title: Bladder cancer microarrays

status: Public on Feb 24 2011

city: Athens

first: George

last: Lambrou

state: Attiki

address: Thivon & Levadeias

department: First Department of Pediatrics

country: Greece

institute: National and Kapodistrian University of Athens

summary:
Background: Current diagnosis and treatment of urinary bladder cancer (BC) has shown great progress with the utilization of microarrays.
Purpose: Our goal was to identify common differentially expressed (DE) genes among clinically relevant subclasses of BC using microarrays.
Methodology/Principal Findings: BC samples and controls, both experimental as well as publicly available datasets, were analyzed by whole genome microarrays. We grouped the samples according to their histology and defined the DE genes in each sample individually as well as in each tumor group, respectively. A dual analysis strategy was followed: First, experimental samples were analyzed and conclusions were extracted; and second, experimental sets were combined with publicly available microarray datasets and were further analyzed in search for common DE genes. The experimental dataset, identified 831 genes that were differentially expressed in all tumor samples, simultaneously. Moreover, 33 genes were up-regulated and 85 genes were down-regulated in all 10 BC samples compared to the 5 normal tissues, simultaneously. Hierarchical clustering partitioned tumor groups in accordance to their histology. K-means clustering of all genes and all samples, as well as clustering of tumor groups, presented 49 clusters. K-means clustering of common DE genes in all samples revealed 24 clusters. Genes manifested various differential patterns of expression, based on PCA. YY1 and NFκB were among the most common transcription factors that regulated the expression of the identified DE genes. Chromosome 1 contained 32 DE genes, followed by chromosomes 2 and 11, which contained 25 and 23 DE genes, respectively. Chromosome 21 had the least number of DE genes. GO analysis revealed the prevalence of transport and binding genes in the common down-regulated DE genes; the prevalence of RNA metabolism and processing genes in the up-regulated DE genes; as well as the prevalence of genes responsible for cell communication and signal transduction in the DE genes that were down-regulated in T1-Grade III tumors and up-regulated in T2/T3-Grade III tumors. Combination of all available samples revealed 17 common genes (BMP4, CRYGD, DBH, GJB1, KRT83, MPZ, NHLH1, TACR3, ACTC1, MFAP4, SPARCL1, TAGLN, TPM2, CDC20, LHCGR, TM9SF1 and HCCS) four of which participate in numerous pathways.
Conclusions/Significance: The identification of the common DE genes among BC samples of different histology can provide further insight into the discovery of new putative markers.

overall_design:
Oligos microarray chips (~57k genes) were obtained from GE HealthCare (IL) and AppliedMicroarrays (MA) (former Amersham Biosciences) (CodeLink 57k Human Whole Genome). Hybridization was performed with the CodeLink RNA amplification and Labeling kit as described by the manufacturer, utilizing the Cy5 fluorescent dye. Slides were scanned with a microarray scanner (ScanArray 4000XL). Images were generated with ScanArray microarray acquisition software (GSI Lumonics, USA). cRNAs from three experimental setups were used in single experiments with internal spikes as controls. The experimental setups consisted of 10 urinary BC samples of different histology and 5 control samples. The scanned images were further processed with the CodeLink Expression Analysis Software v5.0 from Amersham Biosciences (presently GE Health Care Inc.). The experimental setup was analyzed based on the reference-design as described previously. All tumor samples were compared against the mean value of the control samples. Raw microarray data are available as supplementary data and at the GEO microarray database. All microarray data are MIAME compliant.
We used the following publicly available microarray datasets in our analysis: 1) GSE89 dataset (GDS183), comprised of 40 BC samples; 2) GSE3167 dataset (GDS1479), comprised of 60 samples (9 controls and 51 BC samples); 3) GSE7476 dataset, composed of 12 samples (3 controls and 9 BC samples) and 4) GSE12630 dataset, comprised of 19 BC samples. In total, our pooled microarray analysis was composed of 17 control samples (n=5, for the CodeLink platform; and n=12, for the rest microarray platforms) and 129 BC samples (n=10, for the CodeLink platform; and n=119, for the rest microarray platforms). Public data were used in their available normalized form, since background correction and normalization had already been performed.

first: Apostolos

last: Zaravinos

first: Ioannis

last: Boulalas

first: Demetrios

last: Delakas

last: Spandidos


title: Cancer genomics identifies regulatory gene networks associated with the transition from dysplasia to adenocarcinomas

status: Public on Mar 07 2011

city: Hannover

first: Astrid

last: Rohrbeck

state: Niedersachsen

address: Carl-Neuberg-Straße 1

department: Department of Toxicology

country: Germany

institute: Medizinische Hochschule Hannover

summary:
Lung cancer is a leading cause of deaths in the world. There is a need to improve an understanding of mechanisms of malignant transformation and to develop genetic markers of disease for better and targeted therapies.
Here, we report findings with a transgenic disease model where targeted expression of c-raf to respiratory epithelium induced adenocarcinomas. Specifically, by use of laser microdissection we harvested either tumor or transgenic and non-transgenic but otherwise morphologically unaltered cells. We then searched genome wide for regulated genes and validated results by quantitative real-time PCR. Overall, 473 and 541 genes were significantly regulated when cancer versus transgenic and cancer versus non-transgenic cells were compared. Principal component analysis and hierarchical clustering of the data clearly separated the cancer cells from transgenic and non-transgenics and we observed predominately repression of gene expression at advanced stages of tumor growth. Nonetheless genes up-regulated in dysplasia were also up-regulated in solid tumors. We observed groups of genes acting in concert either linked to development with an unexpected high number of genes coding either for the epithelial mesenchymal or mesenchymal endothelial transition. Additionally, genes coding for cell adhesion including the integrins and the tight and gap junction proteins were repressed (integrin alpha 1, integrin alpha 8, claudin 2, claudin 5, gap junction membrane channel protein alpha 5 and cadherin 5) but ligands for the membrane bound epidermal growth factor tyrosine kinase i.e. epi- and amphiregulin were up-regulated. Moreover, molecules in the signalling of vascular endothelial growth factor receptor- 2 and VEGFD, Notch and WNT were regulated as were glycosylases that facilitate cellular recognition. Other regulated signalling molecules included exchange factor such as RAP guanine nucleotide exchange factor 3, RHO guanine nucleotide exchange factor 10, RAS guanine releasing protein 2 and 3, and RAS guanine nucleotide-releasing factor 1 that play a role in an activation of the MAP kinases.
Notably, we found the tumor suppressors MCC (mutated in colorectal cancers), HEY1 (hairy/enhancer-of-split related with YRPW motif 1), FAT3 (FAT tumor suppressor homolog 3), ARMCX1 (armadillo repeat containing, X-linked 1) and RECK (reversion-inducing-cysteine-rich protein with kazal motifs) to be significantly repressed.
Taken collectively, our study provides valuable information for new candidate genes in lung adenocarcinoma induced by exaggerted c-raf kinase activity.

overall_design:
SP-C/c-raf model
SP-C/c-raf transgenic mice were obtained from the laboratory of Prof. Ulf Rapp (University of Würzburg, Germany), who bred the mice in the C57BL/6/DBA/2 hybrid background. We kept the SP-C/c-raf transgenic mice in the C57BL/6 background for at least five generations.
Lung cancer samples were derived from SP-C/c-raf mice (aged 12 – 14 months); unaltered lung tissue were always isolated from the transgenic mouse (aged 5 – 7 months). Endogenous normal lung tissue was studied of non-transgenic mice (aged 7 – 10 months). The non-transgenic littermates (wild-type) served as control for transgenic effects.
Mice were sacrificed and the lung tissues were immediately frozen on dry ice and stored at -80°C until further analysis.
The histopathological diagnosis was based on routinely processed hematoxylin-eosin stains.

Microdissection (LMPC – Laser Microbeam Microdissection and Laser Pressure Catapulting)
From each frozen lung tissue 10-µm thick sections were prepared and transferred on polyethylene napthalate foil-covered slides (Zeiss, P.A.L.M. Microlaser Technologies GmbH, Bernried, Germany).
The sections were fixed in methanol / acetic acid and stained in hematoxylin. The desired cells were microdissected using the PALM MicroLaser systems (Zeiss, P.A.L.M. Microlaser Technologies GmbH, Bernried, Germany) and collected in an adhesive cap (Zeiss, P.A.L.M. Microlaser Technologies GmbH, Bernried, Germany). Microdissected cells were resuspended in a guanidine isothiocyanate-containing buffer (RLT buffer from RNeasy MikroKit, Qiagen, Santa Clarita, CA, USA) with 10 µl/ml β-mercaptoethanol to ensure isolation of intact RNA. Approximately an area of 6 x 106 µm2 were pooled from a specific layer of interest in the same animal and used for RNA extraction.
Following microdissection, total RNA-extraction was performed with the RNeasy Micro Kit (RNeasy MicroKit Qiagen, Santa Clarita, CA, USA) according to the manufacturer’s instruction. A standard quality control of the total RNA was performed using the Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, USA).

cRNA labeling and hybridization to microarrays
Total RNA (median: 175ng; range: 150 – 200ng) was used to generate biotin-labeled cRNA (10 µg) by means of Message Amp aRNA Premium Amplification Kit (Ambion, Austin, TX). Quality control of cRNA was performed using a bioanalyzer (Agilent 2001 Biosizing, Agilent Technologies). Following fragmentation, labeled cRNA of each sample was hybridized to Affymetrix GeneChip® Mouse Genome 430 2.0 Arrays covering over 34.000 genes and stained according to the manufacturer's instructions.

Quantification, normalization and statistical analysis
Array data was normalized using scaling or per-chip normalization to adjust the total or average intensity of each array to be approximately the same.
Microarray chips were analyzed by the GCOS (GeneChip Operating Software) from Affymetrix with the default settings except that the target signal was set to 500 and used to generate a microarray quality control and data report.
CEL files exported from GCOS were uploaded into ArrayTrack software (National Center for Toxicological Research, U.S. FDA, Jefferson, AR, USA (NCTR/FDA)) and normalized using Total Intensity Normalization after subtracting backgrounds for data management and analysis. ArrayTrack software includes some tools common to other bioinformatics software (e.g., ANOVA, T-test and SAM).

SAM
To compare the normalized data from dysplasia, normal lung tissue from transgenic mouse, tumor cells and non-transgenic of different mice, we used the Significance Analysis of Microarrays (SAM) algorithm (ArrayTrack), which contains a sliding scale for false discovery rate (FDR) of significantly up- and down-regulated genes [204]. All data were permuted 100 cycles by using the two classes, unpaired data mode of the algorithm. As cut-off for significance an estimated FDR of 0.001 was chosen. Moreover, a cut-off for fold-change of differential expression of 2 was used.

