title: DDX6 decouples translational repression from RNA degradation of miRNA targets [DGCR8KO Polysome]

status: Public on Jul 25 2018

city: San Francisco

first: Robert

last: Blelloch

address: 513 Parnassus Avenue, Campus Box #0525

institute: University of California, San Francisco

summary: Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.

overall_design: Polysome profiling of wild type and DGCR8 KO embryonic stem cells (ESCs).

first: Jacob

last: Freimer


title: DDX6 decouples translational repression from RNA degradation of miRNA targets [DDX6KO 4sU]

state: CA

country: USA

type: Expression profiling by high throughput sequencing

overall_design:
4-thiouridine (4su) metabolic labeling was performed on wild type and DGCR8 KO embryonic stem cells.

Please note that all samples were sequenced as single end reads to generate the DDX6KO_4su_counts.txt file.  A subset of samples (*_resequenced samples) were re-sequenced as paired-end for more sequencing depth to generate 'DDX6KO_4su_reseq_counts.txt' data. While the BAM files were not merged between the initial single-end samples and the re-sequenced paired-end samples, the counts data were merged (within the scripts used) during further analyses.


title: DDX6 decouples translational repression from RNA degradation of miRNA targets [QuantSeq mRNA]

overall_design: mRNA expression profiling of wild type, DGCR8 KO, and DDX6 KO embryonic stem cells


title: DDX6 decouples translational repression from RNA degradation of miRNA targets [DDX6KO Polysome]

overall_design: Polysome profiling of wild type and DDX6 KO embryonic stem cells (ESCs).


title: Integrative genomic analysis in HCC samples [SNP]

status: Public on Jan 19 2018

city: Beijing

first: Gangqiao

last: Zhou

address: No. 27, Taiping Road, Haidian District

country: China

institute: Beijing Institute of Radiation Medicine

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

summary: We integrated the copy number data with gene expression data from the same HCC samples, and identified fifteen putative driver genes with recurrently genomic aberrations and their associated modules in HCC. We further confirmed empirically that three putative driver genes (MYH10, CEP104 and RRS1) play significant roles in tumor initiation and progression of HCC. Notably, we demonstrated that RRS1 regulates the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolus in HCC. Altogether, these data provide insights into novel cancer driver genes and suggested molecular targets for treatment for HCC.

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from tumor tissues and paired adjacent non-tumor tissues of 31 HCC patients.

first: Peiyao

last: Li

first: Xia

last: Xia

first: Pengbo

last: Cao


title: DDX6 decouples translational repression from RNA degradation of miRNA targets [ESC EpiLC 4sU]

overall_design: 4-thiouridine (4su) metabolic labeling was performed on mouse embryonic stem cells (ESCs) and Epiblast like cells (EpiLCs).


title: DDX6 decouples translational repression from RNA degradation of miRNA targets [DGCR8KO 4sU]

overall_design: 4-thiouridine (4su) metabolic labeling was performed on wild type and DGCR8 KO embryonic stem cells.


title: Differential splicing events in aging Drosophila eye

status: Public on Jun 20 2018

city: WEST LAFAYETTE

first: Vikki

last: Weake

state: INDIANA

address: 175 S. University St.

department: Biochemisty

institute: Purdue University

summary: Purpose: The goal of this study was to identify differential splicing events in the Drosophila eye during aging.

overall_design: Method: RNA extracted from dissected eye tissue of flies aged 10 and 40 days post-eclosion was used to generate cDNA libraries using NuGen Ovation Drosophila RNA seq system. Samples were sequenced using  Illumina HiSeq2500 next generation sequencer  (three biological replicates per time point).

first: Rachel

last: Stegeman

first: Hana

last: Hall

middle: M


title: DDX6 decouples translational repression from RNA degradation of miRNA targets [Ribosome Profiling]

overall_design: Ribosome profilling was performed on mouse embryonic stem cells (ESCs) and Epiblast like cells (EpiLCs).


title: Single Cell RNA-Seq profiling human embryonic kidney cortex cells

status: Public on Apr 13 2018

city: Los Angeles

first: Guilherme

last: de Sena Brandine

address: 1050 Child's Way

department: Quantitative and Computational Biology

institute: University of Southern California

summary: To characterize the cellular diversity in the human kidney cortical nephrogenic niche we dissociated cells from the cortex and performed 10X Genomics single-cell RNA sequencing.

overall_design: Identifying cell types and nephrogenic programs in the developing human kidney

first: Andrew

last: Ransick

first: Albert

middle: D

last: Kim

last: De Sena Brandine

first: Nils

middle: O

last: Lindstrom

last: McMahon


title: Mixed-species RNAseq analysis of human lymphoma cell adhesion to mouse stromal cells identifies a core gene set that is also differentially expressed in the lymph node microenvironment of MCL and CLL patients.

status: Public on Jun 12 2018

city: Uppsala

first: Gustav

last: Arvidsson

state: Uppsala

address: Husargatan 3

department: Department of Medical Sciences

country: Sweden

institute: Uppsala Universitet

summary: Background:A subset of hematological cancer patients is refractory to treatment or suffer relapse, due in part to minimal residual disease, whereby some cancer cells survive treatment via microenvironment interaction. Cell-adhesion mediated drug resistance is an important mechanism, whereby cancer cells receive survival signals via interaction with e.g. stromal cells. No genome-wide studies of in vitro systems have yet been performed to compare gene expression in different cell subsets within a co-culture and cells grown separately. Results: Using RNAseq and species-specific read mapping, we compared transcript levels in human Jeko-1 mantle cell lymphoma (MCL) cells stably adhered to stromal cells or in suspension within a co-culture and in separate culture as well as mouse MS-5 stromal cells in co-culture or in separate culture. 1050 differentially expressed transcripts in adherent MCL cells identified 24 functional categories that together represent four main functional themes, anti-apoptosis, B-cell signaling, cell adhesion/migration and early mitosis. Comparison with previous MCL and chronic lymphocytic leukemia (CLL) patient data identified 116 genes that are differentially regulated in all three studies. From these genes we suggest a gene signature (CCL3, CCL4, DUSP4, ETV5, ICAM1, IL15RA, IL21R, IL4I1, MFSD2A, NFKB1, NFKBIE, SEMA7A, TMEM2) characteristic of cells undergoing cell-adhesion mediated microenvironment signaling in MCL/ CLL cells. Conclusions: The model system developed and characterized here together with suggested signature genes can be used in future studies of pathways that mediate increased cancer cell survival and drug resistance mechanisms.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: RNA-seq; four conditions in quadruplicates, 16 samples in total.

first: Anthony

last: Wright

first: Birgitta

last: Sander


title: Integrative genomic analysis in HCC samples [RRS1]

overall_design: Total RNA obtained from the human HepG2 cells stably expressing of human RRS1 gene or HepG2 cells with empty vector as a control. Three biological replicates each.

first: Aiqing

last: Yang

first: Guangmin

first: Xi

last: Chen


title: Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells

first: Robert

last: Blelloch

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

overall_design: Refer to individual Series


title: Transcriptional organization of autism spectrum disorder

status: Public on Feb 27 2018

city: La Jolla

first: Vahid

middle: H

last: Gazestani

state: California

address: 8110 La Jolla Shores Drive, Suite 201

institute: UCSD


title: Integrative genomic analysis in HCC samples [CEP104]

first: Gangqiao

last: Zhou

overall_design: Total RNA obtained from the human HepG2 cells with CEP104 shRNAs or HepG2 with control shRNA, respectively. Three biological replicates each.

first: Peiyao

last: Li

first: Jinxu

last: Zhang

last: Cao

first: Xia

last: Xia


title: E. coli MazF does not create specialized ribosomes that translate leaderless mRNAs, but instead blocks rRNA maturation and ribosome biogenesis [5'OH-seq]

status: Public on Dec 05 2017

city: Boston

first: Peter

last: Culviner

state: MA

address: 677 Huntington Ave

department: IID

institute: Harvard School of Public Health

summary: The purpose of this experiment was to characterize MazF cleavage specificity with single-nucleotide resolution by enriching and sequencing 5’-OH ends (a 5’-OH end is generated by MazF cleavage).

overall_design: A + MazF and empty vector sample after 20 minutes of induction.

first: Michael

middle: T

last: Laub


title: Multiple mechanisms of global microRNA suppression in vertebrate oocytes [RNA-seq]

status: Public on Dec 31 2017

summary: Mouse oocyte maturation, fertilization, and reprogramming occur in the absence of transcription and thus must be regulated post-transcriptionally. Surprisingly, a major form of post-transcriptional regulation, microRNA-based transcript destabilization and translational inhibition, is lost during this developmental window. Here we evaluate the conservation, timing, and mechanism behind the loss of microRNA activity in oocytes. In both mouse and frogs, microRNA function was active in growing oocytes, but then lost during oocyte maturation. RNA-sequencing of the maturing oocytes uncovered expression of an alternative isoform of Ago2 lacking domains critical for its function. Introduction of full-length Ago2 together with an exogenous microRNA destabilized microRNA luciferase reporters. However, endogenous targets were still largely unaffected. These findings suggest that while it is possible to re-activate some aspects of microRNA activity by introducing full length Ago2, there are additional mechanisms to protect endogenous transcripts from microRNA activity in oocytes.

overall_design: Total RNA from mouse GV and MII oocytes, embryonic stem cells, epi cells

first: Jacob

last: Freimer


title: Clinical Value of RNA Sequencing–Based Classifiers for Prediction of the Five Conventional Breast Cancer Biomarkers: A Report From the Population-Based Multicenter Sweden Cancerome Analysis Network—Breast Initiative [cohort 405]

status: Public on Mar 12 2018

city: Lund

first: Lao

last: Saal

address: Scheelevägen 2, MV404B2

department: Department of Oncology and Pathology

institute: Lund University

summary:
PURPOSE
In early breast cancer (BC), five conventional biomarkers—estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, and Nottingham histologic grade (NHG)—are used to determine prognosis and treatment. We aimed to develop classifiers for these biomarkers that were based on tumor mRNA sequencing (RNA-seq), compare classification performance, and test whether such predictors could add value for risk stratification.

METHODS
In total, 3,678 patients with BC were studied. For 405 tumors, a comprehensive multi-rater histopathologic evaluation was performed. Using RNA-seq data, single-gene classifiers and multigene classifiers (MGCs) were trained on consensus histopathology labels. Trained classifiers were tested on a prospective population-based series of 3,273 BCs that included a median follow-up of 52 months (Sweden Cancerome Analysis Network—Breast [SCAN-B], ClinicalTrials.gov identifier: NCT02306096), and results were evaluated by agreement statistics and Kaplan-Meier and Cox survival analyses.

