title: Effects of DKK1 on gene expression on melanocytes

status: Public on Nov 30 2006

city: Bethesda

first: Vincent

last: Hearing

address: Bldg 37  Rm 2132

department: National Cancer Institute

institute: National Institutes of Health

summary:
Dickkopf 1 (DKK1), which is expressed at high mRNA levels by fibroblasts in the dermis of human skin on the palms and soles, inhibits the function and proliferation of melanocytes in the epidermis of those areas via the suppression of beta-catenin and microphthalmia-associated transcriptor factor (MITF). In this study, we investigated the effects of DKK1 on melanocyte gene expression profiles and on Wnt signaling pathways using DNA microarray technology.
Keywords: compound treatment design

overall_design: Paired cDNA samples, labeled by cyanine 3- and cyanine 5-dUTP incorporation (Qiagen, Valencia, CA) during reverse transcription (Qiagen), were hybridized simultaneously with one oligo-DNA chip (HS-Operon V2vB2.2p13) as per NCI in-house protocol (available at http://mach1.nci.nih.gov/). Two fluorescent intensities of the oligo-DNA chip were scanned using a microarray scanner (GenePix 4000A, Axon Instruments, Inc., Molecular Device Corp., Sunnyvale, CA).


title: Microarray analysis shows multiple signaling pathways are involved in basal cell carcinoma growth

status: Public on Dec 15 2006

city: Vancouver

first: Kevin

last: McElwee

state: BC

department: Dermatology and Skin Science

country: Canada

institute: University of British Columbia

summary:
BACKGROUND: Basal cell carcinoma (BCC) is the most common form of human cancer. Though the genetic mutation and subsequent aberrant signaling role of the Hedgehog pathway in BCC development is understood, little is known about the downstream genetic mechanisms underlying BCC growth. The characterization of molecular events would improve our understanding of carcinogenesis and may define new therapeutic intervention opportunities. OBJECTIVE: To identify differential gene expression associated with tumorigenesis promotion and to define common signaling pathways significant in BCC survival and growth. METHODS: Microarray analysis, using a 21K expanded sequence verified cDNA set was performed on tissues obtained from previously untreated patients undergoing Mohs surgical resection (8 superficial BCC, 8 nodular BCC, 7 morphea form, 8 normal skin). Significantly differentially expressed genes were identified by analysis of microarray results in various data sets and subsequently screened for signaling pathway involvement. Selected genes were validated using real-time PCR analysis using an expanded set of 31 BCC samples. RESULTS: The global gene expression profiles in BCCs and normal skin were distinguishable by unpaired T test. 2429 genes were at least 1.5 fold differentially expressed between BCC (all morphological types) and normal skin (p < 0.01). Multiple singaling pathways were activated, but the hedgehog, WNT, MAPK and calcium signal transduction pathways predominated. CONCLUSION: Our findings may have important implications for understanding the pathogenesis of BCC and suggest targeting of the WNT and MAPK pathways with therapeutic intervention.
Keywords: disease state analysis

overall_design:
Human BCC and normal skin tissues were obtained from 31 patients in the Department of Dermatology and Skin Science, University of British Columbia with approval from the University Clinical Research Ethics Board. For microarray analysis, tissue samples were collected from different subtypes and normal controls as follows: nodular (8), Morphea form (7), Superficial (8) and microdissected normal skin epithelium (8). All of samples were taken from the facial area.
Human Operon v.2.1 (21K) glass arrays were produced (based on human 70mers from Operon Biotechnologies Inc, Huntsville, AL) by the Microarray Facility of the Prostate Centre at Vancouver General Hospital, Vancouver, Canada [17, 18]. RNAs were amplified using the SenseAmp Plus kit (Genisphere Inc, Hatfield, PA). The calculated A 260/280 ratio was used to determine the appropriate amount of sense RNA for labeling. Total RNA from test samples and universal human reference RNA (Stratagene, Cedar Creek, TX) were differentially labeled with Cy5 and Cy3 respectively, with the 3DNA array detection 350 kit (Genisphere Inc, Hatfield, PA) and cohybridized to cDNA microarrays. Following overnight hybridization and washing, arrays were imaged using a ScanArray Express scanner (PerkinElmer, Boston, MA).

first: mei

last: yu

first: David

last: Zloty

first: Bryce

last: Cowan

first: Jerry

last: Shapiro

first: Anne

last: Haegert

first: Robert

last: Bell

first: Larry

last: Warshawski

first: Nicholas

last: Carr

middle: J


title: Comparison of Bleo, Asthma, TH2 and Infection Models

status: Public on Dec 31 2006

city: San Francisco

first: Michael

middle: E.

last: Salazar

state: CA

address: 1550 Fourth Street, RM 545

country: USA

institute: University of California, San Francisco

summary:
Disease-Specific Gene Expression Profiling in Multiple Models of Lung Disease

We profiled lung gene expression in 12 mouse models of infection, allergy, and lung injury. A total of 24 transcripts, including many involved in inflammation and immune activation, were differentially expressed in a substantial majority (9 or more) of the models. Expression patterns distinguished three groups of models: (1) bacterial infection (n = 5), with changes in 89 transcripts, including many related to nuclear factor-B signaling, cytokines, chemokines, and their receptors; (2) bleomycin-induced diseases (n = 2), with changes in 53 transcripts, including many related to matrix remodeling and Wnt signaling; and (3) T helper cell type 2 (allergic) inflammation (n = 5), with changes in 26 transcripts, including many encoding epithelial secreted molecules, ion channels, and transporters.

overall_design: 2 color design with a reference pool

first: Andrea

last: Barczak


title: Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression

status: Public on Dec 21 2006

city: Baltimore

first: Minoru

last: Ko

state: MD

address: 251 Bayview Blvd, Suite 100, 10C

department: National Institute on Aging

institute: NIH

summary:
POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks.
Keywords: development or differentiation design,time series design

overall_design: ZHBTc4, ZHTc6, and EB5 ES cells were cultured without feeder cells in LIF-supplemented medium as described . For differentiation, ZHTc6 cells were cultured in the absence of Tet, which induced the overexpression of Oct3/4. ZHBTc4 cells were cultured in the presence of Tet, repressing Oct3/4 expression. Trophoblast stem (TS) cells and another ES cell line (R1) were cultured as previously described . Three independent samples were prepared for each time point. Microarray experiments were carried out as described  using the NIA Mouse 22K Microarray v1.0.

first: Ryo

last: Matoba

first: Hitoshi

last: Niwa

first: Shinji

last: Masui

first: Satoshi

last: Ohtsuka

first: Mark

middle: G

last: Carter

first: Alexei

middle: A

last: Sharov

middle: S


title: Connexin-dependent transcellular transcriptomic networks in mouse brain

status: Public on Nov 25 2006

city: Prairie View

first: Dumitru

middle: Andrei

last: Iacobas

state: TX

address: Ann Preston St

department: Undergraduate Medical Academy

institute: Prairie View A&M University

summary:
Microarray experiments have generally focused on magnitude of gene expression changes in pathological conditions, thereby using the method as a high throughput screen to identify candidate marker genes and/or to validate phenotypic differences.  We have used novel strategies to extract additional information from array studies, including expression variability and coordination, from which organizational principles of transcriptomes are emerging. We have reported that expression level, variability and coordination of numerous genes are regulated in brains of Gja1-/- mice with respect to wildtypes. Moreover, expression coordination with Gja1 in wildtypes largely predicted expression regulation in Gja1-/- tissues. We now report a remarkable overlap between regulations in Gja1-/- and Gjb1-/- brains, and that both differ markedly from those in Gja9-/- brain. Since in brain these three connexins are expressed in different cell types (Gja1 in astrocytes, and ependymal and vascular cells, Gjb1 in oligodendrocytes, and Gja9 in neurons and microglia), and because astrocytes and oligodendrocytes may form syncytia coupled by gap junction channels, these observations suggest the existence of distinct connexin-dependent panglial and neuronal transcriptomic networks. Such networks, where linkage partners are rearranged and strengths modified in brains of knockouts, may explain downstream and parallel 'ripples' of phenotypic change resulting from single gene alterations as the composition and interactions of transcription factor networks in the wildtype brain were identified and found to be altered disruption of Gja1 or Gjb1. The transcription factors also formed network hubs with genes from other functional categories, thus allowing regulation of one functional pathway through manipulation of another.
Keywords: genetic modification

overall_design: The brain transcriptomes of Gja9(-/-) and Gja9(+/-) P10 mice were compared to that of P10 wildtype mouse using the "multiple yellow" design in which extracts of biological replicas of the same genotype were hybridized with six 27k AECOM mouse cDNA microarrays (4 biological replicas of each genotype). These data were further compared to previously reported data on brain of neonatal wildtype, Gja1(-/-), Gja1(+/-) and Gjb1(-/-) mice (four biological replicas per genotype, reference sample design).

first: Sanda

middle: C

last: Spray


title: Mapping the determinants of gene expression plasticity by genetical genomics in C. elegans

status: Public on Nov 29 2006

city: Haren(GN)

first: Yang

last: Li

address: Kerklaan 30

country: Netherlands

institute: Groningen Bioinformatics Center

summary:
2 Recombinant Inbred Lines (RILs) per array, 40 arrays per Temperature, 2  Temperatures(16C,24C)
Keywords: genetical genomics experiment

overall_design: Hybridization were performed separately for each temperature. RILs were paried on each array so that their genetic distance was maximized (distant pair design, Fu et al. Genetics 2006, PubMed ID: 16361243).

first: Olga

last: Alvarez

first: Evert

middle: W

last: Gutteling

first: Jingyuan

last: Fu

first: Joost

last: Riksen

first: Pjotr

last: Prins

first: Rainer

last: Breitling

first: Ritsert

last: Jansen

first: Jan

middle: E

last: Kammenga


title: The UBX-regulated network in the haltere imaginal disc of D. melanogaster

status: Public on Nov 23 2006

city: Clemson

first: Brad

last: Hersh

state: SC

address: 132 Long Hall

department: Biological Sciences

institute: Clemson University

summary:
Hox proteins have been proposed to act at multiple levels within regulatory hierarchies and to directly control the expression of a plethora of target genes.  However, for any specific Hox protein or tissue, very few direct in vivo-regulated target genes have been identified.  Here, we have identified target genes of the Hox protein Ultrabithorax (UBX), which modifies the genetic regulatory network of the wing to generate the haltere, a modified hindwing. We used whole-genome microarrays and custom arrays including all predicted transcription factors and signaling molecules in the D. melanogaster genome to identify differentially expressed genes in wing and haltere imaginal discs.   To elucidate the regulation of selected genes in more detail, we isolated cis-regulatory elements (CREs) for genes that were specifically expressed in either the wing disc or haltere disc.  We demonstrate that UBX binds directly to sites in one element, and these sites are critical for activation in the haltere disc. These results indicate that haltere and metathoracic segment morphology is not achieved merely by turning off the wing and mesothoracic development programs, but rather specific genes must also be activated to form these structures.  The evolution of haltere morphology involved changes in UBX-regulated target genes, both positive and negative, throughout the wing genetic regulatory network.
Keywords: tissue comparison

overall_design:
Two rounds of microaray expression profiling were performed.
1)Three samples each of wildtype, Cbx mutant, and vg mutant wing imaginal disc tissue were generated.  Each sample consists of 60-100 pooled discs.  Each sample was hybridized to two whole-genome arrays (GPL4573).  Three biological replicates for each condition; two technical replicates for each biological sample (hybridization).
2)Three samples each of wildtype wing and haltere imaginal disc tissue; Cbx mutant wing imaginal disc tissue; vg mutant wing imaginal disc tissue.  Each sample consists of 60-250 pooled discs.  Each sample was hybridized to a single array that contained 4 replicates of each oligonucleotide sequence (GPL4568).  Three biological replicates for each condition.  Since each array contains 4 replicate blocks, 4 normalized values are generated for each gene for a given array.  These replicates are indicated by "Block1, Block2" etc.

