title: Individual-specific variation of gene expression in peripheral blood leukocytes

status: Public on Dec 31 2003

first: Mao

last: Mao

summary:
DNA microarray technology is used to determine gene expression profiles of various cell types, especially abnormal cells, such as cancer. By contrast, relatively little attention has been given to expression profiling of normal tissues. Here we describe studies of gene expression in peripheral blood leukocytes (PBL) from normal individuals sampled multiple times over periods ranging from several weeks up to 6 months. We demonstrate stable patterns of gene expression that differ between individuals. Among the genes whose expression varies by individual is a group of genes responsive to interferon stimulation. Certain individuals ( approximately 10-20% of those tested) showed higher baseline levels and lower inducibility of these genes in response to in vitro interferon stimulation. These studies demonstrate the feasibility of using DNA microarrays to measure the variations in gene expression of PBL from different individuals in response to environmental and genetic factors.
Keywords: other

first: Jerald

last: Radich

first: Sergey

last: Stepaniants

first: Matt

last: Biery

first: Terry

last: Ward

first: Greg

last: Schimmack

first: Sumire

last: Kobayashi

first: Michael

last: Carleton

first: John

last: Castle

first: Johanna

last: Lampe


title: Dynamics of global gene expression changes during mouse preimplantation development

status: Public on Jan 09 2004

city: Baltimore

first: Minoru

last: Ko

state: MD

address: 251 Bayview Blvd, Suite 100, 10C

department: National Institute on Aging

country: USA

institute: NIH

summary:
Understanding preimplantation development is important both for basic reproductive biology and for practical applications including regenerative medicine and livestock breeding. Global expression profiles revealed and characterized the distinctive patterns of maternal RNA degradation and zygotic gene activation, including two major transient waves of de novo transcription. The first wave corresponds to zygotic genome activation (ZGA); the second wave, named mid-preimplantation gene activation (MGA), precedes the dynamic morphological and functional changes from the morula to blastocyst stage. Further expression profiling of embryos treated with inhibitors of transcription, translation, and DNA replication revealed that the translation of maternal RNAs is required for the initiation of ZGA. We propose a cascade of gene activation from maternal RNA/protein sets to ZGA gene sets and thence to MGA gene sets. The large number of genes identified as involved in each phase is a first step toward analysis of the complex gene regulatory networks.
Keywords: other

first: Toshio

last: Hamatani

first: Mark

middle: G

last: Carter

first: Alexei

middle: A

last: Sharov

middle: S


title: Drosophila melanogaster strain comparison

status: Public on Dec 02 2003

city: Bethesda

first: Brian

last: Oliver

address: 50 South Drive

department: LBG

institute: NIDDK, NIH

summary:
Comparison of gene expression in wild type, Oregon[R], Antennapedia[73b], Apterous[56f] Drosophila melanogaster strains.
Keywords: other

first: Rick

last: Johnston

first: Rachel

last: Nutall

last: Doctolero

first: Pamela

last: Edwards

first: Jining

last: Lü

first: Bruce

last: Wang

first: Marina

last: Vainer

first: Huibin

last: Yue

first: Xinhao

first: James

last: Minor

first: Alex

last: Lash

first: Cathy

last: Chan

first: Thomas

last: Goralski

last: Parisi

first: Scott

last: Scott


title: Thyroid RDC8 versus C57Bl6

status: Public on Nov 25 2003

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary:
Mutations of the thyrotropin receptor leading to constitutive activation of the cAMP cascade are responsible for the development of hot nodules, if arising in a somatic cell, and non-auto-immune hyperthyroidism, when occurring in a germinal cell. An animal model of constitutive activation of the thyroid cAMP cascade has been obtained by generating transgenic mice expressing the adenosine receptor (Tg-A2aR) under the control of the thyroglobulin promoter. These mice develop huge goiters and die prematurely due to hyperthyroidism induced cardiac failure. To identify new genes involved in the tumorigenic pathway of the thyroid, we designed a protocol using microarray technology to study the differential expression, between normal and transgenic thyroid, of +/- 13.000 genes. 360 genes or EST showed a strong modulation with background corrected values of fluorescence superior to 2 fold change. The modulated genes were classified according to their proposed gene ontology functions. Approximately half of them were upregulated. The function of the majority of these genes in thyroid physiology is still to be determined. Some of them, like IGF-I, IGF-BP3, IGF-BP5, may play an important role in the development of thyroid nodules through paracrine mechanisms.
Keywords = Thyroid
Keywords = Adenosine Receptor 2a
Keywords: parallel sample

