: Newark

first: Larry

middle: Albert

last: Cogburn

state: DE

address: 531 South College Ave.

department: Animal and Food Sciences

institute: University of Delaware

summary:
This study integrates global transcriptional profiling and the metabolic perturbation induced by fasting and re-feeding. Genetic control of growth and development should be revealed by systematic modeling of metabolic and regulatory pathways. Chicken oligo arrays were used for transcriptional profiling in two time-course experiments. Two critical developmental stages were chosen: immediately after hatchling (Wk1) and prior to marketing of broiler chickens (Wk6). Only male chickens were used to simplify the experimental design. A RNA reference design was employed for microarray hybridization using two reference RNA pools derived from all individuals sampled at either Wk1 or Wk6. Microarray data was acquired using GenePix Pro software. Loess normalization and a linear mixed model were applied in data processing using the R statistical package with LIMMA software [Smyth, G. K. (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology, Vol. 3, No. 1, Article 3]. The results show hundreds of differentially expressed genes, which are regulated by age and the metabolic perturbation of fasting and re-feeding. Numerous common genes were found at both developmental stages (Wk1 and Wk6) that could be candidates for controlling growth and development of chickens. Differential expression revealed by either microarray or qRT-PCR analyses of selected genes was highly consistent. QRT-PCR verification of genes acutely depressed by fasting includes AGO1, ANGTPL3, ATPCL, FASN, FAT, ME1, PPARG, SCD1, SREBP1 and THRSPA. Genes up-regulated by fasting were ALDOB, IL-15, LDHB, LIPIN2, PANK1, PPARA and UPP2. These genes are functionally assigned to metabolic enzymes, transcription factors, acute phase proteins, immune factors and involved in various pathways (i.e., fatty acid and amino acid metabolism, glycolysis, growth factor signaling and immune defense).
Keywords: Hepatic transcripts, oligo-array, chicken, metabolic perturbation, fasting and re-feeding

overall_design: A reference RNA design was used for microarray hybridizations, where the same reference RNA pool was co-hybridized to each target sample on an microarray. The reference RNA pool was made from an equal amount of high-quality amplified RNA (aRNA), derived from all liver samples within each experiment (Wk1 = 50 samples and Wk6 = 30 samples). The reference RNA pool was labeled with Alexa 647 while each target sample was labeled with Alexa 555.

first: Nares

last: Trakooljul

first: Tom

last: Porter

middle: A


title: Gene Expression Profiles of HPV-Positive and -Negative Head/Neck and Cervical Cancers

status: Public on May 15 2007

city: Madison

first: Paul

last: Ahlquist

state: WI

address: 1525 Linden Dr.

department: Oncology

institute: University of Wisconsin-Madison

summary:
Human papillomaviruses (HPVs) are associated with nearly all cervical cancers (CCs), 20-30% of head and neck cancers (HNCs), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue.  Here, we describe genome-wide expression profiling of 84 HNCs, CCs and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells.  This analysis revealed that HPV+HNCs and CCs differed in their patterns of gene expression yet shared many changes compared to HPV-HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+HNCs and CCs were found to be upregulated in their expression of a distinct and larger subset of cell cycle genes than observed in HPV-HNC.  Moreover, HPV+ cancers over-expressed testis-specific genes that are normally expressed only in meiotic cells.  Many, though not all, of the hallmark differences between HPV+HNC and HPV-HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testes specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV- cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers.
Keywords: Gene expression ptofiles of primary cancers

overall_design: All tissue samples were fresh frozen in liquid nitrogen and collected with patients’ consent under approval of the Institutional Review Boards from all participating institutions. Each tissue sample was cryosectioned, and selected sections stained with hematoxylin/eosin, and reviewed to determine tumor content, pathological status, and freedom from necrosis and freezing artifacts. Epithelial cells from all normal samples and tumor cells from HNC or CC samples with less than 80% tumor were laser capture microdissected from adjacent sections using a PixCell II LCM system. For guidance, an adjacent section was briefly stained with hematoxylin to visualize tissue structure. Total RNA was extracted from sectioned and/or microdissected samples as follows: 1 ml of TRIzol (Invitrogen, Carlsbad, CA) was added to each tissue sample, homogenized by passing through a 20 gauge needle, and added to 0.2 ml chloroform. After centrifugation at 20,000 xg for 20 min at 4oC, RNA in the aqueous phase was precipitated with an equal volume of isopropanol for 30 min at 4oC, pelleted, and washed twice with cold 70% ethanol. Double strand (ds) cDNA was synthesized from this RNA using a SuperScript ds cDNA synthesis kit (Invitrogen) and T7 promoter-linked oligo (dT)24. Complementary RNA (cRNA) was synthesized from T7 promoter-linked ds cDNA using a MEGAscript high transcription kit (Ambion, Austin, TX). To obtain a sufficient cRNA for 2 microarray hybridizations, this amplification process was repeated. Second round cRNA was biotin labeled using a BioArray High Yield RNA Transcript Labeling Kit (Enzo Life Sciences, Farmingdale, NY) and stored at -80oC until hybridized. cRNA quality and quantity was determined by gel electrophoresis and UV spectrophotometry. Whole human gene expression was profiled using Affymetrix Human Genome U133 Plus 2.0 arrays.