RESULTS
Pathologist concordance was high for ER, PgR, and HER2 (average κ, 0.920, 0.891, and 0.899, respectively) but moderate for Ki67 and NHG (average κ, 0.734 and 0.581). Concordance between RNA-seq classifiers and histopathology for the independent cohort of 3,273 was similar to interpathologist concordance. Patients with discordant classifications, predicted as hormone responsive by histopathology but non–hormone responsive by MGC, had significantly inferior overall survival compared with patients who had concordant results. This extended to patients who received no adjuvant therapy (hazard ratio [HR], 3.19; 95% CI, 1.19 to 8.57), or endocrine therapy alone (HR, 2.64; 95% CI, 1.55 to 4.51). For cases identified as hormone responsive by histopathology and who received endocrine therapy alone, the MGC hormone-responsive classifier remained significant after multivariable adjustment (HR, 2.45; 95% CI, 1.39 to 4.34).

CONCLUSION
Classification error rates for RNA-seq–based classifiers for the five key BC biomarkers generally were equivalent to conventional histopathology. However, RNA-seq classifiers provided added clinical value in particular for tumors determined by histopathology to be hormone responsive but by RNA-seq to be hormone insensitive.

overall_design:
Illumina paired-end RNA-sequencing and expression estimation were performed for two cohorts: a training cohort with 405 samples (GSE81538), and a validation cohort with 3273 samples (of which 136 cases have technical replicates) (GSE96058).  A comprehensive histopathological evaluation was performed on the 405-cohort to estimate inter-pathologist variability on original diagnostic slides as well as on repeat immunostains, leading to consensus scores for five clinical biomarkers.  Subtyping was performed using the PAM50 gene list.

Due to the patient consent, Swedish law, the potential that the sequencing data contains personally-identifiable information and hereditary mutations, and the right to privacy, the submitter cannot make available the raw sequence data in a public repository.

first: Christian

last: Brueffer

first: Johan

last: Vallon-Christersson

first: Dorthe

last: Grabau

first: Anna

last: Ehinger

first: Jari

last: Häkkinen

first: Cecilia

last: Hegardt

first: Janne

last: Malina

first: Yilun

first: Pär-Ola

last: Bendahl

first: Jonas

last: Manjer

first: Martin

last: Malmberg

first: Christer

last: Larsson

first: Niklas

last: Loman

first: Lisa

last: Rydén

first: Åke

last: Borg


title: Multiple mechanisms of global microRNA suppression in vertebrate oocytes [expression]

first: Robert

last: Blelloch

overall_design: Total RNA obtained from GV oocytes that express a lox-stop-lox-myc-gfp-human Ago2 from the Rosa26 locus. Samples are Zp3-Cre positive or negative and with or without exogenous miR-15a mimic.

first: Jacob


title: E. coli MazF does not create specialized ribosomes that translate leaderless mRNAs, but instead blocks rRNA maturation and ribosome biogenesis

first: Peter

last: Culviner


title: E. coli MazF does not create specialized ribosomes that translate leaderless mRNAs, but instead blocks rRNA maturation and ribosome biogenesis [Ribo-Seq]

summary: The purpose of this experiment was to assess translation of mRNA after MazF expression to determine if cleavage events resulted in a loss in ribosome footprints.

overall_design: A + MazF sample at 5 minutes and 25 minutes after induction and an empty vector sample at 15 minutes of induction

first: Michael

last: Laub


title: RNA-seq of primary murine lung adenocarcinoma cells from KP and JKP mice

status: Public on Sep 26 2017

city: London

first: Gavin

last: Kelly

state: London

address: 1 Midland Road

country: United Kingdom

institute: Francis Crick institute

summary: The AP-1 transcription factor c-Jun is required for Ras-driven tumorigenesis in many tissues. Surprisingly, we found that inactivation of c-Jun increased tumor burden in a model of K-RasG12D-induced lung adenocarcinoma.

overall_design: mRNA-seq of KP vs. JKP isolated adenocarcinoma cell lines, in triplicate

first: Markus

last: Diefenbacher

first: Eva

last: Riising

first: Axel

last: Behrens


title: mRNA and miRNAs Establish and Maintain Uniform Cellular Phenotypes during the Architecture of Complex Tissues

status: Public on Aug 22 2017

city: New Haven

first: Stefania

last: Nicoli

state: CT

address: 300 George street

department: Internal Medicine

institute: Yale University

type: Non-coding RNA profiling by high throughput sequencing


title: microRNAs Establish and Maintain Uniform Cellular Phenotypes during the Architecture of Complex Tissues

summary: Proper functioning of tissues requires cells to behave in uniform, well-organized ways. Conversely, many diseases involve increased cellular heterogeneity due to genetic and epigenetic alterations. Defining the mechanisms that counteract phenotypic variability is therefore critical to understand how tissues sustain homeostasis. Here, we carried out a single-cell resolution screen of zebrafish embryonic blood vessels upon mutagenesis of single microRNA (miRNA) genes and multi-gene miRNA families. We found that miRNA mutants exhibit a profound increase in cellular phenotypic variability of specific vascular traits. Genome-wide analysis of endothelial miRNA target genes identified antagonistic regulatory nodes of vascular growth and morphogenesis signaling that allow variable cell behaviors when derepressed. Remarkably, lack of such miRNA activity greatly sensitized the vascular system to microenvironmental changes induced by pharmacological stress. We uncover a previously unrecognized role of miRNAs as a widespread protective mechanism that limits variability in cellular phenotypes. This discovery marks an important advance in our comprehension of how miRNAs function in the physiology of higher organisms.

overall_design: Analysis of differential genes expression in Zebrafish endothelial cells for 4 different developmental stages in duplicate

first: Dionna

last: Kasper

first: Emma

last: Ristori

first: Albertomaria

last: Moro

first: Anand

last: Narayanan

first: Guillermina

last: Hill-Teran

first: Elizabeth

last: Fleming

first: Miguel

last: Moreno-Mateos

first: Charles

last: Vejnar

first: Jing

last: Zhang

first: Donghoon

last: Lee

first: Mengting

last: Gu

first: Mark

last: Gerstein

first: Antonio

last: Giraldez


title: Multiple mechanisms of global microRNA suppression in vertebrate oocytes

first: Robert

last: Blelloch


title: Perturbational proteomic and transcriptional profiles of drug perturbations from Broad Institute LINCS Proteomic Characterization Center for Signaling and Epigenetics and Broad Institute LINCS Center for Transcriptomics (U54HG008097) (n=5,063)

status: Public on Aug 24 2017

city: Cambridge

first: Jacob

last: Jaffe

address: 415 Main St.

institute: The Broad Institute

summary:
The Library of Integrated Cellular Signatures (LINCS) is an NIH program which funds the generation of perturbational profiles across multiple cell and perturbation types, as well as read-outs, at a massive scale. The LINCS PCCSE uses two high-throughput liquid chromatography-mass spectrometry (LCMS) assays to study the proteomic changes induced by drug and genetic perturbations. P100 monitors ~100 phosphorylated peptides from cellular proteins that serve as a reduced representation of the phosphoproteome. GCP monitors ~60 modified peptides from histones (e.g., methylated, acetylated, and combinations thereof) encompassing nearly every well-studied post-translational modification on the core nucleosomal histone proteins. Closely complementing these assays is the L1000 high-throughput gene-expression assay. The files available here contain P100, GCP, and L1000 data for 90 small-molecule perturbations in six cell lines (five cancer cell lines and a neurodevelopmental cell model). These data were generated under the auspices of the NIH LINCS Program (www.lincsproject.org). Note: Related GEO projects include a large corpus of additional L1000 data, available at GSE92742.

The Platform for the L1000 data is GPL20573: Broad Institute Human L1000 epsilon
http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL20573

For questions or assistance with this dataset, please email the Connectivity Map support team at: clue@broadinstitute.org

overall_design: These data represent three different read-outs (phosphosignaling, chromatin modifications, and transcriptional changes) of the same 90 small-molecule perturbations in six cell lines. The duration of treatment was 3 hours for P100, 24 hours for GCP, and 6 hours for L1000. These data are available at multiple levels of processing: level 1 is fluorescence intensity (for L1000) or mass spectrometry extracted ion chromatogram traces (for P100, GCP); level 2 is gene expression or proteomic values without normalization; level 3 is normalized; and level 4 is differential (i.e., each sample is compared to all other samples on a plate).


title: Genome-wide maps of Spt6 occupancy in yeast strains with mutations in Spt6 and Rpb1

status: Public on Oct 24 2017

city: Salt Lake City

first: Tim

last: Formosa

state: UT

address: 15 N Medical Dr East RM 4100

department: Biochemistry

institute: University of Utah School of Medicine

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We determined that the tandem SH2 domain of S. cerevisae Spt6 binds the linker region of the RNA polymerase II subunit Rpb1, rather than the expected sites in its heptad repeat domain. The 4 nM binding affinity requires phosphorylation at Rpb1 S1493 and either T1471 or Y1473. Crystal structures showed that pT1471 binds the canonical SH2 pY site while pS1493 binds an unanticipated pocket 70 Å distant. Remarkably, the pT1471 phosphate occupies the phosphate-binding site of a canonical pY complex, while Y1473 occupies the position of a canonical pY side chain, with the combination of pT and Y mimicking a pY moiety. Biochemical data and modeling indicate that pY1473 can form an equivalent interaction, and we find that pT1471/pS1493 and pY1473/pS1493 combinations occur in vivo. ChIP-seq and genetic analyses demonstrate the importance of these interactions for recruitment of Spt6 to sites of transcription and for the maintenance of repressive chromatin.

sample_organism:
Saccharomyces cerevisiae
Nakaseomyces glabratus

overall_design: WT and 6 mutant yeast strains were analyzed with antisera against Spt6 in triplicate. A preimmune serum was included for the WT samples, for a total of 30 immunoprecipitations and 30 DNA input samples, with Candida glabrata used as a reference control for all samples.