first: Jean-Christophe

last: Goffard

first: Ling

last: Jin

first: Hortensia

last: Mirescu

first: Paul

last: Van Hummelen

first: Catherine

last: Ledent

first: Jaques Emile

last: Dumont

first: Bernard

last: Corvilain


title: Thyroid C57Bl6 versus RDC8 (Color Flip)


title: diabetic nephropathy streptozotocin db db

status: Public on Jan 20 2004

city: Bronx

first: Weijia

last: Zhang

state: NY

address: 1300 Morris Park Ave

department: Medicine

institute: Albert Einstein College of Medicine

summary:
diabetes, mouse models, diabetic nephropathy, streptozotocin db/db
Keywords: other

first: Katalin

last: Susztak

first: Erwin

first: Akiva

last: Novetsky

first: Dan

last: Liang

first: Yanqing

last: Zhu

first: Emilio

last: Ciccone

first: Dona

last: Wu

first: Stephen

last: Dunn

first: Peter

last: McCue

first: Kumar

last: Sharma


title: Gene Expression Profile in thyroid of Transgenic Mice over-expressing the Adenosine Receptor 2a

first: Rekin's

last: Janky

summary:
Mutations of the thyrotropin receptor leading to constitutive activation of the cAMP cascade are responsible for the development of hot nodules, if arising in a somatic cell, and non-auto-immune hyperthyroidism, when occurring in a germinal cell. An animal model of constitutive activation of the thyroid cAMP cascade has been obtained by generating transgenic mice expressing the adenosine receptor (Tg-A2aR) under the control of the thyroglobulin promoter. These mice develop huge goiters and die prematurely due to hyperthyroidism induced cardiac failure. To identify new genes involved in the tumorigenic pathway of the thyroid, we designed a protocol using microarray technology to study the differential expression, between normal and transgenic thyroid, of +/- 13.000 genes. 360 genes or EST showed a strong modulation with background corrected values of fluorescence superior to 2 fold change. The modulated genes were classified according to their proposed gene ontology functions. Approximately half of them were upregulated. The function of the majority of these genes in thyroid physiology is still to be determined. Some of them, like IGF-I, IGF-BP3, IGF-BP5, may play an important role in the development of thyroid nodules through paracrine mechanisms. This study demonstrates the feasibility of sequentially after the cascade of events leading to the formation of benign tumors such as hot thyroid nodule or hyperfunctional goitre.
Keywords: other

first: Jean-Christophe

last: Goffard

first: Ling


title: Malaria resistance

status: Public on Oct 06 2003

city: Montreal

first: Gundula

last: Min-Oo

state: Quebec

department: Biochemistry

country: Canada

institute: McGill University

summary:
Examination of molecular basis of malaria resistance.  Spleens from malaria resistant AcB55 and AcB61strains compared with A/J mice.

