title: mRNA expression data from in vitro modelling of erythroid differentiation in a leukemia cell line model

status: Public on Dec 24 2016

city: Freiburg

first: Rainer

last: Claus

address: Hugstetter Str. 55

department: Hematology, Oncology and Stem Cell Transplantation

institute: University of Freiburg Medical Center

summary:
One major mode of action of DNA hypomethylating agents such as decitabine (DAC) is reactivation of gene expression and induction of differentiation. Prompted by observations of differentiation induction in leukemic myeloid cells and upregulation of fetal hemoglobin (HbF) in adult patients suffering from hemoglobinopathies, we aimed at systematically investigating the potential and significance of DAC for in vitro and in vivo induction of erythroid differentiation and HbF expression.  In K562 (bcr-abl positive) and HEL (bcr-abl negative) myeloid leukemia cell line models, both with bilineage differentiation potential, erythroid differentiation and hemoglobin synthesis but not megakaryocytic differentiation could be induced by DAC treatment. The induction of erythroid differentiation was accompanied by a specific transcriptome signature that shared common patterns and groups of genes with the changes observed in K562 cells treated with the hemin, a known inducer of erythropoesis. Top regulated groups of transcripts in DAC treated cells were related to erythropoesis and iron metabolism. DAC treatment led to reactivation and upregulation of alpha globin and genes of the beta globin locus including the gamma globins resulting in HbF tetramer protein synthesis in K562 cells. This DAC-induced erythroid differentiation and HbF induction was accompanied by 2-3 fold upregulation of the key erythroid transcription factor GATA1. In contrast, PMA, an inducer of megakaryocytic differentiation, conversely led to a loss of GATA1 expression in K562 cells. Serial HbF measurements in DAC treated AML (n=25) and high-risk MDS (n=15) patients revealed that induction of HbF or persistent elevated HbF levels during treatment can also be detected in a significant proportion of patients in vivo (61,5%, p=0.033). Here, early HbF induction (after 2 courses) was significantly associated with platelet increment (rs=0.534, p=0.027) and strongly predicted neutrophil recovery (rs=0.554, p=0.021). The presence of elevated HbF levels in patients achieving CR upon DAC and exhibiting complete (cytogenetic) clearance of the malignant clone suggests that HbF induction does not occur in cells of the malignant clone but rather in non-malignant, polyclonal erythroid precursor cells.  One major mode of action of DNA hypomethylating agents such as decitabine (DAC) is reactivation of gene expression and induction of differentiation. Prompted by observations of differentiation induction in leukemic myeloid cells and upregulation of fetal hemoglobin (HbF) in adult patients suffering from hemoglobinopathies, we aimed at systematically investigating the potential and significance of DAC for in vitro and in vivo induction of erythroid differentiation and HbF expression.
In K562 (bcr-abl positive) and HEL (bcr-abl negative) myeloid leukemia cell line models, both with bilineage differentiation potential, erythroid differentiation and hemoglobin synthesis but not megakaryocytic differentiation could be induced by DAC treatment. The induction of erythroid differentiation was accompanied by a specific transcriptome signature that shared common patterns and groups of genes with the changes observed in K562 cells treated with the hemin, a known inducer of erythropoesis. Top regulated groups of transcripts in DAC treated cells were related to erythropoesis and iron metabolism. DAC treatment led to reactivation and upregulation of alpha globin and genes of the beta globin locus including the gamma globins resulting in HbF tetramer protein synthesis in K562 cells. This DAC-induced erythroid differentiation and HbF induction was accompanied by 2-3 fold upregulation of the key erythroid transcription factor GATA1. In contrast, PMA, an inducer of megakaryocytic differentiation, conversely led to a loss of GATA1 expression in K562 cells. Serial HbF measurements in DAC treated AML (n=25) and high-risk MDS (n=15) patients revealed that induction of HbF or persistent elevated HbF levels during treatment can also be detected in a significant proportion of patients in vivo (61,5%, p=0.033). Here, early HbF induction (after 2 courses) was significantly associated with platelet increment (rs=0.534, p=0.027) and strongly predicted neutrophil recovery (rs=0.554, p=0.021). The presence of elevated HbF levels in patients achieving CR upon DAC and exhibiting complete (cytogenetic) clearance of the malignant clone suggests that HbF induction does not occur in cells of the malignant clone but rather in non-malignant, polyclonal erythroid precursor cells.

overall_design: We chose two myeloid leukemia cell line models with differentiation potential towards a more mature erythroid or a more mature megakaryocytic lineage by hemin and phorbol ester (PMA), respectively. In addition, we treated both cell lines with the hypomethylating agent Decitabine (DAC) and investigated differences and similarities of mRNA expression patterns compared to hemin and PMA treated leukemia cell lines.

first: Michael

last: Lübbert


title: Conserved white-rot enzymatic mechanism for wood decay in the Basidiomycota genus Pycnoporus

status: Public on Feb 21 2017

city: Marseille

first: Marie-Noëlle

last: Rosso

address: 163 avenue de Luminy

department: Biodiversity and Biotechnology of Fungi - BBF

country: France

institute: INRAE - Aix Marseille University

type: Expression profiling by high throughput sequencing

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

sample_organism:
Trametes cinnabarina
Trametes coccinea
Trametes sanguinea

overall_design: Refer to individual Series


title: Alcohol Consumption and Breast Tumor Gene Expression

status: Public on Aug 31 2017

city: Boston

first: Rulla

middle: M

last: Tamimi

state: MA

address: 181 Longwood Avenue

department: Medicine

country: USA

institute: Brigham and Women's Hospital

summary: Investigating the association of alcohol and gene expression of breast tumors and tumor-adjacent tissues.

overall_design: Total of 1110 samples which includes 602 tumor and 508 tumor-adjacent tissues from participants of the Nurses' Heath Study I and II diagnosed with invasive breast cancer. Limma analyses compared how alcohol intake at 0, >0-<10 and 10+ grams/day influenced gene expression in breast tumor and tumor-adjacent tissues.

first: Jun

last: Wang

first: Yujing

middle: J

last: Heng

first: A

middle: H

last: Eliassen

first: Aditi

last: Hazra

first: Vincent

last: Carey

first: Christine

middle: B

last: Ambrosone

first: Victor

last: Piana de Andrade

first: Adam

last: Brufsky

first: Fergus

last: Couch

first: Tari

middle: A

last: King

first: Francesmary

last: Modugno

first: Celine

last: Vachon

first: David

last: Hunter

first: Andrew

last: Beck

first: Susan

middle: E

last: Hankinson


title: MiRNAs (microRNAs) involved in the regulation of chemo-resistance of breast cancer cells

status: Public on Oct 04 2016

city: Hangzhou

first: Wengong

last: Si

state: Zhejiang Province

address: 866 Yuhangtang Road

country: China

institute: Zhejiang university

summary: By comparing the miRNA expression profiles of parental breast cancer cell and multidrug resistant breast cancer cells, we are trying to find out some miRNAs which are involved in the regulation of chemo-resistance in breast cancer cells.

overall_design: By approximately imitating the schedules of “time-increasing method” and “dose-escalation method” administration with paclitaxel, two novel multidrug resistant (MDR) cell lines Bads-200 and Bats-72 were successfully developed from drug-sensitive breast cancer cell line BCap37, respectively. We compared miRNA expression in these three cells with a 16.0 version of the miRNA microarray, and each cell was tested in triplicate. These changes of expression of miRNAs were considered to be a candidate for regulation the chemo-resistance in breast cancer cells, which will be further verified by functional experiment.