Two clustering approaches were used to determine components of variation in the data in this study as follows.
A) Principal-component analysis (PCA) that was used to obtain a simplified visualization of entire datasets. PCA is a useful linear approach to obtain a simplified visualization of entire datasets, without losing experimental information (variance). PCA allowed the dimension of complex data to be reduced and highlights the most relevant features of a given dataset to be highlighted.
B) Hierarchical gene clustering (HCA) where the data points were organized in a phylogenetic tree in which the branch lengths represent the degree of similarity between the values.
Lists of significantly differentially expressed genes were uploaded to Ingenuity Pathways Analysis (IPA, Ingenuity Systems Inc., Redwood City, CA, USA) (www.Ingenuity.com) and functional annotation and pathway analysis was performed. IPA is a commercial, web-based interface that uses a variety of computational algorithms to identify and establish cellular networks that statistically fit the input gene list and expression values from experiments. The analysis uses a database of gene interactions culled from literature and updated every quarter of the year.
Additionally, Venn diagrams were used to examine the overlap of resulting lists of genes differentially expressed between the different sample sets.

first: Jürgen

last: Borlak


title: High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes

status: Public on Mar 01 2011

city: Marseille

first: Pascal

last: FINETTI

state: BdR

address: 232 Bd Ste Marguerite

department: Centre de cancérologie de Marseille

country: France

institute: Institut Paoli-Calmettes

type:
Expression profiling by array
Genome variation profiling by array

summary: Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples. Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent “complex” patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs.

overall_design: Pre-treatment tumor tissues were collected from 197 patients with invasive adenocarcinomas. Patients underwent surgical biopsies or initial surgery at the Institut Paoli-Calmettes (IPC, Marseille, France) between 1987 and 2007. Each patient gave written informed consent and the study was approved by the IPC “Comité d’Orientation Stratégique”. Tumor samples were macrodissected and frozen in liquid nitrogen within 30 minutes of removal. Before RNA extraction, tumor sections were reviewed by two pathologists and contained more than 60% of tumor cells. Gene expression data of the 197 BCs were quantified using whole-genome DNA microarrays (HG-U133 Plus 2.0, Affymetrix).

first: I

last: Bekhouche

first: P

last: Finetti

first: J

last: Adelaïde

first: A

last: Ferrar

first: C

last: Tarpin

first: E

last: Charafe-Jauffret

last: Charpin

first: G

last: Houvenaeghel

last: Jacquemier

last: Bidaut

first: D

last: Birnbaum

last: Viens

first: M

last: Chaffanet

first: F

last: Bertucci


title: Molecular characterization of lung dysplasia induced by c-raf-1

last: Rohrbeck

summary:
Background: Lung cancer is a multistage process with poor prognosis and high morbidity. Importantly, the genetics of dysplasia, a facultative cancer, at the edge of malignant transformation is unknown.
Results: We employed laser microdissection to harvest dysplastic as opposed to transgenic but otherwise morphologically unaltered epithelium and compared findings to non-transgenic lung. We then employed microarrays to search genome wide for gene regulatory networks. A total of 120 and 287 genes were significantly regulated, respectively. Dysplasia was exclusive associated with up-regulation of genes coding for cell growth and proliferation, cell-to-cell signalling and interaction, lipid metabolism, development, and cancer. Likewise, when dysplasia was compared with non-transgenic cells up-regulation of cancer associated genes, tight junction proteins, xenobiotic defence and developmental regulators was observed. We additionally confirmed regulation of some genes by immunohistochemistry and therefore demonstrate good concordance between gene regulation and coded protein.
Conclusion: Our study identified transcriptional networks at successive stages of tumor-development, i.e. from histological unaltered but transgenic lungs to nuclear atypia. Our animal model revealed interesting and novel candidate genes and pathways that provide clues on the mechanism forcing respiratory epithelium into dysplasia and subsequently cancer, some of which might also be useful in the molecular imaging and flagging of early stages of disease.

overall_design: In our study, we used predominately 5 month old mice to gain information at an early stage of tumor development where isolated foci of transformed cells in distinct areas of the lung are visible. By use of laser microdissection pressure catapulting (LMPC) dysplastic cells in well defined lesions [18] could be isolated. Dysplastic lesions were than compared with transgenic but otherwise normal cells or tumor cells. We applied whole genome microarrays to determine differentially expressed genes as to identify the gene regulatory networks associated with dysplasia and, as will be reported in a second part of our study, the subsequent malignant transformation. Overall, our study revealed interesting and novel genes and pathways that may contribute to the early stages of lung cancer development many of which are worthy for their exploration as candidate biomarkers and for molecular imaging of early stages of disease.

first: Volker

last: Müller


title: Deep sequencing of small RNAs from Tribolium castaneum

status: Public on Dec 29 2010

city: Colchester

first: Antonio

last: Marco

address: Wivenhoe Park

department: School of Life Sciences

country: United Kingdom

institute: University of Essex

type: Non-coding RNA profiling by high throughput sequencing

summary: Characterization of miRNAs in red flour beetle Tribolium castaneum by deep sequencing of two different RNA libraries.

overall_design: Sequencing of Tribolium small RNAs from adults and embryos.

first: Jerome

middle: H

last: Hui

first: Matthew

last: Ronshaugen

first: Sam

last: Griffiths-Jones


title: Trichoderma atroviride transcript levels during mycoparasitism

status: Public on Jul 01 2011

city: Paris

first: Stéphane

last: LE CROM

address: 46 rue d'Ulm

department: Biology Institute - IBENS

institute: École normale supérieure

type: Expression profiling by genome tiling array

summary: To investigate the potential role in mycoparasitism, microarrays were used to examine T. atroviride transcript levels when confronted with a potential prey (the plant pathogen Rhizoctonia solani) before contact, during first physical contact and during overgrowth of the host.

overall_design: Two biological poolw by condition against a common reference control each sample hybridized in dye switch. On the two biological replicates we apply on the pretreated results the linear modeling approach implemented by lmFit and the empirical Bayes statistics implemented by eBayes from the limma R package (Smyth 2004).

first: Christian

last: Kubicek

first: Fanny

last: Coulpier

first: Stephane

last: Le Crom

first: Verena

last: Seidl

first: Susanne

last: Zeilinger


title: Gene expression in mouse lung epithelial cells treated with synthetic TLR ligands to induce resistance

status: Public on Jan 27 2011

city: Houston

first: Scott

middle: E

last: Evans

state: TX

address: 1400 Holcombe Blvd

department: Pulmonary Medicine - Unit 1462

country: USA

institute: University of Texas-M.D. Anderson Cancer Center

summary: Infectious pneumonias exact an unacceptable mortality burden worldwide.  Efforts to protect populations from pneumonia have historically focused on antibiotic development and vaccine-enhanced adaptive immunity.  However, we have recently reported that the lungs’ innate defenses can be therapeutically induced by inhalation of a bacterial lysate that protects mice against otherwise lethal pneumonia.  Here, we tested in mice the hypothesis that Toll-like receptors (TLRs) are required for this antimicrobial phenomenon, and found that resistance could not be induced in the absence of the TLR signaling adaptor protein MyD88.  We then attempted to recapitulate the protection afforded by the bacterial lysate by stimulating the lung epithelium with aerosolized synthetic TLR ligands.  While most single or combination treatments yielded no protection, simultaneous treatment with ligands for TLR2/6 and TLR9 conferred robust, synergistic protection against virulent Gram-positive and Gram-negative pathogens.   Protection was associated with rapid pathogen killing in the lungs, and pathogen killing could be induced from lung epithelial cells in isolation.  Taken together, these data demonstrate the requirement for TLRs in inducible resistance against pneumonia, reveal a remarkable, unanticipated synergistic interaction of TLR2/6 and TLR9, reinforce the emerging evidence supporting the antimicrobial capacity of the lung epithelium, and may provide the basis for a novel clinical therapeutic that can protect patients against pneumonia during periods of peak vulnerability.

overall_design: MLE-15 cells were treated with 20 ul volumes of PBS (sham treatment), ODN2395 (0.4 ug), Pam2CSK4 (0.2 ug) or ODN2395+Pam2CSK4.  At least 5 unique samples per group. Treated for 2 hours. Hybridized to Illumina Sentrix MouseRef-8 v2 Beadhips.


title: Comparison of genomic, morphological, and behavioral responses among fathead minnow (Pimephales promelas ) and zebrafish (Danio rerio) to acute RDX exposure

status: Public on Feb 08 2011

city: Vicksburg

first: Mitchell

last: Wilbanks

state: MS

address: 3909 Halls Ferry Road

department: Environmental Laboratory

institute: US Army Engineer Research and Development Center

summary: Paper Abstract. Extrapolating toxicological sensitivity information across species can require the use of highly conservative safety factors as prescribed by ecological risk assessment protocols.  The objective of our study was to use multipule factors to understand the dynamics of stress responses by comparing ecotoxicological, developmental, and genomic data to quantitatively determine the relative sensitivity of two common model aquatic vertebrates to assess the potential for developing refined safety factors among species.   Larval (3-d old) zebrafish (Danio rerio) and fathead minnows (Pimephales promelas) were concurrently exposed in 96-h static exposures to the widely-used military energetic compound cyclotrimethylenetrinitramine (RDX).  Endpoints assessed included mortality, incidence of vertebral deformities, swimming behavior, and differential gene (transcript) expression.  Analytically verified treatment concentrations ranged from 0.9 to 27.7 mg/L RDX.  While RDX concentrations prepared for exposures included 0, 0.9, 1.8, 3.5, 7.5, 15.0, and 30.0 mg/L, analytically verified treatment concentrations were 0, 0.88, 1.75, 3.46, 6.96, 13.79, and 27.7 mg/L, respectively.  Changes in prepared RDX concentrations and analytically verified treatment concentrations are a result of chemical breakdown, a well known characteristic of RDX    Our results indicated a higher sensitivity to RDX in P. promelas than in D. rerio in both mortality (LOECs 13.79 and 27.7 mg/L, respectively) and vertebral deformity (LOECs 13.79 and >13.79, respectively) endpoints.  Swimming behavior was assessed in 10 min behavioral trials using Noldus EthoVision® digital tracking software.  Swimming behavior trials indicated non-significant trends of decreased velocity, distance moved, and increased meander (change in direction per cm traveled) for P. promelas.  No such trends were apparent in D. rerio swimming behavior.  A comprehensive genomic analysis is in progress to determine the genes, gene ontology elements, metabolic pathways and metabolic networks affected in common among species in the RDX exposure.  Taken as a whole, the ecotoxicological, developmental and genomic results will provide valuable insights into the similarity in response among these fish species to RDX.