first: Bradley

middle: M

first: Craig

last: Nelson

first: Samantha

last: Stoll

first: Jason

last: Norton

first: Thomas

last: Albert

first: Sean

middle: B

last: Carroll


title: Mouse Stromal Response to Tumor Invasion

status: Public on Oct 03 2006

city: Torino

first: Paolo

last: Provero

address: Via Nizza 52

department: Molecular Biotechnology and Health Sciences

country: Italy

institute: University of Turin

summary:
Primary and metastatic tumor growth induce host tissue responses that are believed to support tumor progression. Understanding the molecular changes within the tumor microenvironment during tumor progression may therefore be relevant not only for discovering potential therapeutic targets but also for identifying putative molecular signatures that may improve tumor classification and predict clinical outcome.  To selectively address stromal gene expression changes during cancer progression we performed cDNA microarray analysis of laser-microdissected stromal cells derived from prostate intraepithelial neoplasia (PIN) and invasive cancer in a multistage model of prostate carcinogenesis. Human orthologs of genes identified in the stromal reaction to tumor progression in this mouse model were observed to be expressed in several human cancers and to cluster prostate and breast cancer patients into groups with statistically different clinical outcomes. Univariate Cox analysis showed that overexpression of these genes is associated with shorter survival and recurrence free periods. Taken together our observations provide evidence that the expression signature of the stromal response to tumor invasion in a mouse tumor model can be used to probe human cancer and provide a powerful prognostic indicator for some of the most frequent human malignancies.
Keywords: disease state analysis

overall_design: Samples from 10 mice, 6 with invasive cancer and 4 with prostate intraepithelial neoplasia (PIN), were analyzed. The common reference (control) for all 10 samples was provided by pooled mRNA from the 4 PIN samples. In each of the 10 microarrays the control RNA (pooled from 4 PIN samples) was labeled with Cy3 and the test RNA (derived from each PIN lesion and invasive carcinoma) with Cy5.

first: Marina

last: Bacac

first: Nathalie

last: Mayran

first: Jean-Christophe

last: Stehle

first: Carlo

last: Fusco

first: Ivan

last: Stamenkovic


title: Growth heterosis in larvae of the Pacific oyster as revealed by MPSS

status: Public on Nov 10 2006

city: Hayward

first: Christian

middle: D

last: Haudenschild

address: 25861 Industrial Blvd

institute: Solexa, Inc.

summary:
Compared to understanding of biological shape and form, knowledge is sparse regarding what regulates growth and body size of a species.  For example, the genetic and physiological causes of heterosis (hybrid vigor) have remained elusive for nearly a century.  Here we investigate gene-expression patterns underlying growth heterosis in the Pacific oyster (Crassostrea gigas) in two partially inbred (f=0.375) and two hybrid larval populations produced by a reciprocal cross between the two inbred families.  We cloned cDNA and generated 8.6 million sequence tags with massively parallel signature sequencing (MPSSâ).  The sequences contain 23,277 distinct signatures that are expressed at statistically non-zero levels and show a highly positively skewed distribution with median and modal counts of 9.25 and 3 transcripts per million, respectively.  Approximately 9100 nuclear transcripts are found in all four larval populations, in agreement with the number of genes expressed in sea urchin embryo.  For half of the 23,277 signatures, expression level depends on genotype and is predominantly non-additive (hybrids deviate from the inbred average).  Statistical contrasts suggest ~350 candidate heterosis genes that exhibit concordant non-additive expression in reciprocal hybrids.  Patterns of gene expression, which include dominance for low expression and even underdominance of expression, are more complex than predicted from classical dominant or overdominant explanations of heterosis.  Preliminary identification of ribosomal proteins among candidate genes supports the suggestion from previous studies that efficiency of protein metabolism plays a role in heterosis.
Keywords: MPSS heterosis larvae expression profiling

overall_design: Two partially inbred (f=0.375) and two hybrid larval populations produced by a reciprocal cross of two inbred lines were surveyed. The two inbred lines originated from the naturalized population of Pacific oysters in Dabob Bay, WA.

first: Dennis

last: Hedgecock

first: Jing-Zhong

last: Lin

first: Shannon

last: DeCola

first: Eli

last: Meyer

first: Donal

middle: T

last: Manahan

first: Ben

last: Bowen


title: Tubercolosis and healthy infected patients PBMC_TB_vs_Pool_LTBI

status: Public on Oct 27 2006

city: Berlin

first: Marc

last: Jacobsen

address: Chariteplatz 1

department: Immunology

country: Germany

institute: Max-Planck-Institute for Infection Biology

summary:
Comparison of PBMC tuberculosis patients and healthy infected control donors via an reference RNA pool from non-infected controls
Keywords: Case control study

overall_design: common reference design

first: Dirk

last: Repsilber

first: Andrea

last: Gutschmidt

first: Albert

last: Neher

first: Knut

last: Feldmann

first: Hans

last: Mollenkopf

first: Stefan

middle: H

last: Kaufmann


title: FGF2 stimulation experiment with CD1 mouse embryonic fibroblasts

city: Münster

first: Boris

last: Greber

address: Röntgenstraße 20

department: Cell and Developmental Biology

institute: Max Planck Institute for Molecular Biomedicine

summary:
Mouse embryonic fibroblasts stimulated with 40 ng/ml of FGF2 in conventional hES cell medium were analysed on whole-genome expression chips to reveal altered expression of genes encoding secreted proteins.
Keywords: Growth factor stimulation experiment

overall_design: as detailed for the individual samples

last: Lehrach

first: James

last: Adjaye


title: FGF2 stimulation experiment with NMRI mouse embryonic fibroblasts


title: Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells

status: Public on Sep 30 2006

first: Minoru

last: Ko

summary:
To characterize Klf4 downstream genes, we performed microarray analyses of the ES cells knocked down by siRNA of Klf4 gene.
Keywords: individual genetic characteristic design

overall_design: ES cells grow without feeders on gelatin coated in complete ES medium. Cells were incubated at 37 0C; 5% CO2. ES cells were transfected with siRNA and pCAGEGFP-IP plasmid. After transfection, cells were cultured for 24 hours, following to drag selection for more 24 hours in the presence of puromycin to ensure concentration of transfectants. Total RNA were extracted with Trizol reagent (Sigma) according to the manufacturer’s instructions.

first: Yuhki

last: Nakatake

first: Nobutaka

last: Fukui

first: Yuko

last: Iwamatsu

first: Shinji

last: Masui

first: Kadue

last: Takahashi

first: Rika

last: Yagi

first: Kiyohito

first: Jun-ichi

last: Miyazaki

first: Ryo

last: Matoba

first: Hitoshi

last: Niwa


title: Role of transcriptional co-repressor proteins Ssn6, Tup11 and Tup12

status: Public on Nov 15 2006

city: Huddinge

first: Anthony

last: Wright

address: Blickagången 6

country: Sweden

institute: Karolinska Institute

type: Genome binding/occupancy profiling by array

type: Genome binding/occupancy profiling by genome tiling array

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

overall_design: Refer to individual Series

first: Fredrik

last: Fagerström-Billai

middle: P


title: Oncogenic potential of RAS isoforms in melanocytes

status: Public on Oct 30 2006

city: Las Vegas

first: Sheri

last: Holmen

state: NV

address: 10441 W. Twain Ave.

department: Drug Development

institute: Nevada Cancer Institute

summary:
We compared the transformation efficiencies of mutant NRAS and KRAS in immortal, non-transformed Ink4a/Arf-deficient melanocytes. NRAS mutation leads to increased cellular proliferation and is potently tumorigenic. In contrast, KRAS mutation does not enhance melanocyte proliferation and is only weakly tumorigenic on its own. While both NRAS and KRAS activate MAPK signaling, only NRAS enhances MYC activity in these cells. Our data suggests that the activity of specific RAS isoforms is context dependent and provides a possible explanation for the prevalence of NRAS mutations in melanoma.In addition, understanding this mechanism will have important implications for cancer therapies targeting RAS pathways.
Keywords: RAS isoforms

overall_design: Common Reference

first: Karl

last: Dykema


title: Graded Expression of IRF4 Coordinates Isotype Switching with Plasma Cell Differentiation

status: Public on Nov 24 2006

first: Louis

middle: M.

last: Staudt

address: 9000 Rockville Pike, Bldg 10, Rm 4N114

department: Lymphoid Malignancies Branch

institute: National Cancer Institute

summary:
Determine irf4 target genes in mouse B cells undergoing LPS differentiation to plasma cells in vitro. Determine targets of IRF4 by overexpression in a human GCB cell line.
Keywords: cell type comparison design

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Mouse lymphochip arrays consisted of a reference pool vs mouse Irf4+/- and mouse Irf4-/- samples. Human lymphochip arrays consisted of non-transduced vs IRF-4-transduced human cell line Oci-Ly7. Design included biological repeats at each time point. Only data from sequence-verified features were published. The mouse lymphochip consists of 701 confirmed features.