first: Donghai

last: Jiang

first: Weimin

last: Fan


title: R-ChIP Using Inactive RNase H Reveals Dynamic Coupling of R-loops with Transcriptional Pausing at Gene Promoters

status: Public on Oct 12 2017

city: Nanjing

first: Jia-Yu

last: Chen

state: CA

address: No 163 of XianlinAvenue, Qixia District

department: School of Life Sciences

institute: Nanjing University

summary: R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome instability and regulated gene expression. To enable precision analysis of R-loops in vivo, we develop an RNase H-based approach, revealing predominant R-loop formation near gene promoters with strong G/C skew and propensity to form G-quadruplex in non-template DNA, corroborating with all biochemically established properties of R-loops. Transcription perturbation experiments further indicate that R-loop induction correlates to transcriptional pausing. Interestingly, we note that most mapped R-loops are each linked to a nearby free RNA end, and by using a ribozyme to co-transcriptionally cleave nascent RNA, we demonstrate that such free RNA end coupled with a G/C-skewed sequence is necessary and sufficient to induce R-loop. These findings provide a topological solution for RNA invasion into duplex DNA and suggest an order for R-loop initiation and elongation in an opposite direction to that previously proposed.

overall_design:
We initially developped our R-ChIP technology in HEK293 cells to characterize the genome-wide in vivo R-loops, and also applied it on K562 cell to compare with existing R-loop detection methods. Furthermore, to examine the functional interplay between R-loop and RNAPII pausing and pause release at promoter region, we generated two sets of biologically replicated R-ChIP libraries, each set on mock-treated HEK293T cells [DRB(-)] or cells treated with DRB for 2 hrs [DRB(+)] or after DRB removal for 30 min [post-DRB]. We also performed GRO-seq to monitor transcriptionally engaged RNAPII under these conditions. All R-ChIP data have two to three replicates and controls, and GRO-seq data have two replicates.

*The narrow peaks for HEK293-D210N and K562-D210N samples can be downloaded from UCSC session: http://genome.ucsc.edu/s/Jerry%20Chen/NarrowPeak

first: Liang

first: Xiang-Dong

last: Fu


title: Gene expression data in obinuzumab treated Karpas-1106P PMBL cell line

status: Public on Dec 01 2016

city: Valhalla

first: Sanghoon

last: Lee

state: NY

address: 40 Sunshine Cottage Road, Vos 145

department: Pediatrics

institute: New York Medical College

summary:
Primary Mediastinal large B-cell lymphoma (PMBL) is a rare form of non-Hodgkin lymphoma (NHL) representing 2% of mature B-cell NHL in patients less than 18 years of age.We compared the gene expression profiling between fully humanized anti-CD20 targeted monoclonal antibody recognizing a unique CD20 type II epitope, obinutuzumab and IgG or PBS treated Karpas Primary Mediastinal B-cell lymphoma (PMBL) cell line.
-

overall_design: Total RNA obtained from PBS, IgG and obinutuzumab treated Karpas PMBL cells and perforemd using Illumina Human HT-12 v4 array.

first: S


title: Easy Hi-C: A simple efficient protocol for 3D genome mapping in small cell populations

status: Public on Oct 31 2017

city: Cleveland

first: Fulai

last: Jin

state: OH - OHIO

address: 10900 Euclid Avenue

institute: Case Western Reserve University

summary: Despite the growing interest in studying the mammalian genome organization, it is still challenging to map the DNA contacts genome-wide. Here we present easy Hi-C (eHi-C), a highly efficient method for unbiased mapping of 3D genome architecture. The eHi-C protocol only involves a series of enzymatic reactions and maximizes the recovery of DNA products from proximity ligation. We show that eHi-C can be performed with 0.1 million cells and yields high quality libraries comparable to Hi-C.

overall_design: We tested the eHi-C protocol in IMR90 cells with both low-depth and high-depth sequencing

first: Leina

last: Lu

first: Xiaoxiao

last: Liu

first: Yan

last: Li


title: Elevated Hedgehog signalling suppresses DNA damage responses in ageing haematopoietic stem cells

status: Public on Oct 01 2016

city: Ulm

first: Martin

middle: David

last: Burkhalter

state: Badern-Württemberg

address: Albert-Einstein-Allee 11

department: Institute for Biochemistry and Molecular Biology

country: Germany

institute: Ulm University

summary:
Background and Aims: Detection of aging induced changes in the transcriptome of common myeloid progenitors of wild type mice.
Methods: Common myeloid progenitors were harvested from bone marrow of young and aged wild-type mice.

overall_design: Common myeloid progenitors derived from young adult (3-4 month old) and aged (22-26 month old) C57BL/6J mice were FACS sorted and RNA was extracted. Agilent Mouse 8x60K arrays were used.

middle: D

last: Burkhalte

first: K

middle: L

last: Rudolph


title: Androgen-induced lncRNA SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells

status: Public on Aug 01 2016

city: Itabashi-ku

first: Ken-ichi

last: Takayama

address: Sakaecho

country: Japan

institute: Tokyo Metropolitan Institute of Gerontology

type: Non-coding RNA profiling by high throughput sequencing


title: Expression data of epithelial brushing from Unbiased BIOmarkers in Prediction of REspiratory Disease outcomes (U-BIOPRED) Project

status: Public on Sep 30 2016

city: London

first: Chih-hsi

middle: Scott

last: Kuo

address: South Kensington Campus

department: Department of Computing

country: United Kingdom

institute: Imperial College London

summary:
Asthma is a heterogeneous disease requiring understandings at molecular level that characterizes subgroups of patients with specific biomarkers to facilitate the development of targeted thearpies.
We used Affymetrix U133 Plus 2.0 PM only arrays to explore the gene expression profile from epithelial brushing of 99 moderate/severe asthmatic patients.

overall_design:
A cross-sectional study of 99 participants with moderate-to-severe asthma from the U-BIOPRED underwent fiberoptic bronchoscopy for epithelial brushing

contributors: U-BIOPRED Consortium Project Team members


title: Expression data of bronchial biopsies from Unbiased BIOmarkers in Prediction of REspiratory Disease outcomes (U-BIOPRED) Project

summary:
Asthma is a heterogeneous disease requiring understandings at molecular level that characterizes subgroups of patients with specific biomarkers to faciliate the development of targeted thearpies.
We used Affymetrix U133 Plus 2.0 PM only arrays to explore the gene expression profile from bronchial biopsies of 91 moderate/severe asthmatic patients.

overall_design:
A cross-sectional study of 91 participants with moderate-to-severe asthma from the U-BIOPRED underwent fiberoptic bronchoscopy for bronchial biopsies

contributors: U-BIOPRED Consortium Project Team members


title: Expression data of bronchial biopsies and epithelial brushing from Unbiased BIOmarkers in Prediction of REspiratory Disease outcomes (U-BIOPRED) Project


title: Nitric oxide(CysNO) mediated transcriptome profiling in Arabidopsis thaliana

status: Public on May 13 2016

city: Daegu

first: Sang-Uk

address: 80 Daehakro, Bukgu

country: South Korea

institute: Kyungpook National University

summary: This study provides comprehensive information about plant responses to nitrosative stress at transcript level and would prove helpful in understanding and incorporating mechanisms associated with nitrosative stress responses in plants.

overall_design: 1mM CysNO Treatment to Leaf disc, Transcriptome profiling

first: Adil

last: Hussain

first: Bong-Gyu

last: Mun

first: Qari

last: Imran

first: Teferi

last: Adamu

first: Kyung-Min

last: Kim

first: Byung-Wook

last: Yun


title: Effects of SOCS2-AS1 inhibition in prostate cancer cells

summary: Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. We identified a novel androgen-regulated long non-coding (lnc) RNA, SOCS2-AS1.

overall_design:
In order to investigate the SOCS2-AS1 function in prostate cancer cells, we performed gene expression in AR-positive prostate cancer cell lines (LNCaP and LTAD) after siSOCS2-AS1 or siSOCS2 treatment. We also treated cells with vehicle or androgen to analyzed the effects of siSOCS2-AS1 on AR function.
Observation of androgen dependent gene expression changes after treatmet with siSOCS2-AS1 with microarray.

