title: tRNA gene identity acts as a determinant of gene positioning

status: Public on Jun 14 2012

city: Auckland

first: Justin

middle: M.

last: O'Sullivan

address: 85 Park Road, Grafton

department: Liggins Institute

country: New Zealand

institute: University of Auckland

summary: Here we report that the spatial organization of yeast tRNA genes depends upon both locus position and tRNA identity; supporting the idea that the genomic organization of tRNA loci utilizes tRNA dependent signals within the nucleoprotein-tRNA complexes that form into clusters. We use high-throughput sequencing coupled to Circular Chromosome Conformation Capture to detect interactions with two wild type tRNAs and these same positions replaced with suppressor tRNAs (SUP4-1).

overall_design:
Detect DNA-DNA interactions (Circular chromosome conformation capture; 4C) with two wild type tRNAs and these same positions replaced with suppressor tRNAs (SUP4-1)

Supplementary files:
Alignment files generated by Topography v1.19 software.

first: J

first: D

last: Engelke

last: Pai

first: C

last: Rodley


title: A Key Role for Chd1 in Histone H3 Dynamics at the 3' Ends of Long Genes in Yeast (gene expression)

status: Public on Jun 08 2012

city: Santa Cruz

first: Grant

middle: A

last: Hartzog

state: CA

address: 349 Sinsheimer Labs

department: MCD Biology

country: USA

institute: UC Santa Cruz

summary: Chd proteins are ATP-dependent chromatin remodeling enzymes implicated in biological functions from transcriptional elongation to control of pluripotency. Here, we examine roles of Chd1 in replication- independent dynamics of histone H3 in yeast.  Using genome-wide ChIP on chip analysis, we find that Chd1 influences histone turnover at the 5’ and 3’ ends of genes, accelerating H3 replacement at the 5’ ends of genes while protecting the 3’ ends of genes from excessive H3 turnover. Although consistent with a direct role for Chd1 in exchange, these results may indicate that Chd1 stabilizes nucleosomes perturbed by transcription. Curiously, we observe a strong effect of gene length on Chd1’s effects on H3 turnover. Finally, we show that Chd1 also affects histone H3K4 and H3K36 methylation patterns over genes, likely as a consequence of its effects on histone replacement. In control experiments, we measure effects of deletion of CHD1 on RNA polymerase II distribution across the genome and on gene expression.  We also examine the effect of deleting the TOP1 gene, alone and in combination with deletion of CHD1, on histone replacement.  Taken together, our results emphasize a role for Chd1 in histone replacement in both budding yeast and Drosophila, and surprisingly show that the major effects of Chd1 on turnover occur at the 3’ ends of genes.

overall_design: This series compares gene expession in wild type to that in chd1 mutant cells.  Two biological replicates with dye swaps.

first: Marta

last: Radman-Livaja

first: Tiffani

middle: K

last: Quan

first: Lourdes

last: Valenzuela

first: Jennifer

last: Armstrong

first: Tibor

last: van Welsem

first: TaeSoo

last: Kim

first: Laura

middle: J

last: Lee

first: Stephen

last: Buratowski

first: Fred

last: van Leeuwen

first: Oliver

last: Rando


title: Inactivation of the Lactobacillus reuteri 100-23 ureC gene affects in vitro acid tolerance, and impairs ecological fitness in vivo

status: Public on Sep 30 2012

city: Oak Ridge

first: Charlotte

last: Wilson

state: Tennessee

address: 1 Bethel Valley Road

department: Biosciences Bldg 1520

institute: ORNL

summary: Lactobacillus reuteri 100-23 is an autochthonous inhabitant of the rodent gastrointestinal system that adheres to the non-secretory epithelium of the forestomach and forms biofilms. Microarray analysis of the expression profile of L. reuteri 100-23 cells harvested from the stomach of ex-Lactobacillus-free mice, compared to those of L. reuteri 100-23 in laboratory culture, revealed an in vivo upregulation of a urease gene cluster by greater than 50-fold. Genes for urease production were absent in all publically available Lactobacillus genome sequences except L. reuteri 100-23 and have recently been identified as specific to rodent strains of L. reuteri (Frese et al. 2011).  In the current study, the urease enzyme was shown to be functional. Supplementation with 2% urea allowed L. reuteri 100-23 to increase the pH of the culture medium.  A mutant strain of L. reuteri 100-23 was developed by insertional inactivation of the ureC gene, which encodes the largest subunit of the urease enzyme. The mutant strain was unable to hydrolyze urea to increase the pH of culture medium, and did not survive acid stress at pH 2.5 for 6 h, even in the presence of urea. In contrast, the wild type strain was still viable after 6 h when 2% urea supplementation was included.  When mice free of lactobacilli were inoculated with a mixture of equal numbers of wild type L. reuteri 100-23 and ureC mutant cells, the wild type constituted 99% of the resulting Lactobacillus population in the stomach, caecum and jejunum after one week (108 cells/gram of sample). This study has therefore shown the importance of a functional urease enzyme in the ecological fitness of L. reuteri 100-23.

sample_organism: Limosilactobacillus reuteri subsp. rodentium

overall_design: Analysis of the microarray data was obtained from two independent biological replicates.

middle: M

first: Diane

last: Loach

first: Paul

middle: W

last: O'Toole

first: Gerald

last: Tannock

first: Ian

last: Sims


title: Rat Pancreatic Tissue From Animals Fed Either an Iron Deficient or Iron Loaded vs. Iron Adequate Diet

status: Public on Feb 27 2013

city: Gainesville

first: Richard

last: Coffey

state: Florida

address: 517 sw12th st apt 1

department: Food Science and Human Nutrition

institute: University of Florida

summary: Microarray analysis of pancreatic tissue comparing gene expression in rats fed an iron deficient or iron loaded diet vs. iron adequate diet. Goal was to determine changes in gene expression in response to iron status.

overall_design: 2 separate two-condition experiments: iron deficient (FeD) vs. iron adequate (FeA), and iron overload (FeO) vs. iron adequate (FeA). Performed in dye-switched duplicates. Samples pooled (n=6).

first: Mitchell

last: Knutson


title: Analyzing the cytoskeletal transcriptome: sex differences in rat hypothalamus

status: Public on Jun 05 2012

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: The transcriptomes of young male and (in estrus) female hypothalami were profiled and compared to learn about the sex dichotomy of the cytoskeletal genomic fabric(CGF), defined as the most inter-coordinately and stably expressed gene web whose encoding proteins form the intracellular scaffolding.

overall_design: RNA samples collected from hypothalami of 4 young rat males and 4 (in estrus) females were hybridized with Agilent rat (4x44k 60 mer features, 4 microarrays per slide) gene expression chips. Novel analytical tools were used to reveal hidden features of the cytoskeletal transcriptome

first: Sanda

first: Genevieve

last: Neal-Perry


title: Analysis of ccRCC derived cell lines

status: Public on Nov 01 2012

city: Groningen

first: Klaas

last: Kok

department: Genetics

country: Netherlands

institute: UMCG

type: Genome variation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: High-resolution analysis of copy number changes in circulating and disseminated tumor cells in breast cancer patients

status: Public on Nov 19 2012

city: Oslo

first: Randi

last: Mathiesen

address: Montebello

department: Dept. of genetics

country: Norway

institute: Institute for cancer research Oslo University Hospital Radiumhospitalet

summary: The aim of this study was to establish a single-cell array comparative genomic hybridization (SCaCGH) method providing in-depth genomic analysis of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs). The robustness and resolution limits of the method were estimated with different cell amounts of the breast cancer cell line SKBR3 using 44k and 244k arrays. Subsequent adjustments of the method were conducted analyzing the copy number profiles of 28 CTCs in combination with four hematopoietic cell (HC) controls from eight metastatic patients and of 24 DTCs, three probable HCs, and five HC controls from seven breast cancer patients and one healthy donor. The frequency of the major genomic gains and losses of the analyzed DTC revealed similarities to primary breast tumor samples with some evident differences. Three of the patients had available profiles for DTC and the corresponding primary tumor. In 2/3 of the examined DTCs, equivalent genomic changes and common aberration breakpoints were disclosed, both to each other and to the corresponding primary tumors. Interestingly, similar copy number changes were found in DTCs taken at time of diagnosis or in DTCs collected at 3-years relapse-free follow up. Residual immunomorphological characterized tumor cells showed balanced profiles with only minor aberrations. Three cells with unclear morphological identification showed either balanced profiles (n=2) or aberrations comparable to the primary tumor and DTC (n=1). SCaCGH may be a powerful tool for molecular characterisation of immunostained and morphological identified CTCs and DTCs to explore the malignant potential, therapeutic targets and tumor heterogeneity of single tumor cells.

overall_design: 24 DTCs, 3 probable HCs, and 5 HCs from 7 early-stage breast cancer patients, 28 CTCs and 4 HCs from 8 metastatic breast cancer patients, and 1 healthy donor were analysed. Comparison with the primary tumor was done in 3 patients. The reference for the patients was DNA from multiple anonymous female donors. This submission does not include the SKBR3 data obtained from the 44k array.

