title: Transcriptome Response and Spatial Pattern of Gene Expression in the Primate Subventricular Zone Neurogenic Niche After Cerebral Ischemia

status: Public on Aug 23 2019

first: Haifang

last: Wang

address: NO 320, Yue Yang Road

institute: Institute of Neuroscience

summary: The main stem cell niche for neurogenesis in the adult mammalian brain is the subventricular zone (SVZ) that extends along the cerebral lateral ventricles. We aimed at characterizing the initial molecular responses of the macaque monkey SVZ to transient, global cerebral ischemia. We microdissected tissue lining the anterior horn of the lateral ventricle (SVZa) from 7 day post-ischemic and sham-operated monkeys. Transcriptomics shows that in ischemic SVZa, 541 genes were upregulated and 488 genes were down-regulated. The transcription data encompassing the upregulated genes revealed a profile typical for quiescent stem cells and astrocytes. In the primate brain the SVZ is morphologically subdivided in distinct and separate ependymal- and subependymal regions. The subependymal contains predominantly neural stem cells (NSC) and differentiated progenitors. To determine in which SVZa region ischemia had evoked transcriptional upregulation, sections through control and ischemic SVZa were analyzed by high-throughput in situ hybridization for a total of 150 upregulated genes shown in the www.monkey-niche.org image database. The majority of the differentially expressed genes mapped to the subependymal layers on the striatal or callosal aspect of the SVZa. Moreover, a substantial number of upregulated genes was expressed in the ependymal layer, implicating a contribution of the ependyma to stem cell biology. The transcriptome analysis yielded several novel gene markers for primate SVZa including the apelin receptor that is strongly expressed in the primate SVZa niche upon ischemic insult.

overall_design: To uncover, on a transcriptome-wide scale, the changes in gene expression upon ischemia in the macaque SVZa niche, we performed transient global brain ischemia (Anton Tonchev, Molecular and Cellular Neuroscience, 2006). Tissue samples from three control (sham) and three postischemic monkeys were dissected from the striatal side of the periventricular region of the right hemisphere. Samples were subjected to deep RNA sequencing (RNA-Seq).

first: Anton

last: Tonchev


title: RNA sequencing for RWPE1 cells, OLFM4-Active RWPE1 cells and OLFM4-KO RWPE1 cells

status: Public on Aug 05 2019

city: Bethesda

first: Mehdi

last: Pirooznia

state: MD

address: 12 SOUTH DR

country: USA

institute: National Institutes of Health

type: Expression profiling by high throughput sequencing

summary: OLFM4 gene expressing in RWPE1 stem/progenitor-like cells. To study OLFM4 gene functions and molecular mechanisms, we generated OLFM4-avtive and OLFM4-knock out-GFP reporter RWPE1 cells with CRISP-Cas 9 system. The cell transcriptome was studied with RNA sequencing.

overall_design: Comparision of gene expressing signature between OLFM4-knock out RWPE1 and OLFM4-wild RWPE1 cells; OLFM4-Active RWPE1 cells and OLFM4-wild RWPE1 cells.


title: Genome-wide DNA methylation analysis of non-cancerous urothelium obtained from patients with urothelial carcinomas and corresponding cancerous tissue

status: Public on Aug 15 2019

city: Shinjyuku-ku

first: Yae

last: Kanai

state: Tokyo

address: 35, Shinano-machi

country: Japan

institute: Keio University School of Medicine

type: Methylation profiling by genome tiling array

summary: The aim of this study was to establish criteria for carcinogenetic risk estimation in the urothelium. Forty-six samples of non-cancerous urothelium showing no remarkable histological findings obtained from patients with urothelial carcinomas (N), and 46 samples of the corresponding cancerous tissue (T), i.e. 92 tissue samples in total, were analyzed. Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation 450K BeadChip.

overall_design: Bisulphite converted DNA from the 92 samples were hybridised to the Illumina Infinium HumanMethylation 450K BeadChip.