title: Transcriptional Profiling of Subjects from the Iowa Adoption Studies

status: Public on Nov 14 2006

city: Iowa City

first: Gi-yung

last: Ryu

state: IA

address: EMRB 200A

department: Neurosurgery

institute: University of Iowa

summary:
Transcriptional profiling has been used to identify gene expression patterns indicative of general medical illnesses such as atherosclerosis.    However, whether these methods can identify common psychiatric disorders has not been established.  To answer this question with respect to nicotine use, we used genome wide expression profiling lymphoblast cell lines from six actively smoking Iowa Adoption Studies subjects and nine ?clean? control subjects, followed by real-time PCR (RT-PCR) of gene expression patterns in lymphoblast derived RNA from 94 subjects in the Iowa Adoption Studies.  As compared to those from controls without a history of smoking (n=9), the expression levels of 579 of 29,098 genes were significantly up-regulated and expression levels of 584 of 29,098 genes were significantly down-regulated in lymphoblast lines from currently smoking subjects (n=6).  RT-PCR confirmation of four select RNA levels confirmed the validity of the overall profile and revealed highly significant relationships between the expression of some of these transcripts and 1) major depression, 2) antisocial personality, 3) nicotine dependence and 4) cannabis dependence.  We conclude that the use of expression profiling may contribute significant insights into the biology of complex behavioral disorders.
Keywords:  substance use, major depression, SLC6A4, AUTS2, CAPN2, ELN, lymphoblast
Keywords: disease state analysis

overall_design: case vs control

first: Robert

last: Philibert

first: Anup

last: Madan

first: Gi-Yung

first: Jae-Geun

last: Yoon

first: Tracy

last: Gunter


title: Minimum regions of imbalance involved in testicular germ cell tumours

status: Public on Oct 31 2006

city: Sutton

first: Ian

last: Giddings

state: Surrey

address: 15 Cotswold Road

department: Section of Molecular Carcinogenesis

country: United Kingdom

institute: Institute of Cancer Research

summary:
Identifying changes in DNA copy number can pinpoint genes that may be involved in tumor development. Here we have defined the smallest overlapping regions of imbalance (SORI) in testicular germ cell tumors other than the 12p region, which has been previously investigated. Definition of the regions was achieved through comparative genomic hybridization (CGH) analysis of a 4559 cDNA clone microarray. A total of 14 SORI were identified, which involved at least five of the 11 samples analysed. Many of these refined regions were previously reported using chromosomal or allelic imbalance studies. The SORI included gain of material from the regions 4q12, 17q21.3, 22q11.23 and Xq22, and loss from 5q33, 11q12.1, 16q22.3 and 22q11. Comparison with parallel chromosomal CGH data supported involvement of most regions. The various SORI span between one and 20 genes and highlight potential oncogenes/tumor suppressor genes to be investigated further.
Keywords: Tumour vs normal comparison

overall_design: 16 samples  - 8 Primary Seminoma TGCTs and 3 Non Seminoma TGCTs versus

first: A

last: McIntyre

first: B

last: Summersgill

first: O

last: Jafer

first: S

last: Rodriguez

first: G

last: Zafarana

first: J

last: Oosterhuis

last: Gillis

first: L

last: Looijenga

first: C

last: Cooper

first: R

last: Huddart

last: Clark

last: Shipley


title: Genome-wide screening for complete genetic loss in PCa by CGH onto cDNA arrays

status: Public on Oct 28 2006

summary:
We demonstrate that comparative genomic hybridisation (CGH) onto cDNA microarrays may be used to carry out genome-wide screens for regions of genetic loss, including homozygous (complete) deletions that may represent the possible location of tumour suppressor genes in human cancer. Screening of the prostate cancer cell lines LNCaP, PC3 and DU145 allowed the mapping of specific regions where genome copy number appeared altered and led to the identification of two novel regions of complete loss at 17q21.31 (500 kb spanning STAT3) and at 10q23.1 (50-350 kb spanning SFTPA2) in the PC3 cell line.
Keywords: Tumour vs normal comparison, array CGH

overall_design: 8 samples  - Comparison of 3 Prostate Cell lines with Male Genomic DNA in duplicate

last: Edwards

last: Feber

first: P

last: Flohr

first: M

last: John

first: I

last: Crossland

middle: R

last: Stratton

last: Wooster

last: Campbell


title: Genomewide demarcation of RNA PolII transcription units by physical fractionation of chromatin- ALL Arrays

status: Public on Aug 30 2006

city: Chapel Hill

first: Jason

last: Lieb

state: NC

address: 203 Fordham Hall

department: Biology

institute: University of North Carolina at Chapel Hill

summary:
Epigenetic modifications of chromatin serve an important role in regulating the expression and accessibility of genomic DNA. We report here a genomewide approach for fractionating yeast chromatin into two functionally distinct parts, one containing RNA polymerase II transcribed sequences, and the other comprising noncoding sequences and genes transcribed by RNA polymerases I and III. Noncoding regions could be further fractionated into promoters and segments lacking promoters. The observed separations were apparently based on differential crosslinking efficiency of chromatin in different genomic regions. The results reveal a genomewide molecular mechanism for marking promoters and genomic regions that have a license to be transcribed by RNA polymerase II, a previously unrecognized level of genomic complexity that may exist in all eukaryotes. Our approach has broad potential use as a tool for genome annotation and for the characterization of global changes in chromatin structure that accompany different genetic, environmental, and disease states.
Keywords: Genomewide demarcation of RNA PolII transcription units by physical fractionation of chromatin- Intergenic enrichment

overall_design:
This series contains all the arrays associated with Nagy et al (PNAS 2003 May 27;100(11):6364-9).  The arrays can be divided into four logical sets: Intergenic enrichment (GSE5648), ORF enrichment (GSE5649), ORF-Intergenic enrichment (GSE5650), and Neutral enrichment (GSE5651).  Shown with each logical set is a series accession number containing the arrays associated with that set.  Below is an explanation for the experimental procedure used to derived the samples for this manuscript.

Standard DNA Preparation- (Experiments 1–8) All DNA was prepared by glass-bead disruption of cells and a standard phenol-chloroform extraction. The extract was centrifuged for 5 s at 14,000 x g, and the supernatant was sonicated and subsequently phenol-chloroform extracted.

Intergenic Enrichment Procedure- (Experiments 9–27) Whole cells were fixed by addition of 37% formaldehyde/11% methanol to the growth medium to a final concentration of 1% formaldehyde at 30°C for 30 min. Glycine was added to 125 mM from a 2.5 M stock and incubated for 5 min. The cells were centrifuged in a Sorvall RT7 at 3,000 rpm for 5 min at 4°C and washed twice with PBS and once with sterile water. Without reversing crosslinks, extracts were prepared by glass-bead disruption, sonication (fragment size 200–2,000 bp, peak at 900 bp), and standard phenol-chloroform extraction.

ORF Enrichment Procedure- (Experiments 31–32) Cells were crosslinked as above, and isolated nuclei were used to prepare solubilized chromatin. Crosslinks were then reversed by incubation at 65°C, and DNA was prepared. In initial experiments (nos. 28–30), immunoprecipitation using antimethyl-lysine histone H3 antibody was performed before the crosslinks were reversed. However, the IPs were not required for ORF enrichment .

first: Peter

middle: L

last: Nagy

first: Michael

last: Cleary

first: Patrick

middle: O

last: Brown


title: Amplification and overexpression of E2F3 in human bladder cancer.

first: Ian

last: Giddings

summary:
We demonstrate that, in human bladder cancer, amplification of the E2F3 gene, located at 6p22, is associated with overexpression of its encoded mRNA transcripts and high levels of expression of E2F3 protein. Immunohistochemical analyses of E2F3 protein levels have established that around one-third (33/101) of primary transitional cell carcinomas of the bladder overexpress nuclear E2F3 protein, with the proportion of tumours containing overexpressed nuclear E2F3 increasing with tumour stage and grade. When considered together with the established role of E2F3 in cell cycle progression, these results suggest that the E2F3 gene represents a candidate bladder cancer oncogene that is activated by DNA amplification and overexpression.
Keywords: Tumour vs normal comparison, array CGH

overall_design: 10 samples  - 4 Bladder Cancer Cell lines and 2 Primary Bladder Tumours compared with Male Genomic DNA

last: Goodwin

last: Dodson

last: Smith

last: Fletcher

last: Falconer

first: T

last: Roe

last: Kovacs

first: N

last: Dennis

last: Fisher

last: Foster


title: Imiquimod treated Basal Cell Carcinoma

status: Public on Oct 04 2006

city: Doha

first: Francesco

middle: Maria

last: Marincola

address: Al Nasr Tower, AL Corniche Street, PO Box 26999

country: Qatar

institute: Sidra Medical and Research Center

summary:
Imiquimod is a Toll-like receptor (TLR)-7 agonist capable of inducing complete clearance of basal cell carcinoma (BCC) and other cutaneous malignancies. We hypothesized that the characterization of the early transcriptional events induced by imiquimod may provide insights about immunological events preceding acute tissue and/or tumor rejection. We report a paired analysis of adjacent punch biopsies obtained pre- and post-treatment from 36 patients with BCC subjected to local application of imiquimod (N = 22) or vehicle cream (N=14) in a blinded, randomized protocol. Four treatments were assessed (q12 applications for 2 or 4 days, or q24 hrs for 4 or 8 days). RNA was amplified and hybridized to 17.5K cDNA arrays. All treatment schedules similarly affected the transcriptional profile of BCC; however, the q12 X 4days regimen, associated with highest effectiveness, induced the most changes with 637 genes unequivocally stimulated by imiquimod. A minority of transcripts (98 genes) confirmed previous reports of interferon-  involvement. The remaining 539 genes portrayed additional immunological functions predominantly involving the activation of cellular innate and adaptive immune-effector mechanisms. Importantly, these effector signatures recapitulate previous observations of tissue rejection in the context of cancer immunotherapy, acute allograft rejection and autoimmunity. This study based on a powerful and reproducible model of cancer eradication by innate immune mechanisms provides the first insight in humans of the early transcriptional events associated with immune rejection. This model is likely representative of constant immunological pathways through which innate and adaptive immune responses combine to induce tissue destruction.
Keywords: compound treatment design


title: Genomewide demarcation of RNA PolII transcription units by physical fractionation of chromatin- ORF-INT enrichment

summary:
Epigenetic modifications of chromatin serve an important role in regulating the expression and accessibility of genomic DNA. We report here a genomewide approach for fractionating yeast chromatin into two functionally distinct parts, one containing RNA polymerase II transcribed sequences, and the other comprising noncoding sequences and genes transcribed by RNA polymerases I and III. Noncoding regions could be further fractionated into promoters and segments lacking promoters. The observed separations were apparently based on differential crosslinking efficiency of chromatin in different genomic regions. The results reveal a genomewide molecular mechanism for marking promoters and genomic regions that have a license to be transcribed by RNA polymerase II, a previously unrecognized level of genomic complexity that may exist in all eukaryotes. Our approach has broad potential use as a tool for genome annotation and for the characterization of global changes in chromatin structure that accompany different genetic, environmental, and disease states.
Keywords: Genomewide mapping of regulatory elements through differential fractionation of crosslinked chromatin based on nucleosome occupancy.

overall_design:
ORF-INT enrichment- Whole cells were fixed by addition of 37% formaldehyde/11% methanol to the growth medium to a final concentration of 1% formaldehyde at 30°C for 30 min. Glycine was added to 125mM from a 2.5 M stock and incubated for 5 min. The cells were centrifuged in a Sorvall RT7 at 3,000 rpm for 5 min at 4°C and
washed twice with PBS and once with sterile water. Without
reversing crosslinks, extracts were prepared by glass-bead disruption,
sonication (fragment size 200-2,000 bp, peak at 900
bp), and standard phenol-chloroform extraction.


title: Genomewide demarcation of RNA PolII transcription units by physical fractionation of chromatin- ORF enrichment

overall_design: ORF enrichment- Cells were crosslinked and nuclei isolated to prepare solubilized chromatin. Crosslinks were then reversed by incubation at 65°C, and DNA was prepared. In initial experiments, immunoprecipitation using antimethyl-lysine histone H3 antibody was performed before the crosslinks were reversed. However, the IPs were not required for ORF enrichment.