first: Lars

middle: O

last: Baumbusch

first: Bjørn

last: Naume

first: Michael

middle: R

last: Speicher

first: Klaus

last: Pantel

first: Anne-Lise

last: Børresen-Dale

first: Ole

middle: C

last: Lingjærde

last: Mauermann

first: Anna

last: Obenauf

first: Ida

last: Schneider

first: Inga

middle: H

last: Rye

first: Elin

last: Borgen

first: Knut

last: Liestøl

first: Sabine

last: Riethdorf

first: Jochen

middle: B

last: Geigl

first: Eldri

middle: U

last: Due

first: Renathe

last: Fjelldal


title: Copy number variation profiling of gastric tissues: Cancer Samples vs. Matched Adjacent Noncancerous Samples

status: Public on May 23 2012

city: Shanghai

first: Cheng

last: Lei

address: 151 Li Bing Road

country: China

institute: National Engineering Center for Biochip at Shanghai

summary: Copy number variation profiling of gastric tissues comparing gastric cancer tissues with matched adjacent noncancerous tissues. Goal was to determine the effects of chromosomal imbalances on gene expression and carcinogenesis or progression.

overall_design: 27 pairs of gastric tissues: gastric cancer tissues vs. matched adjacent noncancerous tissues.

first: Lei

last: Cheng

first: Sheng

last: Yang

first: Yanqing

first: Wen

last: Zhang

first: Huasheng

last: Xiao

first: Junsong

last: Han

first: Qinghua


title: Kinetochore protein Cnn1 promotes sister chromatid bi-orientation by modulating intraKMN affinities in a biphasic, phospho-regulated manner.

status: Public on May 06 2012

city: Milan

first: Rodrigo

last: Bermejo

state: Lombardy

address: Via Adamello 16

country: Italy

institute: IFOM-IEO-Campus

type: Genome binding/occupancy profiling by genome tiling array

summary: Kinetochores are large proteinaceous structures that assemble on centromeres to align sister chromatids to the mitotic spindle and orchestrate their segregation to the daughter cells. At the core of kinetochores lies a network of proteins known  as KMN, whose microtubule-binding activity is regulated by the Ipl1/Aurora B and Mps1 kinases. Here, we have characterized a novel structural yeast kinetochore protein named Cnn1 and show that it regulates KMN-spindle activity by modulating the affinity between the KMN subcomplexes at their basis. Cnn1 supports KMN from S phase to anaphase, and is controlled by the Cdc28, Mps1 and Ipl1 kinases. Cnn1 has evolved to associate the KMN complexes into a coherent network activity to ensure efficient

overall_design: S.cerevisiae oligonucleotide microarrays were provided by Affymetrix (S.cerevisiae Tiling 1.0R, P/N 900645). ChIP-chip analyses were carried out as described (Bermejo et al., Cell, 2009).

first: Lucy

last: Bock

first: Cinzia

last: Pagliuca

first: Norihiko

last: Kobayashi

first: Ryan

last: Grove

first: Yusuke

last: Oku

first: Claudio

last: Alfieri

first: Cristina

last: Golfieri

first: Amanda

last: Oldani

first: Marianna

last: Dal Maschio

first: Tony

last: Hazbun

first: Tomoyuki

last: Tanaka

first: Peter

last: De Wulf


title: Analysis of Chromosome VIII of EC-C1 strains (S. cerevisiae)

status: Public on May 18 2012

city: Taipei

first: Jun-Yi

last: Leu

address: 128 Academia Road, Section 2, Nankang

department: Insititute of Molecular Biolody

country: Taiwan

institute: Academia Sinica

summary: The genomic DNA of rearranged chromosome VIII (~900kb) of EC9 diploid strain was extracted from the gel of pulsed field gel electrophoresis (PFGE), and analyzed by array-CGH to identify it's  amplified regions

overall_design: After PFGE, The ChrVIII DNA was purified from agarose gel and purified by column. Then the DNA was amplified by GenomePlex Whole Genome Amplification Kit for Array-comparative genomic hybridization.

first: Shang-Lin

last: Chang


title: Study on the genomic changes in ColIa2 Cre x RBP-Jkappa loxp/loxp mice

status: Public on May 01 2012

city: Epalinges

first: Bing

last: Hu

address: Chemin des Boveresses 155

department: Department of Biochemistry

country: Switzerland

institute: University of Lausanne

type: Expression profiling by high throughput sequencing

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Skin tumor formed in the ColIa2 Cre x RBP-Jkappa loxp/loxp mice was analyzed for genomic changes by comparing with normal tissues from the same mice.

overall_design: Genomic DNA were isolated from each individual tumor and compared with the DNA extracted from the brain tissue in the same mouse.

first: Gian

middle: P

last: Dotto


title: Analysing of Chromosome VIII of EC9-7 after experimental evolution (S. cerevisiae)

status: Public on Nov 13 2011

summary: The genomic DNA of wild-type chromosome VIII of evolved EC9-7 cells was extracted from the gel of pulsed field gel electrophoresis (PFGE), and analyzed by array-CGH to identify its  chromosomal composition

overall_design: Yeast genomic DNA was extracted using QIAGEN Genomic-tip 100/G kit. After PFGE, The ChrVIII DNA was purified from agarose gel and purified by column. Then the DNA was amplified by GenomePlex Whole Genome Amplification Kit.


title: Seeking novel mammalian genes using transcript profiling and genotyping of a human radiation hybrid panel

status: Public on Apr 09 2012

city: Los Angeles

first: Richard

middle: T

last: Wang

address: 650 Charles E Young Drive South

institute: UCLA

type:
Expression profiling by array
Genome variation profiling by array

summary: Using a human-hamster radiation hybrid panel (G3), we have mapped loci regulating gene expression due to copy number increase.

sample_organism:
Homo sapiens
Cricetulus griseus

overall_design:
Copy number from radiation hybrid clones were measured relative to the A23 hamster recipient line.
Expression from 79 radiation hybrid clones were measured in duplicate and compared to expression of the A23 hamster recipient line (GA_illumina_expression1 and GA_illumina_expression2). Expression of liver, kidney and heart from human and hamster are also included (GA_illumina_expression_R).


title: Genomic profiling of typical and atypical chronic lymphocytic leukemia patients using Agilent Whole Human Genome microarrays

status: Public on Oct 20 2011

city: lille

first: frédéric

last: leprêtre

address: Boulevard du Pr Leclercq

department: CHU of Lille, CBP

country: France

institute: Lille University

summary: Deciphering typical and atypical chronic lymphocytic leukemia genomics.

overall_design: DNA was isolated from peripheral blood leucocyte samples of each patient using the QIAamp kit in order to compare typical and atypical chronic lymphocytic leukemia patients using Agilent Whole Human Genome 44K and 244K microarrays.

first: X

last: Troussard


title: Single-cell copy number varation detection

status: Public on Aug 24 2011

city: Leuven

first: Jiqiu

last: Cheng

address: Kasteelpark Arenberg 10

department: Electrical Engineering

country: Belgium

institute: Katholieke Universiteit Leuven

summary: Detection of genomic rearrangements from a single cell instead of a population of cells is an emerging research technique with important applications in the study of human fertility, constitutional chromosomal disorders, and tumor progression. Here, we develop a method to improve the detection of single-cell genome-wide copy number variation.

overall_design: At this study,  7 amplified single cell DNA samples derived from EBV-line [47,XY,+21],   [46,XY,der(20),t(18;20)(p11.21;p13)],  [46,XX,del(18)(p11.21->pter)],  [46,X,der(X),t(X;14)(q21.1;q12.2)] were analyzed by Agilent 244K array CGH.  For these single cell Agilent 244K array CGH analyses: non-amplified genomic DNA extracted from the blood of a Klinefelter patient (XXY) was used as a reference sample. As a validation, the corresponding non-amplified genomic DNA samples were analyzed by 250K Nsp I SNP arrays (platform GPL3718). Non-amplified genomic DNA extracted from the blood of a Klinefelter patient (XXY) was used as a reference sample for BAC array CGH

first: Evelyne

last: Vanneste

first: Pete

last: r Konings

first: Thierry

last: Voet

first: Joris

last: Vermeesch

first: Yves

last: Moreau


title: Mesothelioma tumor aCGH profiles

status: Public on Sep 26 2011

city: New York

first: Yupu

last: Liang

state: NY

address: 1230 York Avenue

institute: The Rockefeller University

summary: Malignant pleural mesotheliomas (MPMs) often show CDKN2A and NF2 inactivation but other highly recurrent mutations have not been described. To identify additional driver genes, we used an integrated genomic analysis of 53 MPM tumor samples to guide a focused sequencing effort that uncovered somatic inactivating mutations in BAP1 in 23% of MPM. The BAP1 nuclear deubiquitinase is known to target histones (together with ASXL1 as a Polycomb repressor subunit) and the HCF1 transcriptional co-factor, and we show that BAP1 knockdown in MPM cell lines affects E2F and Polycomb target genes. These findings implicate transcriptional deregulation in the pathogenesis of MPM.

overall_design:
DNA from 53 malignant pleural mesothelioma tumors was collected and hybridized to aCGH arrays.  Data were analyzed to create gain and loss profiles for each tumor.