first: Matthew

middle: A

last: Sdano

first: James

last: Fulcher

first: Sowmiya

last: Palani

first: Mahesh

middle: B

last: Chandrasekharan

first: Frank

middle: G

last: Whitby

first: Christopher

middle: P

last: Hill


title: Genome wide DRIP-seq in control knockdown HeLa cells

status: Public on Jul 27 2017

city: Stanford

first: Karlene

middle: Anne

last: Cimprich

address: 318 Campus Drive

institute: Stanford University

summary: We mapped the location of RNA:DNA hybrids in HeLa cells that had been knocked down with a control siRNA. We found that the levels of RNA:DNA hybrids around origins of replication (defined from data from Pretyk et al, Nat Commun 2016) strongly correlated to the directionality of transcription around these origins (defined from GRO-seq data from GEO dataset GSM1518913.) Specifically, in regions where the replication fork travels antiparallel (Head-On) to the direction of transcription we find elevated RNA:DNA hybrids, and in regions where the replication fork travels parallel to the direction of replication (Co-directional) we find reduced RNA:DNA hybrids. These results imply that the relative directions of replication and transcription have an effect on the levels of RNA:DNA hybrids across the genome.

overall_design: Input and IP for two replicates of a DRIP-seq experiment in HeLa cells treated with a control siRNA

last: Cimrich

first: Stephan

last: Hamperl

first: Michael

last: Bocek

first: Joshua

last: Saldivar


title: mRNAs Establish and Maintain Uniform Cellular Phenotypes during the Architecture of Complex Tissues

first: Stefania

last: Nicoli

overall_design: Analysis of differential genes expression in Zebrafish endothelial cells for 4 different developmental stages

first: Dionna

last: Kasper

first: Emma

last: Ristori

first: Albertomaria

last: Moro

first: Anand

last: Narayanan

first: Guillermina

last: Hill-Teran

first: Elizabeth

last: Fleming

first: Miguel

last: Moreno-Mateos

first: Charles

last: Vejnar

first: Jing

last: Zhang

first: Donghoon

last: Lee

last: Gu


title: Genome-wide analysis of keratinocytes laser captured from skin biopsies during the mucocutaneous HSV-2 reactivation

status: Public on May 05 2017

city: Seattle

first: Tao

last: Peng

state: WA

address: 1100 Fairview Ave N/FHCRC/E5-110

department: Medicine

institute: University of Washington

summary: We aim to analyze the transcriptional profiles of keratinocytes near dermal-epidemal junction during HSV-2 reactivation in humans, including lesion, post healed (4 and 8 weeks post healing) and contra-lateral control biopsies. Since keratinocytes are the main target cells for HSV-2 infection, the goal is to define the intrinsic immunity of keratinocytes during HSV-2 reactivation in humans.

overall_design: CD8 cells were immunofluorescently stained and keratinocytes above base membrane were laser captured from genital skin biopsies at lesion,  4 and 8 weeks post healed and contra-lateral controls; total RNA were purified from captured cells and cDNA were amplified from the total RNA using NuGEN pico kits.


title: SIRT7 Antagonizes TGF-β Signaling and Inhibits Breast Cancer Metastasis

status: Public on Jun 03 2017

city: shenzhen

first: Xiaolong

last: Tang

address: 3688 Nanhai Ave, Nanshan District

institute: shenzhen university

summary: Protein deacetylase SIRT7 is significantly downregulated in lung metastases of human patient and mouse tissues, and predicted metastasis-free survival. To explore the roles of SIRT7 in breast cancer, we analysed the gene expressions in breast cancer BT549 cells with SIRT7 knockdown or not.

overall_design: The mRNA profiles of breast cancer BT549 cells with SIRT7 knockdown or not were generated by deep sequencing using Illumina HiSeq-2000

first: Baohua

last: Liu


title: Profiles for long noncoding RNAs in ovarian granulosa cells from polycystic ovary syndrome patients with different serum concentrations of androgen

status: Public on Nov 10 2017

city: Hangzhou

first: Chengliang

last: Zhou

state: Zhejiang

address: No. 866th, Yuhangtang Road

department: School of Medicine

institute: Zhejiang University

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

summary: Polycystic ovary syndrome (PCOS) is a common reproductive system disease, with hyperandrogenism as the core feature. The pathologies remain to be illustrated.  Long noncoding RNAs (lncRNAs) has been proved to be involved in various biological processes of human diseases. However, there were few reports about the research on lncRNAs in PCOS, not to mention hyperandrogenism.

overall_design: microarray screening of lncRNAs and mRNAs was performed in PCOS patients with hyperandrogenism (PCOS-T) and PCOS patients with normal testosterone level (PCOS-N) and control subjects

first: Qian

last: Yang


title: The Australian Mammographic Density Twins and Sisters Study - DNA methylation data

status: Public on Jun 21 2017

city: Parkville

first: John

last: Hopper

state: Victoria

address: 207 Bouverie Street

department: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health

country: Australia

institute: The University of Melbourne

summary: DNA methylation data for 479 women from 130 families including 66 monozygotic twin pairs, 66 dizygotic twin pairs and 215 sisters of twins.

overall_design: Genomic DNA was extracted from dried blood spots. DNA was sodium bisulfite converted using the EZ DNA Methylation-Gold protocol. Epigenome-wide methylation was assessed using the Infinium HumanMethylation450 BeadChip arrays

first: Shuai

last: Li


title: H2A monoubiquitination in Arabidopsis is generally independent of LHP1 and PRC2 activity

status: Public on Mar 21 2017

city: Sevilla

first: Myriam

last: Calonje

address: Americo Vespucio 49

country: Spain

institute: Institute for Plant Biochemistry and Photosynthesis (CSIC -  University of Sevilla)

overall_design: Refer to individual Series


title: Profiling human naive and primed pluripotent states

status: Public on Mar 23 2017

first: Felix

last: Krueger

address: Granta Park

department: Bioinformatics

institute: Altos Labs

summary: Here we analyse transcriptome profiles of naive, primed and intermediate populations of human pluripotent stem cells

overall_design: Transcriptome (mRNA-Seq) from naive, primed, four day-10 flow-sorted populations (Nmin, N3+, N4+ and N4–), and N4+ sorted cells that were propagated for five and ten passages in naive conditions.

first: Amanda

last: Collier

first: Sarita

last: Panula

first: Fredrik

last: Lanner

first: Peter

last: Rugg-Gunn


title: Broad Institute L1000 Connectivity Map and RNAseq gene expression profiles on tissue samples from the GTEx project

status: Public on Mar 03 2017

first: Aravind

last: Subramanian

address: 415 Main Street

summary:
The Library of Integrated Cellular Signatures (LINCS) is an NIH program which funds the generation of perturbational profiles across multiple cell and perturbation types, as well as read-outs, at a massive scale. The LINCS Center for Transcriptomics at the Broad Institute uses the L1000 high-throughput gene-expression assay to profile a range of cellular models and perturbations of cellular state. These data relate to using  RNA-Seq datasets from the GTEx consortium (http://www.gtexportal.org/) to validate the L1000 assay and to improve the statistical model used in imputing the transcriptome.

The Platform is GPL20573: Broad Institute Human L1000 epsilon
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL20573

For questions or assistance with this dataset, please email the CMap support team at: clue@broadinstitute.org

overall_design: The Genotype Tissue Expression (GTEx) project aims to find associations between genomic features and gene expression levels. As part of this project, aliquots of mRNA obtained from 3,176 patient-derived samples from 30 tissue types were profiled on two contemporary gene expression platforms; RNAseq and L1000, a high-throughput gene-expression assay that enables data generation at an unprecedented scale. In L1000, the data are processed through a computational system that converts raw fluorescence intensities into normalized expression profiles generating level 3 (Q2NORM) - gene expression profiles of both directly measured landmark transcripts plus inferred genes. Normalization is done using invariant set scaling followed by quantile normalization. The RNAseq data were collected using Illumina TrueSeq RNA sequencing and converted into reads per kilobase-million (RPKM) units. These RPKM data and underlying read count files are available via the GTEx portal (http://www.gtexportal.org/home/datasets). In this series, the RPKM data were also log2-scaled and quantile normalized as a cohort.


title: H2A monoubiquitination in Arabidopsis is generally independent of LHP1 and PRC2 activity [ChIP-seq]

summary:
BACKGROUND:
Polycomb group complexes PRC1 and PRC2 repress gene expression at the chromatin level in eukaryotes. The classic recruitment model of Polycomb group complexes in which PRC2-mediated H3K27 trimethylation recruits PRC1 for H2A monoubiquitination was recently challenged by data showing that PRC1 activity can also recruit PRC2. However, the prevalence of these two mechanisms is unknown, especially in plants as H2AK121ub marks were examined at only a handful of Polycomb group targets.
RESULTS:
By using genome-wide analyses, we show that H2AK121ub marks are surprisingly widespread in Arabidopsis thaliana, often co-localizing with H3K27me3 but also occupying a set of transcriptionally active genes devoid of H3K27me3. Furthermore, by profiling H2AK121ub and H3K27me3 marks in atbmi1a/b/c, clf/swn, and lhp1 mutants we found that PRC2 activity is not required for H2AK121ub marking at most genes. In contrast, loss of AtBMI1 function impacts the incorporation of H3K27me3 marks at most Polycomb group targets.
CONCLUSIONS:
Our findings show the relationship between H2AK121ub and H3K27me3 marks across the A. thaliana genome and unveil that ubiquitination by PRC1 is largely independent of PRC2 activity in plants, while the inverse is true for H3K27 trimethylation.

overall_design: H2AK121ub and H3K27me3 profiles of 7DAG Arabidopsis seedlings Col-0, strong atbmi1a/b/c triple mutant, clf28/swn7 double mutant and lhp1 mutant. Two independent biological replicates are considered for each genotype.

first: Yue

first: Francisco J

last: Romero-Campero

first: Angeles

last: Gomez-Zambrano

first: Franziska

last: Turck


title: L1000 Connectivity Map perturbational profiles from Broad Institute LINCS Center for Transcriptomics LINCS Pilot PHASE I (n=1,319,138; updated March 03, 2017)

summary:
The Library of Integrated Cellular Signatures (LINCS) is an NIH program which funds the generation of perturbational profiles across multiple cell and perturbation types, as well as read-outs, at a massive scale. The LINCS Center for Transcriptomics at the Broad Institute uses the L1000 high-throughput gene-expression assay to build a Connectivity Map which seeks to enable the discovery of functional connections between drugs, genes and diseases through analysis of patterns induced by common gene-expression changes. These files represent L1000 data generated during the LINCS Pilot Phase (2012-2015), as well as profiles generated for more specific purposes, such as assay development and validation projects or testing custom compounds or non-standard cell lines (not part of the core LINCS cell lines). Note: Related GEO projects include (a) Additional L1000 and RNA-Seq data used to validate the assay and improve the inference model, available at GSE92743 (b)  The LINCS “production phase” (also termed Phase II, 2015-2020) which is generating an additional cohort of L1000 data, available at GSE70138.