first: A

last: Misawa

last: Inoue


title: The transcriptome and chromatin landscape of coronavirus-infected human cells

status: Public on Mar 15 2017

city: Giessen

first: Jochen

last: Wilhelm

state: Hessen

address: Aulweg 132

department: Institute for Lung Health

institute: Justus-Liebig University Giessen

first: Michael

last: Kracht

last: Poppe


title: Global transcriptome responses of a marine diatom to phosphate fluctuations provides insights into its ecological success

status: Public on Jan 01 2016

city: NEW YORK

first: Nam-Hai

last: Chua

state: New York

address: 1230 York Avenue

institute: The Rockefeller University

summary: Phosphate (Pi) is an essential element to all living cells yet fluctuations in Pi concentrations are recurrent in the marine environment. Diatoms are amongst the most successful phytoplankton clade living in the world’s oceans adapting to and surviving long periods of sub-optimal conditions and resuming growth as soon as nutrient concentrations permit. The knowledge of the molecular underpinnings of diatom ecological success is, however, still very incomplete. Using high-throughput RNA sequencing we have identified the dynamics of the model diatom Phaeodactylum tricornutum global transcriptome in response to Pi fluctuations. We report genes encoding previously unidentified putative Pi transporters that, together with the alkaline phosphatases genes highly expressed under Pi depletion, are probably accountable for a very efficient Pi scavenging system. Our data also reveal the complexity of the P. tricornutum responsive sensory and signaling system that combines bacterial two-component systems with more complex pathways reminiscent of metazoans. This intricate set of membrane receptors and signal-transduction related proteins is likely responsible for the detection of environmental nutrient fluctuations, triggering a multitude of signaling cascades leading to gene regulatory events that define new adaptive physiological states. This together with the novel detection of a multitude of long non-coding intergenic RNAs specifically expressed under Pi stress, begins to provide insights into the complex molecular regulatory program involved in the resilience and ecological success of diatoms.

overall_design: Examination of Pi-responsive transcriptoms in diatoms.

first: Maria

last: Cruz de Carvalho

first: Hai-Xi

last: Sun

first: Chris

last: Bowler


title: Gene expression signatures in ex vivo Cytarabine (Ara-C) and Daunorubicin (Dnr) sensitive AML samples

status: Public on Jan 02 2016

city: Vellore

first: Poonkuzhali

last: Balasubramanian

state: Tamil Nadu

address: Ida Scudder Road

department: Department of Haematology

country: India

institute: Christian Medical College Vellore

summary: Wide inter-individual variation in terms of outcome and toxic side effects of treatment exist among patients with AML receiving chemotherapy with cytarabine (Ara-C) and daunorubicin (Dnr). Drug resistance and relapse are considered major causes of treatment failure. Gene expression profiling was undertaken to address possible mechanisms of Ara-C/Dnr resistance. Based on ex vivo Ara-C cytotoxicity at diagnosis, Ara-C sensitive (IC50 <3uM AraC) and Dnr sensitive samples (IC50 < 0.5 uM) (5 samples each) were included for microarray analysis. These were compared with the samples which were drug resistant ex vivo at diagnosis. Our microarray experiment resulted in indentifying differentially expressed genes under ex vivo Ara-C sensitive as well as Dnr sensitive samples compared to ex vivo Drug resistant samples.

overall_design: One-color experiment,Organism: Homo sapiens, Custom Human Whole Genome 8x60k Array designed by Genotypic Technology Private Limited (AMADID: 27114), Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)

first: Ajay

last: Abraham

first: Savitha

last: Varatharajan


title: Early response of three Pycnoporus species to various carbon sources [Pycnoporus coccineus]

first: Marie-Noëlle

last: Rosso

summary: White-rot basidiomycete fungi are potent degraders of plant biomass with the ability to mineralize all lignocellulose components. Recent comparative genomics studies showed that these fungi use a wide diversity of enzymes for wood degradation. Deeper functional analyses are however necessary to understand the enzymatic mechanisms leading to lignocellulose breakdown. In the present study we analyzed the early response of the Polyporales fungi Pycnoporus coccineus CIRM-BRFM310, Pycnoporus cinnabarinus CIRM-BRFM137 and Pycnoporus sanguineus CIRM-BRFM 1264  to various carbon sources including lignocellulosic biomass.

overall_design: Examination of mRNA levels in fungal mycelium after 3 days growth in liquid cultures on maltose, Avicel, xylans-galactomannans, wheat straw, pine or aspen.

first: François

last: Piumi

first: Marie-Pierre

last: Franquin-Gomez

first: Igor

middle: V

last: Grigoriev

first: Anna

last: Lipzen


title: Stereo-sequencing: 3D Transcriptome of the mouse embryo at gastrulation

status: Public on Mar 24 2016

city: Guangzhou

first: Guangdun

last: Peng

address: 190 Kaiyuan Road

department: Guangzhou Institutes of Biomedicine and Health

institute: Chinese Academy of Sciences

summary: To glean an appreciation of the holistic genetic activity in the gastrulating mouse embryo, we performed a genome-wide spatial transcriptome analysis (Stereo-seq), using a low-cell number sequencing protocol on laser microdissected samples of epiblast cells with retained positional address. The 3D transcriptome reveals that (i) the epiblast is partitioned into transcription domains corresponding to regions of epiblast where cells are endowed specifically with ectoderm and mesendoderm potency, (ii) novel lineage markers are identified as genes expressed in epiblast domains populated by cells displaying different lineage fates, (iii) functionally related gene regulatory circuitry and signaling pathways are acting in concert in the transcriptional domains, and (iv) the spatial information provides reference zipcodes for mapping the prospective address of cell samples from different embryos and stem cell lines. The quantified expression data can also be visualized as “3D digitized whole mount in situ hybridization” of all the expressed transcripts in the epiblast.

overall_design:
(i) By using laser-microdissection, we carried out transcriptome profiling on embryo sections at a high resolution of ~20 cells per sample with the spatial information preserved. We then constructed a comprehensive spatial transcriptome map in the mid-gastrulation embryo that is visualized in a 3D embryonic model based on the sequencing data.
Embryo position (A/L/P/R) and section (1-11) descriptors:
A stands for laser capture microdissected samples from the anterior epiblast of the embryo; P for posterior; L for the left lateral epiblast of the embryo; R for the right lateral. The section is collected from distal to proximal, and the section 1 to 11 is the cryosection order, covering the whole embryonic part of a late mid-streak embryo. Section 1 is the most distal section and 11 is the most proximal section. Please be aware that the labels for left (L) and right (R) are from mirrored images and should be considered as right and left positions in real embryo settings. Anterior (A) or Posterior (P) regions do not change.
(ii) Additional samples are RNA-seq data of 70 single cells from E7.0 mouse embryo. These 70 samples were randomly picked from the anterior or posterior embryonic half.

first: Shengbao

last: Suo

first: Jun

last: Chen

first: Naihe

last: Jing

first: Jing-Dong

last: Han


title: Molecular regulation in the hippocampal dentate gyrus in the onset and treatment of depression

status: Public on Jul 02 2015

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

institute: Helmholtz Zentrum Muenchen

summary:
Major depression is a multidimensional disorder highly prevalent in modern society. Although several classes of antidepressants (ADs) are currently available to treat depression, the effectiveness of treatment is still limited, as many patients do not show full remission; thus, there is a need to find better patients’ directed therapeutic strategies. Neuroplastic changes in several brain regions, namely in the hippocampal dentate gyrus (DG), are amongst the best correlates of depression and of ADs actions. In this study the targets and molecular mediators of chronic stress and of four ADs from different pharmacological classes (fluoxetine, imipramine, tianeptine and agomelatine) were investigated in the DG.
Using the unpredictable chronic mild stress (uCMS) animal model of depression, the molecular commonalities and specificities of the ADs were determined. All ADs, except agomelatine, could reverse the behavioral deficits produced by uCMS, and the neuroplastic changes in the DG; agomelatine reversed only the anhedonic profile in the sucrose consumption test. Chronic stress induced mild but relevant molecular changes that were mostly reversed by fluoxetine, imipramine and tianeptine. Fluoxetine reduced pro-inflammatory response and increased cell metabolism pathways. Its actions were mostly dependent on molecular changes occurring in neurons. Similarities were found between imipramine and tianeptine molecular actions and targets, as both activated pathways related to cellular protection. Moreover, no particular neural cell type enrichment was found with both treatments. Agomelatine presented a very dissimilar molecular pattern impacting greatly on Rho-GTPases-related pathways in oligodendrocytes and neurons. The recognition of these molecular alterations contributes to the understanding of the processes implicated in the onset and treatment of depression and may pave the way for more effective therapeutic interventions.