This submission includes gcNormalized-data.

first: Marc

last: Ladanyi

first: Matthew

last: Bott


title: Single-cell copy number varation detection: blastomeres

status: Public on Aug 10 2011

summary:
Detection of genomic rearrangements from a single cell instead of a population of cells is an emerging research technique with important applications in the study of human fertility, constitutional chromosomal disorders, and tumor progression. Here, we develop a method to improve the detection of single-cell genome-wide copy number variation.
Additional information about the blastomeres can be found in GSE11663.

overall_design: At this study,  14 amplified single blastomere DNA samples derived from 3-day-old and 4-day-old human embryos were analyzed by Agilent 244K array CGH.  For these single cell Agilent 244K array CGH analyses: non-amplified genomic DNA extracted from the blood of a Klinefelter patient (XXY) was used as a reference sample. As a validation, the corresponding non-amplified genomic DNA samples were analyzed by 250K Nsp I SNP arrays (platform GPL3718 and GSE11663).

first: Peter

last: Konings


title: Comparative Genomic Hybridization of S. cerevisiae industrial and laboratory strains

status: Public on Sep 15 2011

city: Hangzhou

first: Daoqiong

last: Zheng

state: Zhejiang

address: 866 Yuhangtang Road

department: Institute of Microbiology

institute: College of Life Sciences, Zhejiang University

summary: The environmental stresses and inhibitors encounted by Saccharomyces cerevisiae strains are main limiting factors in bioethanol fermentation. Investigation of the molecular mechanisms underlying the stresses-related phenotypes diversities within and between S. cerevisiae populations could guide the construction of yeast strains with improved stresses tolerance and fermentation performances. Here, we explored the genetic characteristics of the bioethanol S. cerevisiae strains, and elucidated the genetic variations correlated with its advantaged traits (higher ethanol yield under sever conditions and better tolerance to multiple stresses compared to an S288c derived laboratory strain BYZ1). Firstly, pulse-field gel electrophoresis combined with array-comparative genomic hybridization was used to compare the genome structure of industrial strains and the laboratory strain BYZ1.

overall_design:
Yeast cells were cultured in YPD medium. Genome DNA was isolated and sonicated. The average length of DNA fragments was 200-1000bp. The shearing DNA was labeled with Cy5/Cy3 and hybridized to NimbleGen S.cerevisiae Whole-Genome Tiling arrays, which is single array design containing all chromosomes with 32bp median probe spacing and totally covered by ~385,000 probes. Scanning was performed with the Axon GenePix 4000B microarray scanner.
YJS329 vs BYZ1
ZK2 vs BYZ1

first: Xuechang

last: Wu

first: Pinmei

first: Yudong

last: Li


title: Differential Response of Streptococcus mutans Towards Friend and Foe in Mixed-Species Cultures

status: Public on May 01 2011

city: Oklahoma City

first: Fengxia

last: Qi

state: OK

address: 975 NE 10th St. BRC366

department: microbiology/immunology

institute: university of Oklahoma Health sciences center

summary: In the oral biofilm, the mitis streptococci are among the first group of organisms to colonize the tooth surface. Their proliferation is thought to be an important factor required for antagonizing the growth of cariogenic species such as Streptococcus mutans.  In this study, we used a 3-species mixed culture to demonstrate that another ubiquitous early colonizing species, Veillonella parvula, could greatly impact the competitive outcome of a mixed culture of S. mutans and S. gordonii.  Transcriptome analysis further revealed that S. mutans responds differentially to its friend (V. parvula) and foe (S. gordonii).  In the mixed culture with S. gordonii, all but one S. mutans sugar uptake and metabolic genes were down-regulated, while genes for alternative energy source utilization and H2O2 tolerance were up-regulated, resulting in a slower but persistent growth. In contrast, when cultured with V. parvula, S. mutans grew equally well or better than in monoculture and exhibited relatively few changes within its transcriptome.  When V. parvula was introduced into the mixed culture of S. mutans and S. gordonii, it rescued the growth inhibition of S. mutans.  In this 3-species environment, S. mutans increased the expression of genes required for the uptake and metabolism of minor sugars, while genes required for oxidative stress tolerance were down-regulated.  We conclude that the major factors affecting the competition between S. mutans and S. gordonii are carbohydrate utilization and H2O2 resistance.  The presence of V. parvula in the tri-species culture mitigates these two major factors and allows S. mutans to proliferate, despite the presence of S. gordonii.

overall_design: In this study, we used microarrays to investigate how S. mutans responds to different species. S. mutans was grown as either monospecies, dual-species cultures with S. gordonii or Veillonella, or tri-species cultures with S. gordonii and Veillonella. The transcriptional profile of the whole genome was examined with microarray.

first: Jinman

last: Liu

first: Chenggang

first: I-Hsiu

last: Huang

first: Justin

last: Merritt


title: Comparative genomic hybridization of 20 patients with Sézary syndrome

status: Public on Jul 07 2011

city: Berlin

first: Reinhard

last: Ullmann

department: Human Molecular Genetics

country: Germany

institute: MPIMG

summary: The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the proto-oncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells following restoration of E2A expression, we identify a number of E2A-regulated genes that interfere with oncogenic signaling pathways including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity.

overall_design: During this study we analyzed 20 patients with Sézary syndrome by array-based comparative genomic hybridization (array CGH). Initial array CGH was done by means of a submegabase resolution BAC array (GPL5114; 17 samples). Aberrations encompassing chromosome arm 19p were verified and fine-mapped by hybridizations onto a whole genome 400k (GPL9777; 14 samples) and a customized oligonucleotide array (GPL10304; 3 samples), respectively. FISH analyses were used for further verification.


title: Role of chaperones and a cytoplasmatic protease in recombinant protein production in E. coli at suboptimal growth temperature

status: Public on Nov 24 2010

city: Ljubljana

first: Spela

last: Baebler

address: Vecna pot 111

department: Department of Biotechnology and Systems Biology

country: Slovenia

institute: National Institute of Biology

summary: Recent studies have revealed that at lower cultivation temperatures (25°C) much higher percentage of correctly folded recombinant proteins can be extracted from inclusion bodies. The goal of our research was to investigate mechanisms determining characteristics of non-classical inclusion bodies production using gene expression profiling. Two strains of recombinant E. coli [BL21 (DE3)] grown at three different temperatures (25°C, 37°C and 42°C) were included in experiment.

overall_design: Gene expression was studied in two recombinant strains (production and control strain), grown at three different temperatures (25, 37 and 42 oC) in three biological replicates. Cells were harvesed at OD=4, except for the cells grown at 25 oC, here they were harvested at OD=4 and OD=10.

first: Mitja

last: Mahnič

first: Andrej

last: Blejec


title: Characterization of chromosome rearrangement of EC strain (S. cerevisiae)

status: Public on Aug 03 2010

first: Jun-Yi

last: Leu

summary: The EC strain karyotype was analyzed by array-CGH to identify amplified chromosomal regions.

overall_design: EC9 was chosen as the representative strain of EC-C1 strain

first: Shang-Lin

last: Chang


title: Array-based CGH analysis of ccRCC derived cell lines

status: Public on Nov 01 2012

first: Klaas

last: Kok

summary:
arrayCGH profiling of 10 cell lines derived from clear cell Renal Cell Carcinoma
The goal of this study was to make a detailed genomic profile of these cell lines, including aCGH, miRNA expression, and mRNA expression profiles. The miRNA and mRNA expressiion profiles are submitted to GEO separately. One paper is in preparation to link the miRNA expression data with the arayCGH data. For mRNA expression data see GEO Series accession number GSE20491.

overall_design: CGH arrays used to analyse 10 cell lines

first: Gerben

last: Duns


title: MMRC aCGH reference collection

status: Public on Jan 26 2011

city: Cambridge

first: Michael

middle: Anthony

last: Chapman

state: MA

address: 7 Cambridge Center

institute: Broad Institute

summary: The MMRC reference collection is a dataset of gene expression profiling, array comparative genomic hybridization, and re-sequencing created as a resource for the Multiple Myeloma research community.

overall_design: CD138 purified bone marrow cells from patients with newly diagnosed and relapsed Multiple Myeloma.