The Platform is GPL20573: Broad Institute Human L1000 epsilon
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL20573

For questions or assistance with this dataset, please email the CMap support team at: clue@broadinstitute.org

overall_design:
LINCS aims to enable a functional understanding of biology by cataloging changes in gene expression and other cellular processes that occur when cells are exposed to a variety of perturbing agents. The Broad Institute LINCS Center for Transcriptomics contributes to this collaborative effort by application of the Connectivity Map concept. In brief, the study design involves the generation of a compendium of transcriptional expression data from cultured human cells treated with small-molecule and genetic loss/gain of function perturbagens. These measurements are made using the L1000 high-throughput gene-expression assay that enables data generation at an unprecedented scale.  The data are processed through a computational system, that converts raw fluorescence intensities into differential gene expression signatures. The data at each stage of the pre-processing are available: Level 1 (LXB) - raw, unprocessed flow cytometry data from Luminex scanners. One LXB file is generated for each well of a 384-well plate, and each file contains a fluorescence intensity value for every observed analyte in the well. Level 2 (GEX) - gene expression values per 1,000 genes after deconvolution from Luminex beads. Level 3 (Q2NORM) - gene expression profiles of both directly measured landmark transcripts plus inferred genes. Normalized using invariant set scaling followed by quantile normalization. Level 4 (Z-SCORES) - signatures with differentially expressed genes computed by robust z-scores for each profile relative to control (PC relative to plate population as control; VC relative to vehicle control). Level 5 (SIG) consists of the replicates, usually 3 per treatment, aggregated into a single differential expression vector derived from the weighted averages of the individual replicates.

Please note that a description of the latest file, and a table listing the contents of the 'Broad_LINCS_auxiliary_datasets.tar.gz' file are updated in the following document;
https://docs.google.com/document/d/1q2gciWRhVCAAnlvF2iRLuJ7whrGP6QjpsCMq1yWz7dU/edit#heading=h.l6bq0r1aih50


title: Datasets Used in Evaluation Of RNAi And CRISPR Technologies By Large Scale Gene Expression Profiling In The Connectivity Map

status: Public on Oct 30 2017

summary:
This GEO Series contains datasets used in the paper "Evaluation Of RNAi And CRISPR Technologies By Large Scale Gene Expression Profiling In The Connectivity Map".  The application of RNA interference (RNAi) to mammalian cells has provided the means to perform phenotypic screens to determine the functions of genes. Although RNAi has revolutionized loss of function genetic experiments, it has been difficult to systematically assess the prevalence and consequences of off-target effects. The Connectivity Map (CMAP) represents an unprecedented resource to study the gene expression consequences of expressing short hairpin RNAs (shRNAs). Analysis of signatures for over 13,000 shRNAs applied in 9 cell lines revealed that miRNA-like off-target effects of RNAi are far stronger and more pervasive than generally appreciated. We show that mitigating off-target effects is feasible in these datasets via computational methodologies to produce a Consensus Gene Signature (CGS). In addition, we compared RNAi technology to clustered regularly interspaced short palindromic repeat (CRISPR)-based knockout by analysis of 373 sgRNAs in 6 cells lines, and show that the on-target efficacies are comparable, but CRISPR technology is far less susceptible to systematic off-target effects. These results will help guide the proper use and analysis of loss-of-function reagents for the determination of gene function.  Note: Related GEO projects include a large corpus of additional L1000 data, available at GSE92742.

The Platform is GPL20573: Broad Institute Human L1000 epsilon
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL20573

For questions or assistance with this dataset, please email the CMap support team at: clue@broadinstitute.org

overall_design: The datasets in this Series were generated as part of the LINCS project, which aims to enable a functional understanding of biology by cataloging changes in gene expression and other cellular processes that occur when cells are exposed to a variety of perturbing agents. The Broad Institute LINCS Center for Transcriptomics contributes to this collaborative effort by application of the Connectivity Map concept. In brief, the study design involves the generation of a compendium of transcriptional expression data from cultured human cells treated with small-molecule and genetic loss/gain of function perturbagens. These measurements are made using the L1000 high-throughput gene-expression assay that enables data generation at an unprecedented scale.  The data provided here include Levels 4 and 5, as well as additional data described in the README:  Level 4 (Z-SCORES) - signatures with differentially expressed genes computed by robust z-scores for each profile relative to control (PC relative to plate population as control; VC relative to vehicle control). Level 5 (SIG) consists of the replicates, usually 3 per treatment, aggregated into a single differential expression vector derived from the weighted averages of the individual replicates.  For more data levels and their descriptions, please consult GSE92742.


title: Genome-wide DNA methylation profiling of mouse liver

status: Public on Jun 13 2016

city: Abu Dhabi

first: Kirsten

last: Sadler Edepli

state: Abu Dhabi

department: Biology

country: United Arab Emirates

institute: New York University Abu Dhabi

type: Methylation profiling by high throughput sequencing

summary: To determine whether differences between background strains or housing conditions altered the hepatic methylome, We report the generation and analysis of genome-wide DNA methylation profiles at nucleotide resolution in mouse liver from two male mice on a mixed background (mixed-1, mixed-2) and two males on a pure Black-6 (B6-1, B62) background. Using Enhanced high-throughput Reduced Representation Bisulfite Sequencing (ERRBS), we enriched CpG islands in mouse liver, and covered a representative sampling of conserved non-coding elements, transposons and other genomic features, for mouse liver. We found that the total CpG methylation of each methylome was strikingly similar among the 4 mouse liver samples from two different genetic backgrounds. Analysis of all CpG sites with at least 10x coverage showed a bimodal distribution of methylation, with all samples having 25% of hypermethylated CpG sites and 60% as hypomethylated CpG sites. Given the high percent of genome coverage and robust depth at single nucleotide level, these datasets provide a resource for investigation into changes in DNA methylation patterns in liver disease, tumorigenesis and regeneration.

overall_design: Ehanced reduced representation bisulfite sequencing (MspI 70~320bp size fraction) of liver tissue

first: Chi

last: Zhang

middle: S

last: Edepli

first: Amaia

last: Lujambio


title: DNA methylation and hydroxymethylation assessment through 450K analysis of paired bisulfite and oxidative-bisulfite conversion.

status: Public on Jul 01 2016

city: Atlanta

first: Carmen

last: Marsit

state: GA

address: 1518 Clifton Road

department: Environmental Health

institute: Rollins School of Public Health at Emory University

type: Methylation profiling by genome tiling array

summary:
Analysis of genome-wide hydroxymethylation within infant placental tissue collected at term.
These samples have been collected from the RhodeIsland Child Health Study (RICHS) cohort.

overall_design: Bisulfite and oxidative biulfite converted DNA was hybridized to the 450k platform and processed at the University of Minnesota Genomic Core

middle: J


title: Distinct features in establishing H3K4me3 and H3K27me3 in pre-implantation embryos

status: Public on Sep 15 2016

city: Shanghai

first: Shaorong

last: Gao

state: Shanghai

address: 1239 Siping Road, Yangpu District

department: School of life science and technology

institute: Tongji University

summary: Histone modifications play critical roles in regulating developmental genes expression during embryo development in mammals1,2. However, genome-wide analysis of histone modifications in pre-implantation embryos has been impeded by technical difficulties and the scarcity of required materials. Here, by using a small-scale chromatin immunoprecipitation sequencing (ChIP-seq) method3, for the first time, we mapped the genome-wide profile of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), associated with gene activation and repression respectively, in mouse pre-implantation embryos. We found that the establishment of H3K4me3 mark occurs much more rapidly than that of H3K27me3 following fertilization. Furthermore, H3K4me3 and H3K27me3 possess distinct features in sequence preference and dynamics in pre-implantation embryos. Although most H3K4me3 signature constantly exists on transcription start site (TSS) region, the breadth of H3K4me3 domain is of high-dynamic feature. Interestingly, the broad H3K4me3 peak (wider than 5kb) is associated with higher transcription activity and cell identity not only in pre-implantation embryos but also in the process of deriving embryonic stem cells (ESCs) from the inner cell mass (ICM) and trophoblast stem cells (TSCs) from the trophectoderm (TE). Unlike those observed in ESCs, we found that the bivalency (containing both H3K4me3 and H3K27me3) is unstable and not frequently observed in early cleavage stage embryos until the morula to blastocyst transition. Taken all together, our study provides a genome-wide map of H3K4me3 and H3K27me3 modifications in pre-implantation embryos, which offers us opportunities to further understand the epigenetic regulation mechanism in early embryo development.

overall_design: We mapped the H3K4me3 and H3K27me3 modifications on embryos from 2-cell stage to blastocyst stage (with separated ICM and TE). The mouse metaphase II (MII) oocytes, as well as mouse embryonic stem cells (mESCs) and mouse trophoblast stem cells (mTSCs) were also analyzed. In the ChIP-seq analysis on pre-implantation embryos, 500 cells were used for per reaction and two or three replicates were performed for each stage.

first: Xiaoyu

last: Liu

first: Chenfei

last: Wang

first: Jingyi

first: Wenqiang

first: Haibo

first: Hong

first: Yong

first: Yawei


title: Long non-coding and circular RNA expression profiles in human aortic vascular smooth muscle cells (HAVSMCs)

status: Public on Jan 28 2016

city: shi jia zhuang

first: shaoguang

last: sun

state: Hebei

address: zhong shan dong lu 361

department: biochemistry and molecular biology

institute: Hebei medical university

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


title: Translation efficiency is maintained during heat shock in Escherichia coli

status: Public on Nov 19 2016

city: La Jolla

first: Evan

middle: Thomas

last: Powers

address: 10550 North Torrey Pines Rd

department: Chemistry

institute: The Scripps Research Institute

summary: We utilize ribosome profiling to directly monitor translation in E. coli at 30 °C and investigate how this changes after 10-20 minutes of heat shock at 42 °C. Translation is controlled by the interplay of several RNA hybridization processes, which are expected to be temperature sensitive. We observe that translation efficiencies are robustly maintained after thermal heat shock and after mimicking the heat shock response transcriptional program at 30 °C.