title: Expression profiling defines a recurrence signature in lung squamous cell carcinoma

status: Public on Nov 21 2006

city: Brisbane

first: Jill

middle: Everland

last: Larsen

state: Queensland

address: Rode Road, Chermside

department: Thoracic Medicine

country: Australia

institute: The Prince Charles Hospital

summary:
Lung cancer remains the leading cause of cancer death worldwide. Overall 5-year survival is about 10-15% and despite curative intent surgery, treatment failure is primarily due to recurrent disease. Conventional prognostic markers are unable to determine which patients with completely resected disease within each stage group are likely to relapse. To identify a gene signature associated with recurrent squamous cell carcinoma (SCC) of lung, we analyzed primary tumour gene expression for a total of fifty-one SCCs (stage I-III) on 22,323 element microarrays, comparing expression profiles for individuals who remained disease-free for a minimum of 36 months with those from individuals whose disease recurred within 18 months of complete resection. Cox proportional hazards modeling with leave-one-out cross-validation identified a 70-gene capable of predicting the likelihood of tumor recurrence and a 79-gene signature predictive for overall survival. These two signatures were pooled to generate a 111-gene classifier which achieved an overall predictive accuracy for disease recurrence of 72% (77% sensitivity, 67% specificity) in an independent set of fifty-eight stage I-III SCCs. This classifier also predicted differences in survival (log-rank P=0.0008, hazard ratio (HR), 3.8 [95% confidence interval, 1.6-8.7]), and was superior to conventional prognostic markers such as TNM stage or N stage in predicting patient outcome. Genome-wide profiling has revealed a distinct gene expression profile for recurrent lung SCC which may be clinically useful as a prognostic tool.
Keywords: non-small cell lung carcinoma, squamous cell, tumor recurrence, expression profiling

overall_design: Expression profiling using 22K element microarrays of 51 primary lung squamous cell carcinomas.

first: Sandra

middle: J

last: Pavey

first: Linda

last: Passmore

first: Rayleen

middle: V

last: Bowman

first: Belinda

last: Clarke

first: Nicholas

middle: K

last: Hayward

first: Kwun

last: Fong


title: Identification of the gene transcription mediated by TGF-β-Smad2/3-Smad4 signaling

city: Beijing

first: yu

last: jian

state: Beijing

address: Qinghuayuan

department: Medical Systems Biology Research Center

country: China

institute: Tsinghua University

summary:
TGF-β signaling is known to be very much dependent on the formation of Smad2/3-Smad4 transcription regulatory complexes. However, the signaling functions of Smad2/3-Smad4 in TGF-β-induced responses are obscure as TGF-β also initiates a number of other signaling pathways. In this study, we systematically assessed the contribution of TGF-β-Smad2/3-Smad4 signaling to target gene transcription. Individual Smads were selectively knocked down in Hep3B cells by stable RNA interference (RNAi). We identified TGF-β-responsive genes using genome-wide oligonucleotide microarrays and confirmed their dependency on Smad2, Smad3 or Smad4 by the combination of RNAi and microarray assay. The major finding from our microarray analysis was that of the 2039 target genes seen to be regulated via TGF-β induction, 190 were differentially transcriptionally controlled by Smad2-Smad4 and Smad3-Smad4 signaling and the latter control mechanism appeared to be functionally more important. We also found evidence of competition between Smad2 and Smad3 for their activation when controlling the transcription of target genes.
Keywords: cell type comparison

overall_design: Large-scale microarray analysis was employed for comparison between the responses of wild-type Hep3B cell line and each knockdown cell line, with and without TGF-β induction, to identify target genes and any false positive genes.

first: Yu

last: Jian

first: Zhang

last: Liang


title: Gene Expression Profiling of Familial and Sporadic Cases of Interstitial Pneumonia

status: Public on Oct 01 2006

city: Denver

first: Ivana

last: Yang

state: CO

address: 1400 Jackson Street

department: Medicine

institute: National Jewish Health

summary:
Rationale: Idiopathic interstitial pneumonia (IIP) and its’ familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms.  Both the genetics and the histologic type of IIP play a role in understanding the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these subtypes are unknown.
Objectives: To evaluate gene expression in the lung tissue from patients with usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) that were either familial or non-familial in origin and compare them to gene expression from normal lung parenchyma.
Methods: We profiled RNA from lungs of 16 patients with sporadic IIP, 10 with familial IIP, and 9 normal controls on a whole human genome oligonucleotide microarray.
Results:  Significant transcriptional differences exist in familial and sporadic IIPs.  The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish IIP from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway.
Keywords: disease state analysis

overall_design: 35 lung RNA samples were profiled against universal human RNA reference (Stratagene) in duplicate with Cy3 and Cy5 dyes swapped.  9 samples are normal lung tissue and 26 samples are subjects with idiopathic interstitial pneumonia (10 have familal form of the disease and 16 have sporadic IIP).

first: Lauranell

last: Burch

first: Mark

last: Steele

first: Jordan

last: Savov

first: John

middle: W

last: Hollingsworth

first: Erin

last: McElvania-Tekippe

first: Katherine

middle: G

last: Berman

first: Marcy

middle: C

last: Speer

first: Thomas

middle: A

last: Sporn

first: Kevin

last: Brown

first: Marwin

middle: I

last: Schwarz

first: David

last: Schwartz


title: 300 ppm Citrinin treatment for 2 h

status: Public on Nov 01 2006

city: Tsukuba

first: Emiko

last: Kitagawa

state: Ibaraki

address: Onogawa 16-1

country: Japan

institute: National Institute of Advanced Industrial Science and Technology


title: Genomewide demarcation of RNA PolII transcription units by physical fractionation of chromatin- Intergenic enrichment

first: Jason

middle: D

last: Lieb

overall_design: Intergenic enrichment- Whole cells were fixed by addition of 37% formaldehyde/11% methanol to the growth medium to a final concentration of 1% formaldehyde at 30°C for 30 min. Glycine was added to 125mM from a 2.5 M stock and incubated for 5 min. The cells were centrifuged in a Sorvall RT7 at 3,000 rpm for 5 min at 4°C and washed twice with PBS and once with sterile water. Without reversing crosslinks, extracts were prepared by glass-bead disruption, sonication (fragment size 200-2,000 bp, peak at 900 bp), and standard phenol-chloroform extraction.

first: Peter

last: Nagy

first: Michael

last: Cleary

first: Patrick


title: Comparison of metastasis-inclined microenvironment (MIM) and metastasis-averse microenvironment (MAM) HCC patients

status: Public on Aug 17 2006

city: Bethesda

first: Xin

middle: Wei

last: Wang

address: 37 Convent Drive

department: Laboratory of Human Carcinogenesis

summary:
To determine the role of the hepatic microenvironment in HCC metastasis, we compared the gene expression profiles of 20 noncancerous surrounding hepatic tissues from two HCC patient groups, those with primary HCC together with venous metastasis which we termed a metastasis-inclined microenvironment (MIM) and those with HCC without detectable metastasis, which we termed a metastasis-averse microenvironment (MAM).
Keywords: disease state design

overall_design: There were a total of 20 cDNA microarrays performed, comparing 9 MIM or 11 MAM HCC patient samples to a common reference pool of 8 normal liver tissues.


title: PACAP dependency of genes regulated in ischemia

first: Babru

middle: Bahan

last: Samal

address: 9000 Rockville Pike

department: SMN

institute: NIMH/NIH

summary:
We investigated the effects of PACAP treatment, and endogenous PACAP deficiency, on infarct volume, neurological function, and the cerebrocortical transcriptional response in a mouse model of stroke, middle cerebral artery occlusion (MCAO). PACAP-38 administered i.v. or i.c.v. one hour after MCAO significantly reduced infarct volume, and ameliorated functional motor deficits measured 24 hours later in wild-type mice. Infarct volumes and neurological deficits (walking faults) were both greater in PACAP-deficient than in wild-type mice, but treatment with PACAP reduced lesion volume and neurological deficits in PACAP-deficient mice to the same level of improvement as in wild-type mice. A 35,546-clone mouse cDNA microarray was used to investigate cortical transcriptional changes associated with cerebral ischemia in wild-type and PACAP-deficient mice, and with PACAP treatment after MCAO in wild-type mice. 229 known (named) transcripts were increased (228) or decreased (1) in abundance at least 50% following cerebral ischemia in wild-type mice. 49 transcripts were significantly up-regulated only at one hour post-MCAO (acute response transcripts), 142 were up-regulated only at 24 hours post-MCAO (delayed response transcripts) and 37 transcripts were up-regulated at both times (sustained response transcripts). More than 50% of these are transcripts not previously reported to be associated with brain ischemia responses. Many of the acutely regulated neurotrauma-associated transcripts, but a larger percentage of the delayed ones, require endogenous PACAP for up-regulation by ischemia, suggesting a more prominent role for PACAP in later response to injury than in the initial response, and consistent with a neuroprotective role for PACAP in late response to injury and neuroprotective efficacy when given post-MCAO. Putative injury effector transcripts regulated by PACAP include ãÑ-actin, midline 2, and metallothionein 1. Potential neuroprotective transcripts include several demonstrated to be PACAP-regulated in other contexts. Prominent among these were transcripts encoding the PACAP-regulated gene Ier3, and the neuropeptides enkephalin, substance P (tachykinin 1), and neurotensin.
Keywords: transcript identification design

overall_design: In the hybridization method employed, equal amounts (2-5ãËg/15.5 ãËl) of total RNA obtained from brain tissue of different experimental groups were separately labeled with two different fluorescent dyes (Cy3 or Cy5) and applied on the same NIMH Mouse 36K cDNA microarray chip containing 13217 distinct Entrez gene IDs (formerly known as LocusLink) and 15888 distinct unigene IDs, the remainders are incompletely annotated IMAGE clones. Probe preparation and hybridization were performed as follows. The total RNA (15-50 ãËg in 15.5 ãËl) was incubated with amine-modified random primer (2 ãËg/ãËl, 2 ãËl) and RNase inhibitor (5 units/ãËl, 1 ãËl) at 70 äaC for 10 min. Primer-RNA solution was then incubated at 42 äaC for 2 hr with the reverse transcriptase mix containing 5X first-strand buffer, 50X aa-dUTP/dNTPs (25 mM dATP, 25 mM dGTP, 25 mM dCTP, 15 mM dTTP and 10 mM aminoallyl dUTP), 0.1 M DDT, and Superscript II reverse transcriptase. The cDNA were labeled with NHS-ester Cy3 or Cy5 dye in the presence of 1 M sodium bicarbonate. Array slides placed in a hybridization chamber (Corning, Corning, NY) were incubated at 42 äaC for 16-24 hr, and successively washed with 0.5X SSC, 0.01% SDS, and 0.06X SSC at room temperature for 10 min each. Arrays were scanned with a GenePix 4000A scanner (Axon, Foster City, CA), and the resulting images were analyzed using IPlab (Fairfax, VA) and a FileMaker Pro 5 (Santa Clara, CA) relational database designed by Zedong Chen, NHGRI. Following background subtraction and normalization, a calculated ratio of Cy3 to Cy5 signal intensities was used to define the relative increase or decrease of a particular transcript. Ratios were calculated only from those spots with a combined ratio quality above 0.3.