first: Mike


title: Functional remodeling of primary and immortalized progenitor and intermediate cells

status: Public on Sep 15 2010

city: Nashville

first: yajun

last: yi

state: TN

address: 2215 Garland Ave

institute: vanderbilt univ

summary: Tissue remodeling or regeneration is believed to initiate from organ-specific stem and/or progenitor cells. We report here the establishment of two spontaneously immortalized adult human benign prostate epithelial cell lines, NHPrE1 and BHPrE1. NHPrE1CD133(++)/CD44(++)/OCT4(++)/CK14(+++) was characterized as a putative progenitor cell, and BHPrE1CD133(+)/CD44(+)/OCT4(+)/CK14(++) as a putative intermediate cell. aCGH analysis demonstrated a largely intact diploid karyotype with DNA amplification of PTEN in NHPrE1 or Beta-Catenin in BHPrE1 cells, respectively. A tissue recombination-xenografting model was utilized to compare remodeling of human prostatic tissues in vivo by the NHPrE1 and BHPrE1 cell lines and their parental primary cells. A series of tissue recombinants, made by mixing different ratios of human prostatic epithelial cells and inductive rat urogenital sinus mesenchyme (UGM), were grafted to the renal capsule of SCID mice. Both cell lines were able to regenerate ductal/acinar structures in vivo containing basal and luminal epithelial populations confirmed by the expression of appropriate cytokeratin profiles. Androgen receptor (AR), prostate specific antigen (PSA), and 15-lipoxigenase-2 (15-LOX-2) expression were appropriately expressed in the regenerated epithelial structures. Regeneration of benign human prostatic ductal/acinar architecture could be achieved using as few as 10 NHPrE1 cells while 200,000 BHPrE1 cells were required to achieve prostatic structure. This suggests a greater proportion of progenitor cells in NHPrE1 facilitated regeneration of prostatic morphology and function. These cell lines provide important data on progenitor and intermediate cell phenotypes and represent significant new tools for the elucidation of molecular mechanisms of human prostatic regeneration, pathogenesis and carcinogenesis.

overall_design: Two channel CGH from Agilent platform was used to detect DNA amplification or deletion in genomic samples from NHPrE1 and BHPrE1 cell lines. A common pooled normal DNA refernce was used.

first: Ming

last: Jiang

first: Douglas

last: Strand

first: Suzanne

last: Fernandez

first: Yue

last: He

first: Yajun

last: Yi

first: Simon

last: Hayward


title: The expression profile under cooper sulfate treatment

status: Public on Aug 26 2011

summary: The expression profile of natural isolate of S. cerevisiae carrying different copy of CUP2 were compared under cooper sulfate stress

overall_design: The gene expression profiles of natural isolate of  S.cerevisiae(EC9-7), EC9-7 cup2∆ and  Ec9-7 cup2∆cup2∆ strains under YPD with 1mM copper sulfate for 1h and rich medium(YPD) were compared.


title: An integrated genomics approach for novel biomarker discovery in squamous cell cervical carcinoma

status: Public on Mar 05 2011

first: Ian

last: Roberts

address: Hills Road

department: Cancer Cell Unit

country: United Kingdom

institute: Hutchison MRC Research Centre

summary:
Detection of copy number dependent gene expression profiles in epithelial tumours has lead to the discovery of genes significant in diagnosis, prognosis and of therapeutic value.
We sought to apply the technologies of gene expression profiling and copy number aberration detection by high density oligonucleotide microarray analysis to detect genes with expression profiles regulated by copy number.  We surveyed copy number aberrations in 27 squamous cell carcinomas tissues and ten cervical carcinoma cell lines by Agilent 244k aCGH, and in a companion study of 77 tissues we obtained transcriptional profiles of a broader ranger of histologies.
Briefly, for normal (NAD) and squamous intraepithelial lesions (SILs), DNA and RNA were extracted from approximately 5 - 25 x 5 mm thin sections of fresh frozen cervical tissue, respectively.  Epithelial were microdissected, pooled and processed as follows.  For RNA extraction, tissue was collected in Trizol (Invitrogen, UK) and subject to homogenization (Polytron), total RNA was recovered following standard processes, and quality assessed by BioAnalyzer (Agilent).  DNA was recovered following Proteinase K digestion, phenol chloroform extraction, and ethanol precipitation.  Contaminating RNA was removed by RNAse A treatment, and a second round of phenol chloroform extraction and ethanol precipitation.  For SCCs,  RNA and DNA was extracted from whole tumour (>85%), following similar strategies as previously described.

overall_design: This submission describes the copy number aberrations of 27 cervical SCC tissues and 10 common cervical SCC cell lines

first: Konstantina

last: Karagavriilidou

first: Stephanie

last: Carter

first: Grace

last: Ng

first: Emma

last: Gooding

first: Anasuya

last: Chattopadhyay

first: Mark

last: Pett

first: Matthew

last: Murray

first: David

last: Winder

first: Baljinder

last: Muralidhar

first: Dawn

last: Ward

first: Pamela

last: Stacey

first: Marie

last: Philips

first: Cinzia

last: Scarpini

first: Geeta

last: Mukherjee

first: Nicholas

last: Coleman


title: Reduced seed region-based off-target activity with lentivirus-mediated RNAi

status: Public on Jun 09 2010

city: West Point

first: Michele

last: Cleary

state: PA

address: 770 Sumneytown Pike

department: Genetics and Pharmacogenomics

institute: Merck and Co., Inc.

summary: In addition to silencing intended target genes, transfected siRNAs regulate numerous unintended transcripts through a mechanism in which the equivalent of a microRNA-like seed region in the siRNA recognizes complementary sequences in transcript 3' UTRs.  The ability to limit such off-target effects would substantially facilitate accurate interpretation of RNA interference (RNAi) experiments and thus greatly enhance their value.  We tested whether lentivirus-mediated delivery of shRNA is prone to the seed region-based off-target activity prevalent in siRNA experiments.  We compared target gene silencing and overall impact on global gene expression caused by multiple 21-mer duplex sequences delivered as both transfected siRNA and lentivirus vector-expressed shRNA.  At equivalent levels of target gene silencing, signatures induced by shRNAs were significantly smaller than those induced by cognate siRNAs and arose less frequently from seed region activity. Interestingly, the low level of seed-region based off-target activity exhibited by shRNAs resulted in down-regulation of transcripts that were largely distinct from those regulated by siRNAs.  On the basis of these observations, we recommend lentivirus-mediated RNA interference for pathway profiling experiments that measure whole genome transcriptional readouts as well as for large-scale screens when resources for extensive follow up are limited.

overall_design: To assess the extent to which lentivirus-mediated RNAi is prone to off-target effects, we compared gene expression profiles induced by siRNAs and shRNAs that encode the exact same 19-mer RNA duplex sequence in HeLa cells. siRNA/shRNA pairs targeting 4 distinct genes (cdkn1a, e2f1, ezh2, and fdxr) were analyzed.  We also generated HCT-116 colon carcinoma cells (wild type for TP53) harboring a stable tetracycline-regulatable expression construct encoding an shRNA designed to silence TP53.  We compared transcript regulation induced by doxycycline-mediated expression of a TP53-targeting shRNA to that induced by transfection of the same cells with a TP53 siRNA with the same 19-mer core sequence.

first: Richard

last: Klinghoffer

first: Jill

last: Magnus

first: Janell

last: Schelter

last: Mehaffey

first: Casey


title: Agilent 244A aCGH array for breast, lung, melanoma, ovary, and prostate

status: Public on Jul 29 2010

city: South San Francisco

first: Peter

last: Haverty

address: 1 DNA Way

department: Bioinformatics

institute: Genentech, Inc.

summary: 373 tumors were profiled for copy-number alterations with the high-resolution Agilent 244A aCGH Array.

overall_design: Tumor samples were assayed on Agilent Human Genome CGH 244A Microarrays with the intent of surveying the landscape of genomic alterations in 5 tumor types. Human male genomic DNA (Promega P/N G1471) was used as reference.  Individual log2 ratios of background subtracted signal intensities were obtained from the Agilent Feature Extraction software version 9.5. The log2 ratios were centered to a median of zero and the resulting log2 ratio values for each probe were segmented using GLAD. All probes within the genomic bounds of a given GLAD-derived segment were given the mean copy number value of probes within that segment.

first: Kan

last: Zhengyan

first: Haverty

last: Peter

first: Neve

last: Richard

first: Seshagiri

last: Somasekar

first: Zora

last: Modrusan


title: Agilent 244A aCGH array for comparison of lung tumor CNA to high-throughput sequencing data

status: Public on May 27 2010

summary: 1 lung tumor was profiled for copy-number alterations with the high-resolution Agilent 244A aCGH Array.

overall_design: One lung tumor sample were assayed on the Agilent Human Genome CGH 244A Microarrays with the intent of comparing the genomic alterations reported by the array platform with those reported by high-thoughput sequencing. Human male genomic DNA (Promega P/N G1471) was used as reference.  Individual log2 ratios of background subtracted signal intensities were obtained from the Agilent Feature Extraction software version 9.5. The log2 ratios were centered to a median of zero and the resulting log2 ratio values for each probe were segmented using GLAD. All probes within the genomic bounds of a given GLAD-derived segment were given the mean copy number value of probes within that segment.

first: William

last: Lee

first: Jiang

last: Zhaoshi

first: Jinfeng

last: Liu

first: Yinghui

last: Guan

first: Jeremy

last: Stinson

first: Peng

last: Yue

first: Yan

last: Zhang

first: Krishna

last: Pant

first: Deepali

last: Bhatt

first: Connie

last: Ha

first: Stephanie

last: Johnson

first: MichaelI

last: Kennemer

first: Sankar

last: Mohan

first: Igor

last: Nazarenko

first: Colin

last: Watanabe

first: Andrew

last: Sparks

first: David

middle: S

last: Shames

first: Robert

last: Gentleman

first: Howard

last: Stern

first: Ajay

last: Pandita

first: Dennis

middle: G

last: Ballinger

first: Radoje

last: Drmanac

first: Somasekar

last: Seshagiri

first: Zemin


title: Yeast genomic DNA: SH6484 vs. FY834

status: Public on May 17 2010

city: kamakura

first: yoji

last: ueda

state: Kanagawa

address: 6-10-1 Tebiro

country: Japan

institute: Toray Industries, Inc.

summary:
To detect genome amplification or deletion of genome reconstructed strain SH6484 compare to parental strain FY833. SH6484 genome was reconstructed using PCS technology.