overall_design: We compared gene expresssion in the dentate gyros of rats which were either untreated, exposed to unpredictable chronic mild stress, or exposed to the same stress and treated with either fluoxetine, imipramine, tianeptine, or agomelatine

first: Patrícia

last: Patrício

first: António

last: Mateus-Pinheiro

first: Martin

last: Irmler

first: Nuno

last: Alves

first: Ana

middle: R

last: Machado-Santos

first: Mónica

last: Morais

first: Joana

middle: S

last: Correia

first: Michal

last: Korostynski

first: Marcin

last: Piechota

first: João

last: Bessa

first: Osborne

middle: F

last: Almeida

last: Sousa

first: Luísa

last: Pinto


title: Transcription Dynamically Patterns the Meiotic Chromosome-Axis Interface [ChIP-Seq]

status: Public on Aug 06 2015

city: New York

first: Andreas

last: Hochwagen

address: 1009 Silver Center 100 Washington Square East

institute: New York University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Meiotic chromosomes are highly compacted yet remain transcriptionally active. To understand how chromosome folding accommodates transcription, we investigated the assembly of the axial element, the proteinaceous structure that compacts meiotic chromosomes and promotes recombination and fertility. We found that the axial-element proteins of budding yeast are flexibly anchored to chromatin by the ring-like cohesin complex and biased towards small chromosomes by a separate modulating mechanism that requires the conserved axial element component Hop1. The ubiquitous presence of cohesin at sites of convergent transcription provides well-dispersed points for axis attachment and thus compaction. Axis protein enrichment at these sites directly correlates with the propensity for recombination initiation nearby. Importantly, axis anchoring by cohesin is adjustable and readily displaced in the direction of transcription by the transcriptional machinery. We propose that such robust but flexible tethering allows the highly structured axial element to promote recombination while easily adapting to changes in chromosome activity.

overall_design: ChIP-seq experiments were undertaken to understand the features of meiotic chromosomal axes assembly in meiosis. The genome-wide distribution of axis proteins including Hop1, Red1 as well as cohesin subunits Rec8 and Smc3 were measured. Axis protein binding pattern is also measured in rec8 mutant and pREC8-SCC1 in rec8 mutant.

first: Xiaoji

last: Sun

first: Tovah

last: Markowitz


title: Transcription Dynamically Patterns the Meiotic Chromosome-Axis Interface

type: Genome binding/occupancy profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Functional Inflammatory Profiles Distinguish Myelin-Reactive T Cells from Patients with Multiple Sclerosis

status: Public on May 18 2015

city: Cambridge

first: Charles

middle: Arthur

last: Whittaker

institute: Koch Institute

summary: Myelin-reactive T cells have been identified in patients with multiple sclerosis (MS) and healthy subjects with comparable frequencies, but the contribution of these autoreactive T cells to disease pathology remains unknown. A total of 13,324 T cell libraries generated from blood of 23 patients and 22 healthy controls were interrogated for reactivity to myelin antigens. Libraries derived from CCR6+ myelin-reactive T cells from patients with MS exhibited significantly enhanced production of IFN-γ, IL-17, and GM-CSF compared to healthy controls. Single-cell clones isolated by MHC/peptide tetramers from CCR6+ T cell libraries also secreted more pro-inflammatory cytokines while clones isolated from controls secreted more IL-10. The transcriptomes of myelin-specific CCR6+ T cells from patients with MS were distinct from those derived from healthy controls, and of note, were enriched in Th17-induced experimental autoimmune encephalitis (EAE) gene signatures and gene signatures derived from Th17 cells isolated other human autoimmune diseases. These data, although not casual, imply that functional differences between antigen specific T cells from MS and healthy controls is fundamental to disease development and support the notion that IL-10 production from myelin-reactive T cells may act to limit disease progression, or even pathogenesis.

overall_design:
Four conditions of purified T cells with between 3 and 5 replicates per condition

Please note that the processed data file was updated on Aug 30, 2020 ('bathomas_samples.CORRECTED.txt').

first: Yonghao

last: Cao

first: Brittany

last: Goods

first: Khadir

last: Raddassi

first: Gerald

middle: T

last: Nepom

first: William

middle: W

last: Kwok

first: J

middle: C

last: Love

first: David

last: Hafler


title: Transcriptome analysis of human sinusoidal endothelial cells, hepatocyte

status: Public on Jan 01 2015

city: Leuven

first: Marc

last: Jacquemin

address: O&N I Herestraat 49 - bus 913

country: Belgium

institute: KU Leuven

summary: We report the transcriptome human primary hepatocytes and liver sinusoidal endothelial cells. Hepatocytes were obtained from commercial sources.  LSECs were isolated based on the coexpression of Tie2 and CD32b, te strategy of purification controlled by RNA-Seq.

overall_design: Comparison of the expression of the Tie-2, CD32b, SELP, FVIII, VWF, Alb, Fg, F7genes

first: Tina

last: Shahani


title: Transcriptome profiling of omental adipose tissues in human obesity by RNA-Seq

status: Public on Feb 11 2015

city: Kajang

first: Hien Fuh

last: Ng

state: SELANGOR

country: Malaysia

institute: UTAR

summary:
Purpose: To profile the transcriptomes of omental adipose tissues from obese and lean humans.
Methods: Omental adipose tissues from obese and lean patients were subjected to RNA-Seq.
Results: Differential expression analysis identified 206 dysregulated genes (p-value < 0.05 by moderated t-test and fold change ≥ 2 in obesity) that are known to be involved in a multitude of functions, including response to stress, inflammatory response and leukocyte adhesion. Differential splicing analysis uncovered the possible role of TLR4 RNA splicing in obesity. Our findings suggest that, as a person experiences weight gain/obesity, the adipose splicing pattern of TLR4 transcripts changes in favor of activation of TLR4 signaling, which in turn may contribute to the progression of obesity-related inflammation and complications.
Conclusion:  This study provides a look into the transcriptome of disease-state adipose tissue in obesity, and demonstrates the potential importance of aberrant RNA splicing and expression in obesity-associated immune dysregulation.

overall_design: Study design is of cross-sectional nature. Seven samples (three obese and four lean) were analyzed.

first: Hien


title: Differential gene regulation by miR-142-3p and miR-K10a isomiRs

status: Public on Jul 31 2015

city: Chicago

first: Eva

middle: Henriette

last: Gottwein

state: IL

address: 320 E Superior St., Tarry building, Room 6-752

department: Microbiology-Immunology

institute: Northwestern University

summary: This study compares changes in gene expression induced by four interrelated miRNAs with similar but staggered 5'-ends: miR-142-3p, miR-142-3p-1, miR-K10a, and miR-K10a+1. miR-K10a and miR-K10a+1 are co-expressed by the Kaposi's sarcoma-associated herpesvirus.

overall_design: Total RNA was harvested from HEK293 cells transfected with individual miRNAs including a negative control miRNA mimic.

first: Mark

last: Manzano


title: LncRNA profile study reveals a three-lncRNA signature associated with the survival of esophageal squamous cell carcinoma patients

status: Public on Mar 07 2014

city: Beijing

first: Jiagen

last: Li

address: 17 Panjiayuannanli Chaoyang District

institute: Cancer Institute, CAMS

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


title: LncRNA profile study reveals a three-lncRNA signature associated with the survival of esophageal squamous cell carcinoma patients (original)

summary: Objective: Globally, esophageal cancer is among the most deadly cancer forms. Long non-coding RNAs (lncRNA) are frequently found to have important regulatory roles. We aim to assess the lncRNA expression profile of esophageal squamous cell carcinoma (ESCC) and identify prognosis related lncRNAs. Design: LncRNA expression profiles were studied by microarray in paired tumor and normal tissues from 119 ESCC patients, and validated by qRT-PCR. The 119 patients were subsequently divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random forest supervised classification algorithm and a nearest shrunken centroid algorithm, and validated in test group and further in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by Multivariable Cox regression analysis. Results: LncRNAs showed significantly altered expression in ESCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885•1, XLOC_013014, and ENST00000547963•1) which classified the patients into two groups with significantly different overall survival (median survival 19•2 months vs. not reached, p<0•0001). The signature was applied to the test group (median survival 21•5 months vs. not reached, p=0•0030) and independent cohort (median survival 25•8 months vs. not reached, p=0•0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for ESCC patients. Stratified analysis suggested that the signature was prognostic within clinical stages. Conclusions: Our results suggest that the three-lncRNA signature can serve as a novel biomarker for the prognosis of ESCC patients. Application of it allows for more accurate survival prediction.