Animals were sacrificed and spleens were rapidly frozen in liquid nitrogen, and subsequently stored at 80oC. Tissues were mechanically homogenized with a polytron and total cellular RNA was extracted using a commercially available reagent (TMTRIzol; Invitrogen). The poly-(A)+ fraction of the RNA was isolated by chromatography with oligo d(T) cellulose beads. For cDNA labeling, either 25 mg of total RNA or 2.5 mg of poly-(A) RNA was converted into cDNA using reverse transcriptase (RT; Super Script II, Invitrogen) and alternatively Cy5 or Cy3-labeled dCTP (1mM, Perkin Elmer-Cetus/NEN, Boston) in a reaction mixture containing 1.5 mL oligo (dT) (100pmol/ mL), 3 mL dNTP-dCTP (6.67mM each), 1 mL dCTP (2mM), 4 mL DTT (100mM), 8 mL 5 X RT Buffer (Invitrogen, California). The reactions were carried out at 42¼C for 3 hrs, after which the RNA was degraded by the addition of 0.5 mL RNase A (1 mg/mL) and 1.5 mL RNaseH 5 units/mL). Labeled cDNA was separated from unincorporated nucleotides (Qiagen column) and further concentrated by evaporation under vacuum.
The arrays were pre-hybridized for 1-2hrs with DIGEasy hybridization buffer (Roche) containing 10ug/ml denatured salmon sperm DNA, and 10ug/ml yeast tRNA. The Cy5 and Cy3 labelled cDNAs were combined and hybridized in the same medium and incubated with the arrays for 16-18hrs at 37Co. Finally, the arrays were washed 3 x 10 mins in 0.1 x SSC (20 X SSC is 3M sodium chloride, 0.3 M sodium citrate, pH 7.0), 0.1%SDS at 50Co, and 4 x 3min in 0.1 x SSC at room temperature, and dried by centrifugation.
Fluorescent array images were collected for both Cy3 and Cy5 with a ScanArray fluorescent scanner and image intensity data were extracted and analyzed with QuantArray 3.0 analysis software. Quantification data was imported in GeneSpring (Silicon Genetics). The import format was modified to maintain information relevant to user-contributed flagging as well as QC parameter furnished by the array manufacturer. Dye swap and Intensity-based normalization (Lowess) were performed using the default settings.
Keywords: other

first: Anny

last: Fortin

first: Mi-Fong

last: Tang

first: Andre

last: Nantel

first: Mary

middle: M

last: Stevenson

first: Philippe

last: Gros


title: fhCMV-H vs fhCMV-T

status: Public on Sep 09 2003

city: Seattle

first: Lynn

last: Graf

state: WA

address: 1100 Fairview Ave. N. D1-100

department: Clinical Research Division

institute: Fred Hutchinson Cancer Research Center

summary:
Cytomegalovirus (CMV) strains with different in vivo and in vitro characteristics may induce different patterns of cellular gene expression. CMV strain fhCMV-H, which spreads rapidly through cell culture, was isolated from a hematopoetic stem cell transplant patient who died of CMV-mediated marrow failure. In contrast  fhCMV-T was isolated from a patient who survived CMV complications and does not spread rapidly in vitro. Fibroblasts were infected with both strains, which had been engineered to express GFP upon cellular infection, and the cellular gene expression profile was compared to that of noninfected controls at 24h.  The gene expression profile of HFF exposed to UV-inactivated virus from the 2 strains was also tested, to differentiate the effects of the initial engagement with virus coat proteins such as glycoprotein B and gene modulation by active virus.
Keywords = cytomegalovirus, glycoprotein B
Keywords: repeat sample

first: Julie

last: Randolph-Habecker

first: Beverly

last: Torok-Storb


status: Public on May 21 2004

city: Portland

first: Yuan

last: Fang

state: OR

address: 3375 SW Terwilliger Blvd

department: Ophthalmology, Casey Eye Institute

institute: Oregon Health & Science University

summary:
Examine the effect of stimulation stress produced by chemical burn to the mice cornea in the lacrimal gland over a time course (0.5 - 360 hours) in comparison with the non-stimulated control animals.
Using silver nitrate applicator (silver nitrate 37.5 mg and potassium nitrate 12.5 mg,  Graham-Field,Inc.,) do two burns per eye, each with a separate applicator.
For animals observed for more than 24 hours, eyes were then treated with gentamicin ointment to minimize infection.
Total RNA were extracted from both burn and control eyes and were covalently coupled separately with Cy5 and Cy3 monoreactive fluors. The Cy5 and Cy3 labelled RNA were hybridized to the microarray.
Fluorescent array images were collected for both Cy3 and Cy5 with ScanArray 4000XL and image intensity data were extracted and analyzed with Imagene analysis software.
Ref:Fang Y, Choi D, Searles RP, Mathers WD.A time course microarray study of gene expression in the mouse lacrimal gland after acute corneal trauma.Invest Ophthalmol Vis Sci. 2005 Feb;46(2):461-9.
Keywords = Corneal injury
Keywords = mouse
Keywords = lacrimal gland
Keywords = gene microarrays
Keywords: time-course