first: Dohun

last: Pyeon

first: Michael

last: Newton

last: Lambert

first: Johan

last: den Boon

first: Srikumar

last: Sengupta

first: Carmen

last: Marsit

first: Joseph

last: Connor

first: Thomas

middle: H

last: Haugen

first: Elaine

middle: M

last: Smith

first: Karl

middle: T

last: Kelsey

first: Lubomir

last: Turek


title: Subpopulations of MDA-MB-231 and Primary Breast Cancers

status: Public on Jul 28 2005

city: New York

first: Agnes

last: Viale

state: NY

address: 1275 York Avenue

department: Molecular Biology

institute: Memorial Sloan Kettering Cancer Center

summary:
Subpopulations of MDA-MB-231 that exhibit different metastatic tropisms when injected into immuno-deficient mice.  Also, a cohort of primary breast cancers surgically resected at the Memorial Sloan-Kettering Cancer Center (MSKCC).
Keywords = Breast cancer
Keywords = lung metastasis
Keywords: parallel sample

first: Andy

middle: J

last: Minn

first: Joan

last: Massague


title: Identification of gene expression profiles in cervical cancer

status: Public on Jun 04 2008

first: Murty

last: Vundavalli

address: 1130 St Nicholas Ave

department: Pathology

institute: Columbia University Medical Center

summary:
This study is aimed in identification of gene expression profiles in  cervical cancer and the role of specific genes in cervical carcinogenesis.
Keywords: Gene expression in cervical cancer

overall_design: A total of 66 samples were included in this study, which include 33 primary tumors, 9 cell lines, and 24 normal cervical epithelium.

first: Vundavalli

last: Murty

first: Gopeshwar

last: Narayan

first: Hugo

last: Arias-Pulido

first: Mahesh

last: Mansukhani

first: Achim

last: Schneider


title: MicroRNA-134 Modulates Mouse Embryonic Stem Cell Differentiation

status: Public on Mar 24 2006

first: Bing

last: Lim

state: Singapore

address: 60 Biopolis street, #02-01 Genome

department: Stem Cell and Developmental Biology

type:
Expression profiling by array
Non-coding RNA profiling by array

summary:
Expression profile of miRNAs during retinoic acid (RA) induced differentiation of mose embryonic stem cells

Expression profile of mRNAs during retinoic acid (RA) amd miR-134 induced differentiation of mouse embryonic stem cells.
Keywords: affymetrix custom array and illumina MouseRef-8

overall_design:
RNA was extracted from mouse embryonic stem cells (mESC ) treated with retinoic acid (RA) over specified time periods (Day 0, 1, 4) and profiled using  acustom microarray designed by Affymetrix. Two biological repeats for every time point was measured.

RNA was extracted from mESCs (Day 0, 2, 4 and 6) as well as from mESCs transfected with miR-134 precursor (134MM; 100nM) or scrambled oligomer or Lipofectamine only (MT) at Day3 post transfection. Two biological repeats for every time point or transfection. These RNA was then profiles using illumina beadarray MouseRef-8

first: Yvonne

last: Tay

first: Wai-Leong

last: Tam

first: Yen-Sin

last: Ang

first: Leng-Siew

last: Yeap

first: Seongjoon

last: Koo

first: Yingqing

last: Sun

first: Sumin

first: Sandy

middle: K

first: Yuefei

last: Lou

first: Jinqui

last: Zhang

first: Wayne

last: Mitchell

first: Isidore

last: Rigoutsos


title: The inferred mechanisms for prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system

status: Public on Nov 04 2010

first: Fon-Jou

last: Hsieh

address: No. 7, Chung-Shan South Rd

department: Department of obstetrics and gynecology

type:
Expression profiling by array
Third-party reanalysis

summary:
Abstract

Aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis primarily in estrogen receptor positive (ER(+)) breast cancers and activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of *STAT3* in ER(+) breast cancers are* *through multiple interacting regulatory pathways including STAT3-MYC, STAT3-ER , STAT3-MYC-ER  interactions and the direct action of activated STAT3. These results predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ER  and STAT3 in regulating their shared target gene-*METAP2* is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the *STAT3* network and a robust one in a subset of patients. *VEGFA*, *ABL1*, *LYN*, *IGF2R* and* STAT3* are suggested therapeutic targets for further study based upon the degree of differential expression in our model.

Keywords: STAT3 transcriptional regulatory network, prognosis, tamoxifen resistance, tumorigenesis, breast cancer.

overall_design:
181 surgical specimens of primary infiltrating ductal carcinoma (IDC) were obtained from patients who underwent surgery at National Taiwan University Hospital (NTUH) between 1998 and 2007. They include 90 ER(+) IDCs and 91 ER(-) IDCs. Tissue samples were excised, snap frozen in liquid nitrogen, and stored at -80℃. Breast cancer samples containing relatively pure cancer as defined by greater than 50% tumor cells per high-power field examined in an adjacent section of tumor sample were for this study (Lien HC, et al. Oncogene 2007; 26: 7859-71). Twenty five non-tumor samples were surgically taken from breast cancer patients in 181 IDC patients to generate 25 gene expression profiles as a control in this study. All patients had given informed consent according to the guidelines approved by the Institutional Review Board at NTUH.

The matrix file linked to the bottom of this Series includes reanalyzed data from the 119 Samples of this Series and 87 Samples from Series GSE9309 and GSE17040.

first: Li-Yu

middle: D

last: Liu

first: Li-Yun

last: Chang

first: Wen-Hung

last: Kuo

first: Hsiao-Lin

last: Hwa

first: Y

last: Lin

first: M

last: Jeng

first: D

last: Roth

first: King-Jen