Keywords: Comparative genomic hybridization

overall_design: SH6484 vs. FY834. There are no biological replicates.

first: Youji

last: Ueda


title: Diverse somatic mutation patterns and pathway alterations in human cancers

status: Public on Aug 24 2010

first: Peter

last: Haverty

summary:
The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics. Here we report the identification of 2,576 somatic mutations across approximately 1,800 megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes.  Additionally, 373 tumors were assayed for copy number alterations via Agilent 244A CGH arrays and 153 breast, lung, and colon samples were assayed for mRNA abundance with Affymetrix HuEx1 Exon Arrays.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series.


title: Dual regulation of nitrogen metabolism by CodY and GlnR in Streptococcus mutans

status: Public on Jul 01 2010

city: Miami

first: Dragana

last: Ajdic

state: Florid

address: 1600 NW 10th Ave, RMSB 2023

department: Dermatology

institute: University of Miami

summary:
CodY and GlnR are two major transcriptional regulators in nitrogen metabolism in Gram-positive bacteria. CodY regulates genes involved in the adaptive response to poor growth conditions, especially to nutrient limitation. GlnR controls nitrogen utilization according to the availability of nitrogen source.
In this study we used microarray to investigate the regulatory roles that CodY and GlnR play in nitrogen metabolism in Streptococcus mutans.

overall_design: Streptococcus mutans UA159 wild-type cells, ΔcodY, ΔglnR, and ΔcodYglnR strains were grown in a chemically-defined medium until the mid-log phase. The nitrogen source was 1% tryptone. Twenty millimolar sodium thiosulfate was added to the medium to support cysteine biosynthesis. The transcriptional profile of the whole genome was examined with microarray.

first: Zhiyun

last: Chen


title: Breast Cancer. Ull-series. 167 samples

status: Public on Jul 06 2010

city: Oslo

first: Hans Kristian

middle: Moen

last: Vollan

address: Ullernschausseen 100

department: Dept of genetics

institute: The norwegian Radium Hospital

summary:
167 Ull-samples 244k array
Tumor tissue from a series of 212 primary breast cancers were sequentially collected at Ullevål University Hospital, Oslo, Norway between 1990 and 1994. Tissues were collected at the time of primary surgery and snap frozen. We performed aCGH on 167 of these samples. DNA was isolated using chloroform/phenol extraction, followed by ethanol precipitation. The aCGH-platform was the Agilent Human genome CGH Microarray 244k. The aim of this study was to investigate the genome wide genomic copy number alterations in a cohort of primary breast cancer patients.

overall_design: 167 tumor samples analyzed with 244k Agilent CGH-arrays, Promega reference DNA, no technical replicates.

first: Hans-Kristian

first: Anne-Lise

last: Børresen-Dale


title: Identification of a Novel Bacteriocin Regulatory System in Streptococcus mutans

status: Public on Aug 15 2010

first: Justin

last: Merritt

address: 975 NE 10th St BRC364

department: Oral Biology

institute: University of Oklahoma Health Sciences Center

summary:
Recently, we described the function of a novel two-gene regulatory system consisting of a LytTR family transcription regulator and a membrane protein, which we referred to as the hdrRM operon.
We determined that the HdrRM system controls the expression of another similar regulatory system annotated as SMU.2080 and SMU.2081. Like hdrRM, the SMU.2080 – 2081 operon encodes a LytTR family transcription regulator and membrane protein, which we now refer to as BrsR and BrsM, respectively. In this study, we used microarray to examine the regulatory role of BrsR and found that it functions as a transcription activator for a variety of bacteriocins and bacteriocin-related genes.

overall_design: Streptococcus mutans UA140 derivatives, lacA ( genotype: ΔbrsRM /pFW5::PlacA ) and lacA2080 (genotype:ΔbrsRM /pFW5::PlacA-brsR),  were cultivated overnight at 37°C in a chemically-defined medium containing 0.5% (wt/vol) glucose as carbon source .  The overnight cultures were diluted 1:30 in CDM with 1% (wt/vol) lactose in a total volume of 30 ml.  The cells were allowed to grow to an optical density at 600 nm of 0.3 and RNA was extracted.  The transcriptional profile of the whole genome was examined with microarray.

first: Zhoujie

last: Xie


title: Agilent 244K aCGH data for colon cancer samples

status: Public on Oct 21 2009

first: Barry

middle: Stephen

last: Taylor

address: 1275 York Avenue, Box #460

institute: Memorial Sloan-Kettering Cancer Center

summary: Mutation of the gene PARK2 is the most common cause of early-onset Parkinson's Disease (PD)1,2.  PARK2 encodes a gene product with E3 ubiquitin ligase activity3.  In a search for multisite tumor suppressors, we identified PARK2 as a frequently targeted gene on chromosome 6q25.2-q27 in cancer.  Here, we describe inactivating somatic mutations and frequent intragenic deletions of PARK2 in human malignancies.  The PARK2 mutations in cancer occur in the same domains, and sometimes, at the same residues as the germline mutations causing familial PD.  Cancer-specific mutations abrogate the growth suppressive effects of PARK2.  PARK2 mutations in cancer decrease the gene product's E3 ligase activity, compromising its ability to ubiquitinate cyclin E and resulting in mitotic instability.  These data strongly point to PARK2 as a tumor suppressor on 6q25.2-q27.  PARK2, a gene that causes neuronal dysfunction when mutated in the germline, may instead contribute to oncogenesis when altered in non-neuronal somatic cells.

overall_design: Human colorectal samples were profiled on Agilent 244K aCGH arrays per manufacturer's instructions. Pooled reference normal DNA was used as the reference.

first: David

last: Solit

first: Timothy

middle: A

last: Chan


title: Chromosomal aberration of malignant pleural mesothelioma cell lines

status: Public on Jun 15 2010

city: Nagoya

first: Hideki

last: Murakami

state: Aichi

address: 1-1 Kanokoden Chukusa-ku

department: Division of Molecular Oncology

institute: Aichi Cancer Center Institute

summary: To identify regions that display DNA copy number alterations in malignant pleural mesothelioma (MPM), we carried out array comparative genomic hybridization (CGH) analysis with 14 MPM cell lines. Regions of genomic aberrations observed in >20% of individuals were 9p21.3, 13q12.11, 16p13, and 22q12.2 of losses. The most frequent alteration was 9p21.3, which include the p16INK4/p14ARF. The loss of 22q12.2 regions include the NF2 was observed in 3 out of 14 cell lines. In 3 cell lines, loss of 13q12.11 region which contains Large Tumor Suppressor, homolog 2 (LATS2) was detected.

overall_design: Human malignant pleural mesothelioma cell lines were profiled on Agilent 244K aCGH arrays according to manufacturer’s instructions. Pooled normal human genomic DNA was used as the reference.

first: Tetsuo

last: Taniguchi

first: Testuya

last: Mizuno

first: Futoshi

last: Ishiguro

first: Yoshitaka

last: Sekido


title: Genomic profiling of gastric adenomas by array-based comparative genomic hybridization

status: Public on Feb 01 2010

city: Yufu-city

first: Yoshiyuki

last: Tsukamoto

state: Oita

address: hasamacho idaigaoka 1-1

department: Molecular Pathology

institute: Oita university, Faculty of Medicine

summary: In this study, we investigated CNAs of 20 gastric CIS (Vienna category 4.2) and 20 adenomas, including 7 low-grade adenomas (LGA; Vienna category 3) and 13 high-grade adenomas (HGA; Vienna category 4.1), by 244k oligonucleotide-based array comparative genomic hybridization (array CGH).

overall_design:
20 gastric adenomas vs. 20 controls.

The supplementary file 'GSE19574_aberrations.txt' file contains a summary of the aberrations in the gastric adenomas as determined by the ADM-2 algorithm.

first: Masahiro

last: Uchida

first: Yoshiyuku

first: Tomohisa

first: Yuta

last: Ichikawa

first: Takayuki

last: Nagai

first: Naoki

last: Hijiya

first: Tung

middle: L

last: Nguyen

first: Chisato

last: Nakada

first: Akiko

last: Kuroda

first: Tadayoshi

last: Okimoto

first: Masaaki

last: Kodama

first: Kazunari

first: Tsuyoshi

last: Noguchi

first: Keiko

last: Matsuura

first: Masato

last: Tanigawa

first: Masao

last: Seto

first: Hisao

last: Ito

first: Toshio

last: Fujioka

first: Ichiro

last: Takeuchi

first: Masatsugu

last: Moriyama


title: Genomic profiling of gastric carcinoma in situ by array-based comparative genomic hybridization

first: Yoshiyuki

last: Tsukamoto

overall_design:
20 gastric carcinoma in situ (CIS) vs. 20 controls.