first: Koji

last: Tsumura

first: Eri

last: Arai


title: Gene expression profiling in  Osteosarcomas

status: Public on Sep 01 2019

city: Guangzhou

first: Changxi

state: Guangdong

address: No.74, Zhongshan second road

country: China

institute: Sun Yat-Sen University

summary: To explore whether KSHV infection is a risk factor for osteosarcoma development in ethnic Uyghur population. Sarcoma specimens including tumor, adjacent normal tissues and paired blood samples were obtained from several osteosarcoma patients of Xinjiang China. Then, osteosarcoma clinical samples were subjected to analysis for the presence of the KSHV genome and proteins. Gene expression profiles of these osteosarcomas were analyzed to reveal the pathogenesis of KSHV-positive and -negative osteosarcomas.

overall_design: mRNA profiles of Osteosarcomas tumors and adjacent normal tissues were generated by high-throughput sequencing, using Illumina Hiseq.

first: Yan

last: Yuan

first: Yuqing

last: Li


title: Differential Gene expression anslysis between artesunate sensitive and resistat Leishmania donovani

status: Public on Aug 30 2019

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: Gene expression analysis was carried out between experimental artesunate resistant Leishmania donovani (adapted to 50 µM artesunate drug pressure) and it's corresponding wild type artesunate sensitive parasite.

overall_design: Organism : Leishmania donovani, Agilent's L.donovani GXP Expression  8x15k Array (AMADID: 027511) desined by Genotypic Technology, Bangalore

first: A

last: Verma

first: S

last: Ghosh

first: P

last: Salotra

first: R

last: Singh

first: Bipin

last: Chand


title: Genome-wide mapping sites of Ulp2 chromatin binding

status: Public on Jul 07 2019

city: New Haven

first: Hong-Yeoul

last: Ryu

state: CT

address: 266 Whitney Ave

department: MB&B

institute: Yale

type: Genome binding/occupancy profiling by high throughput sequencing

summary: To map Ulp2 binding sites on a genome-wide scale, we carried out ChIP experiment combined with sequencing assay

overall_design: Examination of Flag-tagged Ulp2, duplication

first: Christopher

last: Castaldi

first: Dejian

last: Zhao


title: scRNA-seq of Wild Type and Hmgcs2-/-epithelial cells

status: Public on Jul 19 2019

city: Cambridge

first: Chia-Wei

last: Cheng

state: MA

address: 500 Main St

institute: Koch Institute at MIT

summary: We characterized the compositions of cell populations and signaling underlying the lineage commitments of intestinal stem cells upon loss of Hmgcs2.

overall_design: mRNA profiles of flow sorted intestinal crypt cells from adult wild type (WT) and Hmhgcs2-/- mice were generated by 10x sequencing. Single cells were processed through the GemCode Single Cell Platform using the GemCode Gel Bead, Chip and Library Kits (10X Genomics, Pleasanton) as per the manufacturer’s protocol. In brief, single cells were sorted into 0.4% BSA–PBS. 6,000 cells were added to each channel with an average recovery rate of 1,500 cells. The cells were then partitioned into Gel Beads in Emulsion in the GemCode instrument, where cell lysis and barcoded reverse transcription of RNA occurred, followed by amplification, shearing and 5′ adaptor and sample index attachment. Libraries were sequenced on an Illumina NextSeq 500.

first: Moshe

last: Biton

first: Aviv

last: Regev

first: Ömer

middle: H

last: Yilmaz


title: Expression data from colorectal carcinoma HCT-15 treated with oncolytic virus M1 and U0126

city: Guang Zhou

first: Jing

last: Cai

address: Zhongshan School of Medicine, Sun Yat-sen University   74 Zhongshan 2nd Road

institute: Sun yat-sen university

summary:
Virus infection is a kind of immune stimulation, we previously found that inhibition of Ras signaling by U0126 supress the infection of M1 virus, thus we predicted that U0126 might increase the antiviral effect, ultimately inhibit the replication of M1 virus. We plan to figure it out from the expression array data.
We used microarry data to detail the expression of immune factors regulated by oncolytic virus M1 and U0126.