sample_organism:
Danio rerio
Pimephales promelas

platform_organism:
Danio rerio
Pimephales promelas

overall_design: Three-day-old fathead minnow (FHM, Pimephales promelas) or Zebrafish (ZF, Danio rerio) fry were exposed to either control water or one of six concentrations of RDX (0.9, 1.9, 3.8, 7.5, 15, or 27.7 mg/L) in 96-h exposures.  However, microarray analysis was only performed on FHM exposed to 0, 0.9, 1.9, 7.5, or 15 mg/L RDX and ZF exposed to 0, 0.9, 1.9, 3.8, 7.5, or 15 mg/L RDX due to insufficient tissue for microarray analysis due to animal death at the other RDX concentrations.   The experimental design was based on the U.S. EPA (2002) acute testing method for P. promelas, test method 2000.0 and included four replicates per treatment with ten fish per replicate. Whole fish (10 fish per replicate) were investigated for differential expression in response to RDX exposure.

first: Chris

last: Warner

first: Kurt

middle: A

last: Gust

first: Jacob

middle: K

last: Stanley

middle: S

first: Tony

last: Bednar

first: Tanwir

last: Habib

first: Natalia

last: Vinas

first: Edward

middle: J

last: Perkins


title: Genome-wide mapping of the HY5-mediated gene networks in Arabidopsis that involve both transcriptional and post-transcriptional regulations: ChIP-Chip

status: Public on Dec 31 2010

city: New Haven

first: Hang

last: He

state: CT

address: 165 Prospect St

department: MCDB

institute: Yale University

type: Genome binding/occupancy profiling by genome tiling array

summary: LONG HYPOCOTYL 5 (HY5) is a basic leucine zipper transcription factor (TF) that functions downstream of multiple families of photoreceptors. Mutations in the HY5 gene cause a myriad of aberrant phenotypes in Arabidopsis, including elongated hypocotyl, reduced accumulation of pigments, halted chloroplast development in greening hypocotyls, altered root morphology and defective hormonal and stimulus responses. HY5 thus acts as an integrater that links various gene networks to coordinate plant development. Here we report an effort to experimentally map the HY5-mediated gene networks in Arabidopsis by integrating genomic loci occupied by HY5 and HY5-dependent gene expression profiles. Our results indicate HY5 binds to over 9,000 genes, which detectably impact the expression of over 1,100 genes, either positively or negatively. Further, HY5 indirectly regulates many other genes through sub-networks mediated by other regulators. In particular, we show that HY5 regulates eight microRNA (miRNA) genes, which in turn control transcript abundance of specific target genes. Over-expressing the HY5-targeted miR408 resulted in phenotypes that are opposite to hy5 mutants. Together our results revealed both the transcriptional and post-transcriptional components of the HY5-mediated gene networks responsible for the phenotypic complexity in plants.

overall_design: Chromatin isolation was performed with 4-day-old whole seedlings grown under wild type light (WL) or 8hr darkness treatment according to Bowler et al. (2004). The resuspended chromatin pellet was sonicated at 4°C with a Diagenode Bioruptor set at high intensity for 10 min (30 s on, 30 s off intervals). The DNA was sheared to an average size of approximately 500 bp. Chromatin was immunoprecipitated, washed, reverse cross-linked, amplified, and hybridized according to the Affymetrix Chromatin Immunoprecipitation Assay Protocol Rev.3. A polyclonal HY5 antibody purified from anti-HY5 rabbit IgG using Sepharose 4B beads coupled with purified recombinant HY5 protein was used. ‘Flow-through’ IgG devoid of the HY5 antibody was used as a negative control. An aliquot of untreated sonicated chromatin was reverse cross-linked and used as a total input DNA control for ChIP-PCR experiments. Four biological replicates for each experimental condition and two biological replicates for each control condition were hybridized to tiling arrays, resulting in a total of 12 chips.

first: Huiyong

last: Zhang

first: Xuncheng

last: Wang

first: Xiangfeng

first: Xiaozeng

last: Yang

first: Lei

last: Li

first: Xing

middle: W

last: Deng


title: Genome-wide mapping of the HY5-mediated gene networks in Arabidopsis that involve both transcriptional and post-transcriptional regulations

type: Expression profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Genome-wide mapping of the HY5-mediated gene networks in Arabidopsis that involve both transcriptional and post-transcriptional regulations: RNA-Seq

overall_design: DNase I-treated total RNA was prepared from wild type and hy5-215 seedlings grown under wild type light (WL). The mRNA fraction was extracted from total RNA using Dynabeads oligo(dT)25 (Invitrogen) following the manufacturer’s directions. First- and second-strand cDNA were generated usingSuperScript II and random hexamer primers. Double-stranded cDNA was fragmented by nebulization and used for mRNA library construction following the manufacturer’s protocol (Illumina). Bowtie (Langmead et al., 2009) was used to map the sequence reads to the Arabidopsis genome and only uniquely mapped reads were used in subsequent analyses.


title: Warming-induced shifts in Antarctic soil microorganisms disrupt soil functioning

status: Public on Dec 30 2010

city: Montreal

first: Etienne

last: Yergeau

state: Qc

address: 6100 Royalmount Ave

department: Environmental Microbiology

country: Canada

institute: NRC-BRI

summary: Because of severe abiotic limitations, Antarctic soils represent simplified ecosystems, where microorganisms are the principle drivers of nutrient cycling. This relative simplicity makes these ecosystems particularly vulnerable to perturbations, like global warming, and the Antarctic Peninsula is among the most rapidly warming regions on the planet. However, the consequences of the ongoing warming of Antarctica on microorganisms and the processes they mediate are unknown. Here, using 16S rRNA gene pyrosequencing and qPCR, we report a number of highly consistent changes in microbial community structure and abundance across very disparate sub-Antarctic and Antarctic environments following three years of experimental field warming (+ 0.5-2°C). Specifically, we found significant increases in the abundance of fungi and bacteria and in the Alphaproteobacteria-to-Acidobacteria ratio. These alterations were linked to a significant increase in soil respiration. Furthermore, the shifts toward generalist or opportunistic bacterial communities following warming weakened the linkage between bacterial diversity and functional diversity. Warming also increased the abundance of some organisms related to the N-cycle, detected as an increase in the relative abundance of nitrogenase genes via GeoChip microarray analyses. Our results demonstrate that soil microorganisms across a range of sub-Antarctic and Antarctic environments can respond consistently and rapidly to increasing temperatures, thereby potentially disrupting soil functioning.

sample_organism:
environmental samples
environmental samples

overall_design: We conducted in situ warming experiments for three years using open-top chambers (OTCs) at one sub-Antarctic (Falkland Islands, 52ºS) and two Antarctic locations (Signy and Anchorage Islands, 60ºS and 67ºS respectively) (see Supplementary Fig. 1 for a map). OTCs increased annual soil temperature by an average of 0.8°C (at a depth of 5 cm), resulting in 8-43% increase in positive-degree days annually and a decrease in freeze-thaw cycle frequency by an average of 15 cycles per year (8). At each location, we included densely vegetated and bare fell-field soils in the experimental design for a total of six environments. Densely vegetated and bare environments represent two contrasting environments for Antarctic soil microorganisms, with large differences in terms of C and N inputs to soils. Massively parallel pyrosequencing (Roche 454 GS FLX Titanium) of 16S rRNA gene amplicons was used to follow bacterial diversity and community composition [GenBank Accession Numbers: HM641909-HM744649], and functional gene microarrays (GeoChip 2.0)(11) were used to assess changes in functional gene distribution. Bacterial and fungal communities were also quantified using real-time PCR.

first: Stef

last: Bokhorst

first: Sanghoon

last: Kang

first: Jizhong

last: Zhou

first: Charles

last: Greer

first: Rien

last: Aerts

first: George

last: Kowalchuk


title: Gene expression determination in breast muscle associated with the phenotypic expression of feed efficiency (FE) in a single male broiler line

status: Public on Nov 24 2010

city: Fayetteville

first: Walter

middle: G

last: Bottje

state: AR

address: 1260 W. Maple, POSC, O-405

department: Poultry Science

institute: University of Arkansas

summary: Gene expression determination between breast muscle associated with the phenotypic expression of feed efficiency (FE) in a single male broiler line. Goal was to determine the changes of gene expression by feed efficiency (FE).

overall_design: Two-condition experiment, high feed efficiency vs. low feed efficiency. Biological replicates: breast muscles from 4 high feed efficiency male broiler, breast muscles from 4 low feed efficiency male broiler

first: Byung-Whi

last: Kong

first: Jeong-Yoon

last: Lee


title: Molecular Characterization of Breast Cancer Subtypes from Joint Analysis of High Throughput miRNA and mRNA Data (II)

status: Public on Dec 01 2010

city: Oslo

first: Hilde

last: Johnsen

address: Montebello

department: Genetics

country: Norway

institute: Norwegian Radium Hospital

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

summary: MicroRNAs (miRNAs) are a class of short, single-stranded widely expressed noncoding RNAs that regulate the stability or translational efficiency of target messenger RNAs. Date derived from expression profiling of 489 miRNAs in 101 human primary breast tumor samples, along with genome-wide matched mRNA profiling and extensive clinical information were investigated in this study. miRNA and mRNA expression were analyzed using correlations and enrichments analyses. The results show that particular cellular processes such as proliferation, cell adhesion, and immune response are significantly enriched among genes with strong positive or negative correlation to individual or groups of miRNAs. Functional analyses were performed to validate the influence of miRNAs on proliferation. A group of miRNAs was identified that is associated to breast cancer disease free survival. This study provides a comprehensive dataset that can be used as groundwork for further studies of the involvement of miRNA in breast cancer.

overall_design:
miRNA profiling from 101 breast cancer samples was performed. Experiments were mostly performed using duplicate hybridizations (99 samples) on different arrays and time points. Two samples were profiled only once. miRNA signal intensities for replicate probes were averaged across the platform, log2 transformed and normalized to the 75 percentile. miRNA expression status was scored as present or absent for each gene in each sample by default settings in FE v9.5. miRNAs in samples that were run in replicates were considered present if scored in one of the two arrays.
mRNA profiling from 115 breast cancer samples was performed. Replicates not included. Four new arrays were added in this version with 115 samples versus the one with 114 samples (GSE19536). For samples 34, 107 and 185, a new array replaces the old one, generally with only small differences in values. Sample 391 is added to the 115 sample dataset. Replicates not included.