title: 300 ppm Citrinin treatment for 2 h (GPL1945)

summary:
The availability of yeast DNA microarrays provides the possibility of monitoring gene expression levels as a function to toxin exposure, and consequently as a means of determining mechanisms of toxicity. This system possesses the benefit of the essential volume of yeast cultures, the high reproducibility of expression profiles, and the massive functional information. Because small amount of biological sample cultures are required for this analysis, toxicity test for rare chemical such as mycotoxins which is a natural compound and difficult to be artificially synthesized. Citrinin [518-75-2], 4,6-dihydro-8-hydroxy-3,4,5-trimethyl-6-oxo-3H-2-benzopyran-7-crboxylic acid, is the one of the popular mycotoxicin produced by Penicillium and Aspergillus family possibly spread all over the world. This natural chemicals is one of the well characterized mycotoxin but the information especially mechanism of toxic action is limited.
We used two types of microarrays, one have ORF (Open reading Frame) fragment on the surface of the glass as probes and the other have probes as oligonucleotide probes on the microarray with 3 dimensions. We compared data properties and studied the toxicity of citrinin to yeast cells.
Keywords: stress response

overall_design: Series containes 3 hybridization results from independent biological samples, and each experiment have high and low power scanned data respectively.

first: YoungKyung

last: Kim

first: Yoshiteru

last: Suzuki

first: Hitoshi

last: Iwahashi


status: Public on Sep 08 2006

address: CB# 3280, 202 Fordham Hall

department: Department of Biology

summary:
1. Comparison of Leu3 binding in vitro and in vivo
2. comparison of nucleosome occupancy between with Leu3-binding and without Leu3-binding

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series

first: Xiao

last: Liu

first: Cheol-Koo

last: Lee

first: Neil

last: Clarke


title: Alzheimer Disease peripheral blood mononuclear cell expression

status: Public on Oct 13 2006

city: Montreal

first: Olivier

middle: Charles

last: Maes

state: Quebec

address: 3999 Cote Ste Catherine

department: Bloomfield Centre for Research in Aging

institute: Lady Davis Institute for Medical Research

summary:
Comparisons between the sample groups (normal elderly control (NEC) and Alzheimer disease (AD)) allow the identification of genes with disease and gender expression patterns.
Keywords: biological repeat

overall_design: Peripheral blood mononuclear cells were obtained from normal elderly control (NEC) and Alzheimer disease (AD) subjects.  Targets from biological replicates of female (n=7) and male (n=7) NEC and  female (n=7) and male (n=7) AD were generated and the expression profiles were determined using the NIA Human MGC cDNA microarray.

first: Howard

middle: M

last: Chertkow

last: Bergman

first: Hyman

last: Schipper

first: Eugenia


title: Met Expression Signature in Hepatocytes

status: Public on Oct 02 2006

first: Snorri

middle: S

last: Thorgeirsson

address: 37 Convent Dr. # 4146

department: Laboratory of Experimental Carcinogenesis

institute: National Cancer institute/NIH

summary:
To identify HGF/Met regulated genes, we performed expression microarray analysis after inducible activation of Met receptor in primary cultures of hepatocytes established from wild-type control (Alb-Cre +/-) and Met conditional knockout mice (Alb-Cre +/-; Met Fl/Fl).
Keywords: time series design

overall_design: Total RNA was isolated from untreated hepatocyte cultures as well as from cultures treated with 50 ng/ml of HGF for 0.5, 2, 12 or 24 hours. RNA collected from these experiments was converted to fluorescently labeled cDNA and used for hybridizations of oligonucleotide microarrays. All experiments were repeated in triplicates. Total RNA from pooled wild-type mouse hepatocytes was used as universal reference and all hybridizations were repeated following a reverse flourescing.


title: Selection of Neural Differentiation-Specific Genes by Comparing Profiles of Random Differentiation

status: Public on Aug 05 2006

city: Seoul

first: Woong Yang

last: Park

address: 28 Yongondong, Chongnogu

department: Biochemistry and Molecular Biology

country: South Korea

institute: Seoul National University

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


title: Dilated Cardiomyopathy and Non Failing Septal Biopsies

status: Public on Aug 01 2006

city: Heidelberg

first: Ruprecht

last: Kuner

address: Im Neuenheimer Feld 460

department: Molecular Genetics

institute: German Cancer Research Center and National Center of Tumor Diseases

summary:
Dilated cardiomyopathy (DCM) is a common cause of heart failure and a leading cause of cardiac transplantation in western countries. The robust predictive expression profile of cardiomyopathic and NF hearts as well as the functional classification can help to identify promising candidates for DCM and may improve the early diagnosis of
cardiomyopathy.
Keywords: disease state analysis

overall_design:
This series includes dual channel hybridizations of 28 independent
heart biopsy samples on Unigene3.1 cDNA Arrays. The 28 septal myocardial tissue samples were collected from 13 DCM hearts at the time of transplantation and 15 NF donor hearts which were not transplanted because of palpable coronary calcifications. For every independent sample, two technical replicates were performed and further processed as mean values.

first: Holger

last: Sultmann

first: Andreas

last: Buness

first: Markus

last: Ruschhaupt

last: Barth

last: Nabauer


title: Gene Expression data of Arctic Ground Squirrel during the multiple stages of hibernation

status: Public on Aug 03 2006

city: Fairbanks

first: Jun

last: Yan

state: AK

address: 311 Irving Building

department: Institute of Arctic Biology

institute: University of Alaska Fairbanks

summary:
Differential gene expression in a wide range of tissues including brown adipose tissue (BAT), liver, heart, hypothalamus, and skeletal muscle in hibernating arctic ground squirrels during multiple stages in torpor-arousal cycles compared to non-hibernating (post-reproductive) animals with illumina beadarray technology.
Keywords: Multiple stage comparison

platform_organism:
Urocitellus parryii
Ictidomys tridecemlineatus
Callospermophilus lateralis

overall_design: Arctic Ground Squirrels were sampled at four stages of hibernation: early arousal denoted as EA (1-2 hrs after Tb cross 30¡C, n=4), late arousal denoted as LA (7-8 hrs after Tb cross 30¡C, n=4), early torpor denoted as ET (10-20% of torpid episode, n=4) and late torpor denoted as LT (80-90% of torpid episode, n=5), where Tb is the body temperature and the length of torpid episode is estimated from the previous torpor bout. Post-reproductive animals denoted as PR (n=7) were used as non-hibernating control. Five tissue types: brown adipose tissue (BAT), liver, heart, hypothalamus, and skeletal muscle were hybridized on two customized 700-gene beadarray platforms: 1A and 2A on 96-sample Illumina ArrayMatrix. The data of a pilot study involving brown adipose tissue (BAT), liver, and skeletal muscle on 16-sample Illumina BeadChip denoted as 16chip are also included in this series.

first: Franziska

last: Kohl

first: Brian

last: Barnes

first: Thomas

last: Marr


title: Temperature induced differentiation of piA immortalised cell line PrE2.8

status: Public on Jul 28 2006

first: Ian

last: Giddings

summary:
The cell line PrE2.8 was cultured at a permissive growth temperature of 33oC and then half transferred to a non-permissive temperature of 39.5oC for 4days. The two sets of cells were harvested and co-hybridised to identify genes with altered expression  resulting from unduced differentiation.
Keywords: Induction of cellular differentiation

overall_design: Cells were harvested from cultures grown at two temperatures and RNA isolated. RNA from induced and non induced cultures were co-hybridised onto array slides.

first: B

last: Daly-Burns

first: T

middle: N

last: Alam

first: A

last: Mackay

first: J

last: Clark

first: C

last: Shepherd

first: S

last: Rizzo

first: R

last: Tatoud

first: M

last: O'Hare

last: Masters

first: D

middle: L

last: Hudson


title: DNA-Methyltransferases (DNMT) knockouts

first: Ruprecht

last: Kuner

summary:
Alterations in DNA-methylation are a hallmark of human tumor cells. DNMT1 is expressed in three different splice variants and exhibits considerable preference for hemimethylated DNA and is therefore referred to as the maintenance methylase. DNMT3b is generally considered to be responsible for de novo methylation during embryonic development and probably also during tumor development. Recent studies using somatic knock-out of DNA-methyltransferases have shown a reduction in overall methylation and a re-expression of tumor suppressor genes. Cells deficient of both, DNMT1 and DNMT3b may exhibit almost complete demethylation and growth suppression. In the present study, we performed MEK-inhibition via U0126 treatment for the wildtype and every DNMT-knockout to focus on MEK/RAS-target genes regulated by methylation.
Keywords: genetic modification

overall_design:
This series includes dual channel hybridizations of 14 independent HCT-116
cell line lysates on Unigene3.1 cDNA Arrays. In this series, five DNMT-wildtype, three DNMT1-KO, three DNMT3-KO and three DNMT1 and 3B double KO were included with different treatment status (none, DMSO, U0126, Aza-CdR). For every independent sample, two technical replicates were performed and further processed as mean values.

first: Holger

last: Sultmann

last: Buness

last: Ruschhaupt

first: Annemarie

last: Poustka

first: Christine

last: Sers

first: Per

last: Lund

first: Balázs

last: Gyorffy

first: Reinhold

last: Schafer


title: Expression Profiling of a CALM/AF10 leukemia mouse model

status: Public on Jul 20 2006

first: Hendrik

last: Reuter

department: Moleculare Genetics B060

institute: DKFZ

summary:
Expression profiling of three cell populations of a CALM/AF10 leukemia mouse model
Keywords: expression profiling

overall_design: Three populations, i.e. Mac1 single positive, B220 single positive and Mac1/B220 double positive cells of a culture from the Leukemia Mouse Model have been sorted to perform expression profiles

first: Aniruddha

last: Deshpande

first: Christian

last: Buske

first: Meinhard

last: Hahn

first: Peter

last: Lichter


title: Fetal lung development

status: Public on Jul 26 2006

city: Stillwater

first: Tingting

last: Weng

state: OK

address: 264 McElroy Hall

department: Physiological Sciences

institute: Oklahoma State University

summary:
Fetal lung development is a complex biological process, which involves temporal and spatial regulations of many genes. To understand molecular mechanisms of this process, we investigated gene expression profiling of lungs at gestational day 18, 19, 20, 21, new born, and adult rats using in-house rat DNA microarray containing 6,000 known genes and 4,000 ESTs. 1,512 genes passed SAM test and 583 genes (402 known genes and 181 ESTs) had a 2-fold change at least at one time point. K-means cluster analysis revealed 7 major expression patterns. Furthermore, using GeneMapp, we identified 3 regulatory pathways: TGF beta signaling pathway, cell cycle, and G-protein signaling; and 2 metabolism pathways:  proteasome degradation and glycolysis. Our results suggest a complex regulatory pathway for fetal lung development.
Keywords: Time course

overall_design: Loop Design as following: D18-D19-D20-D21-NB-AD-D18

first: Zhongming

last: Chen

first: Lin

last: Liu


title: Expression profiling of liver tissue from (C57BL/6J X C3H/HeJ)F2 mice on ApoE null backgrounds

status: Public on Jul 27 2006

city: Los Angeles

first: Leslie

last: Ingram-drake

department: Medicine/MIMG/Human Genetics

institute: UCLA

summary: The (C57BL/6J X C3H/HeJ)F2 intercross consists of 334 animals of both sexes. All are ApoE null and received a high fat Western diet from 8-24 weeks of age.