overall_design: HCT116 tumoe cells were treated with oncolytic Control, 1MOI of M1 virus, 16μM of U0126 and M1 virus plus U0126 for  24h, and we used microarry data to detail the expression of immune factors regulated by oncolytic virus M1 and U0126.

first: Jiankai

last: Liang


title: Expression data in liver of Lkb1KOlivad mice (hepatocyte-specific Lkb1 deficiency, KO) and control (WT) mice

status: Public on Jun 12 2019

city: Paris

first: Franck

last: Letourneur

address: 22 rue mechain

country: France

institute: INSERM

summary: We used microarrays to investigate gene expression patterns in liver of hepatocyte-specific Lkb1 deficiency

overall_design: We performed microarrays on liver of Lkb1KOlivad mice (hepatocyte-specific Lkb1 deficiency, KO) and control (WT) mice

first: Christine

last: Perret


title: The expression profiles of GBC liver metastasis

status: Public on Jun 06 2019

city: Shanghai

first: Huaifeng

last: Li

address: NO.1665, kongjiang road, Shanghai, China

department: general surgery

institute: Xinhua hospital affiliated to Shanghai jiaotong university, school of medicine

summary: In order to analyze the differential profile of RNAs from patients with liver metastasis.

overall_design: the expression profiles of GBC liver metaststic tumor, primary tumor and adjacent non tumor.

first: Yingbin

last: Liu


title: Acetyl-CoA synthetase 2: a critical linkage in obesity-induced tumorigenesis in myeloma

status: Public on Jun 13 2019

city: Houston

last: Yang

address: 7455 Fannin St

department: Lymphoam & Myeloma

institute: UT MD Anderson Cancer Center

summary: Obesity is often linked to malignancies including multiple myeloma and the underlying mechanisms remain elusive. Here we showed that acetyl-CoA synthetase 2 (ACSS2) may be an important linker in obesity-related myeloma. ACSS2 is overexpressed in myeloma cells derived from obese patients and contributes to myeloma progression. We identified adipocyte-secreted angiotensin II as a direct cause of adiposity in increased ACSS2 expression. ACSS2 interacts with oncoprotein interferon regulatory factor 4 (IRF4), enhances IRF4 stability and IRF4-mediated gene transcription through activation of acetylation. The importance of ACSS2 overexpression in myeloma is confirmed by the finding that an inhibitor of ACSS2 reduces myeloma growth both in vitro and in a diet-induced obese mouse model. Our findings demonstrate a key impact for obesity-induced ACSS2 on the progression of myeloma. Given the central role of ACSS2 in many tumors, this mechanism could be important to other obesity-related malignancies.

overall_design: To investigate the potential abnormalities of myeloma cells in the obese setting, CD138+ malignant plasma cells were purified from the bone marrow aspirates of 9 newly diagnosed myeloma patients with newly diagnosed myeloma. Total RNA was extracted and used for comparing the gene expression profile between patients with normal weights (BMI < 25 kg/m2, n=4) and obese patients (BMI > 30 kg/m2, n=5).

first: Zongwei

first: Huan

first: Jin

last: He

first: Zhiqiang

last: Wang

first: Zheng

last: Yin

first: Gichun

last: You

first: Zhiming

first: Richard E.

last: Davis

first: Pei

last: Lin

first: P. Leif

last: Bergsagel

first: Elisabet E

last: Manasanch

first: Stephen T.C

last: Wong

first: Nestor F

last: Esnaola

first: Jenny C

last: Chang

first: Robert Z.

last: Orlowski

first: Qing

last: Yi


title: A Time-resolved Multi-omic Atlas of the Developing Mouse Liver

status: Public on Jun 01 2019

city: Beijing

first: Tongqing

last: Gong

address: Life Science Park Road 38#

institute: National Center for Protein Sciences (Beijing)