first: Espen

last: Enerly

first: Israel

last: Steinfeld

first: Kristine

last: Kleivi

first: Suvi

last: Leivonen

first: Hege

last: Russnes

first: Jo

last: Rønneberg

first: Roy

last: Navon

first: Einar

last: Rødland

first: Miriam

middle: R

last: Aure

first: Rami

last: Mäkelä

first: Bjørn

last: Naume

first: Merja

last: Perälä

first: Olli

last: Kallioniemi

first: Vessela

middle: N

last: Kristensen

first: Anne-Lise

last: Børresen-Dale

first: Zohar

last: Yakhini


title: The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice

status: Public on Dec 27 2010

city: Los Angeles

first: Giovanni

last: Coppola

state: CA

address: 1524 Gonda, 695 Charles Young Drive South

department: Psychiatry and Neurology

institute: UCLA

summary: Transcriptional dysregulation has emerged as a core pathologic feature of Huntington's disease (HD), one of several triplet-repeat disorders characterized by movement deficits and cognitive dysfunction. Although the mechanisms contributing to the gene expression deficits remain unknown, therapeutic strategies have aimed to improve transcriptional output via modulation of chromatin structure. Recent studies have demonstrated therapeutic effects of commercially available histone deacetylase (HDAC) inhibitors in several HD models; however, the therapeutic value of these compounds is limited by their toxic effects. Here, beneficial effects of a novel pimelic diphenylamide HDAC inhibitor, HDACi 4b, in an HD mouse model are reported. Chronic oral administration of HDACi 4b, beginning after the onset of motor deficits, significantly improved motor performance, overall appearance, and body weight of symptomatic R6/2(300Q) transgenic mice. These effects were associated with significant attenuation of gross brain-size decline and striatal atrophy. Microarray studies revealed that HDACi 4b treatment ameliorated, in part, alterations in gene expression caused by the presence of mutant huntingtin protein in the striatum, cortex, and cerebellum of R6/2(300Q) transgenic mice. For selected genes, HDACi 4b treatment reversed histone H3 hypoacetylation observed in the presence of mutant huntingtin, in association with correction of mRNA expression levels. These findings suggest that HDACi 4b, and possibly related HDAC inhibitors, may offer clinical benefit for HD patients and provide a novel set of potential biomarkers for clinical assessment.

overall_design: Analysis of striatum, cortex, and cerebellum from R6/2(300Q) transgenic mice before and after treatment with the HDAC inhibitor 4b

first: E

last: Thomas

first: G

first: P

last: Desplats

first: B

last: Tang

last: Soragni

first: R

last: Burnett

first: F

last: Gao

first: K

middle: M

last: Fitzgerald

first: J

middle: F

last: Borok

first: D

last: Herman

last: Geschwind

last: Gottesfeld


title: Global gene expression profile of small intestine from wild-type and NKCC1 (SLC12A2)-knockout mice.

status: Public on Nov 17 2010

city: Cincinnati

first: Gary

last: Shull

state: OH

address: 231 Albert Sabin Way ML0524

institute: University of Cincinnati

summary: The objective of this study was to identify changes in gene expression levels between wild-type and NKCC1-knockout small intestine.

overall_design: 6 wild-type and 6 NKCC1-knockout small intestine RNA samples were compared.  Total RNA was collected from both male and female 8-week old wild-type and NKCC1-null mice on an inbred FVB\N background. All comparisons were done between wild-type and NHE4-null samples from age- and gender-matched mice.

first: Emily

last: Bradford


title: Expression data from peptidoglycan stimulated CD11b+ cells from NOD and NOD.Idd3

status: Public on Sep 28 2010

city: Boston

first: Vijay

last: Kuchroo

state: MA

address: 77 Avenue Louis Pasteur, HIM 785

institute: Harvard Medical School

summary: CD11b+ CD11c- cells were isolated by cell sorting from the spleens of NOD and NOD.Idd3 mice.  Cells were then either unstimulated or stimulated with peptidoglycan (5ug/ml) for 4 hours at 37 degrees prior to RNA extraction. Peptidoglycan was chosen as a stimulus due to its know ability to stimulate CD11b+ cells through Toll-like receptor 2 and our previous data showing biological differences between NOD and NOD.Idd3-derived CD11b+CD11c- cells after stimulation with peptidoglycan.

overall_design: CD11b+ cells from NOD and NOD.Idd3 were either unstimulated or stimulated with peptidoglycan(PGN) for 4 hours at 37 degerees prior to RNA extraction.

first: Sue

last: Liu

first: Ana

middle: C

last: Anderson


title: Gene expression profiles of ovarian cancer cell lines in the presence and absence of a DNA methyltransferase inhibitor

city: Durham

first: Susan

middle: K.

last: Murphy

state: NC

address: B226 LSRC B Wing, Research Drive, Box 91012

department: Obstetrics and Gynecology

institute: Duke University Medical Center

summary:
Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies.  Diagnosis usually occurs after metastatic spread, largely reflecting vague symptoms of early disease combined with lack of an effective screening strategy.  Epigenetic mechanisms of gene regulation, including DNA methylation, are fundamental to normal cellular function and also play a major role in carcinogenesis. To elucidate the biological and clinical relevance of DNA methylation in ovarian cancer, we conducted expression microarray analysis of 39 cell lines and 17 primary culture specimens grown in the presence or absence of DNA methyltransferase (DNMT) inhibitors. Two parameters, induction of expression and standard deviation among untreated samples, identified 378 candidate methylated genes, many relevant to TGF-beta signaling. We analyzed 43 of these genes and they all exhibited methylation.  Treatment with DNMT inhibitors increased TGF-beta pathway activity. Hierarchical clustering of ovarian cancers using the 378 genes reproducibly generated a distinct gene cluster strongly correlated with TGF-beta pathway activity that discriminates patients based on age. These data suggest that accumulation of age-related epigenetic modifications leads to suppression of TGF-beta signaling and contributes to ovarian carcinogenesis.

The cancer stem cell hypothesis posits that malignant growth arises from a rare population of progenitor cells within a tumor that provide it with unlimited regenerative capacity. Such cells also possess increased resistance to chemotherapeutic agents.  Resurgence of chemoresistant disease following primary therapy typifies epithelial ovarian cancer and may be attributable to residual cancer stem cells, or cancer initiating cells, that survive initial treatment.  As the cell surface marker CD133 identifies cancer initiating cells in a number of other malignancies, we sought to determine the potential role of CD133+ cells in epithelial ovarian cancer.  We detected CD133 on ovarian cancer cell lines, in primary cancers, and on purified epithelial cells from ascitic fluid of ovarian cancer patients. We found CD133+ ovarian cancer cells generate both CD133+ and CD133- daughter cells, whereas CD133- cells divide symmetrically. CD133+ cells exhibit enhanced resistance to platinum-based therapy, drugs commonly used as first line agents for treatment of ovarian cancer.  Sorted CD133+ ovarian cancer cells also form more aggressive tumor xenografts at a lower inoculum than their CD133- progeny. Epigenetic changes may be integral to the behavior of cancer progenitor cells and their progeny.  In this regard, we found that CD133 transcription is controlled by both histone modifications and promoter methylation. Sorted CD133- ovarian cancer cells treated with DNA methyltransferase and histone deacetylase inhibitors show a synergistic increase in cell surface CD133 expression.  Moreover, DNA methylation at the ovarian tissue active P2 promoter is inversely correlated with CD133 transcription.  We also found that promoter methylation increases in CD133- progeny of CD133+ cells, with CD133+ cells retaining a less methylated or unmethylated state. Taken together, our results show that CD133 expression in ovarian cancer is directly regulated by epigenetic modifications and support the idea that CD133 demarcates an ovarian cancer initiating cell population.  The activity of these cells may be epigenetically detected and such cells might serve as pertinent chemotherapeutic targets for reducing disease recurrence.

overall_design:
The objective of the study was to identify genes that are subject to DNA methylation through pharmacological inhibition of DNA methyltransferase activity in a panel of cancer cell lines. Cells were mock treated with culture media (mock treated) or treated with 5 µM decitabine for 72 hours.  Resulting expression profiles were compared to identify genes with altered expression following decitabine treatment.

These data represent two experiments: In the first, 43 established cell lines were mock treated or treated with decitabine to enable identification of genes differentially expressed as a result of inhibition of DNA methyltransferase activity. HEYA8-decitabine treated cells were run in replicate. In the second experiment, A2780 and PEO1 cells underwent flow activated cell sorting to separate CD133(+) from CD133(-) cells in each cell line; the sorted cell populations were cultured in the same manner as the first experiment and similarly mock treated or treated with decitabine.  All specimens were arrayed in parallel and used for RMA normalization.

first: Andrew

last: Berchuck


title: Gene expression profiles of primary cultured ovarian cells and ovarian cancer cell lines in the presence and absence of a DNA methyltransferase inhibitor


title: Nell-1 primary response gene

status: Public on Sep 01 2010

city: los angeles

first: wei wei

last: chen

address: 10833 Le Conte Avenue

summary: We hypothesized that Nell-1, as a growth factor, is supposed to stimulate some molecular mediators, which transmit signals to downstream and finally affect chondrogenic differentiation. The molecular mediators which respond to Nell-1 in short time are our research objects, we called them primary response genes referred to pervious report . To find out Nell-1 primary response gene candidates, we first used microarray assays to analyze the differences of gene expression profile between rhNell-1 protein (100 ng/ml) and control (PBS) treatment.

overall_design: For screening real primary response genes, which is not regulated by new synthesis protein, ATDC5 cells were subjected to serum starvation, followed by protein synthesis inhibitor CHX (10 μg/ml) treatment for 30 min and then treated with PBS (control) or rhNell-1 protein (100 ng/ml) for another 30 min. Cell total RNA samples were sent to the UCLA DNA Microarray Centre (Los Angeles, CA) where target preparation and hybridization to the Affymetrix Murine 430 2.0 GeneChip was carried out following the standard protocol (http://www.affymetrix.com). This GeneChip contains over 39,000 full-length mouse genes and EST clusters from the UniGene database. The data obtained from the hybridization was preprocessed using Affymetrix GeneChip Command Console Software (AGCC) and Expression Console Software to generate probe set intensity data (Affymetrix, Santa Clara, CA). Expression values were further filtered by retaining only those probe sets with a fold change of at least 1.5 in rhNell-1 protein treatment samples compared with controls.