first: Dongseok

last: Choi

first: Robert

middle: P

last: Searles

first: William

middle: D

last: Mathers


title: stroma+monocytes

status: Public on Dec 22 2003

summary:
Gene expression of adherent cells in a coculture of the human bone marrow stromal cell line HS-27a and peripheral blood monocytes (CD14+ cells) was compared to HS-27a cultured alone. Microarray  experiments were conducted using CD14+ cells from 7 healthy donors over a period of >7 months. Monocytes were isolated by ficoll separation of whole blood, followed by labelling cells with CD14 monoclonal antibody Tuek4 and magnetic bead selection (Milteny rat anti mouse IgG2a+2b beads) on an AutoMacs.
HS27a cells were plated in T75 flasks at approximately 80% confluence. The next day 1.5x10E6 freshly isloated human CD14+ cells were added to the culture. At 3 days the cultures were washed 3x with Hank’s buffer to remove nonadherent monocytes. Co-cultures and HS27a cultured alone were harvested by brief trypsinization followed by pelleting of the cells. All RNA isolation was accomplished with Qiagen RNeasy Mini Kit reagents. The RNA (25 ug) was annealed with 5 ug oligo dT12-18, and reverse-transcribed into cDNA with Superscript II reverse transcriptase for 2h at 42ºC in the presence of 0.5mM dGTP, 0.5mM dCTP, 0.5mM dATP, 0.3mM dTTP, 0.2mM amino-allyl dUTP.  After hydrolysis of RNA in 0.2M NaOH, Tris was removed from the reaction with a Microcon-30 concentrator. The cDNA from HS27a and HS27a-monocyte cocultures was covalently coupled separately with Cy5 and Cy3 monoreactive fluors, respectively, in 50mM sodium bicarbonate, pH 9.0, followed by quenching with 2.7M hydroxylamine. The Cy5 and Cy3 labelled cDNAs were combined and purified with a QIAquick PCR purification kit and suspended in 36 ul of 3X SSC and 0.8 mg/ml of poly-A for hybridization to the microarray.
Fluorescent array images were collected for both Cy3 and Cy5 with a GenePix 4000A fluorescent scanner and image intensity data were extracted and analyzed with GenePix Pro 3.0 analysis software. After background correction and removal of flagged values, log base 2 expression ratios were mean centered and linear transformed to obtain the log and linear values given in the data tables.
Keywords: repeat sample

first: Norihiro

last: Awaya

first: Mineo

last: Iwata


title: Profiling of human bone marrow stromal cell lines HS-5 and HS-27a

status: Public on Jul 16 2003

department: Clinical Research

institute: Fred Hutchinson Cancer Research Institute

summary:
The microarrays were constructed using a set of more than 17,000 sequence-verified clones from Research Genetics (Huntsville, AL). Of the 17,761 features (spots) on the microarray, 186 are control nonexpressed or nonhuman sequences or housekeeping genes. UniGene cluster IDs could be assigned by GenBank to 16,592 of the features as of June 1, 2001 (UniGene Build 133), indicating that they are representatives of nonredundant unique genes. Many have been functionally characterized, and chromosomal location and tissue expression patterns are known for others. Total RNA was isolated from semiconfluent cultures and reverse-transcribed into cDNA in a nucleotide mix containing amino-allyl deoxyuracil triphosphate (dUTP). The cDNA from stromal cells and Universal RNA (Stratagene, La Jolla, CA) was covalently coupled separately with Cy5 and Cy3 monoreactive fluors, respectively. The Universal RNA consists of a mixture of RNA from 10 different human cell lines with a broad expression coverage of over 80% of the sequences on the array, allowing comparison of expression patterns of multiple different samples of different origin. The Cy5- and Cy3-labeled cDNAs were combined for hybridization to the microarray. Fluorescent array images were collected for both Cy3 and Cy5, and image-intensity data were extracted and analyzed to obtain expression ratios to Universal RNA for each stromal cell line. From these the expression in the 2 lines could be compared.
Keywords: other

first: L

first: M

first: B


title: CX43 KO vs WT cortical astrocytes

status: Public on Aug 06 2003

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:
RNA samples extracted from astrocytes cultured from wild type and Cx43 null neonatal mice were dye labeled and individually co-hybridized with a reference of labeled cDNAs pooled from a variety of tissues on eight gene arrays containing 8975 mouse DNA sequences
Keywords: dose response