summary: Liver organogenesis and development is composed of a series of complex, well-orchestrated events. Identification of key factors and pathways governing liver development will help understand this process and may also provide insights for other physiological and pathological processes including cancer. For this purpose, we conducted multi-dimensional omics measurements including profiling of protein, mRNA, and transcription factor (TF) DNA binding activity from mouse liver tissues collected at embryonic day E12.5 to postnatal week W8, encompassing the major developmental stages to provide a molecular and integrative panoramic view of mouse liver development. These datasets revealed dynamic changes of core liver functions as well as canonical signaling pathways governing development at both mRNA and protein levels, and identified novel RNA splicing variants that are confirmed at the peptide level. The TF DNA binding activity dataset provided the first glimpse of liver development from four waves of TF activations and major TFs that may be responsible to drive the transcriptional program to govern liver development. A comparison between mouse liver development and human hepatocellular carcinoma (HCC) proteomic profiles revealed that more aggressive tumors are characterized with the activation of early embryonic development pathways, whereas less aggressive ones maintain liver-function related pathways that are elevated in the mature liver. This work provided a rich resource for liver development research community for future in-depth functional characterization.

overall_design: We collected 3 replicates at proteome and transcriptome levels and one replicates at transcriptome leve of whole livers at 15 time points that covered embryonic days (E12.5, E13.5, E14.5, E15.5, E16.5, E17.5, E18.5), postnatal days (D1, D3, D5), and postnatal weeks (W1, W2, W3, W6, W8).

first: Chunchao

last: Zhang

first: Xiaotian

last: Ni


title: Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+ T regulatory cells activation

status: Public on May 24 2019

city: S. Giovanni Rotondo (FG)

first: Tommaso

last: Mazza

address: Viale Cappuccini, 1

department: Bioinformatics

country: Italy

institute: IRCCS Casa Sollievo della Sofferenza

summary: We recently described the phenotype of HepG2 and Huh-7, hepatocellular carcinoma cells, knocked down for histone variant macroH2A1. Both cell lines acquire a cancer stem cell phenotype (Lo Re O et al., Hepatology 2017, PMID: 28913935; Lo Re O et al., Epigenetics 2018, PMID: 30165787). We found that short hairpin RNA-mediated macroH2A1 knockdown induced acquisition of CSC-like features, including the growth of significantly larger and less differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to chemotherapeutic agents, and stem-like metabolic changes consistent with enhanced hypoxic responses and increased glycolytic pathways. As macroH2A1 is a potent transcriptional modifier we asked how KD of this histone variant might affect patterns of gene expression, and whether we could identify potential mechanistic links to the observed in vitro and in vivo HCC phenotypes.   Here we used RNA-Seq to gain deep mechanistic insight into the distinct functions of macroH2A1 KD and conditioned medium (CM)-exposed Huh-7 cells. Heatmap analysis of the differentially expressed genes between the three groups revealed a similar transcriptomic profile between KD and CM, compared to the control condition. Genes were considered differentially expressed between groups if their expression values significantly differed by >2 fold. Statistical differences in gene expression were assessed by the ANOVA test. Correction for multiple test was achieved by the Benjamini-Hochberg procedure. The significance threshold was set to 0.05.  Using a cut-off of 2 fold change, assessment of differentially expressed genes for Huh-7 macroH2A1 KD  or Huh-7 CM KD versus CTL showed no transcriptional overlap between the different Huh-7 cell lines. 783 and 987 genes were instead significantly differentially-expressed in macroH2A1 KD or CM KD versus control cells, respectively. Interestingly, the significantly enriched transcripts over-represented in KD and CM-exposed cells compared to control cells were implicated in a number of functions and diseases that were also shared between CM versus control comparisons. Specifically, Ingenuity pathway analysis (IPA) identified categories of cancer, gastrointestinal diseases, lipid metabolism, cell-to-cell signaling, nucleic acid metabolism, cell death & survival and others, in common between KD versus CTL and CM versus CTL. These data support a paracrine modulation of gene expression by macroH2A1 KD in HCC cells.

overall_design: Profiling the transcriptome of hepatocellular carcinoma cells Huh-7 control, knocked-down (KD) for macroH2A1,  or exposed to conditioned medium from KD cells, using RNA-Seq.