first: weiwei

first: Xinli

last: zhang

first: Kang

last: Ting

first: Chia

last: Soo


title: Increased hemoglobin expression in NASH livers

status: Public on Oct 21 2010

city: Buffalo

last: Baker

state: NY

address: 3435 Main street, 422 BRB

department: Pediatrics

institute: SUNY at Buffalo

summary: BACKGROUND & AIMS: Recent studies revealed that hemoglobin is expressed in some non-erythrocytes and it suppresses oxidative stress when overexpressed. Oxidative stress plays a critical role in the pathogenesis of non-alcoholic steatohepatitis (NASH). This study was to investigate whether hemoglobin is expressed in hepatocytes and how it is related to oxidative stress in NASH patients. METHODS: Microarray was performed to identify differentially expressed genes in NASH. Quantitative real time PCR (qRT-PCR) was used to examine gene expression levels. Western blotting and immunofluorescence staining were employed to examine hemoglobin proteins. Flow cytometry was used to measure intracellular oxidative stress. RESULTS: Analysis of microarray gene expression data has revealed a significant increase in the expression of hemoglobin alpha (HBA1) and beta (HBB) in liver biopspies from NASH patients. Increased hemoglobin expression in NASH was validated by qRT-PCR. However, the expression of erythrocyte specific marker genes such as SPTA, SPTB, GYPA, GATA1, and ALAS2 did not change, indicating that increased hemoglobin expression in NASH was not from erythropoiesis, but could result from increased expression in hepatocytes. Immunofluorescence staining demonstrated positive HBA1 and HBB expression in the hepatocytes of NASH livers. Hemoglobin expression was also observed in human hepatocellular carcinoma HepG2 cell line. Furthermore, treatment with hydrogen peroxide, a known oxidative stress inducer, induced a dose dependent increase in HBA1 expression in HepG2 cells. Intriguingly, forced hemoglobin expression suppressed oxidative stress. CONCLUSIONS: Oxidative stress upregulates hemoglobin expression in hepatocytes. Suppression of oxidative stress by hemoglobin could be a mechanism to protect hepatocytes from oxidative damage. These findings suggest that hemoglobin is an inducible antioxidant in hepatocytes in response to increased oxidative stress as found in NASH livers.

overall_design: Twelve biopsy diagnosed NASH patients were included in this study. For control groups, total RNA from 5 different subjects were purchased from ADMET. These subjects are free from liver disease.

first: Robert

middle: D

first: Wensheng

first: Norma

last: Nowak

first: Lixin

last: Zhu


title: Differential early pathogenic changes in human ileal gene expression in Crohn's disease and ulcerative colitis

status: Public on Sep 26 2010

city: Stony Brook

first: Tianyi

last: Zhang

address: 1500 Stony Brook Road

institute: Stony Brook University

summary: The aim of this study is to identify early pathogenic changes in ileal gene expression that precede the development of macroscopic disease in inflammatory bowel diseases (IBDs). We focused on two IBD phenotypes that were unlikely to overlap:  1) ileal Crohn’s disease (CD) patients undergoing initial ileocolic resection of diseased ileum; and 2) ulcerative colitis (UC) patients undergoing total colectomy.  The Control patients were those patients without IBD undergoing initial right hemicolectomy or total colectomy.

overall_design: In order to identify early pathogenic changes in the human ileum in inflammatory bowel diseases, we analyzed 99 two-color whole human genome expression profiles (Agilent 4410A) of a test human ileal cRNA probe vs. a common reference human ileal RNA from a Control patient (N17).  A minimum of four biopsies were taken from the macroscopically disease-unaffected proximal ileal margin of freshly resected specimens from 47 ileal Crohn's disease patients undergoing initial ileocolic resection, 27 ulcerative colitis patients undergoing total colectomy and 25 Control patients undergoing either right hemicolectomy or total colectomy.  The test and common reference probes were synthesized using the Agilent Low Input Linear Amplification Kit. Hybridization was carried out in DNA hybridization chambers, washed and scanned on an Axon GenePix 4000B scanner.  The preprocessing, filtering and normalization of the array data was carried out using the R package LIMMA.

first: Ellen

last: Li


title: Life cycle analysis of the model organism Rhodopirellula baltica by transcritpome studies

status: Public on Jul 04 2010

city: Bremen

first: Patricia

last: Wecker

address: Celsiusstr, 1

department: Molecular Ecology

institute: Max Planck Institut for Marine Microbiology

summary: Gene expression was monitored throughout a growth curve of R. baltica culture: Cultures were harvested at different time points (44 h, 62 h, 82h, 96 h and 240 h) and compared with each other

overall_design: Two-condition experiment, one time point compared to another for each Sample.

first: Christine

last: Klockow

first: Margarete

last: Schüler

first: Jerome

last: Dabin

first: Gurvan

last: Michel

first: Frank

middle: O

last: Gloeckner


title: Genome-wide linkage analysis of global gene expression of loin muscle tissue identifies putatively cis-acting candidate genes in pigs

status: Public on Aug 11 2010

city: East Lansing

first: juan

middle: p

last: steibel

state: MI

address: 1205 I Anthony Hall

institute: Michigan State University

summary: 510 F2 Duroc X Pietrain pigs together with their parents and grandparents from a resource population at Michigan State University were genotyped for 124 microsatellite markers. Transcriptional profiling was performed on a subset of 176 F2 pigs using a 70-mer long oligonucleotide microarray containing 20,400 oligos (GPL7435). Pigs were selected for transcriptional profiling using a selective phenotyping strategy which consisted in choosing the two extreme males and females for a trait of interest within each litter.

overall_design: Each two-color array accomodated two littermates of the same sex that were extremes (Status High or Low) for a phenotype of interest (Selection criteria)

first: J

middle: P

last: Steibel

first: C

last: Ernst


title: Why does HAMLET preferentially kill tumor cells? p38-dependent death in tumor but up-regulation of innate immunity in healthy, differentiated cells

status: Public on Aug 25 2010

city: Singapore

first: Henry

last: Yang

address: 8A Biomedical Grove

department: Bioinformatics Group

country: Singapore

institute: SIgN

summary: HAMLET triggers a p38- and ER stress-dependent death response in carcinoma cells. Transcriptome and proteome analysis detected an increase in p38 expression and phosphorylation exclusively in carcinoma cells and p38 inhibitors delayed the death response to HAMLET in carcinoma and lymphoma cells.  ER stress gene expression was also increased in tumor cells and HAMLET triggered rapid XBP1 mRNA splicing, eIF2a phosphorylation, and ATF6 cleavage as well as Hsc70 and CHOP activation, suggesting that ER stress caused by HAMLET may trigger p38 phosphorylation and death. The p38 inhibitor reduced the transcription of both p38 and ER stress gene transcription. Healthy differentiated cells, in contrast, showed no alteration in p38 signaling but a rapid innate immune response was detected and the cells survived HAMLET challenge.

overall_design: 2 cell lines, time course, HAMLET treatment

first: Petter

last: Storm

first: Soyoung

last: Min

first: Chimene

last: Moreilhon

first: Maria

last: Trulsson

first: Yinxia

last: Chao

first: Tomas

last: Westergren

first: Lotta

last: Gustafsson

first: Sonja

last: Aits

first: Ann-Kristin

last: Mossberg

first: James

last: Ho

first: Priscilla

last: Lim

first: Ken

last: Mok

first: Catharina

last: Svanborg


title: Hydrocortisone induces changes in gene expression and differentiation of immature human enterocytes

status: Public on Jun 03 2010

city: Charlestown

first: Lei

last: Lu

address: 114, 16th Street

institute: Massachusetts General Hospital

summary: It It is known that functional maturation of the small intestine occurring during the weaning period is facilitated by glucocorticoids (such as hydrocortisone, HC) including the increased expression of digestive hydrolases. However, the molecular mechanism(s) are not well understood, particularly in human gut. Here we report a microarray analysis of HC- induced changes in gene expression in H4 (a human fetal small intestinal epithelial cell line well-characterized in numerous previous studies). This study identified a large number of HC-affected genes, some involved in metabolism, cell cycle regulation, cell polarity, tight junction formation, and interactions with extracellular matrices.  These effects could play an important role in HC-mediated enterocyte maturation in vivo and in vitro.

overall_design: hydrocortisone effect on gene expression prlfile in H4 cells over time (no HC, HC_12h, HC_24h, HC_48h, HC_5d and T84).  Six samples are analyzed. Control sample is H4 without HC.

first: W

last: Walker


title: Whole tissue mRNA expression from severely obese individuals: subcutaneous and visceral adipose tissues

city: Groningen

first: Lude

last: Franke

state: Groningen

country: Netherlands

institute: University Medical Centre Groningen

summary:
Subcutaneous adipose tissue and visceral adipose tissue samples were obtained from severely obese individuals that underwent bariatric surgery.
The goal of this study was to compare genome-wide gene expression levels in the two tissue types from healthy and unhealthy severely obese individuals.
Whole-transcriptome subcutaneous adipose tissue gene expression levels were determined in 73 individuals with a BMI >35 kg/m2.
Whole-transcriptome visceral adipose tissue gene expression levels were determined in 69 individuals with a BMI >35 kg/m2.
Modules of co-expressed genes likely to be functionally related were identfied and correlated with BMI, plasma levels of glucose, insulin, HbA1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol.

overall_design:
Gene expression data was determined for untreated whole subcutaneous adipose tissue (n=73) from unrelated Dutch severely obese individuals.
Gene expression data was determined for untreated whole visceral adipose tissue (n=69) from unrelated Dutch severely obese individuals.

first: Marcel

last: Wolfs

first: Sander

last: Rensen

first: Elinda

last: Bruin-van Dijk

first: Froukje

last: Verdam

first: Jan-Willem

last: Greve

first: Bahram

last: Sanjabi

last: Bruinenberg

first: Cisca

last: Wijmenga

first: Timon

last: van Haeften

first: Wim

last: Buurman

first: Marten

last: Hofker


title: A Comparative Study of Genome Wide Transcriptional Profiles of Primary Hepatocyte in In Vitro Cultures

status: Public on Jun 01 2010

city: Blacksburg

first: Chris

last: Lasher

state: VA

address: 103 Lucas Dr Apt B

department: Genetics, Bioinformatics, and Computational Biology

institute: Virginia Polytechnic and State University

summary: The liver is one of most important organs in our bodies. It performs many essential functions including metabolism, synthesis, secretion, detoxification, and storage. Hepatocytes are the principal cell type in the liver and are involved in multiple liver-specific functions. There have been several efforts to develop in vitro culture systems capable of maintaining hepatocyte-specific phenotype over long time periods. In hepatic tissue engineering, two commonly used culture systems are the collagen sandwich and monolayers of cells.  In this study, genome-wide gene expression profiles of primary hepatocytes were measured over an 8-day period for each cell culture system using Affymetrix GeneChips and analyzed via Gene Set Enrichment Analysis (GSEA), which is a powerful method to elicit biologically meaningful information from microarray data at the level of gene sets. Results indicate that the gene expression in hepatocytes in collagen sandwich cultures gradually diverges from that in monolayer cultures. Gene sets up-regulated in collagen sandwich cultures include those associated with liver metabolic and synthetic functions.  These functions are associated with lipid, amino acid, carbohydrate, and alcohol metabolism and bile acid synthesis. Nuclear receptors are up-regulated in collagen sandwiches 24 hours after seeding. Signals transmitted from these receptors may cause the up-regulation of other processes in subsequent days.  Cytochrome-P450 monooxygenase expression was initially down-regulated but exhibited up-regulation after 72 hours.  Our results provide a baseline for further explorations into the systems biology of engineered liver mimics as well as 2D and 3D co-cultures of primary hepatocytes and non-parenchymal cells.