overall_design: Livers from 311 F2 female and male mice (animals fed a high fat "Western" diet from 8-24 weeks of age.) derived from C57BL/6J and C3H/HeJ parental strains with both on ApoE null backgrounds.  All samples were compared to a common pool created from equal portions of RNA from each of the samples.  Keywords=Genetics of Gene Expression Keywords=C57BL/6J Keywords=C3H/HeJ


title: Comparison of WT Vs NaS1-/- livers

status: Public on Jul 14 2006

city: St Lucia

first: Sean

last: Grimmond

state: QLD

address: Research Rd

department: Genomics and Bioinformatics

institute: Institute of Molecular Bioscience, Uni of QLD

summary:
Pairwise comparison of gene expression in pools (n=14) of wildtype 4 week old male Vs NaS1-/- knockout mice.
Keywords: normal Vs mutant

overall_design: Pairwise comparison: 4 technical replicates, 2 dye swaps

first: Paul

last: Dawson

first: Brooke

middle: B

last: Gardiner

first: Daniel

last: Markovich


title: Nuclear growth hormone receptor

status: Public on Jul 08 2006

city: Potomac Falls

first: Agnieszka

middle: Maria

last: Lichanska

state: VA

institute: Tessarae, LLC

summary:
Not supplied by submitter
Keywords: time course

overall_design: A Lowess curve was fit to the log-intensity versus log-ratio plot. 50.0% of the data was used to calculate the Lowess fit at each point. This curve was used to adjust the control value for each measurement. If the control channel was lower than 200 then 200 was used instead.


title: Expression profiling of brain tissue from (C57BL/6J X C3H/HeJ)F2 mice on ApoE null backgrounds

status: Public on Jul 07 2006

state: CA

overall_design: Brain from 249 F2 female and male mice (animals fed a high fat "Western" diet from 8-24 weeks of age.) derived from C57BL/6J and C3H/HeJ parental strains with both on ApoE null backgrounds.  All samples were compared to a common pool created from equal portions of RNA from each of the samples.  Keywords=Genetics of Gene Expression Keywords=C57BL/6J Keywords=C3H/HeJ

first: Xia

last: Yang

first: Eric

middle: E

last: Schadt

first: Susanna

last: Wang

first: Hui

first: Arthur

middle: P

last: Arnold

last: Ingram-Drake

first: Thomas

last: Drake

first: Aldons

middle: J

last: Lusis


title: Expression profiling of Adipose tissue from (C57BL/6J X C3H/HeJ)F2 mice on ApoE null backgrounds

overall_design: Adipose from 295 F2 female and male mice (animals fed a high fat "Western" diet from 8-24 weeks of age.) derived from C57BL/6J and C3H/HeJ parental strains with both on ApoE null backgrounds.  All samples were compared to a common pool created from equal portions of RNA from each of the samples.  Keywords=Genetics of Gene Expression Keywords=C57BL/6J Keywords=C3H/HeJ


title: Comparative transcriptional profiling of the lung discriminates S. pneumoniae and Influenza A Virus infections

status: Public on Jul 12 2006

city: Berlin

first: Hans-Joachim

last: Mollenkopf

address: Charitéplatz 1

institute: Max-Planck-Institute for Infection Biology

summary:
Peumonia is the most common cause of death due to infectious diseases in the western hemisphere. The molecular events associated with pulmonary infections caused by Streptococcus pneumoniae and Influenza A virus are incompletely understood. Pathophysiological and protective processes are initiated by immune receptors specifically recognizing pathogenic structures serving to elicit a qualitatively and quantitatively adequate immune response. To provide a molecular framework towards a better understanding of the processes relevant in severe infectious pneumonia we performed a transcriptome analysis of  lungs from mice infected with S. pneumoniae or Influenza A virus. Overall, we detected 1300 genes that exhibit significant differential expression after infection with either pathogen. Of those were approximately 36 % specific for pneumococcal and 30 % specific for the viral infection, yielding pathogen-specific as well as common inflammatory transcriptional signatures. Characteristically, these results resolve not only a differential response on the cytokine and chemokine level, although common induction of type I and type II interferons, TNFa, and  IL-6 underlies both infections, but emphasize the potentially important role exerted by many genes implicated in the regulation and fine tuning of the inflammatory response. Furthermore, we noted a specific decrease in B cells after S. pneumoniae infection, which is not solely confined to the lung. Massive induction of apoptosis in pulmonary B cells could reflect a  pneumococcal virulence strategy aiming against the lymphocyte population that is of utmost importance for the defence against capsulated bacteria. The pathophysiological consequences of Influenza A virus infection become obvious through differential induction of genes implicated in tissue regeneration and proliferation associated with detection of the emerging protective T cell response.  These results may provide new insights into the pathogenesis and protective mechanisms important for the development of improved diagnostic and therapeutic strategies.
Keywords: pathogen comparison, time course

overall_design: Microarray analyses were performed as two-colour hybridizations. RNA was labelled with a Fluorescent Linear Amplification Kit (Agilent Technologies). Briefly, 4 µg total RNA was reverse transcribed with an oligo-dT-T7 promoter primer and MMLV-RT. Second strand synthesis was carried out with random hexamers. Fluorescent antisense cRNA was synthesized with either cyanine 3-CTP (Cy3-CTP) or cyanine 5-CTP (Cy5-CTP) and T7 polymerase. Purified products were quantified at A552nm for Cy3-CTP and A650nm for Cy5-CTP. Prior hybridization, 1.25 µg labelled cRNA each were fragmented, mixed with control targets and hybridization buffer according to the supplier's protocol (Agilent Technologies). Hybridizations were performed for 17 h at 60°C. The slides were washed according to the manufacturer's protocol and scanning of the arrays was performed with 5 µm resolution using a DNA microarray laser scanner (Agilent Technologies). To compensate for dye specific effects, and to ensure validity of the data, a colour swap analysis (fluorescence reversal) was performed. Features were extracted with the image analysis tool Version A6.1.1.1 from Agilent Technologies. Subsequent data analyses were carried out on the Rosetta Inpharmatics platform Resolver Built 3.2.2. Differential expression patterns were identified by applying 2-fold expression level cut-offs and an anti-correlation of the dye reversal experiments with an error weighted p-value < 0.05.

first: Simone

last: Rosseau

first: Andreas

last: Hocke

first: Kerstin

last: Bonhagen

first: Bernd

last: Schmeck

first: Suttorp

last: Suttorp

first: Stefan

middle: H

last: Kaufmann


title: Mouse models of human colon cancer and mouse colon development

city: Cincinnati

first: Bruce

last: Aronow

state: OH

institute: Cincinnati Children's Hospital Medical Center

summary:
Goal of the experiment: To identify transcriptional patterns across tumors from colorectal cancer murine models and normal mouse colon samples at different developmental stages.
Experiment description: Colorectal cancer (CRC) results from multiple genetic and epigenetic events that produce variable histologies and clinical outcomes. To identify gene regulatory programs that underlie colon tumorigenesis, we profiled gene expression in 39 mouse colon tumors from four independent mouse models and compared this to mouse colon embryonic development, as well as with 100 human colon carcinomas. Here, we report a striking recapitulation of embryonic patterns of gene expression in both mouse and human colon tumors. All four of the mouse colon tumor models exhibited large-scale activation of embryonic gene expression signatures. The two nuclear beta-catenin-positive mouse tumors (azoxymethane-treated [AOM] and ApcMin/+), exhibited strong activation of genes characteristic of those expressed in the earliest embryonic stages, while tumors from two other models (Smad3-/- and Tgfb1-/- x Rag2-/-) exhibited lower activation of early stage-specific genes but substantial expression of general embryonic colon genes. Human colon cancer cases over-expressed genes characteristic of both early and late embryonic stages. Examining tumor gene expression through the lens of development has revealed an extensive network of therapeutic targets for cancer control.
Keywords: Tumors from four murine models of colorectal cancer and normal mouse colon samples at different developmental stages

overall_design: Four colorectal tumor models were compared using the approach of finding model-specific differences with gene expression levels referenced to the median gene expression value across all models. A second complementary strategy compared the gene expression levels of the murine tumors to those of mouse normal adult colon.


status: Public on Jun 06 2006

city: Davis

first: Sharon

last: Squazzo

address: 4617 GBSF, 451 E. Health Sci. Dr.

department: Pharmacology

institute: UC Davis Genome Center

summary:
These samples are biological replicates from Ntera cells that were crosslinked on different days.  For each sample a matched total was produced in a parallel.  Amplicons were made from each and hybridized on human 1.5 kb promoter arrays from Nimblegen.
Keywords: ChIP-chip

overall_design: Goal was determination of Oct4 and RNA Pol II target promoters in Ntera cells using ChIP-chip methodology.


title: Role of Yap4 in Yeast Osmotic Stress Response

status: Public on Jun 15 2006

city: Oeiras

first: Claudina

last: Rodrigues-Pousada

address: Av da Republica (EAN)

country: Portugal

institute: Instituto de Tecnologia Quimica e Biologica

summary:
The role of the S. cerevisiae Yap4 transcription factor in the response to hyperosmolarity was investigated in two ways. Firstly, to assess the overall response of the yap4 deleted strain genome wide analysis upon a mild upshift in osmolarity was compared to the same response in the wt strain. Secondly, in order to identify genes whose osmo-expression is differentially regulated in the mutant strain (ie potential Yap4 target genes) the relative abundance of cDNAs of the wt and yap4 mutant strain obtained upon an osmotic upshift were directly compared by microarray analysis.
Keywords: Mutant Stress Response

overall_design:
Expt 1: The response of the wt to mild hyperosmolarity (0.4M NaCl)
Serving as the exptal control, this experiment identifies the response of the wt strain to 0.4M NaCl. cDNAs obtained from total RNA extracted from wt cells subjected (test) or not (reference) to the indicated conditions for 10 minutes were labeled with Cy3 (reference) or Cy5 (test).
Expt 2: Identification of potential Yap4 target genes under mild hyperosmolarity (0.4M NaCl). cDNAs obtained from total RNA extracted from wt (reference) and yap4 mutant (test) cells subjected to 0.4M NaCl for 10 minutes were labeled with Cy3 (reference) or Cy5 (test).
Expt 3: The response of the yap4 mutant to mild hyperosmolarity (0.4M NaCl). cDNAs obtained from total RNA extracted from the yap4 mutant subjected (test) or not (reference)  to 0.4M NaCl for 10 minutes were labeled with Cy3 (reference) or Cy5 (test).