first: Manlio

last: Vinciguerra


title: Pervasive H3K27 acetylation leads to ERV expression and a therapeutic vulnerability in H3K27M gliomas [ChIP-Seq 2]

status: Public on May 13 2019

city: Montreal

first: Nada

last: Jabado

state: Québec

address: 1001 Décarie Boulevard

department: Department of Pediatrics

country: Canada

institute: McGill University

summary: Epigenetic alterations are recurrently observed in cancer and are the subject of active therapeutic investigations. Midline high-grade gliomas (HGGs) are deadly brain tumors characterized by lysine-to-methionine substitutions at position 27 in histone 3 (H3) variants (denoted H3K27M), which are core components of the nucleosome. H3K27M, the first event in midline HGG development, results in a drastic loss of the repressive histone mark H3K27 tri-methylation (H3K27me3), and a notable increase in H3K27 acetylation (H3K27ac), a mark associated with active chromatin and cellular identity. H3K27ac gain was suggested to promote tumorigenesis in H3K27M-HGGs, but how these opposing marks shape oncogenesis remains controversial. We therefore characterized the active regulatory chromatin states in H3.3K27M and H3K27 wild-type HGGs and in H3.3K27M CRISPR/Cas9 knockout tumor-derived cell lines, as an isogenic tumor model of the mutation. We show that H3.3K27M-HGGs have distinct promoter, enhancer, super-enhancer, and core transcription factor circuitries from wild-type HGGs. However, while removal of H3.3K27M restores gross H3K27ac levels to those of wild-type HGGs, we observe minimal disruption of H3K27ac deposition at these active transcriptional elements, suggesting that they are a function of the cell of origin and independent of direct H3K27M mutagenesis and active regulation. Using quantitative ChIP-seq, we show that in H3.3K27M-HGGs, H3K27ac is pervasively deposited across the genome, including at normally silent repeat elements, leading to their increased baseline expression. H3.3K27M cells respond to DNA demethylating agents and histone deacetylase inhibitors, which further increase repeat element expression, including that of specific endogenous retroviral (ERVs) families. Our findings decouple cell lineage programs from H3K27M-dependent pervasive deposition of H3K27 acetylation. De-repression of ERVs may enhance the triggering of innate immune pathways, representing a therapeutic vulnerability in H3.3K27M HGGs.

overall_design: We sequenced 3 H3.3K27WT and 2 H3.3K27M human HGG tumors by H3K27ac ChIP-seq. Additionally, we sequenced unedited (2 replicates) and Crispr/Cas9 H3.3K27M-KO clones (4 replicates) for two cell lines (DIPGXIII and BT245).

first: Brian

last: Krug

first: Nicolas

last: De Jay

first: Ashot

middle: S

last: Harutyunyan

first: Shriya

last: Deshmukh

first: Dylan

middle: M

last: Marchione

first: Paul

last: Guilhamon

first: Kelsey

middle: C

last: Bertrand

first: Leonie

middle: G

last: Mikael

first: Melissa

middle: K

last: McConechy

first: Carol

last: Chen

first: Sima

last: Khazaei

first: Robert

middle: F

last: Koncar

first: Sameer

last: Agnihotri

first: Damien

last: Faury

first: Benjamin

last: Ellezam

first: Alexander

last: Weil

first: Josie

last: Ursini-Siegel

first: Daniel

middle: D

last: De Carvalho

first: Peter

middle: B

last: Dirks

middle: W

last: Lewis

first: Paolo

last: Salomoni

first: Mathieu

last: Lupien

first: Cheryl

last: Arrowsmith

last: Lasko

first: Jacek

last: Majewski

middle: A

last: Garcia

first: Claudia

middle: L

last: Kleinman

first: Stephen

last: Mack


title: Pervasive H3K27 acetylation leads to ERV expression and a therapeutic vulnerability in H3K27M gliomas [ChIP-Seq]

first: Nada

last: Jabado

overall_design: We sequenced 17 human HGG tumors (5 H3.3K27WT, 6 H3.3K27M, 6 IDH1 mutants) and 19 patient-derived cell lines and xenografts (8 H3.3K27WT, 11 H3.3K27M) by H3K27ac ChIP-seq. Additionally, we sequenced unedited (2 replicates) and Crispr/Cas9 H3.3K27M-KO clones (4 replicates) for two cell lines (DIPGXIII and BT245).