The supplementary file 'GSE19566_aberrations.txt' file contains a summary of the aberrations in the gastric CISs as determined by the ADM-2 algorithm.

first: Masahiro

last: Uchida

first: Yoshiyuku

first: Tomohisa

first: Yuta

last: Murakami


title: Genomic profiling of gastric carcinoma in situ and gastric adenomas by array-based comparative genomic hybridization

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

overall_design: Refer to individual Series


title: Identification of SULF2 as a novel transcriptional target of p53 by use of integrated genomic analyses.

status: Public on Apr 01 2009

first: Michele

last: Cleary

summary: Microarray analysis has been useful for identifying the targets of many transcription factors. However, gene expression changes in response to transcription factor perturbation reveal both direct transcriptional targets and secondary gene regulation. By integrating RNA interference, gene expression profiling, and chromatin immunoprecipitation technologies, we identified a set of 32 direct transcriptional targets of the tumor suppressor p53. Of these 32 genes, 11 are not currently associated with the core p53 pathway. From among these novel pathway members, we focused on understanding the connection between p53 and SULF2, which encodes an extracellular heparan sulfate 6-O-endosulfatase that modulates the binding of growth factors to their cognate receptors and that has been shown to function as a tumor suppressor. Genetic and pharmacologic perturbation of p53 directly influences SULF2 expression, and similar to silencing of TP53, RNA interference-mediated suppression of SULF2 results in an impaired senescence response of cells to genotoxic stress. Thus, our integrated genomic approach has led to the identification of a novel mediator of p53 network biology.

overall_design: Expression profiling experiments were performed to perturb the p53 status in cancer cell lines as a means of identifying novel members of the p53 pathway.

first: Nelson

last: Chau

first: Robert

last: Diaz

first: Matthew

last: Saunders

first: Chun

last: Cheng

first: Aaron

last: Chang

first: Paul

last: Warrener

first: Jeffrey

last: Bradshaw

first: Peter

last: Linsley


title: Gene expression profiling of human and dog breast cancers

status: Public on May 06 2009

city: Genoa

first: Paolo

last: Uva

address: Via Gerolamo Gaslini, 5

institute: IRCCS Istituto Giannina Gaslini

summary:
Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved.

Keywords: Expression profiling by array

sample_organism:
Homo sapiens
Canis lupus familiaris

platform_organism:
Homo sapiens
Canis lupus familiaris

overall_design: 26 breast tumors and 7 normal mammary glands from dogs. Each sample was hybridized in duplicate with fluor reversal to systematically correct for dye bias. 68 infiltrating ductal mammary carcinoma and 61 adjacent non-involved tissues from humans. Each sample was hybridized in duplicate with fluor reversal to systematically correct for dye bias.

first: Emanuele

last: de Rinaldis


title: Profiling of Human Adipose Tissue and Effect of Sibutramine on Gene Expression

status: Public on Feb 12 2009

first: Michael

last: Nebozhyn

address: Mail Stop WP53B-120, 770 Sumneytown Pike, Building 53, P.O. Box 4

department: GpGx/Computational System biology

institute: Merck, Inc

summary:
We analyzed the expression of 23,653 transcripts in the adipose tissue of 19 individuals treated with Sibutramine
Keywords: sibutramine effect

overall_design: 157 adipose tissue samples from 19 individuals treated with sibutramin as well as placebo were profiled for gene expression.

first: Andrey

last: Loboda

first: Walter

middle: K

last: Kraft

last: Joseph

first: Bernard

last: Fine

first: Chunsheng

last: Zhang

first: Yudong

last: He

first: Xia

last: Yang

first: Chris

last: Wright

first: Mark

last: Morris

first: Ira

last: Chalikonda

last: Ferguson

first: Hongyue

last: Dai

first: Valur

last: Emilsson

first: Eric

last: Schadt

first: Howard

middle: E

last: Greenberg

first: Pek

middle: Y

last: Lum


title: Altered gene expression in zebrafish embryos exposed to tert-butylhydroquinone and 2,3,7,8-tetrachlorodibenzo-p-dioxin

status: Public on Jan 01 2010

city: Hamilton

first: Andrew

middle: G.

last: McArthur

state: Ontario

address: 1280 Main Street West

department: Biochemistry & Biomedical Sciences

country: Canada

institute: McMaster University

summary:
Oxidative stress is an important mechanism of chemical toxicity, contributing to teratogenesis as well as to cardiovascular and neurodegenerative diseases. Developing animals may be especially sensitive to chemicals causing oxidative stress. To assess the response to chemicals at different stages of development, zebrafish (Danio rerio) embryos at 1, 2, 3, 4, 5, and 6 days post-fertilization (dpf) were exposed to 0.1% dimethyl sulfoxide (DMSO), 2 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or 10 uM tert-butylhydroquinone (tBHQ) for 6 hr.  Transcript abundance was assessed by real-time qRT-PCR and microarray (Agilent 22k). By microarray, 1477 probes were significantly different among the DMSO-, tBHQ-, and TCDD-treated embryos at 4 dpf. Of these, 220 were 2-fold or greater up-regulated and 108 were 2-fold or greater down-regulated by tBHQ.  For TCDD, 17 probes were 2-fold or greater up-regulated and 6 were 2-fold or greater down-regulated. Genes induced by tBHQ, included genes involved in glutathione synthesis and utilization, signal transduction, and DNA damage / stress response.
Keywords: Danio rerio, TCDD, tBHQ, oxidative stress, gene expression

overall_design: Separate groups of 30 embryos generated from TL adults were placed in 15 ml egg water in a 10-cm glass petri and at 1, 2, 3, 4, 5, and 6-dpf were exposed for 6 hr to 0.1% dimethyl sulfoxide (DMSO), 2 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or 10 uM tert-butylhydroquinone (tBHQ) (4 replicates per compound per time point). Embyros were frozen immediately after the 6 hr exposure and RNA isolated for microarray analysis. A Universal RNA Reference Sample was created by mixing equal amounts of total RNA from 2 replicates each from all toxicants (TCDD, tBHQ, DMSO) and timepoints (1, 2, 3, 4, 5, 6-dpf).  Based on qRT-PCR results, the 4 dpf timepoint was selected for microarray analysis, in which the RNA samples (4 replicates per compound) were Cy3 labeled and co-hybridized with Cy5 labeled Universal RNA Reference Sample to generate data for analysis of variance.

last: Hahn

first: Sibel

middle: I

last: Karchner

first: Diana

last: Franks

first: Bruce

middle: R

last: Woodin

first: Katie

last: Barott

middle: J

last: Cipriano


title: mRNA expression of 131 cancer cell lines

status: Public on Nov 18 2008

city: Seattle

first: Tao

last: Xie

state: WA

address: 401 Terry Ave. N.

department: Genetics

institute: Rosetta Inpharmatics

summary:
131 human cancer cell lines' mRNA expression profiles have been characterized.

Keywords: Cell Line Comparison

overall_design: mRNA samples obtained from 131 human cancer cell lines were hybridized to Agilent Human 3.0 A1 arrays and gene expression (mlratio) was measured relative to a common reference RNA pool (Human Universal Reference RNA, Stratagene, La Jolla, CA).

last: Zhang

first: Bin

first: Cliona

last: Molony

last: Roberts

first: John

last: Lamb


title: MicroRNA targeting specificity in mammals: determinants beyond seed pairing

status: Public on Jul 18 2007

first: Lee

last: Lim

summary:
This series consists of samples taken from HeLa transfected with miRNA duplexes.
Keywords: other

overall_design: Please see Molecular Cell article: Grimson et al, 27:91.

last: Grimson

first: Kyle

last: Farh

first: Wendy

last: Johnston

first: Philip

last: Garrett-Engele

first: David

last: Bartel


title: Global transcriptional analysis of S. mutans sugar transporters

status: Public on Jun 15 2007

first: Dragana

last: Ajdic

summary:
The transport of carbohydrates by Streptococcus mutans is accomplished by the phosphoenolpyruvate-phosphotrasferase system (PTS) and ATP-binding cassette (ABC) transporters. To undertake a global transcriptional analysis of all S. mutans sugar transporters simultaneously, we used a whole-genome expression microarray. Global transcription profiles of S. mutans UA159 were determined for several carbohydrates. The results revealed that PTSs were responsible for transport of monosaccharides, disaccharides and sugar alcohols. Six PTSs were transcribed only if a specific sugar was present in the growth medium, thus they were regulated at the transcriptional level. These included transporters for fructose, lactose, cellobiose, trehalose, and two transporters for mannitol. Three PTSs were repressed under all conditions tested. Interestingly, five PTSs were always highly expressed regardless of the sugar source used, presumably suggesting their availability for immediate uptake of most common dietary sugars (glucose, fructose, maltose and sucrose). The ABC transporters were found to be specific for polysaccharides, raffinose, stachyose and isomaltosaccharides. Compared to the PTS, the ABC transporters showed higher transcription under several tested conditions, suggesting that they might be transporting multiple substrates.
Keywords: carbohydrate response

overall_design: Global transcriptional patterns were obtained following growth on different carbohydrates (monosaccharides: glucose, mannose, galactose and fructose; disaccharides: sucrose, lactose, maltose, trehalose and cellobiose; oligosaccharides: raffinose, stachyose and maltotriose; a sugar-alcohol: manitol). To assure reproducibility of the data, the cultures were always grown to the same optical density for RNA extraction and hybridization on Affymetrix microarrays. Fourteen different conditions were analyzed with 2, 4 or 10 replicates for each.