overall_design: The lncRNA expression profiles of cancer and adjacent normal tissues form 119 ESCC patients were studied by microarray and an lncRNA signature that can perdict the survival of ESCC patients was identified.

first: Z

last: Chen

first: L

last: Tian


title: Global transcriptome profiling of poplar bark during stored N remobilization

status: Public on Mar 01 2014

city: college park

first: rongshuang

last: lin

state: MD

address: Plant Sci building

department: Plant sci

institute: Univ Maryland

summary: Seasonal nitrogen (N) storage and reuse is important to the N-use efficiency of temperate deciduous trees. In poplar, bark storage proteins (BSPs) accumulate in protein storage vacuoles of the bark parenchyma and xylem ray cells in the fall. During spring growth, N from stored BSPs is remobilized and utilized by growing shoots. The goal of this study is to investigate global gene expression changes in the bark during BSP remobilization and shoot regrowth under long-day conditions.

overall_design: Long-day (LD) grown poplar (Populus trichocarpa, Nisqually-1) plants were transferred to short-day (SD) for 8 weeks at 20°C followed by an addition 12 weeks of SD at 10°C (day) and 4°C (night).  Following this treatment plants were then moved to LD and 20°C for 3 weeks for regrowth. Bark samples were collected from plants released from dormancy just prior to transfer to LD and at weekly intervals for 3 weeks after exposure to LD at 20°C.

first: Rongshuang

last: Lin

first: Gary

last: Coleman

first: Ganesh

last: Sriram

first: Jianhua

last: Zhu


title: RNA-sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate

status: Public on Jan 09 2014

city: Bruxelles

first: Miriam

last: Cnop

address: Route de Lennik 808 CP618

department: Faculté de Medecine

institute: Université Libre de Bruxelles

summary: Pancreatic beta-cell dysfunction and death are central in the pathogenesis of type 2 diabetes. Saturated fatty acids cause beta-cell failure and contribute to diabetes development in genetically predisposed individuals. Here we used RNA-sequencing to map transcripts expressed in five palmitate-treated human islet preparations, observing 1,325 modified genes. Palmitate induced fatty acid metabolism and endoplasmic reticulum (ER) stress. Functional studies identified novel mediators of adaptive ER stress signaling. Palmitate modified genes regulating ubiquitin and proteasome function, autophagy and apoptosis. Inhibition of autophagic flux and lysosome function contributed to lipotoxicity. Palmitate inhibited transcription factors controlling beta-cell phenotype including PAX4 and GATA6. 59 type 2 diabetes candidate genes were expressed in human islets, and 11 were modified by palmitate. Palmitate modified expression of 17 splicing factors and shifted alternative splicing of 3,525 transcripts. Ingenuity Pathway Analysis of modified transcripts and genes confirmed that top changed functions related to cell death. DAVID analysis of transcription binding sites in palmitate-modified transcripts revealed a role for PAX4, GATA and the ER stress response regulators XBP1 and ATF6. This human islet transcriptome study identified novel mechanisms of palmitate-induced beta-cell dysfunction and death. The data point to crosstalk between metabolic stress and candidate genes at the beta-cell level.

overall_design: 5 human islet of Langerhans preparations examined under 2 conditions (control and palmitate treatment)

first: Decio

last: Eizirik

first: Michael

last: Sammeth

first: Guy

last: Bottu

first: Jean-Valery

last: Turatsinze


title: LncRNA profile study reveals a three-lncRNA signature associated with the survival of esophageal squamous cell carcinoma patients (independent set)

first: J


title: Investigation of androgen-regulated lncRNAs in prostate cancer cells

first: Ken-ichi

last: Takayama

summary: Prostate cancer is the most common cancer in men and androgen receptor (AR) downstream signalings promote prostate cancer cell proliferation. To investigate the AR signaling, we performed directional RNA sequence analysis in AR positive prostate cancer cell line, LNCaP and VCaP. Using Noncode and GENCODE data sets. We identified androgen-regulated long non-coding RNAs (lncRNAs) in prostate cancer cells.

overall_design: Directional RNA sequence analysis of androgen-regulated lncRNAs in prostate cancer cells

first: Satoshi

last: Inoue


title: Expression data for pharmacogenomics antiplatelet therapy

status: Public on Sep 15 2012

city: Sao Paulo

first: Andre

middle: Ducati

last: Luchessi

address: Av. Prof Lineu Prestes, 580

country: Brazil

institute: University of Sao Paulo

summary:
Antiplatelet therapy is the most important treatment to reduce the risk of developing recurrent thrombosis, and to prevent progression to a complete occlusion of coronary arterial disease (CAD) patients after percutaneous coronary intervention
Aim of study was to investigate the relationship between response to antiplatelet drugs and global mRNA gene expression in peripheral blood cells (PBC) in patients with coronary arterial disease (CAD)

overall_design: All patients were treated crhonically with acetylsalicylic acid (ASA) (100 mg/day) and clopidogrel (75 mg/day). Blood samples were drown before PCI to evaluate platelet reactivity by VerifyNow® ASA and P2Y12 assays and mRNA expression was measured by Affymetrix GeneChip Human Exon 1.0 ST array.

first: André

first: Vivian

middle: N

last: Silbiger

first: Rosario

last: Hirata

first: Lidio

middle: G

last: Lima-Neto

first: Debora

last: Cavichioli

first: Andres

last: Iñiguez

first: Marisol

last: Bravo

first: Guillermo

last: Bastos

first: Amanda

last: Sousa

first: Maria

last: Brión

first: Angel

last: Carracedo

first: Mario

middle: H


title: PA1-regulated genes in mouse embryonic fibroblast

status: Public on Dec 31 2013

city: Bethesda

first: Ji-Eun

last: Lee

address: 9000 Rockville pike

department: National Institute of Diabetes and Digestive and Kidney Diseases

institute: National Institutes of Health

summary: PA1 has been identified as a component of a MLL3/4-containing histone methyltransferase complex. PA1 directly interacts with PTIP but not with other complex components. Since biological functions of PA1 are unknown, we used microarrays to determine which genes are regulated by PA1.

overall_design: To identify PA1-regulated genes, immortalized PA1 conditional knockout PA1loxP/loxP MEFs were infected with retroviruses expressing either Cre recombinase or vector alone. We prepared duplicated RNAs from either vector or Cre infected cells (PA1+/+ or PA1-/-) for 4 affymetrix microarrays.

first: Young-Wook

last: Cho

first: Kai

last: Ge


title: Differenetial Gene Expression in Limbs of Wild Type and Lmx1b KO mice during limb dorsalization (e11.5, e12.5 & e13.5)

status: Public on May 22 2012

city: Loma Linda

first: Kerby

last: Oberg

address: 24785 Stewart St

department: Pathology

institute: Loma Linda University

summary: Lmx1b regulates dorsalization of limb fates, but the mechanism of this regulation has not been characterized.  To identify candidate genes regulated by Lmx1b we compared the limbs from Lmx1b KO mice to wild type mice during limb dorsalization (e11.5-13.5).  Differentially expressed genes that we common to all three stages examined were considered to be likely candidates for Lmx1b regulation and further evaluated.

overall_design:
At 11.5 and 12.5 dpc, embryos were harvested and the limb buds with the limb girdles were isolated. Embryos at 13.5dpc were also harvested and their distal limb buds (zeugopods and autopods) were isolated. Embryos were genotyped to confirm Lmx1b homozygosity (-/- or +/+).  RNA from embryonic forelimbs and hindlimbs of wild type (WT) and Lmx1b KO mice was harvested using the Rneasy Kit (Qiagen). RNA was pooled to decrease genetic variability, i.e., six limbs at 11.5 dpc, three limbs at 12.5 dpc and six limbs at 13.5 dpc. Duplicate samples were generated using different embryos for each stage and then hybridized to the Affymetrix GeneChip® Mouse Genome 430 2.0 Array (UCI, Irvine, CA).