first: Marcia

last: Urban-Maldonado

first: Sanda

first: Eliana

last: Scemes

first: David

middle: C

last: Spray


title: Sex-biased gene expression

status: Public on Jun 02 2003

first: Brian

last: Oliver

summary:
Investigatation into how genes with sex-differential expression profiles are distributed among the chromosomes in Drosophila. Assayed the expression of 14,142 predicted transcripts in competitive hybridizations and found a dramatic underrepresentation of X-chromosome genes showing high relative expression in male.  This is the first report of sex-biased expression of the full (predicted) genome. Findings indicate that there is significant sex-biased expression, especially in gonads. Genes showing sex-biased gene expression profiles are likely to have sex-biased functions.
Keywords: other

last: Parisi

first: R

last: Nuttall

first: D

last: Naiman

first: G

last: Bouffard

first: J

last: Malley

last: Andrews

first: S

last: Eastman


title: Cytomegalovirus infection

first: Lynn

last: Graf

summary:
Comparison of gene expression profiles of human foreskin fibroblasts (HFF) infected with 3 clinical isolates of cytomegalovirus strains representing three glycoprotein B genotypes.
Keywords: other

first: Julie

last: Randolph-Habecker

first: Beverly

last: Torok-Storb


title: Lungs from bleomycin-treated 129svJ mice

status: Public on Jun 11 2003

city: San Francisco

first: Dean

last: Sheppard

state: CA

address: UCSF Box 0854

institute: UCSF

summary:
Profile of gene expression of lungs from bleomycin-treated C129svJ mice.
Keywords: parallel sample


title: Lungs from bleomycin-treated A/J mice

summary:
Profile of gene expression of lungs from bleomycin-treated A/J mice.
Keywords: parallel sample


title: Intraspecific variation in gene expression

status: Public on Jul 19 2003

city: Cambridge

first: Colin

last: Meiklejohn

state: MA

address: 16 Divinity Ave

department: Organismic and Evolutionary Biology

institute: Harvard University

summary:
A number of genes associated with sexual traits and reproduction evolve at the sequence level faster than the majority of genes coding for non-sex-related traits. Whole genome analyses allow this observation to be extended beyond the limited set of genes that have been studied thus far. We use cDNA microarrays to demonstrate that this pattern holds in Drosophila for the phenotype of gene expression as well, but in one sex only. Genes that are male-biased in their expression show more variation in relative expression levels between conspecific populations and two closely related species than do female-biased genes or genes with sexually monomorphic expression patterns. Additionally, elevated ratios of interspecific expression divergence to intraspecific expression variation among male-biased genes suggest that differences in rates of evolution may be due in part to natural selection. This finding has implications for our understanding of the importance of sexual dimorphism for speciation and rates of phenotypic evolution.
Keywords: other

first: John

last: Parsch

first: José

last: Ranz

first: Daniel

middle: L

last: Hartl


title: Macrophages infected with Salmonella

city: Stanford

last: Stanford Microarray Database

address: 300 Pasteur Drive

department: Stanford University, School of Medicine

institute: Stanford Microarray Database (SMD)

summary:
Identification of host pathways affected by the Salmonella virulence transcription factor phoP
Keywords: other


title: Lungs from ovalbumen sensitized and challenged A/J mice

summary:
Profile of gene expression in lungs of ovalbumen sensitized and challenged A/J mice.
Keywords: parallel sample


title: Lungs from ovalbumen sensitized and challenged C57 mice

status: Public on Jun 10 2003

summary:
Profile of gene expression of lungs from ovalbumen sensitized and challenged C57 mice.
Keywords: parallel sample


title: Lungs from ovalbumen sensitized and challenged C3H mice

summary:
Profile of gene expression in lungs of ovalbumen sensitized and challenged C3H mice.
Keywords = C3H, lung, ovalbumen, mouse, Mus musculus, mice
Keywords: parallel sample