first: Brian

last: Krug

first: Nicolas

last: De Jay

first: Ashot

last: Harutyunyan

first: Shriya

last: Deshmukh

first: Dylan

last: Marchione

first: Paul

last: Guilhamon

first: Kelsey

last: Bertrand

first: Leonie

last: Mikael

first: Melissa

last: McConechy

last: Chen

last: Khazaei

last: Koncar


title: Pervasive H3K27 acetylation leads to ERV expression and a therapeutic vulnerability in H3K27M gliomas [ATAC-seq]

overall_design:
We sequenced 2 H3.3K27WT (pcGBM2, G477; 2 replicates total) and 2 H3.3K27M (DIPGVI, DIPGXIII; 6 replicates total) patient-derived cell lines as well as Crispr/Cas9 H3.3K27M-KO clones for one of the cell lines (3 replicates total; DIPGXIII-KO) using ATAC-Seq. P-XX designates passages of replicates.

Please note that the G477-LPG sample raw data is not provided due to patient privacy concerns and will be deposited at EGA under accession number EGAS00001003572.

first: Carol

first: Sima

first: Robert

first: Sameer

last: Agnihotri

first: Damien

last: Faury

first: Benjamin

last: Ellezam

first: Alexander

last: Weil

first: Josie

last: Ursini-Siegel

first: Daniel

last: De Carvalho

first: Peter

last: Dirks

last: Lewis

last: Salomoni

last: Lupien

last: Arrowsmith

last: Lasko

last: Majewski


title: Pervasive H3K27 acetylation leads to ERV expression and a therapeutic vulnerability in H3K27M gliomas

first: Nada

last: Jabado

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

overall_design: Refer to individual Series


title: High-throughput tissue dissection and cell purification with digital cytometry [healthy adults]

status: Public on May 06 2019

city: Stanford

first: Aaron

last: Newman

state: California

address: 265 Campus Drive

department: Institute for Stem Cell Biology and Regenerative Medicine, Department of Biomedical Data Science

institute: Stanford University

summary: Tissue composition is a major determinant of phenotypic variation and a key factor influencing disease outcomes. Although scRNA-Seq has emerged as a powerful technique for characterizing cellular heterogeneity, it is currently impractical for large sample cohorts and cannot be applied to fixed specimens collected as part of routine clinical care. To overcome these challenges, we extended Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) into a new platform for in silico cytometry. Our approach enables the simultaneous inference of cell type abundance and cell type-specific gene expression profiles (GEPs) from bulk tissue transcriptomes. The utility of this integrated framework, called CIBERSORTx, is demonstrated in multiple tumor types, including melanoma, where single cell reference profiles are used to dissect primary clinical specimens, revealing cell type-specific signatures of driver mutations and immunotherapy response. We anticipate that digital cytometry will augment single cell profiling efforts, enabling cost-effective, high throughput tissue characterization without the need for antibodies, disaggregation, or viable cells.

overall_design:
Whole blood samples were collected from 12 healthy adult subjects and immediately processed to enumerate leukocyte composition by FACS using an FDA-approved in vitro diagnostic test (IVD Multitest 6-color TBNK, Becton Dickinson) and automated hematology analyzer for blood leukocyte differential counts (Sysmex XE-2100) in a CLIA hematology lab setting (Stanford Clinical Laboratories). Aliquots from the same whole blood samples were stored in PAXgene blood RNA tubes (Qiagen) for subsequent RNA extraction and RNA-Seq library preparation.