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: Ribosome profiling and RNA-seq analysis of E. coli was used to measure translation efficiency. The effect of heat shock was measured under 3 conditions (n=3); overexpression of wildtype (n=3) or constitutively active mutant (n=2) heat shock transcription factor rpoH was compared to cells expressing empty vector (n=4).

first: Gareth

last: Morgan

first: David

last: Burkhardt

first: Jeffery

middle: W

last: Kelly


title: An oncogenic Ezh2 mutation induces tumors in mice through redistribution of global H3K27 trimethylation

status: Public on May 02 2016

city: St. Louis

first: George

middle: P.

last: Souroullas

state: MO

address: 660 S. Euclid Av

institute: Washington University School of Medicine

summary: B cell lymphoma and melanoma harbor recurrent mutations in the gene encoding the EZH2 histone methyltransferase (EZH2), but the carcinogenic role of these mutations is unclear. Here we describe a mouse model in which the most common somatic Ezh2 gain-of-function mutation (EZH2Y646F in human; Ezh2Y641F in mouse) is conditionally expressed. Expression of Ezh2Y641F in mouse B cells or melanocytes caused high-penetrance lymphoma or melanoma, respectively. Overexpression of the anti-apoptotic protein Bcl2, but not the oncoprotein Myc, or loss of the tumor suppressor protein p53 (encoded by Trp53 in mice) further accelerated lymphoma progression.  Expression of mutant Braf oncoprotein but not mutant Nras oncoprotein further accelerated melanoma progression. Although expression of Ezh2Y641F globally increased the abundance of trimethylated Lys27 of histone H3 (H3K27me3), it also caused a widespread redistribution of this repressive mark, including a loss of H3K27me3 that was associated with increased transcription at many loci. These results suggest that Ezh2Y641F induces lymphoma and melanoma through a vast reorganization of chromatin structure, inducing both repression and activation of polycomb-regulated loci.

overall_design: B cells: 3 WT vs 3 Y641F samples, Melanoma: WT (480, 855) vs Y641F (480D, 855D) isogenic cell lines differing only for the presence of WT vs Y641F Ezh2.

first: Norman

middle: E

last: Sharpless

first: Joel

last: Parker

first: Jeremy

last: Simon

first: William

middle: R

last: Jeck


title: An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27m3 through the genome [RNA-seq]

status: Public on May 13 2016

summary: B-cell lymphoma and melanoma harbor recurrent mutations in the gene encoding the EZH2 histone methyltransferase, but the carcinogenic role of these mutations is unclear.  Here we describe a mouse model in which the most common somatic EZH2 gain-of-function mutation (Y646F in human, Y641F in the mouse) can be conditionally expressed. Expression of Ezh2Y641F in mouse B-cells or melanocytes caused high-penetrance lymphoma or melanoma, respectively. Bcl2 overexpression or p53 loss, but not c-Myc overexpression, further accelerated lymphoma progression, and expression of mutant B-Raf but not mutant N-Ras further accelerated melanoma progression. Although expression of Ezh2Y641F increased abundance of global H3K27 trimethylation (H3K27me3), it also caused a widespread redistribution of this repressive mark, including a loss of H3K27me3 associated with increased transcription at many loci. These results suggest that Ezh2Y641F induces lymphoma and melanoma through a vast reorganization of chromatin structure inducing both repression and activation of polycomb-regulated loci.

overall_design: B cells: 4 WT vs 4 Y641F samples, Melanoma: WT (480, 855) vs Y641F (480D, 855D) isogenic cell lines differing only for the presence of WT vs Y641F Ezh2.


title: Expression of four hESC lines in enzymatic and mechanic passaging methods

status: Public on Jun 01 2015

city: Montpellier

first: Qiang

last: BAI

address: 371 Avenue du Doyen Gaston Giraud

country: France

institute: PhyMedExp INSERM U1046

summary:
hESC have morphologic, genetic and genomic alternatiions when cells cultured in different passaging condition.
Here transcriptome of four different hESC lines were compared in two passaging methods.

overall_design: Cells had initially mechanic passaging. From the initiating passage (p13 for HD291, p16 for HD129 and p25 for HS306), cell were switched to enzymatic passaging. At indicated passges, the transcriptome were analysed by microarray.

first: John

last: DE VOS


title: Genome alterations in human pluripotent stem cells as very early events highly dependent on cell passaging conditions


title: Genomic instability of human embryonic stem cells in mechanic and enzymatic passaging culture

summary:
hESC have morphologic, genetic and genomic alternatiions when cells cultured in different passaging condition.
Here sub-karyotypic genome change in three different hESC lines were compared in two passaging methods.

overall_design: Cells had initially mechanic passaging. From the initiating passage (p13 for HD291, p16 for HD129 and p25 for HS306), cell were switched to enzymatic passaging. At indicated passges, the sub-karyotypic changes in genome were analysed by Affymetrix SNP6.0 microarray.


title: An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27m3 through the genome


title: Genomic-scale identification of host genes regulated by EBV during lytic cycle [ChIP-Seq]

status: Public on Mar 18 2015

city: Brighton

first: Alison

middle: Jane

last: Sinclair

state: E. Sussex

address: University of Sussex

department: School of Life Sciences

institute: University of Sussex

summary: Infection of resting primary B-lymphocytes by Epstein Barr virus (EBV) generates a population of cells that are effectively immortal. This represents the first step in the establishment of life-long viral latency in vivo and generates precursors that can develop into the lymphoid malignancies. However, virus spread requires a switch from latency to the lytic replication cycle, a process orchestrated by the virally encoded protein Zta, an AP1-like transcription factor that interacts with a 7 base-pair DNA sequence element. As Zta has the potential to reprogram the patterns of gene expression in the host cell, we undertook global transcriptome analyses (RNA sequencing) in a Burkitts lymphoma derived cell line in which the Zta is expressed from an inducible promoter, mimicking the switch from latency to lytic cycle. We identified 2,263 host genes whose expression levels were altered. In parallel, we performed chromatin precipitation and next-generation DNA sequencing (ChIP-Seq) to identify genes that are direct targets of Zta. Integrating these data sets revealed 277 host genes that appear to be directly regulated by Zta. Surprisingly, the frequency and distribution of the Zta binding peaks suggests that Zta regulates host genes through long-range enhancers, with a median distance of 25.8kb from the transcriptional start site, rather than equivalents of the promoter elements through which Zta regulates viral genes.

overall_design: Surface IgG on Akata cells was cross-linked by application of anti-IgG and 48 hours later chromatin was prepared from 1 x 10^8 cells. An additional sample was treated with acyclovir to halt viral replication prior to EBV genome replication.  Chromatin was fixed, extracted and sheared and precipitated with an antibody to Zta (BZLF1). Sequencing of the precipitated DNA was undertaken and aligned to the EBV and human genomes.

first: Sharada

last: Ramasubramanyan

first: Harshil

last: Patel

first: Kay

last: Osborn

first: Jianmin

last: Zuo

first: Gordon

last: Peters

first: Rajaei

last: Al-Mohammed

first: Martin

last: Rowe

first: Richard

last: Jenner


title: The genomic and epigenomic landscape of atypical teratoid rhabdoid tumors

status: Public on Mar 02 2016

city: Heidelberg

first: Pascal

middle: David

last: Johann

address: Im Neuenheimer Feld 580

department: Pediatric Neurooncology

country: Germany

institute: German Cancer Research Center

type: Genome variation profiling by genome tiling array

summary: Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.

overall_design: 150 human ATRT tumor samples were profiled using the Illumina HumanMethylation450 BeadChip (450k) array.

middle: D

first: Serap

last: Erkek

first: Marcel

last: Kool


title: H2A monoubiquitination in Arabidopsis is generally independent of LHP1 and PRC2 activity [RNA-seq]

first: Myriam

last: Calonje

overall_design: mRNA profiles of 7DAG  Arabidopsis seedlings Col-0 and strong triple mutants atbmi1a/b/c

first: Yue

last: Zhou

first: Francisco J

last: Romero-Campero

first: Angeles

last: Gomez-Zambrano

first: Franziska

last: Turck


title: Mitoscriptome analysis to understand the pathogenesis of Diabetic Retinopathy using tissue microarray

status: Public on Apr 02 2015

city: Bangalore

first: Genotypic

last: technology

state: Karnataka

address: 259, Apoorva 4th cross,80 feet Road,RMV 2ND STAGE

country: India

institute: Genotypic Technology

summary: Diabetic Retinopathy (DR) is a progressive disease affecting the structure and cellular composition of the microvasculature. Several factors like genetic, environmental and biochemical are involved in the development of DR. However, the inheritance pattern of this disease is multi factorial resulting from the interaction of one or more genes but the exact mechanism is not completely understood. Over the decade there has been alot of molecular genetics work done in nuclear genome for DR in different ethnic groups and  identified several candidate genes involved in disease pathogenesis but the role of these genes in the development of disease is not yet clearly understood.  Recently there are very few reports in determining the role of mitochondria in the pathogenesis of DR but no such studies are reported so far in India. The high relevance of mitochondria in the maintenance of cellular structure and function places mitoscriptome analysis as an important piece of the puzzle in understanding the pathogenesis of DR. Therefore we would like to focus on entire Human Mitoscriptome gene expression profile in relation to DR which could help us to identify new biomarker in health and disease condition.

overall_design: One-color experiment,Organism: Homo sapiens ,Custom Human 8x15k Array designed by Genotypic Technology Private Limited (AMADID: 045815), Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)

first: Gowthaman

last: Govindarajan

first: Sundaresan

last: Periasamy


title: Yki-induced intestinal stem cells (ISCs) overproliferation remotely affects muscular gene expression in Drosophila

status: Public on Feb 01 2015

city: Boston

first: Wei

last: Song

email: rocwsong@gmail.com, songw@whu.edu.cn

state: Massachusetts

address: 77 Ave Louis Pasteur, NRB 336

department: Department of Genetics

institute: Harvard Medical School

summary:
Purpose: localized aberrant cell proliferation induced by activation of Yki in ISCs impairs muscle functions. To gain insight into the cross talk between intestine and muscle, we performed a transcriptomic analysis of thoracic muscles in ISC overproliferation flies.
Methods: To extract total RNAs for RNA-Seq experiment, we used 10 thoraces dissected out from both esg-Gal4, tub-Gal80ts, UAS-GFP/+ (Con) and esg-Gal4, tub-Gal80ts, UAS-GFP/UAS-Yki-act (Yki) flies incubated for 8 days at 29°C. After assessing RNA quality with Agilent Bioanalyzer, mRNAs were enriched by poly-A pull-down. Then, sequencing libraries constructed with Illumina TruSeq RNA prep kit were sequenced using Illumina HiSeq2000 at the Columbia Genome Center (http://systemsbiology.columbia.edu/genome-center). We multiplexed samples in each lane, which yields targeted number of single-end 100 bp reads for each sample, as a fraction of 180 million reads for the whole lane. Sequence reads were mapped back to the Drosophila genome (flybase genome annotation version r5.51) using Tophat. With the uniquely mapped reads, we quantified gene expression levels using Cufflinks (FPKM values). Next, we performed data normalization on the read counts and applied a negative binomial statistical framework using the Bioconductor package DESeq to quantify differential expression between experimental and control data.
Results: Gene list enrichment analysis of the downregulated muscle transcriptome by ISCs Yki overexpressioin revealed a striking enrichment of multiple metabolic processes impinging on carbohydrate metabolism, amino acid metabolism, metabolism of vitamins and cofactors, and metabolism of xenobiotics by cytochrome P450. Interestingly, target genes of Foxo, a transcription factor inhibited by insulin/IGF signaling, are enriched in the upregulated muscle transcriptome of ISCs Yki overepxression flies. In particular, induction of InR and Thor, well-characterized targets of Foxo, are validated with qPCR.
Conclusions: Our study represents ISCs overproliferation induced by Yki overepxression remotedly regulates muscle function and gene expression probally via modulation of insulin signaling in muscle. Our results show that RNA-seq offers a comprehensive evaluation of signaling network and biological process in organ communication.