first: Tracy

last: Nevitt

first: Jorge

last: Pereira

first: Miguel

last: Santos


summary:
For each sample a matched total was prepared in parallel.  For each biological replicate the cells were crosslinked on different days.  Amplicons were prepared from each sample and hybridized on mouse 1.5 kb promoter arrays from Nimblegen.
Keywords: ChIP-chip

overall_design: Goal was to determine Suz12, EZH2, EED1, H3me3K27, H3me3K9 and RNA Pol II target promoters in mouse F9 and mES cells using ChIP-chip methodology.


title: Gene expression profiles in AEC II during hyperoxia exposure and recovery

first: Zhongming

last: Chen

department: Deptment of Physiological Sciences

summary:
In this study, type II alveolar epithelial cells (AEC II) were isolated from normal, hyperoxia exposed (day 0) and recovery (day 1,3,5 and 7) rats with high purity (~95%). Total RNA from isolated cells were used for dual color DNA microarray hybridization with 3DNA 50 kit version 2.
Keywords: time-course

first: Teluguagula

last: Narasaraju

first: Jiwang

first: Nili

last: Jin

first: Lin

last: Liu


title: The absence of a Ca(2+) signal during mouse egg activation can affect development and gene expression patterns

status: Public on Jun 20 2006

city: Baltimore

first: Minoru

last: Ko

state: MD

address: 251 Bayview Blvd, Suite 100, 10C

department: National Institute on Aging

institute: NIH

summary:
The absence of a Ca(2+) signal during mouse egg activation can affect parthenogenetic preimplantation development, gene expression patterns, and blastocyst quality.
Gene expression pattern of parthenogenetic mouse embryos by cycloheximide or Sr2+.
Keywords: development or differentiation design

first: Nina

middle: T

last: Rogers

first: Guillaume

last: Halet

first: Yulan

last: Piao

first: John

last: Carroll

first: Karl

last: Swann


title: Gene expression profiling in FSHMD1A muscle

status: Public on Jun 16 2006

city: Padova

first: Gerolamo

last: Lanfranchi

address: Via U. Bassi, 58/B

department: CRIBI - Biotechnology Center and Biology Department

institute: University of Padova

summary:
We used a muscle specific cDNA microarray platform to analyze muscle biopsies of 11 characterized FSHD patients, carrying a variable number of KpnI repeats.
Keywords: FSHD, cDNA microarray, gene expression profiling, deltoid muscle

overall_design: Our muscle specific cDNA microarray platform was used to analyze muscle biopsies of a series of genetically characterized FSHD patients with a range of D4Z4 allele size at the contracted 4qter region and with canonical phenotypes of varying grades of clinical severity. Muscle biopsies were obtained from the distal portion of the left deltoideus muscle. In this study we compared by competitive microarray hybridization the transcription profiles of FSHMD1A muscles with a pool of 10 human deltoideous muscles obtained from normal donors.

first: Barbara

last: Celegato


title: Massachusetts General Hospital (MGH) long oligo experiments for cross-platform study

status: Public on Jun 01 2006

city: Boston

first: Winston

middle: Patrick

last: Kuo

state: MA

address: 188 Longwood Avenue

department: Genetics

institute: Harvard Medical School

summary:
Gene expression microarrays have made a profound impact in biomedical research. The diversity of platforms and analytical methods has made comparison of data from multiple platforms very challenging. In this study, we describe a framework for comparisons across platforms and laboratories. We have attempted to include nearly all the available commercial and “in-house” platforms. Using probe sequences matched at the exon level improved consistency of measurements across the different microarray platforms compared to annotation-based matches. Generally, consistency was good for highly expressed genes, and variable for genes with lower expression values as confirmed by QRT-PCR. Concordance of measurements was higher between laboratories on the same platform than across platforms. We demonstrate that, after stringent pre-processing, commercial arrays were more consistent than “in-house” arrays, and by most measures, one-dye platforms were more consistent than two-dye platforms.
Keywords: cross platform microarrays

overall_design: RNA samples used were aliquoted from two pools of samples: C57/B6 adult mouse retina (MR) and Swiss-Webster postnatal day one (P1) mouse cortex (MC). The mouse cortex was used as a reference sample for the dual-dye platforms.Five replicates of each sample were used to assess the degree of variation in the expression data within each platform.


title: Mergen experiments for cross-platform study including site 2 data


title: Agilent experiments for cross-platform study


title: Arthritis_RA_OA_VNS

first: Ruprecht

last: Kuner

summary:
Pigmented villonodular synovitis (PVNS) represents a rare group of lesions with morphological features suggesting an inflammatory as well as a neoplastic nature. Rheumatoid arthritis (RA) is characterized by a chronic inflammation of the synovial tissue and a tumor-like proliferation (TLP) of synovial stroma cells. Osteoarthritis (OA) shows modest inflammatory infiltrates and no TLP.
All three diseases result in a progressive destruction of affected joints and remain a diagnostic difficulty because of nonspecific symptoms. This study aimed to identify molecular markers and genes correlated with the development of RA, OA, and PVNS using human whole genome cDNA microarrays and tissue samples obtained from knee surgery.
Keywords: disease state analysis

overall_design:
This series includes dual channel hybridizations of 48 independent
synovial membrane samples on Unigene3.1 cDNA Arrays. The 48 biopsies were collected from 18 patients with RA, 19 patients with OA and 11 patients with PVNS. For every independent sample, minimum of two technical replicates were performed and further processed as mean values.

first: Katharina

last: Finis

first: Holger

last: Sultmann

first: Markus

last: Ruschhaupt

first: Andreas

last: Buness

first: Irina

last: Berger

first: Bernd

last: Fink


title: Expression profiling of Muscle tissue from (C57BL/6J X C3H/HeJ)F2 mice on ApoE null backgrounds

first: Leslie

last: Ingram-drake

overall_design: Muscle from 319 F2 female and male mice (animals fed a high fat "Western" diet from 8-24 weeks of age.) derived from C57BL/6J and C3H/HeJ parental strains with both on ApoE null backgrounds.  All samples were compared to a common pool created from equal portions of RNA from each of the samples.  Keywords=Genetics of Gene Expression Keywords=C57BL/6J Keywords=C3H/HeJ

first: Xia

last: Yang

first: Eric

last: Schadt

first: Susanna

last: Wang

first: Hui

first: Arthur

last: Arnold

last: Ingram-Drake

first: Thomas

middle: A

last: Drake

first: Aldons

last: Lusis


title: Mouse colon development series

first: Bruce

last: Aronow

summary:
Goal of the experiment: To identify transcriptional patterns across tumors from colorectal cancer murine models and normal mouse colon samples at different developmental stages.
Experiment description: Colorectal cancer (CRC) results from multiple genetic and epigenetic events that produce variable histologies and clinical outcomes. To identify gene regulatory programs that underlie colon tumorigenesis, we profiled gene expression in 39 mouse colon tumors from four independent mouse models and compared this to mouse colon embryonic development, as well as with 100 human colon carcinomas. Here, we report a striking recapitulation of embryonic patterns of gene expression in both mouse and human colon tumors.  All four of the mouse colon tumor models exhibited large-scale activation of embryonic gene expression signatures.  The two nuclear beta-catenin-positive mouse tumors (azoxymethane-treated [AOM] and ApcMin/+), exhibited strong activation of genes characteristic of those expressed in the earliest embryonic stages, while tumors from two other models (Smad3-/- and Tgfb1-/- x Rag2-/-) exhibited lower activation of early stage-specific genes but substantial expression of general embryonic colon genes.  Human colon cancer cases over-expressed genes characteristic of both early and late embryonic stages.  Examining tumor gene expression through the lens of development has revealed an extensive network of therapeutic targets for cancer control.
Keywords: Tumors from four murine models of colorectal cancer and normal mouse colon samples at different developmental stages


title: Molecular Correlate to Gleason Grade in Prostate Adenocarcinoma

city: Seattle

first: Denise

last: Mauldin

state: WA

address: 1100 Fairview Ave N D4-100

department: Human Biology

institute: Fred Hutchinson Cancer Research Center

summary:
Twenty-nine radical prostatectomy samples were laser capture microdissected (LCM) to obtain the most common Gleason patterns (patterns 3, 4, and 5) and matched benign adjacent luminal prostate epithelial cells.  We performed cDNA microarrays on matched cancer and adjacent normal samples and identified an 86-gene model capable of distinguishing low Gleason grade (pattern 3) from high Gleason grade (pattern 4 and 5) cancers, which contributes a set of potential targets for modulating the development and progression of the lethal prostate cancer phenotype.
Keywords: disease state analysis

overall_design: 12 Gleason pattern 3, 12 Gleason pattern 4, and 8 Gleason pattern 5 laser-capture microdissected prostate cancers hybridized with random dye-swaps against patient-matched normal-adjacent controls.

first: Lawrence

last: True

first: Ilsa

last: Coleman

first: Sarah

last: Hawley

first: Alan

last: Huang

first: David

last: Gifford

first: Roger

first: Thomasz

last: Beer

first: Edward

last: Gelman

first: Milton

last: Datta

first: Elahe

last: Mostaghel

first: Beatrice

last: Knudsen

first: Paul

last: Lange

first: Robert

last: Vessella

first: Daniel

last: Lin

first: Leroy

last: Hood

first: Peter

last: Nelson


title: Microarray analysis of Rgg-dependent transcriptional regulation in NZ131 Streptococcus pyogenes strain

city: Kansas City

first: Alexander

middle: V

last: Dmitriev

state: KS

address: 3901 Rainbow Boulevard

institute: Kansas University Medical Center

summary:
Streptococcus pyogenes growth-phase dependent and Rgg-dependent transcription was analyzed
Keywords: transcriptional regulation

overall_design: Microarray analysis was performed using RNA samples isolated from wild-type NZ131 strain during mid-exponential and early-stationary phases of growth as well as RNA isolated from NZ131 rgg isogenic mutant strain during mid-exponential, late-exponential and early-stationary phases of growth

first: Emily

last: McDowell

first: Kyle

last: Kappeler

first: Michelle

last: Chaussee

first: Michael


title: Yeast cell cycle

first: Tata

last: Pramila

address: 1100, Fairview Avenue N

department: Basic Sciences

institute: FHCRC

summary:
Transcription profiles across the yeast cell cycle. W303a cells were arrested with alpha factor in YEPD media. After release from arrest cells were sampled every 5 min for 2 hr.
Keywords: cell cycle

overall_design: Alpha factor synchronized cells were followed across 2 cell cycles.  Dye-swap technical replicates were included in the experiment.

first: Linda

last: Breeden


title: The gene expression program of the developing mammary gland

status: Public on May 22 2006

city: Indianapolis

first: Hosein

last: Kouros-Mehr

state: IN

address: 533 Merrill St.