title: Interferon induction by shRNA

status: Public on Feb 21 2003

city: Bordeaux

first: Richard

last: Iggo

address: 229 cours de l'Argonne

department: Bergonie Cancer Institute

country: France

institute: University of Bordeaux

summary:
Embryonic lung fibroblasts (HLF) infected with either control lentivirus (GSM3892), or lentivirus expressing MRG15 and MRGX small hairpin RNAs from the H1 polIII promoter (GSM3891). The MRG15 shRNA induces an interferon response that is unrelated to silencing of MRG15.
Keywords: other

first: A

middle: J

last: Bridge

last: Pebernard

last: Ducraux

last: Nicoulaz


status: Public on Jul 01 2003

first: Xin

last: Chen

institute: Stanford University

summary:
The data set contains 67 array (lymphochip cDNA array), published in N Engl J Med 2003 Jul 10;349(2):125-38. PMID: 12853585. TITLE: Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. BACKGROUND: The causes and clinical course of acute rejection vary, and it is not possible to predict graft outcome reliably on the basis of available clinical, pathological, and genetic markers. We hypothesized that previously unrecognized molecular heterogeneity might underlie some of the variability in the clinical course of acute renal allograft rejection and in its response to treatment.  METHODS: We used DNA microarrays in a systematic study of gene-expression patterns in biopsy samples from normal and dysfunctional renal allografts. A combination of exploratory and supervised bioinformatic methods was used to analyze these profiles.  : We found consistent differences among the gene-expression patterns associated with acute rejection, nephrotoxic effects of drugs, chronic allograft nephropathy, and normal kidneys. The gene-expression patterns associated with acute rejection suggested at least three possible distinct subtypes of acute rejection that, although indistinguishable by light microscopy, were marked by differences in immune activation and cellular proliferation. Since the gene-expression patterns pointed to substantial variation in the composition of immune infiltrates, we used immunohistochemical staining to define these subtypes further. This analysis revealed a striking association between dense CD20+ B-cell infiltrates and both clinical glucocorticoid resistance (P=0.01) and graft loss (P<0.001).  CONCLUSIONS: Systematic analysis of gene-expression patterns provides a window on the biology and pathogenesis of renal allograft rejection. Biopsy samples from patients with acute rejection that are indistinguishable on conventional histologic analysis reveal extensive differences in gene expression, which are associated with differences in immunologic and cellular features and clinical course. The presence of dense clusters of B cells in a biopsy sample was strongly associated with severe graft rejection, suggesting a pivotal role of infiltrating B cells in acute rejection.
A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied.
Disease State: normal vs disease
Keywords: disease_state_design

overall_design: Using regression correlation

first: Minnie

last: Sarwal


title: Effect of RNA concentration in cross-species hybridization

status: Public on May 27 2003

city: Rockville

first: Jo Ann

middle: S.

last: Rinaudo

address: 13 Taft Court, Suite 101

department: Microbiology

institute: Georgetown University

summary:
Total RNA from adult woodchuck liver was analyzed on human membrane arrays.  The effect of RNA concentration on signal intensity was determined by using a series of RNA concentrations (0.1 to 10ug)
Keywords: other


title: Diauxic shift

status: Public on Feb 12 2002

summary:
Exploring the metabolic and genetic control of gene expression on a genomic scale in yeast.
This study is described in more detail in DeRisi JL et al. 1997. Science 278:680-6
Keywords: time-course

last: DeRisi

first: V

middle: R

last: Iyer

first: P

middle: O

last: Brown


title: Woodchuck and human liver comparison

summary:
Total RNA from adult human and woodchuck liver was analyzed on human membrane arrays. Two human and two woodchuck liver samples were analyzed in duplicate. The samples were numbered H1a, H1b, H2a, H2b, WC1a, WC1b, WC2a, and WC2b. H, represents human liver; WC represents woodchuck liver. The numbers 1 and 2 were the two individual samples. The a and b represent replicates of the same RNA sample.
Keywords = liver, adult, normal, human, woodchuck
Keywords: other

sample_organism:
Homo sapiens
Marmota monax

first: J


title: Clontech RNA samples

status: Public on May 14 2002

city: La Jolla

last: Rouse

address: 9500 Gilman Drive

institute: UCSD

summary:
A series of experiments used to compare Clontech spleen plyA, Clontech liver plyA and Clontech universal RNA for microarrays on our available human array printed on Amersham type 7 * slides.
Keywords = human, clontech, automated slide processor, spleen, liver, universal RNA
Keywords: other