overall_design: Thoraces mRNA profiles of both esg-Gal4, tub-Gal80ts, UAS-GFP/+ (Con) and esg-Gal4, tub-Gal80ts, UAS-GFP/UAS-Yki-act (Yki) flies incubated for 8 days at 29°C were generated by deep sequencing, in replicate, using Illumina HiSeq2000.

first: Norbert

last: Perrimon

first: Young

last: Kwon


title: The long non-coding RNA(lncRNA)  expression profiles in human aortic vascular smooth muscle cells (HAVSMCs)

first: shaoguang

last: sun

summary: To explore the potential involvement of lncRNAs in the vascular smooth muscle cell (VSMC) proliferation, we conducted lncRNA profiling in three pairs of proliferative HAVSMCs and quiescent HAVSMCs by microarray. Our results showed that lncRNAs were aberrantly expressed in proliferative HAVSMCs compared with quiescent HAVSMCs, and provided potential targets for novel insights into VSMC proliferation or vascular remodeling diseases.

overall_design: The lncRNA expression profiles of three paired proliferative HAVSMCs and quiescent HAVSMCs were analyzed using the microarry platform.

first: Shaoguang

last: Sun

first: Xin

last: Xu

first: Shanhu

last: Cao

first: Fangfang

last: Li

first: Mei

last: Han


title: Concurrent Gene Signatures for Han Chinese Breast Cancers [Affymetrix]

status: Public on Jan 07 2014

city: New Taipei City

first: Chi-Cheng

last: Huang

address: No.2, Lane 59, Jiancheng Rd. Xizhi Dist.

department: Department of Medical Education and Research

country: Taiwan

institute: Cathay General Hospital SiJhih

summary: The interplay between copy number variation (CNV) and differential gene expression may be able to shed light on molecular process underlying breast cancer and lead to the discovery of cancer-related genes. In the current study, genes concurrently identified in array comparative genomic hybridization (CGH) and gene expression microarrays were used to derive gene signatures for Han Chinese breast cancers.   We performed 23 array CGHs and 81 gene expression microarrays in breast cancer samples from Taiwanese women. Genes with coherent patterns of both CNV and differential gene expression were identified from the 21 samples assayed using both platforms. We used these genes to derive signatures associated with clinical ER and HER2 status and disease-free survival.   Distributions of signature genes were strongly associated with chromosomal location: chromosome 16 for ER and 17 for HER2. A breast cancer risk predictive model was built based on the first supervised principal component from 16 genes (RCAN3, MCOLN2, DENND2D, RWDD3, ZMYM6, CAPZA1, GPR18, WARS2, TRIM45, SCRN1, CSNK1E, HBXIP, CSDE1, MRPL20, IKZF1, and COL20A1), and distinct survival patterns were observed between the high- and low-risk groups from the combined dataset of 408 microarrays. The risk score was significantly higher in breast cancer patients with recurrence, metastasis, or mortality than in relapse-free individuals (0.241 versus 0, P<0.001). The concurrent gene risk predictive model remained discriminative across distinct clinical ER and HER2 statuses in subgroup analysis.  We conclude that parallel analysis of CGH and microarray data, in conjunction with known gene expression patterns, can be used to identify biomarkers with prognostic values in breast cancer.

first: Shih-Hsin

last: Tu

first: Heng-Hui

last: Lien

first: Jaan-Yeh

last: Jeng

first: Ching-Shui

first: Chi-Jung

first: Liang-Chuan

last: Lai

first: Eric

middle: Y

last: Chuang


title: Chemerin inhibits cancer progression by impairing the maturation of neovessels

status: Public on May 05 2019

city: Brussels

first: Frederick

last: Libert

address: 808 route de Lennik

department: IRIBHM

country: Belgium

institute: ULB

summary: Chemerin is a leukocyte chemoattractant and an adipokine. Overexpression of chemerin by tumor cells or the host inhibits tumor progression in different mouse models, through a mechanism involving the chemerin receptor CMKLR1 and impairment of endothelial cell/pericyte interactions in neovessels.

overall_design: mRNA profiles of LLC tumors (5 days following graft in the back of syngeneic C57BL/6 mice) expressing or not chemerin were generated, in duplicate, using Illumina Hiseq1500.

first: Ingrid

last: Dubois-Vedrenne

first: Virginie

last: Robert

first: Olivier

last: De Henau

first: Diana

last: Al Delbany

first: Maxime

last: Vernimmen

last: Vosters

first: Francina

last: Langa-Vives

first: Frédérick

first: Souphalone

last: Luangsay

first: Valérie

last: Wittamer

first: Marc

last: Parmentier


title: Concurrent Gene Signatures for Han Chinese Breast Cancers

first: Chi-Cheng

last: Huang

type:
Expression profiling by array
Genome variation profiling by array

overall_design: Refer to individual Series


title: The effects of a novel agrochemical in alleviating salinity stress

status: Public on Jan 15 2013

city: Lancaster

first: Michael

last: Roberts

address: Bailrigg

department: Lancaster Environment Centre

institute: Lancaster University

summary:
Yield losses as a result of abiotic stress factors present a significant challenge for the future of global food production. While breeding technologies provide potential to combat negative stress-mediated outcomes over time, interventions which act to prime plant tolerance to stress, via the use of phytohormone-based elicitors for example, could act as a valuable tool for crop protection. However, the translation of fundamental biology into functioning solution is often constrained by knowledge-gaps.
Photosynthetic and transcriptomic responses were characterised in young tomato (Solanum lycopersicum) seedlings in response to pre-treatment with a new plant health activator technology, ‘Alethea,’ followed by a subsequent 100 mM salinity stress. Salinity treatment led to a maximal 47% reduction in net photosynthetic rate 8 d following NaCl treatment. In Alethea pre-treated seedlings, sensitivity to salinity stress was markedly reduced during the experimental period. Microarray analysis of leaf transcriptional responses showed that while salinity stress and Alethea individually impacted on largely non-overlapping, distinct groups of genes, Alethea pre-treatment substantially modified the response to salinity. Alethea affected the expression of genes related to biotic stress, ethylene signalling, cell wall synthesis, redox signalling and photosynthetic processes.  Since Alethea had clear effects on photosynthesis/chloroplastic function at the physiological and molecular levels, we also investigated the ability of Alethea to protect plants against methyl viologen, a potent generator of oxidative stress in chloroplasts. Alethea pre-treatment produced dramatic reductions in visible foliar necrosis caused by methyl viologen compared with non-primed controls.

overall_design: Tomato leaves from four groups of treated plants were harvested at a single point following treatment for RNA extraction and hybridization on Affymetrix microarrays. Plants came from two initial groups, pre-treated either with water (control) or the Alethea product. Equal numbers of plants from within these groups were subsequently treated either with water (control) or salinity (100 mM NaCl), generating 4 main experimental groups in a 2x2 factorial design. Samples were collected from 3 biological replicate experiments, and each sample included leaves pooled from 3 individual plants from each treatment group.

first: Jason

last: Wargent


title: Whole genome gene expression profiling in Adult T-cell Leukemia (ATL) cells and in Normal CD4+ T-cells

status: Public on Feb 23 2012

city: Tokyo

first: Kazumi

last: Nakano

address: 4-6-1, Sirokanedai, Minatoku

department: Department of Medical Genome Sciences, Graduate School of Frontier Sciences

country: Japan

institute: The University of Tokyo

summary: HTLV-1 infected individuals stay as carriers for their lifetimes, while the rest of 5% are killed by ATL. ATL leukemogenesis is a complex process involving accumulation of multiple genetic abnormalities in HTLV-1 infected cells. To clarify genetic events underlying ATL leukemogenesis, we conducted comprehensive gene expression profiling in 52 ATL patients  and in 21 healthy volunteers.

overall_design: Total RNA samples from PBMC of ATL patients (mostly HTLV-1 inefcted CD4+ T-cells) and from CD4+ T-cells from healthy donors were subjected to Cy-3 labeling followed by human whole genome gene expression microarray analyses.

first: K

first: A

last: Sato

last: Uchimaru

last: Utsunomiya

last: Yamaguchi

first: T

last: Watanabe


title: AUTS2 confers transcriptional activation to PRC1 in the CNS

status: Public on Dec 18 2014

city: New york

first: Zhonghua

last: Gao

state: NY

address: 522 1st Avenue, SML 203

department: Biochemistry and Molecular Pharmacology

institute: New York University School of Medicine


title: Transcriptome of embryonic stem cells cultured in enzymatic and mechanic passaging methods [RNA-seq]

first: Qiang

last: BAI

summary: hESC have morphologic, genetic and genomic alternatiions when cells cultured in different passaging condition.

overall_design: Cells had initially mechanic passaging. From the initiating passage p13, cell were switched to enzymatic passaging after 15 passage (p13+EP15). Another sample was from cells after 15 mechanic passages (p13+MP15) which was designed as control. The transcripome of p13, p13+EP15 and p13+MP15 was analyzed with RNA sequencing by Illumina HiSeq2000 next-generation sequencer.

first: John

last: DE VOS


title: Next Generation Sequencing (RNAseq) of non-small cell lung cancer

status: Public on Jun 01 2016

city: Solna

first: Björn

middle: M

last: Hallström

state: Stockholm

address: Tomtebodavägen 23A

department: Science for Life Laboratory

institute: Royal Institute of Technology, Stockholm

summary: Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small cell lung cancer (NSCLC), we compared RNAseq data of 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the CTdatabase, 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase. Cluster  analysis revealed that CTA expression is histology-dependent and concurrent expression is common. Immunohistochemistry confirmed tissue specific protein expression of selected genes. Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from the Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer, was not confirmed, neither in our RNAseq-cohort nor in an independent meta-analysis of 1117 NSCLC cases.