department: Oncology

institute: Eli Lilly

summary:
The developing mammary gland contains distinct microenvironments that perform specialized functions for branching and ductal invasion.  These microenvironments include the terminal end buds (TEBs) at the tips of invading primary ducts and the more differentiated proximal ducts that give rise to side branches.  We have devised a novel microarray approach to identify genes that are expressed in the epithelium and stroma of these distinct microenvironments.
Keywords: spotted oligonucleotide

overall_design: Total RNA from microdissected terminal end buds and mature ducts were compared to epithelium-free distal stroma of 5 week old mammary glands.  B-actin-GFP reporter mice were used to visualize the mammary glands for microdissection.

first: Zena

last: Werb


title: Gene expression in white adipose tissue stimulated by beta 3 adrenergic receptor agonist

status: Public on May 17 2006

city: Baton Rouge

first: Xiaotuan

last: Liu

state: LA

address: 6400 Perkins Rd.

institute: Pennington Biomedical Research Center

summary:
Experiment designed to identify differences in gene expression profile in white adipose tissue upon stimulation by beta 3 adrenergic receptor agonist. This series compares 2 groups of C57BL/6J acutely treated with CL-316,243 or Saline for 3 hours.
Keywords: parallel sample

first: David

last: York

first: George

last: Bray


title: OPMD_mouse_celline (I & II)

status: Public on Apr 20 2006

city: Leiden

first: Ellen

last: Sterrenburg

address: Wassenaarseweg 72

department: Center for Human and Clinical Genetics

institute: Leiden University Medical Center

summary:
stable transfected cell lines
IM2 = untransfected
WTA = wildtype pabpn1 transfected high
WTD = wildtype pabpn1 transfected low
D7E = mutant pabpn1 transfected high
D7F = mutant pabpn1 transfected low
Keywords: cell type comparision

overall_design:
5 cell lines
triplicate cultures
dye-swap

first: Samantha

last: Routledge


title: ANA1 picolinic acid

city: Genoa

first: Paolo

last: Fardin

address: Largo G. Gaslini 5

department: Molecular Biology

institute: Istiuto Giannina Gaslini

summary:
We performed the analysis of the gene expression profile in the murine ANA-1 macrophage  cell line treated with picolinic acid for 18h.
Keywords: compound response

overall_design: ANA-1 cells treated with picolinic acid versus ANA-1 cells untreated (control). The experiment was performed in duplicate.


title: Role of PI3K pathway in serum/growth factor response of quiescent fibroblasts

status: Public on Apr 12 2006

city: Austin

first: Vishy

last: Iyer

state: TX

address: 2500 Speedway Dr. MBB 3.212

department: Molecular Biosciences

institute: University of Texas at Austin

summary:
PI-3K inhibitor (LY294002) was added to quiescent fibroblasts 30 minutes prior growth factor/serum treatments. The role of PI-3K pathway was thus monitored by comparing with untreated samples.
Keywords: time course, growth factor response, cell line comparison

overall_design: Overall design was similar to growth factor/serum treatment series. Each time point was compared to 0 hour time point before LY294002 treatment.

first: Jian

last: Gu

first: Vishwanath


title: response to persistent beta 2-adrenergic receptor signaling

status: Public on Mar 22 2006

first: Bruce

last: Aronow

summary:
These results revealed an unanticipated beneficial therapeutic effect of beta-agonists, PLN downregulation, which acts to diminish airway hyperreactivity. Agents that inhibit PLN, and thus decrease constrictive responses, may act synergistically with the bronchodilating action of beta-agonists.
A number of other genes related to  [Ca2+]I are also differentially regulated by beta2AR activity some of which may act to oppose, or augment, the therapeutic efficacy of  chronic beta-agonists. These genes or pathways may also represent additional targets in the treatment of asthma and related obstructive lung diseases.
Keywords: genetic modification

overall_design: To ascertain the effects of persistent beta2AR activation on gene expression, cultured airway smooth muscle cells derived from wild-type and transgenic mice overexpressing beta2AR were subjected to DNA microarray analysis

first: Dennis

middle: W

last: McGraw

first: Kevin

last: Fogel

first: Sue

last: Kong

first: Evangelia

middle: G

last: Kranias

first: Stephen

last: Liggett


title: Profiling Gene Expression in Intra-abdominal Adhesion Formation

status: Public on May 24 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: Adhesion formation in the peritoneal cavity is the most-common cause of intestinal obstruction. The aim of this study was to analyze the dynamic gene expression patterns in the small bowel of mice featuring surgically-induced intra-abdominal adhesion.
Methods: In an experimental study, mRNA was extracted from the small bowels of sham control mice and small bowel-scraping mice following surgically-induced intra-abdominal adhesion at 1, 3, 7, and 14 days post surgery. The mouse cDNA microarray was used to monitor the dynamic changes of the tested genes.
Results: We identified 520 genes with a greater than 1.5 fold change across all studied mice groups. Quantitative RT-PCR and immunohistochemical staining certified, respectively, the expression of certain selected genes. The number of apoptotic cells contained within the adhesion tissue increased in a time-dependent manner. The serum concentration of neuropeptide Y was significantly greater for the test mice compared to the controls.
Conclusions: Surgical intervention to the small bowel induces an adaptive response of damaged tissue in order to eliminate excessive complement-mediated lysis, prevent oxidative injuries, and enhance cell proliferation. These findings may provide insights into the pathogenesis of complications following adhesion formation and might also help to identify some new target genes for specific diagnostic tools and novel therapeutic strategies.
Keywords: Time course study

overall_design: To identify genes of small bowels affected in the progression of intra-abdominal adhesion, the mice were divided into 5 groups (sham control, and 1, 3, 7, and 14 after surgical intervention), and the cDNA microarray was used to simultaneously assess the expression profiles of 6,144 mouse genes in abraded small bowels of mice. Microarrays were performed in duplicate using cDNA probes derived from different cohorts.

first: Sher

last: Singh

first: Huei-Wen

last: Chen

first: Hsuan-Yu

first: Pan-Chyr

last: Yang

first: Han-Shiang

first: Shyr-Chyr


title: Dye Bias Array Set

city: Rockville

middle: K

last: Dobbin

address: 6130 Executive Blvd EPN 8124

institute: National Cancer Institute

summary:
Spot intensity serves as a proxy for gene expression in dual-label microarray experiments. Dye bias is defined as an intensity difference between samples labeled with different dyes attributable to the dyes instead of the gene expression in the samples. Dye bias that is not removed by array normalization can introduce bias into comparisons between samples of interest. But if the bias is consistent across the samples for the same gene, it can be corrected by proper experimental design and analysis. If the dye bias is not consistent across samples for the same gene, but is different for different samples, then removing the bias becomes more problematic, perhaps indicating a technical limitation to the ability of fluorescent signals to accurately represent gene expression. Thus, it is important to characterize dye bias to determine: (1) whether it will be removed for all genes by array normalization, (2) whether it will not be removed by normalization but can be removed by proper experimental design and analysis and (3) whether dye bias correction is more problematic than either of these and is not easily removable.
Keywords: dye swap design

overall_design: For two dual-label experiments, one with cDNA arrays and the other with printed oligonucleotide arrays, Stratagene universal human reference RNA was used as a standard for testing with RNA from cell lines MCF10a, LNCAP, L428, SUDHL, OCILY3 and Jurkat. All arrays were dye-swapped at least twice. There were a total of 28 cDNA arrays and 30 oligonucleotide arrays.


title: Genome-wide occupancy profile of mediator and the srb8-11 module reveals interactions with coding regions.

status: Public on Mar 01 2006

city: Gothenburg

first: Claes

middle: M

last: Gustafsson

address: Medcinaregatan 9A

department: Department of Medical biochemistry and cell biology

institute: Gothenburg University

summary:
Genome wide interaction of mediator
Keywords: Genome wide interaction of mediator

overall_design: The Mediator complex is involved in preinitiation complex formation and required for the regulated expression of many genes. Mediator exists in two distinct forms, a free form, which contains the Med12, Med13, CDK8, and CycC subunits (Srb8-11), and a smaller form, which lacks these four subunits and associates with RNA polymerase II to form a holoenzyme. Here we use chromatin immuno-precipitation and DNA microarrays to investigate the genome wide localization of Mediator and the Srb8-11 module in fission yeast. Mediator and the Srb8-11 module display very similar genome-wide binding patterns and the Srb8-11 module remains present also at highly transcribed genes.  The occupancy profile of Mediator and the Srb8-11 module is distinct from both Pol II and general transcription factors. Unexpectedly, Mediator binds not only to promoters and upstream activating sequences, but also to the downstream coding regions of many genes. Codon region binding does not correlate significantly with transcription activity, but increased Mediator occupancy can be observed after induction of some highly transcribed genes.

first: Xuefeng

last: Zhu

first: Marana

last: Wiren

first: Indranil

last: Sinha

first: Tomas

last: Linder

first: Karl

last: Ekwall

first: Nina

last: Rasmussen

first: Steen

last: Holmberg


title: Resveratrol-induced gene expression profiles in human prostate cancer cells

status: Public on Mar 08 2006

city: Stanford

last: Stanford Microarray Database

address: 300 Pasteur Drive

department: Stanford University, School of Medicine

institute: Stanford Microarray Database (SMD)

summary:
Abstract: OBJECTIVE: The transhydroxystilbene resveratrol is found at high levels in red wine and grapes, and red wine consumption may be inversely associated with prostate cancer risk. To gain insights into the possible mechanisms of action of resveratrol in human prostate cancer, we did DNA microarray analysis of the temporal transcriptional program induced by treatment of the human prostate cancer cell line LNCaP with resveratrol.
METHODS: Spotted DNA microarrays containing over 42,000 elements were used to obtain a global view of the effects of resveratrol on gene expression. Prostate-specific antigen (PSA) and androgen receptor (AR) expression were determined by Northern blot and immunoblot analyses. Cell proliferation was determined by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay and cell cycle analysis by flow cytometry. RESULTS: We observed time-dependent expression changes in >1,600 transcripts as early as 6 hours after treatment with resveratrol. Most striking was the modulation of a number of important genes in the androgen pathway including PSA and AR. Resveratrol also down-regulated expression of cell cycle and proliferation-specific genes involved in all phases of the cell cycle, induced negative regulators of proliferation, caused accumulation of cells at the sub-G1 and S phases of the cell cycle, and inhibited cell proliferation in a time- and dose-dependent manner.
CONCLUSION: Resveratrol produces gene expression changes in the androgen axis and cell cycle regulators that may underlie its putative anticancer activities in prostate cancer.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Androgen arrays for Resveratrol-Induced Gene Expression Profiles in Human Prostate Cancer

status: Public on Feb 25 2006

summary:
Arrays for Expression levels of androgen-responsive genes in LNCaP cells exposed to dihydrotestosterone, R1881. Gene-expression changes in LNCaP treated with 1 nmol/L R1881 at 7, 9, 18, 24, 50, and 72 hours; 10 nmol/L dihydrotestosterone at 18 and 50 hours; 100 nmol/L dihydrotestosterone and 1 5mol/L dihydrotestosterone at 24 hours; and androgen deprivation at 46 and 70 hours.
This set corresponds to Figure 2 of the publication.
An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract.
Keywords: all_pairs

overall_design: Computed

first: Samuel

last: DePrimo