Grant ID: 5R03HD039421-02
Funding source: Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH)
Title: Dorsoventral Patterning in Limb Development
Recipient: Kerby C. Oberg

first: Jennifer

middle: M

last: Feenstra

first: Kohei

last: Kanaya

first: Charmain

middle: U

last: Pira

first: Sarah

middle: E

last: Hoffman

first: Richard

middle: J

last: Eppey


title: Marked Reduction of AKT1 Expression and Deregulation of AKT1-associated Pathways in Peripheral Blood Mononuclear Cells of Schizophrenia Patients

status: Public on Jul 01 2013

city: rotterdam

first: nico

middle: jm

last: van beveren

address: dr molewaterplein

department: psychiatry

country: Netherlands

institute: erasmus university medical center

summary:
Recent studies have suggested that deregulated AKT1 signaling is associated with schizophrenia. We hypothesized that if this is indeed the case, we should observe both decreased AKT1 expression as well as deregulation of AKT1 regulated pathways in Peripheral Blood Mononuclear Cells (PBMCs) of schizophrenia patients. We therefore examined PBMC expression levels of AKT1 in schizophrenia  patients  versus controls, and examined whether functional biological processes in which AKT1 plays an important role are deregulated in schizophrenia patients.   We performed a case-control study, investigating whole-genome PBMC gene expression in male, recent onset (<5 years) schizophrenia patients (N=43) as compared to controls (N=29). Genes, differentially expressed between patients and controls were identified using ANOVA with Benjamini-Hochberg correction (false discovery rate (FDR)= 0.05).   Functional aspects of the deregulated set of genes were investigated with the Ingenuity Pathway Analysis (IPA) Software Tool.
From each participant 30 ml of blood was drawn into heparinized tubes. All blood samples were obtained between 10.00 and 11.00 am to minimize diurnal variation. PBMC’s were isolated by Ficoll gradient separation, started within 20 minutes after the drawing of blood and performed with minimum time variation. Cells were subsequently disrupted (Qiashredder kit; Qiagen), and RNA was isolated (RNeasy minikit; Qiagen) with an additional DNAse digestion step (RNase-free DNase set; Qiagen), all according to the manufacturer’s protocol, diluted in nuclease free water, and frozen at –80 C before use. Before freezing, RNA purity and quantity was assessed with the NanoDrop ND-1000 spectrophotometer (NanoDrop Technologies). After thawing the isolated RNA was biotinylated into cRNA using the One-Cycle Target Labeling and Control Reagents Kit (Affymetric Co) according to the manufacturer’s protocol. Before hybridisation RNA quality and integrity was assessed using the Agilent 2100 BioAnalyzer (Agilent). Biotinylated cRNA was hybridized to the Affymetrix Human Genome U133 plus 2.0 GeneChip© microarray containing 54,675 probe sets (Affymetrix Co). Each sample was individually biotinylated and hybridized to an individual microarray. Biotinylation was performed in batches with randomisation of patients and controls according to their ratios across the batches. The arrays were scanned and analyzed using Affymetrix Microarray Suite 4.2 software. Scanning was performed in three batches with randomization of patients and controls according to their ratios across the batches.

overall_design: A case-control study, investigating whole-genome PBMC gene expression in male, recent onset (<5 years) schizophrenia patients (N=43) as compared to controls (N=29). Patients consisted of two subgroups: acutely admitted, severely psychotic (N=22), and remitted patients (N=21). Genes, differentially expressed between patients and controls were identified using ANOVA with Benjamini-Hochberg correction (false discovery rate (FDR)= 0.05).

first: Nico

last: van Beveren

first: Sigrid

last: Swagemakers


title: Primary effusion lymphoma cell lines BC-1 and BC-3

status: Public on Nov 16 2011

first: Eva

last: Gottwein

summary: Microarray analysis of primary effusion lymphoma cell lines BC-1 and BC-3

overall_design: Total RNA from BC-1 and BC-3 cell lines was processed for analysis in one replicate on Human Gene 1.0 ST arrays to obtain data on whether genes are expressed and to compare to existing microarray data.

first: David

middle: L

last: Corcoran

first: Neelanjan

last: Mukherjee

first: Rebecca

last: Skalsky

first: Markus

last: Hafner

first: Jeffrey

middle: D

last: Nusbaum

first: Priscilla

last: Shamulailatpam

first: Cassandra

last: Love

first: Sandeep

last: Dave

first: Thomas

last: Tuschl

first: Uwe

last: Ohler

first: Bryan

middle: R

last: Cullen


title: Whole-genome nucleosome mapping in meiotic diploid S. cerevisiae

status: Public on Mar 07 2011

first: Scott

last: Keeney

address: 1275 York Ave

department: Molecular Biology Program

institute: Memorial Sloan Kettering Cancer Center

summary: We determined nucleosome positions throughout the genome in diploid S. cerevisiae undergoing early stages of synchronous meiosis. This study sought to assess if systematic reorganization of nucleosomes occurs during meiotic prophase at or near sites of DNA double strand break formation.

overall_design: Six samples were sequenced, each a separate time point from either of two meiotic time courses. Dataset N1 consists of samples collected at 0, 1, 2, and 3 hr in meiosis; Dataset N2 consists of samples collected at 0 and 4 hr. Time courses, sample preparation, and sequencing were carried out in separate laboratories for the two datasets: Hochwagen lab (Whitehead Institute) for Dataset N1; Keeney lab (Howard Hughes Medical Institute; Memorial Sloan-Kettering Cancer Center) for Dataset N2.

first: Jing

last: Pan

first: Mariko

last: Sasaki

first: Ryan

last: Kniewel

first: Hajime

last: Murakami

first: Hannah

last: Blitzblau

first: Sam

last: Tischfield

first: Xuan

last: Zhu

first: Matthew

last: Neale

first: Maria

last: Jasin

first: Nicholas

last: Socci

first: Andreas

last: Hochwagen


title: Loss of Rab25 promotes the development of intestinal neoplasia

status: Public on Dec 04 2010

city: Nashville

first: Pengcheng

last: Lu

state: TN

address: 2200 Pierce Avenue

institute: Vanderbilt University

summary: Analysis of Rab25 in human colon samples

overall_design: The adenoma dataset (n=6) contains 6 colonic adenomas for use in comparison to colon adenocarcinoma datasets.

first: J

last: Smith

first: R

last: Beauchamp


title: microRNA Targetome Analysis of Latently KSHV-infected Primary Effusion Lymphoma Cell lines Using PAR-CLIP [Illumina]

first: Eva

last: Gottwein

summary: Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) and frequently also harbors Epstein-Barr virus (EBV). The expression of KSHV- and, often, EBV-encoded microRNAs (miRNAs) in PELs suggests a role for these miRNAs in viral latency and lymphomagenesis. Here we report the direct and transcriptome-wide identification of miRNA target sites for all miRNAs expressed in PEL cell lines. The resulting dataset revealed that KSHV miRNAs directly target more than 2000 cellular mRNAs encoding proteins that function in pathways with relevance to KSHV pathogenesis. Moreover, ~50% of these mRNAs are also targeted by EBV miRNAs, via distinct binding sites. In addition to a known viral analog of miR-155, we show that KSHV encodes a viral miRNA that mimics cellular miR-142-3p function. In summary, these experiments identify an extensive list of mRNAs targeted by KSHV miRNAs and indicate that these are likely to strongly influence viral replication and pathogenesis.