overall_design:
Fresh frozen tumor tissue from 199 patients diagnosed with NSCLC and surgically treated 2006-2010 at the Uppsala University Hospital, Uppsala, Sweden and 19 paired normal lung tissues. Clinical data were retrieved from the regional lung cancer registry.
Several of the new CTAs are poorly characterized

Sample characteristics values represent;
pTNM: decided by Hans Brunnström, pathologist in Lund Spring 2013
Stage according to pTNM: 1=1a 2=1b 3=2a 4=2b 5=3a 6=3b 7=IV
Histology diagnosis spring 2013 HB:
1=squamous cell cancer 2=AC unspecified 3=Large cell/ NOS
Surgery date: the date when sample arrived at Patologen UAS
Age: age when surgery was performed
Vital date: day of death or latest contact
Dead: 0=no 1= yes
Smoking history : 1=current 2=ex >1year 3=never
WHO performance status: Performance status 0-4

Please note that the L608T_2122, L771T_1 data columns (in the processed data files) are associated with L608T and L771T samples, respectively.

first: Dijana

last: Djureinovic

first: Masafumi

last: Horie

first: Johanna

last: Mattsson

first: Linnea

last: La Fleur

first: Linn

last: Fagerberg

first: Hans

last: Brunnström

first: Cecilia

last: Lindskog

first: Katrin

last: Madjar

first: Jörg

last: Rahnenführer

first: Simon

last: Ekman

first: Elisabeth

last: Ståhle

first: Hirsh

last: Koyi

first: Eva

last: Brandén

first: Karolina

last: Edlund

first: Jan

last: Hengstler

first: Mats

last: Lambe

first: Akira

last: Saito

first: Johan

last: Botling

first: Fredrik

last: Pontén

first: Mathias

last: Uhlén

first: Patrick

last: Micke


title: Long noncoding RNAs and mRNAs expression analysis of gallbladder cancer

status: Public on Oct 15 2014

first: Ming

middle: zhe

last: Ma

address: 270 DongAn Road

department: Department of Gastric Surgery

institute: Fudan University Shanghai Cancer Center

summary: Although many protein-coding genes have been identified to be aberrantly expressed in gallbladder cancer, the mechanism that account for the development and progression of gallbladder cancer remains unclear. In recent years, long noncoding RNAs have been shown to play vital roles in mammalian cell biology. In this study, we found that a small number of  lncRNAs that are aberrantly expressed.

overall_design: A ten chip study using total RNA recovered five separate gallbladder cancer tissues and five matched adjacent gallbladder normal tissues

first: M

middle: Z

last: Zhang

last: Weng

first: Y

last: Qin

first: W

last: Gong

first: Z

last: Quan


title: Expression data from canine osteosarcoma primary tumors (Affymetrix Canine 2.0 array)

status: Public on Sep 22 2010

city: Fort Collins

first: Liza

middle: Emily

last: O'Donoghue

state: CO

address: 300 W. Drake Rd

department: Clinical Sciences

institute: Colorado State University

summary: Some dogs respond well to amputation and chemotherapy and are disease free longer than the median 200 days whereas others experience rapid lung metastasis. Microarrays were used to compare primary tumors of dogs with a disease free interval (DFI) >300 days (n=7) to those with a DFI<100 days (n=8).

overall_design: Chemotherapy naïve primary tumors were collected at the time of amputation and archived at the Animal Cancer Center.  Arrays were performed on a total of 15 dogs.

first: Dawn

middle: L

last: Duval


title: AUTS2 confers transcriptional activation to PRC1 in the CNS (ChIP-Seq)

first: Zhonghua

last: Gao

summary: Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity and AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq of AUTS2 shows that it regulates neuronal gene expression through promoter association. Conditional CNS targeting of Auts2 in a mouse model leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases.

overall_design: ChIP-seq experiments of PRC1 components, PolII as well as histone modifications were performed either in mouse whole brain or in human 293T-REx lines expressing FLAG/HA-tagged subunits. RNA-seq was performed to analyze the expression profile of mouse whole brain.

first: Danny

last: Reinberg

first: Pedro

last: Lee

first: James

last: Stafford

first: Melanie

last: von Schimmelmann

first: Anne

last: Schaefer


title: Transcriptome changes triggered by Hyaloperonospora parasitica arabidopsis Noco2 in WT and wrky72 mutants at 96 hpt

status: Public on Aug 09 2010

city: Riverside

first: Kishor

middle: Kumar

last: Bhattarai

state: CA

address: 9000 University Avenue

department: Plant Pathology

institute: University of California

summary: Functional characterization of AtWRKY72 using Arabidopsis T-DNA insertion lines showed that this gene is important for basal defense to root-knot nematode (RKN) and Hyaloperonospora parasitica arabidopsis (Hpa), but not several tested R gene-mediated defenses.To profile transcriptional reprogramming associated with AtWRKY72-dependent basal defense we used Affymetrix ATH1 GeneChips representing ~24,000 Arabidopsis genes. Three independent biological replicates were performed with Col-0, wrky72-1 and wrky72-2 plants at 96 hpt with HpaNoco2 or mock treatment. Using a false discovery rate of less than 0.05 we identified for each of these three lines genes that showed significant transcriptional changes in response to HpaNoco2 compared to the mock-treated controls. Identification of downstream targets of WRKY72 in Arabidopsis by this microarray suggests that WRKY72 uses a unique signaling pathway that involves AP2/ERF TFs independent of the ethylene signaling pathway.

overall_design: We intended to identify Arabidopsis genes that are regulated in WRKY72-dependent manner in response to Hyaloperonospora parasitica arabidopsis (Hpa) at 96 hpt. For this, we used Col-0 and two wrky72 mutant lines and compared the differentially expressed genes with the hypothesis ‘genes that are specifically regulated in Col-0 but not in wrky72 mutants are WRKY72-dependent genes’.

middle: K

first: Isgouhi

last: Kaloshian

first: Thomas

last: Eulgem


title: Epigenetic signature of birth-weight discordance in Danish twins

status: Public on Dec 15 2014

city: Denmark

first: Qihua

last: Tan

address: J. B. Winsløws Vej 9B

country: Denmark

institute: University of Southern Denmark

summary: Epigenetic profiling of birth-weight discordant twins using Illumina's 450K Human DNA methylation BeadChip

overall_design: Comparing DNA methylation difference in birth-weight discordant twin pairs

first: Lene

last: Christiansen

first: Morten

last: Frost


title: GENE EXPRESSION OF AN ANTI-INFLAMMATORY PENTAPEPTIDE ON CIA MURINE DEVELOPMENT

status: Public on Feb 07 2009

city: Zacatecas

first: Juan

last: Velazquez

state: Zacatecas

address: Alameda 45

country: Mexico

institute: Instituto Mexicano del Seguro Social

summary:
Monocyte Locomotion Inhibitory Factor (MLIF), an amoebic peptide, has an anti-inflammatory role,  delaying the arrival of mononuclear cells to inflammatory sites, down regulating adhesin molecules and chemokines.
We used microarrays to detail the global  gene expression underlying anti-inflammatory effect of MILF in an inflammatory model. Collagen type II (CII) emulsified on complet Freund adjuvant, was injected on the tail of the base of DBA1J mice, 8 weeks older, and booster with CII emulsified in incomple Freund adjuvant three weeks later. MLIF was administrated intranasally weekly since one week before induction.

Keywords: comparison effect

overall_design: Articular tissues of all mices were collected at the peak time of clinical severity (four weeks before booster),  for RNA extraction and hybridization on Affymetrix microarrays. We induces CIA with chicken collagen type II, emulsified with Complet Adjuvant of Freund, and the controls were mice induced only with Complet Adjuvant of Freund with or without MLIF

first: Susana

last: Godina-González

first: Luis

last: Terán


title: Concurrent Gene Signatures for Han Chinese Breast Cancers [Agilent]

first: Chi-Cheng

last: Huang

overall_design: We performed 23 array CGHs and 81 gene expression microarrays in breast cancer samples from Taiwanese women. Genes with coherent patterns of both CNV and differential gene expression were identified from the 21 samples assayed using both platforms. We used these genes to derive signatures associated with clinical ER and HER2 status and disease-free survival.

first: Shih-Hsin

last: Tu

first: Heng-Hui

last: Lien

first: Jaan-Yeh

last: Jeng

first: Ching-Shui

first: Chi-Jung

first: Liang-Chuan

last: Lai

first: Eric

last: Chuang


title: miRNA expression after moderate Spinal Cord Injury in Rats

status: Public on Jul 01 2011

city: Toledo

first: Rodrigo

last: Maza

state: Toledo

address: Finca La Peraleda s/n

department: Unidad de Neurología Experimental

institute: Hospital Nacional de Parapléjicos (SESCAM)

summary:
Identification of temporal variations in miRNA expression after spinal cord injury caused by thoracic (T8) moderate (200 Kdynes) contusion.
Expression changes were analyzed 1, 3 and 7 days after injury and compared to expression of control (untreated) and sham (laminectony but no contusion) individuals.