overall_design: To better understand differences in quality of in vitro growth of rat hepatocytes between culture on a monolayer of collagen gel and sandwiched between two layers of gel, we measured gene expression in hepatocytes in these two culture conditions in triplicate for four time points: 1 day, 2 days, 3 days, and 8 days of culturing. Overall, we obtained Affymetrix microarray data for 24 samples, divided to 12 samples from monolayer and double layer cultures each, each of which are divided into four time points with 3 sample replicates.

first: Yeonhee

last: Kim

first: Christopher

first: Logan

last: Milford

first: T

last: Murali

first: Padma

last: Rajagopalan


title: Gene expression analysis of peripheral whole blood RNA following ischemic stroke

city: Bethesda

first: Taura

middle: L

last: Barr

state: MD

address: Bldg 10 CRC Room 2-1339

department: Tissue Injury Unit

institute: NINR/NIH

summary: The purpose of this project was to elucidate gene expression in the peripheral whole blood of acute ischemic stroke patients to identify a panel of genes for the diagnosis of acute ischemic stroke. Peripheral blood samples were collected in Paxgene Blood RNA tubes from stroke patients who were >18 years of age with MRI diagnosed ischemic stroke and controls who were non-stroke neurologically healthy.  The results suggest a panel of genes can be used to diagnose ischemic stroke, and provide information about the biological pathways involved in the response to acute ischemic stroke in humans.

overall_design: Total RNA extracted from whole blood in n=39 ischemic stroke patients compared to n=24 healthy control subjects.

first: Yvette

last: Conley

first: Jinhui

last: Ding

first: Allissa

last: Dillman

first: Steven

last: Warach

first: Andrew

last: Singleton

first: Mar

last: Matarin


title: Genome-wide SNP array data from Human Variation Panel by Illumina 650K

status: Public on Sep 25 2010

city: Rochester

first: Liewei

last: Wang

state: MN

address: 200 First street SW

department: Molecular Pharmacology and Experimental Therapeutics

institute: Mayo Clinic

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

summary: Radiation therapy is used to treat half of all cancer patients. Response to radiation therapy varies widely among patients. Therefore, we performed a genome-wide association study (GWAS) to identify biomarkers to help predict radiation response using 277 ethnically defined human lymphoblastoid cell lines (LCLs). Basal gene expression levels (Affymetrix) and 1.3 million genome-wide SNP markers (Illumina) were assayed for all 277 human LCLs. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays for radiation cytotoxicity were also performed to obtain area under the curve (AUC) as a radiation response phenotype for use in the association studies. Functional validation of candidate genes, selected from an integrated analysis that used SNP, expression and AUC data, was performed with multiple cancer cell lines using specific siRNA knockdown, followed by MTS and colony-forming assays. 27 loci, each containing at least 2 SNPs within 50kb with p-values <10-4, were associated with radiation AUC. 270 expression probe sets were associated with radiation AUC with p<10-3. The integrated analysis identified 50 SNPs in 14 of the 27 loci that were associated with both AUC and the expression of 39 genes that were also associated with radiation AUC (p<10-3). Functional validation using siRNA knockdown in multiple tumor cell lines showed that C13orf34, MAD2L1, PLK4, TPD52 and DEPDC1B each significantly altered radiation sensitivity in at least 2 cancer cell lines. Studies performed with LCLs can help to identify novel biomarkers that might contribute to variation in response to radiation therapy and enhance our understanding of mechanisms underlying that variation.

overall_design: EBV-transformed LCLs from 95 African-American (AA) unrelated healthy subjects (sample sets HD100AA) were purchased from the Coriell Cell Repository (Camden, NJ).

first: Richard

last: Weinshilboum


title: Genome-wide SNP array data from Human Variation Panel by Illumina 550K

overall_design: EBV-transformed LCLs from 96 Caucasian-American (CA), and 96 Han Chinese-American (HCA) unrelated healthy subjects (sample sets HD100CAU, HD100CHI) were purchased from the Coriell Cell Repository (Camden, NJ).


title: Widespread transcription at neuronal activity-regulated enhancers

status: Public on Apr 15 2010

city: boston

first: jesse

last: gray

address: 77 avenue louis pasteur, NRB 356

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We used genome-wide sequencing methods to study stimulus-dependent enhancer function in neurons. We identified ~12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Remarkably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 that is mono-methylated at lysine 4 (H3K4me1). The level of eRNA expression at neuronal enhancers positively correlates with the level of mRNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.

overall_design: Examination of genome-wide binding of three types of modified histones, four transcription factors, and RNA polymerase II (ChIP-Seq), as well as RNA expression (RNA-Seq) before and after membrane depolarization via application of extracellular potassium.

first: Tae-Kyung

first: Martin

last: Hemberg

first: Jesse

last: Gray

first: Gabriel

last: Kreiman

first: Michael

middle: E

last: Greenberg


title: Comparison of Enteral versus Parenteral Feeding in Healthy Human Subjects (Supported by NIH grant GM34695)

status: Public on Apr 29 2010

city: New Brunswick

first: Stephen

last: Lowry

state: NJ

address: 125 Paterson St

department: Surgery

institute: UMDNJ

summary:
Literature suggests that the route of feeding may impact the immune system. This study examines changes in gene expression due to route of feeding in healthy volunteers.
Healthy volunteers were fed contniuous parenteral diet or continuous enteral diet for 72 hours

overall_design: Blood samples were collected prior to feeding and 72 hours after feeding. Monocytes were purified using Rosette Sep protocol. We used microarrays to identifiy genes with significantly changed expression.


title: Comprehensive Homozygous Deletion Mapping of Myeloma Defines a Poor Prognosis Cell Death Gene Expression Signature

status: Public on Mar 22 2010

city: Sutton

first: Brian

middle: A

last: Walker

address: 15 Cotswold Road

department: Haemato-Oncology Research Unit

institute: The Institute of Cancer Research

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

summary: Myeloma is a clonal malignancy of plasma cells.  Poor prognosis risk is currently identified by clinical and cytogenetic features.  However, these indicators do not capture all prognostic information.  Gene expression analysis can be used to identify poor prognosis patients and this can be improved by combination with information about DNA level changes.  Using SNP-based gene mapping in combination with global gene expression analysis we have identified homozygous deletions in genes and networks that are relevant to myeloma.  From these, we have generated an expression-based signature associated with shorter survival in 247 patients and confirmed this signature in data from 2 independent groups totalling 800 patients. We identified 170 genes with homozygous deletions and corresponding loss of expression. Deletion within the “Cell Death” network was over-represented and cases with these deletions have impaired overall survival.  We defined a gene expression signature of 97 cell death genes that reflects prognosis confirmed this in two independent data sets.  We developed a simple 6-gene expression signature from the 97-gene signature that can be used to identify poor prognosis myeloma in the clinical environment.  The signature can form the basis of future trials aimed at improving the outcome of poor prognosis myeloma.

overall_design: 247 expression samples from CD138+ cell selection, 168 SNP-based gene mapping data from CD138+ cell selection and peripheral white blood cell

first: Nicholas

last: Dickens

first: Gareth

last: Morgan


title: Epigenome analysis of normal and preinvasive cervical smear samples

status: Public on Mar 01 2010

city: London

last: Teschendorff

address: 72 Huntley Street

department: UCL Cancer Institute/Institute for Women's Health

institute: University College London

summary:
Genome wide DNA methylation profiling of normal and preinvasive cervical smear samples infected with the human papilloma virus (HPV)
The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in liquid based cytology (LBC) cervical smear samples. Samples included 19 normal smears without HPV, 11 normal smears with HPV infection, and 18 smears with HPV and exhibiting dysplasia.
email: a.teschendorff@ucl.ac.uk

Keywords: DNA methylation

overall_design: Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2


title: Human Variation Panel: Gene Expression and Genotype

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

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

overall_design: Refer to individual Series


title: Microarray analysis of expressed genes from R. microplus larvae, adult ovary, adult female gut associated with B bovis.

status: Public on Dec 01 2009

city: Kerrville

first: Leonel

middle: (Leo)

last: Saldivar

address: 2700 Fredericksburg Rd.

department: Agriculture

institute: USDA

summary:
Babesia bovis exposed tissues:  Three tissues were looked at.  1. Adult Female Gut  2. Adult Ovary  3. Larvae.     In all there are 24 measurements for feature (EST), and 4 measurements per treatment for each of the 6 treatment groups.      The 6 treatment groups are: Gut infected (GI), Gut control (GC), and similarly for Ovary and Larval: OI, OC, LI, LC.  There are 12 chips, each with a spot replicate.
**Note:  contact person:  Felix D. Guerrero
email:  felix.guerrero@ars.usda.gov
Keywords: Rhipicephalus (Boophilus) microplus, Babesia,  microarrays.

overall_design: In the study presented here, 12 hybridizations were performed.  Expression profiles for 13601 unique ESTs were analyzed.   Uninfected ticks were collected in one batch, as were the infected ticks.  Replicates performed are technical.

first: Felix

last: Guerrero

first: Kylie

last: Bendele

first: Kelly

last: Brayton

first: Glen

last: Scoles


title: Genome-wide SNP array data from Human Variation Panel by Illumina 510S

first: Liewei

last: Wang

overall_design: EBV-transformed LCLs from 96 African-American (AA), 96 Caucasian-American (CA), and 96 Han Chinese-American (HCA) unrelated healthy subjects (sample sets HD100AA, HD100CAU, HD100CHI) were purchased from the Coriell Cell Repository (Camden, NJ).


title: Gene Expression Profile of Androgen Modulated Genes in the Murine Fetal Developing Lung

status: Public on Jan 15 2010

city: Quebec

first: Eva

last: Bresson

state: Quebec

address: 2705, boul. Laurier, bloc T-1-49

department: Reproduction, santé périnatale et santé de l'enfant

institute: CHUL-CHUQ-Laval University

summary:
Accumulating evidences suggest that sex affects lung development. During the fetal period, male lung maturation is delayed compared with female and surfactant production appears earlier in female than in male fetal lungs.
We analyzed by microarrays the expression of genes showing a sexual difference and those modulated by endogenous androgens (flutamide).