first: Gary

last: Hardiman

first: Katrine

last: Verdun


title: Copper regulon in S. cerevisiae

summary:
In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mac1. Ace1 mediates Cu-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions. DNA microarray hybridization experiments revealed a limited set of yeast genes differentially expressed under growth conditions of excess copper or copper deficiency. Mac1 activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1, FRE7, YJL217w and YFR055w. Two of the last three newly identified Mac1 target genes have no known function, the third, YFR055w, is homologous to cystathionine gamma-lyase encoded by CYS3. Several genes that are differentially expressed in cells containing a constitutively active Mac1, designated Mac1up1, are not direct targets of Mac1. Induction or repression of these genes is likely a secondary effect of cells due to constitutive Mac1 activity. Elevated copper levels induced the expression of the metallothioneins CUP1 and CRS5, and two genes, FET3 and FTR1, in the iron uptake system. Cu-induced FET3 and FTR1 expression arises from an indirect Cu effect on cellular Fe pools.
This study is described in more detail in Gross C et al.(2000) J Biol Chem 275:32310-6
Keywords: other

first: C

last: Gross

first: M

last: Kelleher

first: D

last: Winge


title: Cyclin overexpression

last: Stanford Microarray Database

summary:
Yeast cells were arrested either in G1 (for CLN3 overexpression) or in G2/M (for CLB2 overexpression). The cyclin was then induced, and samples were taken.
This study is described in more detail in Spellman PT et al.(1998) Mol Biol Cell 9:3273-97
Keywords: other

middle: T

last: Spellman

first: G

last: Sherlock

middle: Q

last: Zhang

first: K

last: Anders

middle: B

last: Eisen

last: Botstein

first: B

last: Futcher


title: Sporulation in yeast

summary:
Diploid cells of budding yeast produce haploid cells through the developmental program of sporulation, which consists of meiosis and spore morphogenesis. DNA microarrays containing nearly every yeast gene were used to assay changes in gene expression during sporulation. At least seven distinct temporal patterns of induction were observed. The transcription factor Ndt80 appeared to be important for induction of a large group of genes at the end of meiotic prophase. Consensus sequences known or proposed to be responsible for temporal regulation could be identified solely from analysis of sequences of coordinately expressed genes. The temporal expression pattern provided clues to potential functions of hundreds of previously uncharacterized genes, some of which have vertebrate homologs that may function during gametogenesis.
This study is described in more detail in Chu S, et al. 1998. Science 282:699-705
Keywords: time-course

first: S

last: Chu

last: DeRisi

last: Mulholland

first: I

last: Herskowitz


title: cdc15 block-release

summary:
Yeast cells were blocked in telophase using a cdc15-2 temperature senstive mutant at restrictive temperature. The culture was then shifted to permissive temperature (25oC), and released into the cell cycle. Samples were then taken during the course of almost three full cell cycles.
This study is described in more detail in Spellman PT et al.(1998) Mol Biol Cell 9:3273-97
Keywords: time-course

last: Iyer

last: Brown


title: Elutriation time course

summary:
Small G1 daughter yeast cells were isolated by centrifugal elutriation. They were then released into YEP ethanol, and followed through one cell cycle, with samples being taken every 30 minutes.
This study is described in more detail in Spellman PT et al.(1998) Mol Biol Cell 9:3273-97
Keywords: time-course


title: Alpha-factor block-release

summary:
These data are from a time series, where yeast were arrested in alpha-factor, then the alpha-factor was washed out, and the cells were release into fresh medium. Samples were taken every 7 minutes as the cells went through the cell cycle.
This study is described in more detail in Spellman PT et al.(1998) Mol Biol Cell 9:3273-97
Keywords: time-course


title: Manipulation in phospate levels

summary:
The arrays were used to study the effects of modifying phosphate levels in yeast, either through mutation, or chemical manipulation.
This study is described in more detail in Ogawa N et al.(2000) Mol Biol Cell 11:4309-21
Keywords: other

first: N

last: Ogawa


title: snf/swi mutants of S. cerevisiae.