first: Vi

last: Pham


title: Using transient nondisjunction to generate disomic strains of yeast

status: Public on Jan 13 2009

city: Spokane

first: Kirk

last: Anders

address: 502 E. Boone Ave, AD 5

department: Biology

institute: Gonzaga University

summary:
Background. Most methods for constructing aneuploid yeast strains that have gained a specific chromosome rely on spontaneous failures of cell division fidelity. In Saccharomyces cerevisiae, extra chromosomes can be obtained when errors in meiosis or mitosis lead to nondisjunction, or when nuclear breakdown occurs in heterokaryons. We describe a strategy for constructing N+1 disomes that does not require such spontaneous failures. The method combines two well-characterized genetic tools: a conditional centromere that transiently blocks disjunction of one specific chromosome, and a duplication marker assay that identifies disomes among daughter cells. To test the strategy, we targeted chromosomes III, IV, and VI for duplication. Results. The centromere of each target chromosome was replaced by a conditional centromere that can be blocked by growth in galactose, and ura3::HIS3, a duplication marker. Transient exposure to galactose induced the appearance of colonies carrying duplicated markers for chromosomes III or IV, but not VI. Microarray-based comparative genomic hybridization (CGH) confirmed that disomic strains carrying extra chromosome III or IV were generated. Chromosome VI contains several genes known to be deleterious when overexpressed, including the beta-tubulin gene TUB2. To test whether a tubulin stoichiometry imbalance prevents viability in cells carrying an extra chromosome VI, we supplied the parent strain with extra copies of the alpha-tubulin gene TUB1, then induced nondisjunction. Galactose-dependent chromosome VI disomes were produced, as revealed by CGH. Some chromosome VI disomes also carried extra, unselected copies of additional chromosomes. Conclusions. This method causes efficient nondisjunction of a targeted chromosome and allows resulting disomic cells to be identified and maintained. We used the method to test the role of tubulin imbalance in the apparent lethality of disomic chromosome VI. Our results indicate that a tubulin imbalance is necessary for disomic VI lethality, but it may not be the only dosage-dependent effect.

Keywords: comparative genomic hybridization, CGH

overall_design: Candidate disomes (Ura+His+) were compared to their euploid parents by CGH. 27 candidate strains were examined with 27 arrays. 4 candidates targeted chromosome III (3 induced, 1 spontaneous), 14 candidates targeted chromosome IV (8 induced, 6 spontaneous), and 9 candidates targeted chromosome VI (all induced).

first: Julie

last: Kudrna

first: Isaac

last: Strong

first: Kirstie

last: Keller

first: BreAnna

last: Kinghorn

first: Elizabeth

middle: M

last: Miller

first: Daniel

last: Pauw

first: Anders

last: Peck

first: Christopher

last: Shellooe

first: Justin

last: Platon


title: Mapping Replication Fork Pause Sites in S. cerevisiae

status: Public on Jun 15 2009

city: Princeton

first: Anna

last: Azvolinsky

state: NJ

address: Washington Road

department: Molecular Biology

institute: Princeton University

type: Genome binding/occupancy profiling by array

summary: Replication forks face multiple obstacles that slow their progression. By two-dimensional gel analysis, yeast forks pause at stable DNA protein complexes, and this pausing is greatly increased in the absence of the Rrm3 helicase. We used a genome wide approach to identify 96 sites of very high DNA polymerase binding in wild type cells. Most of these binding sites were not previously identified pause sites. Rather, the most highly represented genomic category among high DNA polymerase binding sites was the open reading frames (ORFs) of highly transcribed RNA polymerase II genes. Twice as many pause sites were identified in rrm3 compared to wild type cells as pausing in this strain occurred at both highly transcribed RNA polymerase II genes and the previously identified protein DNA complexes. ORFs of highly transcribed RNA polymerase II genes are the first class of natural pause sites that are not exacerbated in rrm3 cells. We alse mapped pause sites using a second replication fork component, Rrm3-13MYC and got similar results.

overall_design: Genomic input (labelled with Cy3) and IP'ed DNA (labelled with Cy5) using a MYC Ab of either DNA Pol2-13MYC or Rrm3-MYC from asynchronously grown S. cerevisiae cells in rich media were hybridized to whole-genome PCR-based arrays containing ORF and intergenic regions of the entire genome (Ivery et al 2001). At least three biological replication and one technical replicate (dye swap) were performed. Log2 transformed median normalized ratios (IP/IN) were averaged for each experiment and significant peaks of either DNA Pol2 or Rrm3 association were identified

first: Paul

last: Geresi

first: Jason

middle: D

last: Lieb

first: Virginia

last: Zakian


title: Gene Expression Profiling in the Lungs of Patients with Chronic Obstructive Pulmonary Disease (COPD) and Lung Cancer

status: Public on Nov 10 2007

first: serguei

middle: b

last: stepaniants

address: 401 Terry  Ave. N

department: Rosetta

institute: Merck

summary:
COPD is a common and disabling lung disease for which very few therapeutic options are currently available. We reasoned that global gene expression profiling of COPD lungs could reveal previously unidentified disease pathways for potential therapeutic interventions. Forty-eight human lung samples were obtained from lungs or lobes resected for small peripheral lung lesions (5 non-smokers, 21 GOLD 0, 9 GOLD 1, 10 GOLD 2 and 3 GOLD 3 patients). mRNA from the specimens was profiled using Agilent’s Functional ID v2.0 array which contains 23,720 sequences. Quantitative morphometric analysis of the specimens revealed that the samples contained a variable proportion of airways, blood vessels and parenchyma. Incorporating these data into a model relating gene expression to % predicted forced expiratory flow between 25 and 75% of forced expiratory volume (FEF 25-75 % P) revealed a signature gene set of 203 transcripts. Genes involved in extracellular matrix synthesis/degradation, oxidative stress and cell proliferation were among the up-regulated genes whereas genes which participate in nicotine metabolism, elastic fiber homeostasis and anti-inflammatory response were down-regulated. Immunohistochemistry confirmed expression of urokinase (PLAU), urokinanse receptor (PLAUR) and thrombospondin (THBS1) by alveolar macrophages and small airway epithelial cells. Genes in this pathway have been shown to be involved in transforming growth factor beta-1 (TGFβ1) and matrix metalloproteinase (MMP) activation and are subject to inhibition by serpin E2. Interestingly, both TGFβ1 and serpin E2 have been identified as candidate genes in COPD genetic linkage and association studies. The results thus provide a possible link between these two powerful approaches to identify potential therapeutic targets.   (255 words)
Keywords: Pulmonary emphysema, phenotype, transcriptional analysis, cigarette smoking

first: I-Ming

last: Wang

first: Sergey

last: Stepaniants

first: Yves

last: Boie

first: James

last: Mortimer

first: Brian

last: Kennedy

first: Mark

last: Elliott

first: Shizu

last: Hayashi

first: Leanna

last: Loy

first: Silvija

last: Coulter

first: Sandra

last: Cervino

first: Jennifer

last: Harris

first: Michele

last: Thornton

first: Richard

last: Raubertas

first: Chris

last: Roberts

first: Jim

last: Hogg

first: Michael

last: Crackower

first: Gary

last: O’Neill

first: Peter

last: Paré


title: Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression

status: Public on Feb 01 2007

city: Boston

first: Julja

last: Burchard

address: 33 Avenue Louis Pasteur

department: Computational & Systems Biology

institute: Merck & Co., Inc.

summary:
microRNAs (miRNAs) are abundant, ~21 nucleotide (nt) non-coding regulatory RNAs. Each miRNA may regulate hundreds of mRNA targets, but the identities of these targets and the processes they regulate are poorly understood. Here we have explored the use of microarray profiling and functional screening to identify targets and biological processes triggered by transfection of miRNAs into human cells. We demonstrate that a family of miRNAs sharing sequence identity with miR-16 negatively regulates cellular growth and cell cycle progression. miR-16 down-regulated transcripts were enriched for genes whose silencing by siRNAs causes cell cycle accumulation at G0/G1. Simultaneous silencing of these genes was more effective at blocking cell cycle progression than disruption of the individual genes. Thus, miR-16 coordinately regulates targets that may act in concert to control cell cycle progression.
Keywords: miRNA, microRNA, miR-16, target, cell cycle, G0/G1, microarray profiling, functional screen,

overall_design: Please see for details: Linsley PS, Schelter J, Burchard J, Kibukawa M, Martin MM, Bartz SR, Johnson JM, Cummins JM, Raymond CK, Dai H, Chau N, Cleary M, Jackson AL, Carleton M, and Lim L.  MCB (2007).