overall_design: Following flutamide or vehicle administration to pregnant mothers, fetal mouse lungs were studied at gestational day 17 (GD17) and GD18. RNA was extracted and hybridized on Affymetrix microarrays.

first: Tommy

last: Seaborn

first: Mélissa

last: Côté

first: Geneviève

last: Cormier

first: Pierre

last: R. Provost

first: Bruno

last: Piedboeuf

first: Yves

last: Tremblay


title: modENCODE Drosophila RNA Binding Protein RNAi RNA-Seq Studies

status: Public on Oct 09 2009

city: Farmington

first: Brenton

last: Graveley

address: 400 Farmington Avenue

department: Genetics and Genome Sciences

institute: University of Connecticut Health Center

summary:
Deep Sequencing of mRNA from the Drosophila melanogaster S2-DRSC cells that have been RNAi depleted of mRNAs encoding RNA binding proteins.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

overall_design: Analysis of Poly(A)+ RNA from S2-DRSC Cells depleted of mRNAs encoding RNA binding proteins

first: Li

last: Yang

first: Michael

last: Duff

first: Angela

last: Brooks

first: Kasper

last: Hansen

first: Steven

last: Brenner

first: Sandrine

last: Duidot

first: Jane

last: Landolin

first: Ken

last: Wan

first: Susan

last: Celniker


title: Genome-wide DNA methylation profiling of Acute Myeloid Leukemia

status: Public on Jan 12 2010

city: Miami

first: Maria

middle: Eugenia

last: Figueroa

state: FL

address: 1501 NW 10th Ave, BRB 709A, Locator code C227

department: Human Genetics

institute: University of Miiami

type: Methylation profiling by genome tiling array

summary:
We hypothesized that DNA methylation distributes into specific patterns in cancer cells, which reflect critical biological differences. We therefore examined the methylation profiles of 344 patients with acute myeloid leukemia (AML). Clustering of these patients by methylation data segregated patients into 16 groups. Five of these groups defined new AML subtypes that shared no other known feature. In addition, DNA methylation profiles segregated patients with CEBPA aberrations from other subtypes of leukemia, defined four epigenetically distinct forms of AML with NPM1 mutations, and showed that established AML1-ETO, CBFb-MYH11 and PML-RARA leukemia entities are associated with specific methylation profiles. We report a 15-gene methylation classifier predictive of overall survival in an independent patient cohort (p<0.001, adjusted for known covariates).

Keywords: DNA methylation profiling

overall_design: DNA methylation profiling of a cohort of 344 AML patients from Erasmus Medical Center and enrolled in clinical trials from the Dutch-German cooperative group HOVON. Additionally, a control group consisting of 8 CD34+ bone marrow samples from healthy donors was also studied.

first: Ari

last: Melnick

first: Ruud

last: Delwel


title: Effect of T0901317, AM580 or T0901317+AM580 on monocyte gene expression

status: Public on Oct 01 2009

city: DIJON

first: Cédric

last: REBE

address: 2 av marechal de Lattre de Tassigny

department: Hopital du Bocage

summary: The aim of this study was to investigate the effect of T0901317 LXR agonist on Retinoic Acid Receptor (RAR) family gene expression. T0901317 alone increase RARalpha gene expression in monocytes and the effects of the co treatment of the cells with T0901317 and a specific RARalpha agonist (AM580) were further studied. For this monocytes were treated for 24h with DMSO or T0901317 to induce RARalpha expression and in a second step cells were treated or not with AM580 for another 24h period. Gene expression was analysed for all the treatments (T0901317, AM580 or T0901317+AM580) and we focussed on genes which expression was synergitically induced by the co treatment as compared to the cells treated either by T0901317 or AM580.

overall_design: Monocytes were obtained from 2 healthy donors with inform consent. Cells were treated in vitro with the vehicle (DMSO 0,1%) or 10µM of the LXR agonist T0901317 for 24 hours. Then after cells were treated for another 24 hour period with or without 100nM of the RARalpha specific agonist AM580.

last: Rebe

first: Magalie

last: Raveneau

first: Angélique

last: Chevriaux

first: Daniela

last: Lakomy

first: Annie

last: Costa

first: Ginette

last: Bessede

first: Eric

last: Solary

first: Philippe

last: Gambert

first: David

last: Masson


title: Dissecting the developmental transcriptomes of rice

status: Public on Jan 20 2010

city: Wuhan

first: Weibo

last: Xie

state: Hubei

address: Luoshi Road

department: College of Life Science and Technology

country: China

institute: Huazhong Agricultural University

summary:
Transcriptional programs are important for the development of complex eukaryotic organisms. Suites of genes expressed with temporal and spatial controls by regulatory networks in response to environmental cues are the cornerstone for achieving the specification of morphology and physiology of the tissue or organ systems. Thus, an important issue of developmental biology is to define the subsets of expressed genes and their expression patterns that are related to the organ or tissue system. Rice is a model plant for cereal genome research. Although large amounts of data of whole genome expression have been generated in recent years in rice, the majority of the studies were designed to identify differentially expressed genes between controls and treatments with certain experimental conditions such as biotic, abiotic or light, or to investigate the comparative expression patterns between wild type and mutants of certain genes. Only in a few cases were the datasets designed for studying the transcriptomes of a limited number of organs and cell types. Thus, there is still insufficiency in the available datasets that would allow for the establishment of expression patterns for suits of genes during the developmental processes of rice.
In this study, we collected 39 tissues/organs covering the life cycle of the rice from two indica varieties Minghui 63 and Zhenshan 97, and the Affymetrix GeneChip Rice Genome Array was used to investigate the transcriptomes of these organs. The objective was to develop a genomic resource of genome-wide dynamic transcriptome of the rice plant, which could be used as the reference gene expression map for rice and other cereals. Also, the dataset is used to identify the candidates of genes with potential functions in regulating the development of rice or breeding practice.   Keywords: rice, expression profiling, life cycle, development, inflorescence

overall_design: To dissect the developmental transcriptomes of rice, a total of 39 tissues covering the entire tissue culture process and life cycle were sampled from two indica varieties Minghui 63 and Zhenshan 97. And the Affymetrix Genechip rice Genome Array was used to investigate their dynamic transcriptomes. Two independent biological replicates were sampled from most tissues, except two seedling and three panicle tissues, for which three independent biological replicates each with two technical replicates were sampled, resulting in a dataset of 190 microarrays.

first: Lei

last: Wang

first: Ying

last: Chen

first: Weijiang

last: Tang

first: Jiangyi

last: Yang

first: Rongjian

last: Ye

first: Li

last: Liu

first: Caiguo

last: Xu

first: Yongjun

last: Lin

first: Jinghua

last: Xiao

first: Qifa

last: Zhang


title: Molecular characterization of Georgia cohort of primary breast cancer FFPE tissues on custom breast cancer DASL panel

status: Public on Oct 23 2009

city: Atlanta

first: Benjamin

last: Barwick

state: GA

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

department: Hematology and Medical Oncology

institute: Emory University

summary: Analysis of 143 formalin-fixed, paraffin-embedded (FFPE) primary breast tumors using a Custom Breast Cancer Panel and Human Cancer Panel for the DASL platform. Molecular markers between the pathology defined subtypes of breast cancer were assessed to hypothesize potential therapeutic targets specific to the subtypes

overall_design: Molecular Characterization of 143 primary breast carcinomas including 101 triple negative (TN: ER-, PR-, HER2-), 3 HER2-positive (HER2+: ER-, PR-, HER2+), and 39 hormone receptor-positive (HR+: ER+ and/or PR+)

first: Brian

last: Leyland-Jones


title: Expression analysis to identify inducible genes in T cells

status: Public on Jun 01 2009

city: Bruce

first: Kristine

last: Hardy

state: ACT

address: University of Canberra

country: Australia

institute: University of Canberra

summary:
Expression microarrays were employed to identify genes induced by phorbol ester and ionomycin stimulation of EL4 cells. EL4 is a murine T cell line. To identify induced genes that were independent of new protein synthesis cells were pre-treated with cycloheximide. This expression study was used in conjunction with histone acetylation ChIP-chip to determine if inducible genes had a specific histone acetylation profile and whether the acetylation profile differed for genes with different kinetics of induction.

Keywords: drug treatment comparison

overall_design: Cells were pre-treated with either DMSO or cylcoheximide in DMSO, then they were stimulated with PMA and Ionomycin for either 0h or 4h. 3 biological replicates were used for each treatment-stimulation combination.

first: Chloe

last: Lim

first: Frances

last: Shannon

first: Lina

last: Ma

first: Kaimen

last: Peng


title: Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders

status: Public on Dec 22 2009

city: Washington

first: Valerie

middle: Wailin

last: Hu

state: DC

department: Biochemistry and Molecular Medicine

institute: The George Washington University School of Medicine and Health Sciences

summary: Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests.  The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders.  DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into 3 phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls.  Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity.  Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups.  Among the findings unique to the most severely affected ASD group are genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism.  Among the genes common to all 3 subgroups of ASD are 5 novel genes which appear to associate with androgen sensitivity, which may underlie the strong 4:1 bias towards affected males.

overall_design: Gene expression profiling of 116 LCL from autistic (87) and nonautistic (29) individuals were obtained using a custom-printed DNA microarray containing 39,936 elements (TIGR 40K Human array, GPL3427) and a reference design in which each sample was compared to the Stratagene Universal Human RNA standard.  The 87 autistic samples were divided into phenotypic subgroups (language, mild, savant) on the basis of cluster analyses of scores from an autism diagnostic questionnaire, the Autism Diagnostic Interview-Revised instrument.  Differentially expressed genes were determined for all autistic vs. control groups, as well as for each of 3 phenotypic ASD groups and controls.

middle: W

first: Tewarit

last: Sarachana

first: Kyung

middle: S

last: Kim

first: AnhThu

last: Nguyen

first: Mara

last: Steinberg

first: Truong

last: Luu

first: Yinglei

last: Lai

first: Norman

middle: H

last: Lee


title: Expression data from human colonic biopsy sample

status: Public on Jan 29 2009

city: Budapest

first: Norbert

last: Solymosi

state: Budapest

address: István u. 2.