Raw data are not available for this Series due to patient privacy concerns.

first: Chloe

last: Steen

first: Chih-Long

last: Liu

first: Andrew

middle: J

last: Gentles

first: Aadel

last: Chaudhuri

first: Florian

last: Scherer

first: Michael

last: Khodadoust

first: Mohammad

last: Shahrokh Esfahani

first: Bogdan

last: Luca

first: David

last: Steiner

first: Maximilian

last: Diehn

first: Ash

last: Alizadeh


title: Unlocking the transcriptomic potential of formalin-fixed paraffin embedded clinical tissues: Comparison of gene expression profiling approaches [RNA-Seq]

status: Public on May 04 2019

city: Edinburgh

first: Carlos

last: Martinez-Perez

address: Western General Hospital, Crewe Road South

department: Institute of Genetics and Molecular Medicine

country: United Kingdom

institute: The University of Edinburgh

summary:
Background: High-throughput transcriptomics has matured into a very well established and widely utilised research tool over the last two decades since the first mRNA profiling microarrays. Clinical datasets generated on a range of different platforms continue to be deposited in public repositories provide an ever-growing, valuable resource for reanalysis. Cost and tissue availability normally preclude processing samples across multiple technologies, making it difficult to directly evaluate performance, reliability and to what extent gene expression data from different platforms can be compared or integrated.
Purpose: In this study, we describe our experiences using nine new and established mRNA profiling techniques including Lexogen QuantSeq, Qiagen QiaSeq, BioSpyder TempO-Seq, Ion AmpliSeq, Nanostring, Affymetrix Clariom S or U133A, Illumina BeadChip and Ion Total RNA-seq of formalin-fixed paraffin embedded (FFPE) and fresh frozen (FF) sequential patient-matched breast tumour samples.
Results: The number of genes represented and reliability were found to vary between the platforms, but overall all methods provided data which were largely comparable. Crucially we found that it is possible to integrate data for combined analyses across FFPE/FF and platforms using established batch correction methods as required to increase cohort sizes. However, some platforms appear to be better suited to FFPE samples, particularly archival material. Overall, we illustrate that technology selection is a balance between required resolution, sample quality, availability and cost.

overall_design: Sequencing of patient-matched sets of human breast cancer biopsy samples using 9 different mRNA profiling platforms. We assess the feasibility of integrating data from FFPE or FF tissue sequenced using different platforms and compare these different technoolgies.

first: Arran

last: Turnbull

first: Cigdem

last: Selli

last: Sims


title: Dementia Comparison: VaD vs. AD vs. Controls

status: Public on Apr 23 2019

city: Grand Rapids

first: Erin

middle: Catherine

last: McKay

state: MI

address: 400 Monroe Ave NW

department: TSMM

institute: Michigan State University

summary: Gene expression profiling was performed on frontal and temporal cortex from vascular dementia (VaD), Alzheimer's disease (AD), and non-demented controls (Control) obtained from the University of Michigan Brain Bank. Controls and AD cases had no infarcts in the autopsied hemisphere. Vascular dementia cases had low Braak staging.

overall_design:
Each sample (VaD=8), (AD=12), (Controls=11) was run, at a minimum, in duplicate with a dye swap (Cy3/Cy5) on Agilent Human 8x60k v2 microarrays.

These are dual channel arrays, but have been processed as a single channel analysis. Normalized log2 signal is provided for each sample.  Raw files are included in a tar archive on the series record. Please see 'Description' field for the name of the raw file for each sample.

first: John

last: Beck

first: Mary

last: Winn

first: Karl

last: Dykema

last: Lieberman

first: Henry

last: Paulson

first: Scott

last: Counts


title: Hepatic transcriptomic analyses revealing the molecular pathogenesis of T2DM associated NAFLD in the ZDF rats

status: Public on May 01 2019

first: Fei

last: Chen

address: NO.1 Beichen West Road, Chaoyang District

institute: Beijing Institute of Genomics

type: Non-coding RNA profiling by high throughput sequencing

summary: The ZDF rat, with spontaneous homozygous mutation of the leptin receptor gene (fa/fa), is one of the widely used animal model for studying the human type 2 diabetes mellitus (T2DM). Male ZDF rats have the symptoms of obesity and insulin resistance at a young age, accompanying with impaired islet function. However, their hepatic pathogenesis is still unclear. Based on the successive observations and the transcriptomic analyses of the liver tissue at 22 weeks old, we detected the typical clinical indications of T2DM, severe hepatic metabolic remodeling and the inflammatory liver injury in the ZDF rats. The integrin linked kinase signaling, as well as the endoplasmic reticulum stress and its downstream p38 MAPK signaling, seemed to play crucial roles in it. We have proved the ZDF rats could better simulate the pathogenesis of the human T2DM associated nonalcoholic fatty liver disease (NAFLD), and provided targets and reference for future T2DM studies.