summary:
The Saccharomyces cerevisiae Snf/Swi complex has been previously demonstrated to control transcription and chromatin structure of particular genes in vivo and to remodel nucleosomes in vitro. We have performed whole-genome expression analysis, using DNA microarrays, to study mutants deleted for a gene encoding one conserved (Snf2) or one unconserved (Swi1) Snf/Swi component. This analysis was performed on cells grown in both rich and minimal media. The microarray results, combined with Northern blot, computational, and genetic analyses, show that snf2Delta and swi1Delta mutations cause similar effects on mRNA levels, that Snf/Swi controls some genes differently in rich and minimal media, and that Snf/Swi control is exerted at the level of individual genes rather than over larger chromosomal domains. In addition, this work shows that Snf/Swi controls mRNA levels of MATalpha-specific genes, likely via controlling transcription of the regulators MATalpha1 and MCM1. Finally, we provide evidence that Snf/Swi acts both as an activator and as a repressor of transcription, and that neither mode of control is an indirect effect of the other.
This study is described in more detail in Sudarsanam P et al.(2000) Proc Natl Acad Sci U S A 97:3364-9
Keywords: other

last: Sudarsanam

first: F

last: Winston


title: Yeast Stress Response

last: Stanford Microarray Database

summary:
We explored genomic expression patterns in the yeast Saccharomyces cerevisiae responding to diverse environmental transitions. DNA microarrays were used to measure changes in transcript levels over time for almost every yeast gene, as cells responded to temperature shocks, hydrogen peroxide, the superoxide-generating drug menadione, the sulfhydryl-oxidizing agent diamide, the disulfide-reducing agent dithiothreitol, hyper- and hypo-osmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. A large set of genes (approximately 900) showed a similar drastic response to almost all of these environmental changes. Additional features of the genomic responses were specialized for specific conditions. Promoter analysis and subsequent characterization of the responses of mutant strains implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators.  Physiological themes in the genomic responses to specific environmental stresses provided insights into the effects of those stresses on the cell.
Study is described in more detail in Gasch AP et al.(2000) Mol Biol Cell 11:4241-57
Keywords: other

first: A

last: Gasch

last: Kao

first: O

last: Carmel-Harel

last: Storz


title: SBF-MBF genomic distribution

summary:
The first 18 experiments are ordered according to the legend in Figure 3 of the published paper. Experiment 19 is the gene expression profile of the swi4 deletion strain compared to the wild-type strain.
This study is described in more detail in Iyer VR, et al.(2001) Nature 409:533-38
Keywords: other

first: V

middle: E

last: Horak

last: Scafe

last: Snyder


title: Non-genotoxic Hepatocarcinogens

status: Public on Jun 23 2007

city: Mountain View

first: Jeremy

last: Gollub

address: 325 E. Middlefield Rd.

institute: Iconix Biosciences

summary:
There is no accurate and well-validated short-term test for non-genotoxic carcinogens, necessitating an expensive two year rodent bioassay before a risk assessment can begin. We have developed a short-term in vivo rat assay that predicts whether non-genotoxic chemicals are likely to induce hepatic tumors based on transcript profiles in the liver. Using a large independent test set, assay accuracy was found to be superior to existing pathological and genomic markers. Comparison of the test chemical's signature profile to reference carcinogens of known mechanism can also identify a potential mode(s) of action, allowing an early assessment of human cancer risk.

Guidelines for commercial use:
http://www.iconixbiosciences.com/guidelineCommUse.pdf
Keywords: dose response, time course, compound treatment

overall_design: Treatment of male Sprague-Dawley rats with 147 non-genotoxic compounds at various doses and durations, in biological triplicate, along with vehicle-matched control animals.  Liver samples were assayed for gene expression.  Hepatocarcinogenic and non-carcinogenic compounds were included.  A classifier for carcinogenicity was built on a training set of 25 carcinogens and 75 noncarcinogens (randomly selected compounds, maximum tolerated dose, 5 day timepoints), and tested on the remaining 47 compounds at various timepoints.  A total of 990 samples were hybridized to single-channel CodeLink RU1 arrays.  Biological triplicates were combined with matched control samples to calculate log ratios.

first: Mark

last: Fielden

first: Richard

last: Brennan