country: Hungary

institute: ATE

summary:
Gene expression profile based classification of colonic diseases are suitable for identification of diagnostic mRNA expression patterns which can establish the basis of a new molecular biological diagnostic method
Keywords: whole genomic expression

overall_design: Total RNA was extracted from colonic biosy samples CRC and hybridized on Affymetrix HGU133 Plus 2.0 microarrays

first: Orsolya

last: Galamb

first: Bela

last: Molnar

first: Sandor

last: Spisak

first: Ferenc

last: Sipos


title: Functional ER alpha transcriptional regulatory network for cell cycle in an ER(+) breast cancer subgroup

status: Public on Jul 24 2009

city: Taipei

first: Fon-Jou

last: Hsieh

address: No. 7, Chung-Shan South Rd

department: Department of obstetrics and gynecology

country: Taiwan

institute: National Taiwan University

summary: To better characterize group IE like human breast cancer based on the gene profiles of estrogen actions through estrogen receptor alpha (ER alpha), we identified an ER alpha transcriptional regulatory network for cell cycle in silico. We used two datasets from cell line (Data 1) and clinical samples (Data 2), respectively.  Analyses on Data 1 via trajectory clustering and Pathway-Express confirmed the significant estrogen effect on up-regulating cell cycle activities. The gene expression relationships between ER alpha and cell cycle genes were re-identified in Data 2 by three statistical methods – Galton-Pearson’s correlation coefficient, Student’s t-test and the coefficient of intrinsic dependence. They were mostly (56.09%)(46/82) re-confirmed by literature search. E2F1 was found to be the major ER alpha target in regulating cell cycle gene expressions (83.72%)(36/43) via suppressive mode. However, enhanced cell cycle progression via up-regulating some cell cycle genes was predicted in silico possibly involving E2F2, in part. Both tumorigenic and tumor suppressing activities indicated by this network were predicted. This network clearly provides a robust way for uncovering estrogen actions in an ER(+) subtype specific manner.

overall_design: Two clinical datasets were used in this study. One, the 37 clinical arrays (abbreviated as 37A) consist of 26 A for patients positive in estrogen receptor alpha (ER) and in progesterone receptor (PR) immunohistochemical stain (IHC) and 11A for patients negative in ER IHC. This dataset was designated as Data 2. The 31 clinical arrays (31A) consist of 20A for patients positive in ER status but negative in PR status and 11A which are the same as in 37A. This dataset was used for data comparison. All the signals from the mRNA profile of each sample in the experiments were normalized using the internal control RNA- Stratagene's human common reference RNA via statistical method 'rank consistant lowess. Finally, those ratios were transformed by Log2.

first: Li-Yun

last: Chang

first: Tzu-L

last: Phang

first: Li-Yu

last: Liu

first: Wen-Hung

last: Kuo

first: Hsiao-Lin

last: Hwa

first: King-Jen


title: Molecular characterization of Quebec Cohort of Primary Breast Cancer FFPE Tissues on the Human Cancer Panel

first: Benjamin

middle: G

last: Barwick

summary: Analysis of 97 formalin-fixed, paraffin-embedded (FFPE) primary breast tumors using Illumina DASL microarray technology on a Custom Breast Cancer Panel and the Illumina Human Cancer Panel. Molecular markers between the pathology defined subtypes of breast cancer were assessed to hypothesize potential therapeutic targets specific to the subtypes

overall_design: Molecular Characterization of 97 primary breast tumor formalin-fixed, paraffin-embedded (FFPE) specimens including 24 triple negative (TN: ER-, PR-, HER2-), 9 HER2-positive (HER2+: ER-, PR-, HER2+), and 64 hormone receptor-positive (HR+: ER+ and/or PR+). 91 of the 97 specimens were characterized on the Illumina Human Cancer DASL Panel and 86 of 97 specimens were characterized on a custom Breast Cancer DASL Panel, 80 of these specimens were common to both the Human Cancer DASL Panel and the custom Breast Cancer DASL Panel.

first: Mark

last: Abramovitz

first: Brian

middle: R

last: Leyland-Jones


title: Gene expression profiling in heterophils with Salmonella enteritidis challenge using a chicken 44K Agilent microarray

status: Public on Sep 01 2008

city: College Station

first: Huaijun

last: Zhou

state: TX

address: Rm 418D Kleberg Center,Texas A&M University

institute: Texas A&M University

summary:
To determine the transcriptional response to Salmonella enterica serovar Enteritidis (SE) infection, a newly developed chicken 44K Agilent array was used to analyze total RNA of heterophils from SE-resistant (line A) and SE–susceptible chickens (line B), treated with in vitro infection of SE (I) or non SE medium (N) for 1 hr. A dual-color balanced design was used to provide a direct comparison between SE-infected and non-infected groups (AI/AN, BI/BN) and between line A and line B (AN/BN, AI/BI). Data retrieved from 426 immunologically important genes were used for functional analysis. The results indicated that: In the comparisons of SE infection with non-infection, 39 genes were found differentially expressed (P < 0.05 with at least 2-fold) after Salmonella infection, while 21 genes were found differentially expressed between different lineages. Numerous of members in Toll-like receptor (TLR) signaling pathway were identified which include receptors: MD-2, TLR-4, -5, -15; adaptors: TLR adaptor molecule1 (TICAM1/TRIF), MAP kinase kinase 3 (MKK3) and NFkB-1, as well as cytokines, chemokines and costimulatory molecule: interleukin (IL)-1β, IL-6, IL-8, IL-12, chemokine (C-X-C motif) ligand 1, chemokine (C-C motif) ligand 4, CCL 5, and CD80. Most of immune genes were up-regulated after SE infection, and the magnitude of up-regulation was higher in line A than line B in general. The results suggested that a similar TLR regulatory network exists in both lines with strong response in resistant line. This finding has laid the foundation for further study of molecular and cellular modulation of SE infection in chickens.
Keywords: disease state analysis

overall_design: A dual color, balanced design was carried on for all of heterophils samples from sixteen chickens. Each sample type (AI, AN, BI and BN) includes four biological replication for labeling. A Dye swap was used in each pair of comparisons including AI/AN, BI/BN, and AI/BI, and AN/BN. Background subtracted signal intensity were collected from 16 arrays and normalized for data analysis.

first: Hsin-I

last: Chiang

first: Christina

last: Swaggerty

first: Michael

last: Kogut

first: Scot

last: Dowd

first: Xianyao

last: Li

first: Igal

middle: Y

last: Pevzner


title: Normoxia and Hyperoxia time series

status: Public on Aug 18 2008

city: Boston

first: Atul

last: Butte

state: MA

address: 300 Longwood Avenue

institute: Children's Hospital, Boston

summary:
These are two time-series of affymetrix MOE430A microarrays of mouse retina ranging from 7 to 12 days. The two conditions are normoxia and hyperoxia
Keywords: time-course


title: Phytophthora infestans gene expression during potato infection 2-5 days post inoculation

status: Public on Feb 16 2009

city: Cambridge

last: Haas

address: 7 Cambridge Center

institute: Broad Institute

summary: The expression of genes in P. infestans was monitored over a five day time course of a potato infection. Genes encoding known and putative effector proteins were found induced at two days post-inoculation with expression decaying over the five day time course.

platform_organism:
Solanum lycopersicum
Phytophthora infestans

overall_design: The expression of genes in P. infestans was monitored over a five day time course of a potato infection.  Genes induced or repressed during infection were identified by comparing expression intensities derived from samples of infected potato to baseline expression intensities provided by samples derived from mycelia growing in media (Pea, V8, or RS agar).  Biological replicates were generated for each sample.  Total RNA samples were submitted to NimbleGen for full microarray expression services, including cDNA conversion, Cy3 labeling, hybridizations, and scans.

first: Liliana

last: Cano

first: Chad

last: Nusbaum

first: Sophien

last: Kamoun


title: Metastasizing anaplasic ependymoma in an adult

status: Public on Nov 01 2008

city: Valencia

first: Manolo

last: Mata

address: Avda. Blasco Ibanez, 17

department: UCIM

country: Spain

institute: university of valencia

summary:
Study of a metastatic progression of an ependimoma. Chromosomal imbalances, metaolic and gene expression profiles.

Keywords: comparative genomics

overall_design: 2 samples

first: M

last: Cerdá-Nicolas

first: C

last: Lopez-Gines

first: B

last: Celda

first: R

last: Ferrer-Luna


title: Expression data from 2 wildtype and 8 C. elegans ETC mutants

status: Public on Feb 14 2008

city: Philadelphia

first: Marni

middle: J

last: Falk

state: PA

address: 3615 Civic Center Blvd

department: Pediatrics/ Human Genetics

institute: CHOP

summary:
Utilizing C. elegans as a model of mitochondrial dysfunction provides insight into cellular adaptations which occur as a consequence of genetic alterations causative of human disease.  We characterized genome-wide expression profiles of hypomorphic C. ele
Our goal was to detect concordant changes among clusters of genes that comprise defined metabolic pathways utilizing gene set enrichment analysis.
Keywords: Wildtype vs mutant comparison as a method for studying contributors to disease processes

overall_design: 3 biological replicates of each C. elegans strain were used as sources of total RNA combined for hybridization to a single Affymetrix whole-genome microarray.  Comparison of the data was intended to reveal metabolic pathways downstream of the mutation.

first: Zhe

last: Zhang


title: Mucus overproduction

status: Public on Feb 08 2008

city: Binghamton

first: Eric

last: Hoffman

state: NY

address: PO Box 6000

department: Pharmaceutical Sciences

institute: Binghamton University - SUNY

summary:
Our data demonstrates an increased number of submucosal glands in the sinus mucosa of pediatric patients with chronic rhinosinusitis (CRS). Additionally, data in the literature indicates differentially altered expression of innate markers of immunity and of inflammatory mediators in the sinus mucosa of adult patients with cystic fibrosis, non-CF controls, and controls.
Keywords: Differciation Study

overall_design: Analyses will focus on inflammatory/immune response genes to identify genes in CRS or CF patients that are involved in pathways that impact on pathogenesis in these diseases. Analysis will also focus on genes in developmental pathways to identify mediators implicated in the development of submucosal glandular hyperplasia in pediatric patients with CRS.

first: Mary

last: Rose


title: Expression data from wildtype and C. elegan mutants

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

overall_design: Refer to individual Series


title: U2OS ad-HIC1 target identification

status: Public on Dec 13 2007

summary:
The tumor suppressor gene HIC1 (Hypermethylated in Cancer 1) is essential for mammalian development and is epigenetically silenced in many human tumors. Functionally, HIC1 is involved in a complex pathway regulating P53 tumor-suppression activity. HIC1 encodes a sequence-specific transcriptional repressor containing five Krüppel-like C2H2 zinc fingers but only a few genes regulated by HIC1 have been reported, including SIRT1.
Keywords: Time Series Design

overall_design: We performed genome-wide expression profiling analyses to identify new HIC1 target genes, in U2OS human osteosarcoma cells infected with adenoviruses expressing either HIC1 or GFP as control.

first: Brain

last: Rood