overall_design:
small RNA sequencing, 3 samples

Ago2 (EIF2C2) PAR-CLIP, 2 samples

first: David

last: Corcoran

first: Neelanjan

last: Mukherjee

first: Rebecca

last: Skalsky

first: Markus

last: Hafner

first: Jeffrey

last: Nusbaum

first: Priscilla

last: Shamulailatpam

first: Cassandra

last: Love

first: Sandeep

middle: S

last: Dave

first: Thomas

last: Tuschl

first: Uwe

last: Ohler


title: MRE11 Deficiency Increases Sensitivity to Poly(ADP-ribose) Polymerase Inhibition in Microsatellite Unstable Colorectal Cancers.

status: Public on Apr 07 2011

city: Houston

first: Eduardo

last: Vilar-Sanchez

state: Texas

address: 1515 Holcombe Blvd, Unit 1360

institute: UT MD Anderson Cancer Center

summary: We have performed bioinformatic approaches to identify the level of enrichment between gene expression profiles characterizing MSI tumors and gene changes induced in vitro by the PARP-1 inhibitor Phenanthridinone and others using the Connectivity Map tool. In a first step, we have anyzed the expression of 300 colorectal cancers from the MECC study and generated a gene expression signature by microsatellite status. The criteria followed for selection of probe sets and detailed lists to be submitted subsequently to the Connectivity Map have been published previously by us in Clinical Cancer Research in 2009. In a second step, once we observed that deficiency in MRE11 exist among MSI tumors, our interest was focused on assessing if the homologous recombination pathway showed evidence of deregulation in MSI tumors. Therefore, we examined the expression levels of those genes integrated in the KEGG pathway hsa03440 using the previously generated gene expression data set.

overall_design: The dataset generated from our samples included a total of 300 colorectal fresh frozen tumors collected from the MECC study and were analyzed in two batches. The first batch was hybridized to the Affymetrix U133A chip and the second one to U133 Plus 2.0 (Supplementary Table S3). The final list of probe sets defining gene expression of MSI-H compared to MSS tumors was selected based on the strength of multiplicity adjusted P-values (cut-off P-value of < 0.001) and ratio of mean expression values across the two groups (cut-off Fold-change >1.3 and <0.7). It contained 442 upregulated and 480 downregulated probe sets. Then, MSI-H tumors present with changes in gene expression related to the homologous recombination pathway. Therefore, we examined the expression levels of those genes integrated in the KEGG pathway hsa03440 using the same data set. A total of 14 genes out of 30 were significantly differentially expressed in MSI-H compared to MSS tumors (Multiplicity adjusted Benjamini-Hochberg  P-value<0.05). MRE11 and RAD50 probe sets showed a lower expression in MSI-H tumors and simultaneously other probe sets such as PARP-1 were significantly upregulated, probably secondary to the deficiency in the MRN complex proteins. This data provides evidence of significant differential expression of the homologous recombination pathway in MSI tumors.

last: Vilar

first: Stephen

middle: B

last: Gruber

first: Gad

last: Rennert

first: Catherine

last: Bartnik

first: Stephanie

last: Stenzel

first: Maria

last: Iniesta

first: Leon

last: Raskin

first: Bhramar

first: Jaeil

last: Ahn

first: Victor

last: Moreno

first: Meredith

middle: A

last: Morgan


title: Rice plants treated with D-psicose

status: Public on Jan 31 2010

city: Miki-cho

first: Kazuya

last: Akimitsu

state: Kagawa

address: 2393 Ikenobe

department: Agriculture

institute: Kagawa University

summary: Rare sugars are monosaccharides that are rarely present in nature. One of the rare sugars, D-psicose, had a negative effect on shoot growth of rice. This negative effect to rice growth was observed previously with D-allose, but not observed in other tested rare sugars. To clarify the response to D-psicose in rice at the gene expression level, we performed a microarray analysis using the Agilent Rice Oligo Microarray (44k, custom-made; Agilent Technologies, Redwood City, CA, USA). As a result, treatment of D-psicose caused high induction of many defense-related genes including pathogenesis-related (PR) genes in rice.

overall_design: An Agilent Rice Oligo Microarray (44k, custom-made; Agilent Technologies, Redwood City, CA, USA) was used for the microarray analysis. By using the RNeasy plant mini kit (Qiagen, Hilden, Germany), total RNA was extracted from shoots of two-leaf stage rice plants that had been treated with 0.5 mM D-psicose or no sugar for 2 days. For each biological replicate, material from at least five rice plants was pooled to provide a single sample for RNA extraction. We performed 3 biological replicates for each treatment. All microarray procedures and data analyses were performed according to the manufacturer’s instructions. RNA integrity was checked using an Agilent 2100 Bioanalyzer (Agilent Technologies, Redwood City, CA, USA). Total RNA (400 ng) was labeled with Cy3 or Cy5 using an Agilent Low RNA Input Fluorescent Linear Amplification Kit (Agilent Technologies). Fluorescently labeled targets were hybridized to Agilent Rice Oligo Microarrays for 17 h at 65°C. After hybridization, wash processes were performed according to the manufacturer’s instructions, and hybridized microarrays were scanned using an Agilent Microarray Scanner (G2505B and software G2565BA; Agilent Technologies). Feature extraction software (version 9.1; Agilent Technologies) was used to delineate and measure the signal intensity of each spot in the array, and to normalize intensities. The background was measured around each spot as local background, calculated by the Feature Extraction software. Statistical data extraction processes were performed according to the manufacturer’s instructions.

first: Y

last: Yamasaki-Kokudo

first: T

last: Fukumoto

first: K

last: Ohtani

first: A

last: Kano

last: Tada

last: Gomi


title: microRNA Targetome Analysis of Latently KSHV-infected Primary Effusion Lymphoma Cell lines Using PAR-CLIP

first: Eva

last: Gottwein

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

overall_design: Refer to individual Series


title: An Experimentally Derived Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients

status: Public on Dec 01 2009

first: Pengcheng

last: Lu

summary:
Functional genomics approach to metastatic colon cancer
Mouse model translated to human colon cancer

overall_design: Gene expression array differences between highly invasive mouse colon cancer cells and non-invasive colon cancer cells

first: J

last: Smith

first: R

last: Beauchamp


title: BJAB Cell Lines Transduced with lentiviral vector pNL-SIN-CMV-AcGFP expressing KSHV miRNAs miR-K1, miR-K12-11, or miR-K4-3p

type:
Expression profiling by array
Third-party reanalysis

summary: BJAB cells were infected with pNL-SIN-CMV-AcGFP (see accession number GSE8867 for data) or pNL-SIN-CMV-AcGFP expressing KSHV miR-K1, miR-K12-11 or miR-K4-3p and sorted 48 hours after infection. 12 or 16 days after transduction, cytoplasmic RNA was harvested and gene expression analysis of independent BJAB cell pools was performed using Human Operon v3.0.2 arrays. Each sample was run against Universal Human Reference RNA, Stratagene. The samples listed here were processed in parallel to those with accession number GSE8867, which includes all matched control cell lines.

overall_design: 6 independent B cell pools each expressing KSHV miR-K1, miRK12-11, or miR-K4-3p are included. Matched controls include unmodified BJAB (3 arrays) and cells transducted with parental vector pNL-SIN-CMV-AcGFP (6 replicates).

first: David

last: Corcoran

first: Neelanjan

last: Mukherjee

first: Rebecca

last: Skalsky

first: Markus

last: Hafner

first: Jeffrey

last: Nusbaum

first: Priscilla

last: Shamulailatpam

first: Cassandra

last: Love

first: Sandeep

last: Dave

first: Thomas

last: Tuschl

first: Uwe

last: Ohler

first: Bryan

last: Cullen


title: Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients (VMC Samples)

status: Public on Nov 14 2009

summary:
Background and Aims: Staging inadequately predicts metastatic risk in colon cancer patients.  We used a gene expression profile derived from invasive murine colon cancer cells that were highly metastatic in an immunocompetent mouse model to identify colon cancer patients at risk for recurrence in a phase I, exploratory biomarker study.