last: Linsley

first: Janell

last: Schelter

first: Miho

last: Kibukawa

first: Melissa

last: Martin

first: Steven

last: Bartz

first: Jason

last: Johnson

first: Jordan

last: Cummins

first: Christopher

last: Raymond

first: Hongyue

last: Dai

first: Nelson

last: Chau

last: Cleary

first: Aimee

last: Jackson

last: Carleton

first: Lee

last: Lim


title: Chronic Oxidative DNA Damage Due to DNA Repair Defects Causes Chromosomal Instability in Saccharomyces cerevisiae

status: Public on Feb 10 2008

city: Durham

first: Piotr

middle: Andrzej

last: Mieczkowski

state: NC

address: CARL Building

department: Molecular Genetics and Microbiology

institute: Duke University Medical Center

summary:
Oxidative DNA damage is likely to be involved in the etiology of cancer and is thought to accelerate tumorigenesis via increased mutation rates. However, the majority of malignant cells acquire a specific type of genomic instability characterized by large-scale genomic rearrangements, defined as chromosomal instability (CIN). The molecular mechanisms underlying CIN are largely unknown. We utilized Saccharomyces cerevisiae as a model system to delineate the relationship between genotoxic stress and CIN. It was found that elevated levels of chronic, unrepaired oxidative DNA damage cause chromosomal aberrations at remarkably high frequencies under both selective and non-selective growth conditions. In this system, exceeding the cellular capacity to appropriately manage oxidative DNA damage results in a “gain of CIN” phenotype and leads to profound karyotypic diversification. These results illustrate a novel mechanism for genome destabilization, which is likely to be relevant to human carcinogenesis.
Keywords: CGH-array

overall_design: Genomic DNA from each of 9 strains was competitively hybridized to DNA from the parent diploid strain (Cy3/green). Gains of genomic segments in the survivors were detected as continuous regions of positive Log2 Red:Green ratios, while losses were detected as negative Log2 Red:Green ratios.

first: Natalya

middle: P

last: Degtyareva

first: Lingling

last: Chen

first: Tomas

last: Petes

first: Paul

middle: W

last: Doetsch


title: A comparison of high density oligonucleotide and PCR-based array platforms for chIP chip in yeast

status: Public on Dec 13 2006

city: Urrbrae

first: Anthony

last: Borneman

state: South Australia

address: Paratoo Rd

country: Australia

institute: The Australian Wine Research Institute

summary:
ChIP chip data was obtained for the factors Tec1, Ste12 and Sok2 in S. cerevisiae using high density oligonucleotide arrays. This data was then compared to results obtained previously for the same factors under the same growth conditions but using spotted PCR arrays (Borneman et al Genes Dev 2006). This showed the high density arrays to be more reproducible using fewer numbers of replicates. In addtion, the high density arrays provided increased accuracy, sensitivity and reproducibity when compared to the PCR arrays.
Keywords: ChIP-chip

overall_design:
ChIP chip was performed for three factors, Tec1, Ste12 and Sok2.
For each factor, 3 biological replicates were performed, with one replicate for each factor treated as a dye swap.

first: Zhengdong

last: Zhang

first: Joel

last: Rozowsky

first: Michael

last: Seringhaus

first: Mark

last: Gerstein

last: Snyder


title: Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing

status: Public on Sep 07 2006

city: Carlsbad

state: CA

address: 1896 Rutherford Rd

institute: Regulus Therapeutics

summary:
Transfected siRNAs regulate numerous transcripts sharing limited complementarity to the RNA duplex.  This unintended (“off-target”) silencing can hinder the use of RNAi to define gene function.  Here we describe position-specific, sequence-independent chemical modifications that reduced silencing of partially-complementary transcripts by all siRNAs tested.  Silencing of perfectly-matched targets was unaffected by these modifications.  The chemical modification also reduced off-target phenotypes in growth inhibition studies.  Key to the modification was 2’-O-methyl ribosyl substitution at position 2 in the guide strand, which reduced silencing of most off-target transcripts with complementarity to the seed region of the siRNA guide strand.  The sharp position-dependence of 2’-O-methyl ribosyl modification contrasts with the broader position dependence of base pair substitutions within the seed region, suggesting a role for position 2 of the guide strand distinct from its effects on pairing to target transcripts.
Keywords: Microarray analysis, chemical modification walk, dose response

overall_design: Please see RNA. 2006 Jul;12(7):1197-205 for details.  We used consensus genelists for clustering; please see attached tables for genelists.

first: Julja

last: Burchard

first: Devin

last: Leake

first: Angela

last: Reynolds

first: Janell

last: Schelter

first: Jie

last: Guo

first: Jason

last: Johnson

first: Jon

last: Karpilow

first: Kim

last: Nichols

first: William

last: Marshall

first: Anastasia

last: Khvorova

first: Peter

middle: S

last: Linsley


title: Genome-wide resources of endoribonucleotide-prepared short interfering RNAs for specific loss-of-function studies

status: Public on Apr 10 2007

first: Aimee

last: Jackson

summary:
RNA interference (RNAi) has become an important technique for loss-of-gene functionstudies in mammalian cells. To achieve reliable results in an RNAi experiment, efficientand specific silencing triggers are required. Here we present genome-wide data sets forthe production of endoribonuclease-prepared short interfering RNAs (esiRNAs) for human, mouse and rat. We used an algorithm to predict the optimal region for esiRNA synthesis for every protein-coding gene of these three species. The database RiDDLE was installed for retrieval of target sequences and primer information. To test this in silico resource experimentally, we generated 16,242 esiRNAs that can be used for RNAi screening in human cells. Comparative analyses with chemically synthesized siRNAs demonstrated a high silencing efficacy of esiRNAs and a 12-fold reduction of downregulated off-target transcripts as detected by microarray analysis. Hence, the presented esiRNA libraries offer an efficient, cost-effective, and specific alternative to currently available mammalian RNAi resources.

Consensus gene lists used to generate the clusters appearing in the associated publication have been linked as supplementary files at the foot of the Series record. There is a consensus genelist for each gene in the study:

GSE6807_KIAA1387_ConsensusGeneList.txt
GSE6807_MAPK14_ConsensusGeneList.txt
Keywords: RNAi, off-target effects, esiRNA

overall_design: Synthetic siRNAs or endoribonucleotide-prepared siRNAs were transfected into human cells in culture.  RNA was isolated at 12 or 24 hours post-transfection and anaylzed by microarray for target gene silencing as well as silencing of unintented transcripts (off-target effects).  siRNA pool profiles were clustered with all transcripts on the microarray.  siRNA versus esiRNA clusters were generated with consensus gene lists.

first: Ralf

last: Kittler

first: Vineeth

last: Surendranath

first: Anne-Kristin

last: Heninger

first: Mikolaj

last: Slabicki

first: Mirko

last: Theis

first: Gabriele

last: Putz

first: Kristin

last: Franke

first: Antonio

last: Caldareli

first: Hannes

last: Grabner

first: Karol

last: Kozak

first: Jan

last: Wagner

first: Effi

last: Rees

first: Bernd

last: Korn

first: Christoph

last: Sachse

first: Birte

last: Sonnichsen

first: Bianca

last: Habermann

first: Frank

last: Buchholz


title: Blood and Adipose tissue samples

status: Public on Jun 13 2007

first: Valur

last: Emilsson

address: 401 Terry Avenue N

summary:
We analyzed the expression of 23,720 transcripts in the adipose tissue of 701 individuals and the blood of 1021 individuals.
Keywords: microarray profiling, genetics, gene expression

overall_design: Adipose tissue samples from 701 individuals and blood samples from 1021 individuals were profiled for gene expression.

first: Gudmar

last: Thorleifsson

first: Amy

last: Leonardson

first: Florian

last: Zink

first: Sonia

last: Carlson

first: Agnar

last: Helgason

first: Bin

last: Zhang

first: G

middle: B

last: Walters

first: Steinunn

last: Gunnarsdottir

first: Magali

last: Mouy

first: Valgerdur

last: Steinthorsdottir

first: Gudrun

middle: H

last: Eiriksdottir

first: Gyda

last: Bjornsdottir

first: Inga

last: Reynisdottir

first: Daniel

last: Gudbjartsson

first: Anna

last: Helgadottir

first: Aslaug

last: Jonasdottir

first: Adalbjorg

first: Unnur

last: Styrkarsdottir

first: Solveig

last: Gretarsdottir

first: Kristinn

last: Magnusson

first: Hreinn

last: Stefansson

first: Ragnheidur

last: Fossdal

first: Kristleifur

last: Kristjansson

first: Huortur

middle: G

last: Gislason

first: Tryggvi

first: Bjorn

last: Leifsson

last: Thorsteinsdottir

first: John

last: Lamb

first: Jeffrey

last: Gulcher

first: Marc

last: Reitman

first: Augustine

last: Kong

first: Eric

last: Schadt

first: Kari