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus
Human alphaherpesvirus 1
Human betaherpesvirus 5
Murid betaherpesvirus 1
human gammaherpesvirus 4
JC polyomavirus
Human immunodeficiency virus 1
Murid gammaherpesvirus 4
Human gammaherpesvirus 8
Betapolyomavirus hominis
Betapolyomavirus macacae

overall_design: Included groups: control (untreated), 1 day after lesion, 3 days after lesion, 7 days after lesion, 1 days after SHAM cirugy, 3 days after SHAM cirugy, and 7 days after SHAM cirugy. Each of these 7 groups included 5 biological replicates.

first: Mónica

last: Yunta

first: Manuel

last: Nieto-Diaz

first: Francisco

middle: J

last: Esteban


title: Identification of Hipk2 as an essential regulator of white fat development

status: Public on Jan 01 2014

city: San Francisco

first: David

last: Quigley

address: 1450 Third St. Room 207

department: Helen Diller Comprehensive Cancer Center

institute: UCSF

summary: Homeodomain interacting protein kinase 2 (Hipk2) has previously been implicated in control of several transcription factors involved in embryonic development, apoptosis, cell proliferation and tumour development1–3. Analysis of gene expression in tissues from genetically heterogeneous mouse or human populations can reveal motifs associated with the structural or functional components of the tissue, and may predict roles for genes of unknown function4,5. Here we have applied this network strategy to uncover a novel role for the Hipk2 gene in the transcriptional system controlling adipogenesis. Both in vitro and in vivo models were used to show that knockdown or loss of Hipk2 specifically inhibits white adipose cell differentiation and tissue development. In addition, loss of Hipk2 leads to induction of pockets of multilocular brown fat-like cells in remaining white adipose depots. These cells express markers of brown and beige fat such as uncoupling protein 1 (Ucp1) and transmembrane protein 26 (Tmem26), and thermogenic genes including PPAR-γ coactivator 1a (Ppargc1a), and cell death-inducing DFFA-like effector a (Cidea). These changes are accompanied by increased insulin sensitivity in Hipk2 knock-out mice and reduced high fat diet-induced weight gain, highlighting a potential role for this kinase in diseases such as diabetes and obesity. Our study underscores the versatility and power of a readily available tissue, such as skin, for network modelling of systemic transcriptional programs involved in multiple pathways, including lipid metabolism and adipogenesis.

overall_design: Mammary fat pads from 115 distinct untreated 8 week old [FVB/N x Spret/Ei] x FVB/N Backcross mice

first: Jonas

last: Sjölund

first: Facundo

middle: G

last: Pelorosso

middle: A

first: Reyno

last: DelRosario

first: Allan

last: Balmain


title: Gene Expression Commons: an open platform for absolute gene expression profiling

status: Public on Jul 18 2012

city: Stanford

first: Jun

last: Seita

address: Lokey Stem Cell Building #G3101, 265 Campus Drive

department: Institute for Stem Cell Biology and Regenerative Medicine

institute: Stanford University

type:
Expression profiling by array
Third-party reanalysis

summary: Gene expression profiling using microarray has been limited to profiling of differentially expressed genes at comparison setting since probesets for different genes have different sensitivities.  We overcome this limitation by using a very large number of varied microarray datasets as a common reference, so that statistical attributes of each probeset, such as dynamic range or a threshold between low and high expression can be reliably discovered through meta-analysis. This strategy is implemented in web-based platform named “Gene Expression Commons” (http://gexc.stanford.edu/ ) with datasets of 39 distinct highly purified mouse hematopoietic stem/progenitor/functional cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, any scientist can explore gene expression of any gene, search by expression pattern of interest, submit their own microarray datasets, and design their own working models.

overall_design:
Gene expression profiling of entire mouse hematopoiesis system (39 populations) by Gene Expression Commons system.
The Samples (101) below comprise new and re-processed data and represent 37 populations.
The complete dataset comprising new, re-processed, and third-party reanalyzed data (107 samples), and representing all 39 populations, is linked below as a supplementary file.

first: Debashis

last: Sahoo

first: Derrick

last: Rossi

first: Deepta

last: Bhattacharya

first: Thomas

last: Serwold

first: Matthew

last: Inlay

first: Lauren

middle: I

last: Ehrlich

first: John

middle: W

last: Fathman

last: Dill

first: Irving

last: Weissman


title: Comparison of Clinical hVISA Parent and Laboratory-Derived VISA Mutants

status: Public on Mar 25 2010

city: Las Cruces

middle: E

last: Gustafson

email: jgustafs@nmsu.edu, amuthai@gmail.com

state: NM

address: PO Box 30001 Dept. 3AF

department: Department of Biology and Molecular Biology Program

institute: New Mexico State University

summary: The mechanisms leading to the vancomycin-intermediate Staphylococcus aureus (VISA) phenotype are incompletely understood. In an effort to identify VISA determinants, clinical hVISA strain MM66 and its 1st-step VISA mutants were compared. S. aureus microarrays, array data analysis protocols (NIAID's Pathogen Functional Genomics Resource Center), as well as comparative genomic sequencing (CGS) were utilized to determine VISA transcriptome alterations and mutations that define the MM66 VISA mechanism. In addition, whole cell autolysis, antimicrobial susceptibility tests, growth in the presence of salt, coagulase and hemolysis assays were performed to confirm VISA transcriptional alterations. Overall, 2 MM66 VISA demonstrated 85 up-regulated and 8 down-regulated genes in common. SAMMD (Staphylococcus aureus Microarray Metadatabase) analysis identified a significant differential gene expression overlap between the global stress response regulator sigB-controlled genes in MM66-3 and MM66-4.  CGS analysis on a MM66 VISA revealed two mutations in: a sensory box histidine kinase (yycG) and a putative adenine phosphoribosyltransferase (apt). The yycFG two-component system has been reported to regulate whole cell autolysis and MM66 VISA demonstrated reduced whole cell autolysis. Five ssaA homologues (putative amidases) and a gene that expresses a bifunctional autolysin (atlA) controlled by YycFG were downregulated in MM66 VISA. One MM66 VISA mutant demonstrated drastic downregulation of a gene cluster (betA, gbsA, betB, and cudT) required for the osmoprotective response of S. aureus and MM66 VISA mutants demonstrated reduced growth in high salt media compared to MM66. Virulence genes were also downregulated (coa, hla, hlb, hlgA, hlgB, and hlgC) in 2 MM66 VISA mutants which also demonstrated reduced coagulase and hemolytic activities compared to MM66. pur operon genes were also upregulated in MM66 VISA and it is interesting that we have also found an apt mutation, since Apt activity can be inhibited by high AMP levels and reduces the conversion of AMP into adenine. Conclusion: Mutations in yycG and apt allow hVISA to acquire the VISA phenotype and yycFG is involved with altered autolytic activity in MM66 VISA.

overall_design: S. aureus pangenome microarrays were utilized to determine transcriptome alterations occurring in VISA mutants MM66-3 and MM66-4 isolated from a clinical hVISA parent strain MM66. Total bacterial RNA was isolated as previously described from S. aureus strains MM66, MM66-3 and MM66-4 grown in Luria broth to an OD580nm of 0.7 (37°C, 200 rpm). The RNA samples were then converted to fluorescently-labeled cDNA and hybridized to S. aureus microarrays version 4 (NIAID's Pathogen Functional Genomics Resource Center). The Staphylococcus aureus microarray meta-database (SAMMD) was used to compare and analyze the microarray data obtained from this experiment to the microarray data obtained from different published protocols and experiments. Real-time PCR and physiological experiments were performed to validate the microarray data.

first: Reena

last: Lamichhane-Khadka

first: Joanne

last: Dupre

first: Jesus

last: Cuaron

first: Arunachalam

last: Muthaiyan

first: Alejandro

last: Delgado

first: Sharear

last: Zaman

first: Tracy

last: Reynolds

first: Vijayaraj

last: Nagarajan

first: Mohamed

middle: O

last: Elasri

first: Brian

last: Wilkinson

first: Wanqin

last: Yu

first: Zhong

last: Li


title: Genome-wide map of H3K4me3 in 12 day post-partum mouse spermatocytes

status: Public on Feb 24 2014

city: Bar Harbor

first: Christopher

middle: Lee

last: Baker

state: ME

address: 600 Main Street

department: Research

institute: The Jackson Laboratory

summary: Here we characterize the genome-wide chromatin modification by PRDM9, a histone H3 lysine 4 methyltransferase. In order to detect PRDM9 binding sites we created coisogenic strains of mice differing only in the zinc finger array of PRDM9. One strain is C57BL/6J, which carries the Prdm9Dom2 allele, the other strain was created using genomic replacement and named B6.PRDM9Cst (also called KI), and contains the Prdm9Cst allele originally found in CAST/EiJ mice. Many H3K4me3 positions are common between strains and represent other methyltransferase activity (such as promoters), sites that are unique to one mouse strain likely represent the binding position of that allele of PRDM9.

overall_design: Identify PRDM9-dependent H3K4me3 sites by comparing modified chromatin from mice coisogenic for Prdm9.

first: Kenneth

last: Paigen


title: Expression Profiling of brain samples from wt and SCA3 tg animals after CCI-779 and placebo treatment

status: Public on Sep 12 2009

city: Tuebingen

first: Michael

last: Bonin

state: BW

address: CAlwerstr. 7

department: Medical Genetics

institute: University Tuebingen

summary: Spinocerebellar ataxia type 3 is a neurodegenerative disorder caused by the expansion of the polyglutamine repeat region within the ataxin-3 protein. The mutant protein forms intracellular aggregates in the brain. However, the cellular mechanisms causing toxicity are still poorly understood and there are currently no effective treatments. In this study we show that administration of a rapamycin ester, CCI-779, improves motor performance in a transgenic mouse model of SCA3. CCI-779 inhibits mammalian target of rapamycin (mTOR) and hence upregulates protein degradation by autophagy. CCI-779 reduces the number of aggregates seen in the brains of transgenic mice and decreases levels of cytosolic soluble mutant ataxin-3, while endogenous wild-type protein levels remain unaffected. CCI-779 is designed for long-term use in patients and therefore represents a possible therapeutic strategy for the treatment of SCA3. Using this disease model and treatment paradigm we employed a microarray approach to investigate transcriptional changes that might be important in the pathogenesis of SCA3. This approach identified Usp15, which showed expression changes at both the mRNA and protein level. Usp15 levels were also changed in mice expressing another mutant polyglutamine protein, huntingtin. In total we identified 16 transcripts that were decreased in transgenic ataxin-3 mice that were normalised following CCI-779 treatment, as the number of transcripts changed was low and the magnitude of these changes was small we suggest that transcriptional dysregulation may not be an important step in the primary pathogenesis of SCA3.

overall_design: We analyzed 19 brain samples in total. 4 samples from wt animals after placebo treatment. 5 samples from wt animals after CCI-779 treatment. 5 samples from SCA3 tg animals after placebo treatment. 5 samples from SCA3 tg animals after CCI-779 treatment.

first: Fiona

last: Menzies

first: Jeannette

last: Huebener

first: Maurizio

last: Renna

first: Olaf

last: Riess

first: David

middle: C

last: Rubinsztein


title: Expression of genes in adult hepatocytes and fetal hepatoblasts

status: Public on Apr 11 2014

city: Isehara

first: Akihide

last: Kamiya

state: Kanagawa

address: 143 Shimokasuya

institute: Tokai University

summary: To analyze stem/progenitor cell function, we purified hepatocytes derived from adult livers and fetal hepatoblasts derived from embryonic day 13 livers.

overall_design: Compared gene expression in E13 hepatoblasts and adult hepatocytes derived from C57BL/6NCr mice

first: Hiromitsu

last: Nakauchi

first: Keiichi

last: Ito