Methods:  55 colorectal cancer patients from Vanderbilt Medical Center (VMC) were used as the training dataset and 177 patients from the Moffitt Cancer Center were used as the independent dataset. The metastasis-associated gene expression profile developed from the mouse model was refined using comparative functional genomics in the VMC gene expression profiles to identify a 34-gene classifier associated with high risk of metastasis and death from colon cancer.  A recurrence score derived from the biologically based classifier was tested in the Moffitt dataset.

Results:  A high score was significantly associated with increased risk of metastasis and death from colon cancer across all pathological stages and specifically in stage II and stage III patients.  The recurrence score was shown to independently predict risk of cancer recurrence and death in both univariate and multivariate models.  For example, among stage III patients, a high score translated to increased relative risk for cancer recurrence (hazard ratio = 4.7 (95% CI=1.566-14.05)).  Furthermore, the recurrence score identified stage III patients whose five-year recurrence-free survival was >88% and for whom adjuvant chemotherapy did not provide improved survival.

Conclusion: Our biologically based gene expression profile yielded a potentially useful classifier to predict cancer recurrence and death independently of conventional measures in colon cancer patients.

Keywords: Functional genomics, metastatic colon cancer, mouse model, human colon cancer

overall_design: Gene expression array differences between highly invasive mouse colon cancer cells and non-invasive colon cancer cells were used to develop a metastasis gene expression profile.  It was refined using gene expression data from 55 patient (VMC) samples and trained using 177 patient (Moffitt) samples.


title: Experimentally Derived Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Gene Expression-Based High Throughput Screening: Primary Patient AML Blasts, Normal Neutrophils, and Normal Monocytes

status: Public on Jan 30 2004

first: Ken

last: Ross

address: 7 Cambridge Center

department: Cancer Genomics

institute: Broad Institute

summary:
We developed a general approach to small molecule library screeening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation.

This data set contains 3 primary patient AML samples, 3 normal human neutrophil and 3 normal human monocyte samples. This data set was used to identify the genes that distinguish AML cells from normal human myeloid cells for the purpose of selecting marker genes for the screen.
Keywords = AML
Keywords = neutrophil
Keywords = monocyte
Keywords = chemical genomics
Keywords: repeat sample

first: Kimberly

last: Stegmaier

first: Kenneth

first: Sierra

last: Colavito

first: Shawn

last: O'Malley

first: Brent

last: Stockwell

first: Todd

last: Golub


title: Aberrantly activated Gli2-KIF20A axis is crucial for the growth of hepatocellular carcinoma and predicts poor prognosis

status: Public on Feb 14 2017

city: NANCAHNG

first: Shiwen

last: Luo

state: JiangXi

address: 17 Yong Wai street

department: Center for experimental medicine

institute: The Frist Affiliated Hospital of Nanchang University

summary: Analysis of gene expression levels in response to inhibition of Hh signaling in hepatocellular cancer cells using a cDNA microarray technique. Microarray analyses revealed that 136 genes were up-regulated and 335 gene were down-regulated after treatment with both cyclopamine (an antagonist of SMO) and GANT61 (a specific, small-molecular molecule inhibitor of Glis).

overall_design: HCC-LM3 cells were treated with GANT61 (20 μM for 48 hr), Cyclopamine (20μM for 48 hr) and control vehicle DMSO, respectively.

first: S

first: C

last: Shi


title: Rice plants treated with D-allose

status: Public on Apr 02 2009

city: Miki

first: Kazuya

last: Akimitsu

address: 2393, Ikenobe

department: Faculty of Agriculture

summary: Rare sugars are monosaccharides that are rarely present in nature. One of the rare sugars, D-allose had a negative effect on shoot growth of rice. This negative effect to rice growth was not observed in other tested rare sugars. To clarify the response to the D-allose in rice at gene expression level, we performed a microarray analysis using the Agilent Rice Oligo Microarray (44k, custom-made; Agilent Technologies, Redwood City, CA, USA). As a result, treatment of D-allose caused high induction of many defense-related genes including pathogenesis-related (PR) genes in rice.

overall_design: An Agilent Rice Oligo Microarray (44k, custom-made; Agilent Technologies, Redwood City, CA, USA) was used for the microarray analysis. By using RNeasy plant mini kit (Qiagen, Hilden, Germany), total RNA was extracted from shoots of two-leaf stage rice plants that had been treated with 0.5 mM D-allose, 0.5 mM D-glucose, or no sugar for 2 days. For each biological replicate, material from at least five rice plants was pooled to provide a single sample for RNA extraction. We performed 3 biological replicates for each treatment. All microarray procedures and data analyses were performed according to the manufacturer’s instructions. RNA integrity was checked using an Agilent 2100 Bioanalyzer (Agilent Technologies, Redwood City, CA, USA). Total RNA (400 ng) was labeled with Cy-3 or Cy-5 using an Agilent Low RNA Input Fluorescent Linear Amplification Kit (Agilent Technologies). Fluorescently labeled targets were hybridized to Agilent Rice Oligo Microarrays for 17 h at 65°C. After hybridization, following wash processes were performed according to the manufacturer’s instructions, and hybridized microarrays were scanned using an Agilent Microarray Scanner (G2505B and software G2565BA; Agilent Technologies). Feature extraction software (version 9.1; Agilent Technologies) was used to delineate and measure the signal intensity of each spot in the array, and to normalize intensities. The background was measured around each spot as local background, calculated by the Feature Extraction software. Statistical data extraction processes were performed according to the manufacturer’s instructions.

first: Y.

last: Yamasaki-Kokudo

first: M.

last: Satoh

first: K.

last: Gomi

first: A.

last: Kano


title: Transcriptional Analysis of S. aureus Response to Ramoplanin

status: Public on Feb 04 2009

city: Durham

first: John

middle: W.

last: Schmidt

state: NC

department: Chemistry

institute: Duke University

summary: The common research strain S. aureus NCTC 8325-4 was subjected to serial passage in increasing concentrations of ramoplanin.  The resulting strain, RSPA16, had reduced susceptibility to not only ramoplanin but vancomycin and nisin as well.  Electron microscopy revealed that the cell wall of RSPA16 was double the thickness of the susceptible progenitor strain, a phenotype commonly observed in vancomycin intermediate resistant S. aureus (VISA) strains.  RSPA16 was also less susceptible to lysis induced by Triton X-100 than its progenitor strain.  Transcriptional profiling experiments were performed with NCTC 8325-4 and RSPA16 without antibiotic exposure and exposed to ramoplanin.  Increased expression of genes associated with cell wall stress was observed when either strain was treated with ramoplanin.  We also observed that treatment with ramoplanin altered of the expression levels of numerous genes encoding proteins involved with amino acid biosynthesis, central metabolic pathways, nucleotide biosynthesis, iron acquisition, ABC transporters and regulation of transcription.  Comparison of the transcriptional profiles of RSPA16 and NCTC 8325-4 not exposed to ramoplanin revealed alterations in the expression of levels of several genes involved with biosynthesis of teichoic acids, biosynthesis of peptidoglycan, central metabolism, DNA replication, nucleotide biosynthesis, iron acquisition, ABC transporters, and regulation of transcription.  These transcriptional profiles provide insights into the possible sources of the reduced susceptibility of RSPA16 to peptide antibiotics.

overall_design: Mid log phase (OD620 = 0.4) batch TSB cultures of ramoplanin susceptible (NCTC 8325-4) and resistant (RSPA16) strains of S. aureus were exposed to ramoplanin for 30 minutes at 37 C.  Untreated controls were performed for each strain as well. The transcriptional response was determined using Affymetrix Gene Chip Arrays.  This study also examines the transcriptional alterations which confer reduced susceptibility to ramoplanin as the transcriptional profiles of NCTC 8325-4 and RSPA16 each untreated were compared.

middle: W

first: Dewey

last: McCafferty


title: Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients (Moffitt Samples)

first: Pengcheng

last: Lu

first: J

last: Smith

first: R

last: Beauchamp