overall_design: Examined two samples and each has two repeats


title: High-throughput tissue dissection and cell purification with digital cytometry

first: Aaron

last: Newman


title: Pervasive H3K27 acetylation leads to ERV expression and a therapeutic vulnerability in H3K27M gliomas [RNA-Seq]

first: Nada

last: Jabado

overall_design: There are 6 H3.3K27WT and 7 H3.3K27M patient-derived cell lines. We sequenced unedited (7 replicates) and Crispr/Cas9 H3.3K27M-KO clones (7 replicates) for two cell lines (DIPGXIII and BT245). Furthermore, we sequenced the treated the unedited and KO clones with panobinostat, 5-azacytidine and a combination of both for each of the cell lines. We sequenced 6 H3.3K27WT and 7 H3.3K27M patient-derived cell lines as well as 17 HGG-H3.3K27M and 15 HGG-WT human tumors by RNA-seq.  We sequenced unedited (7 replicates) and Crispr/Cas9 H3.3K27M-KO clones (7 replicates) for two cell lines (DIPGXIII and BT245) as well as cells that were treated with panobinostat, 5-azacytidine and a combination of both for each of the cell lines.

first: Brian

last: Krug

first: Nicolas

last: De Jay

first: Ashot

last: Harutyunyan

first: Shriya

last: Deshmukh

first: Dylan

last: Marchione

first: Paul

last: Guilhamon

first: Kelsey

last: Bertrand

first: Leonie

last: Mikael

first: Melissa

last: McConechy

first: Carol

first: Robert

last: Koncar

first: Sameer

last: Agnihotri

first: Damien

last: Faury

first: Benjamin

last: Ellezam

first: Alexander

last: Weil

first: Daniel

last: De Carvalho

first: Peter

last: Dirks

last: Lewis

first: Paolo

last: Salomoni

first: Mathieu

last: Lupien

first: Cheryl

last: Arrowsmith

first: Jacek

last: Majewski

last: Garcia

first: Claudia

last: Kleinman


title: Alzheimer's gene expression by cell type - SFG

status: Public on Apr 17 2019

city: South San Francisco

first: Brad

last: Friedman

state: CA

address: 1 DNA Way

institute: Genentech, Inc.

summary:
AD patients all had Braak stages V or VI, and were also pathologically confirmed to have amyloid plaque.
The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech.
The ID of this project in Genentech's ExpressionPlot database is PRJ0018621

overall_design: RNA from purified cell types from AD and control post-mortem frozen superior frontal gyrus of AD and control patients.

first: David

last: Hansen


title: Long non-coding RNA RP11-820 promotes extracellular matrix production via regulating miR-3178/MYOD1 in human trabecular meshwork cells

status: Public on Feb 07 2019

city: Tianjin

first: Bingqing

last: Huang

address: Nanjing Road 288, Heping District

department: Department of Pathology

institute: Chinese Academy of Medical Sciences and Peking Union Medical College

summary: To further explore t of the role lncRNAs in glaucoma patients, we have employed lncRNAs microarray expression profiling as a discovery platform to identify abnormal genes under oxidative stress in HTMCs. Our results revealed that lncRNA-RP11 was significantly up-regulated under oxidative stress in HTMCs. Further studies found that lncRNA-RP11-820 directly binds miR-3178, through which regulates the expression of MYOD1. Importantly, MYOD1 can transcriptionally activate ECM genes. Furthermore, MYOD1 binds STAT3 to form a transcription complex, and transcriptionally activates ECM genes expression in HTMCs. Taken together, our data established taht oxidative stress induced lncRNA-RP11-820 plays a key role in regulating miR-3178/MYOD1/ECM axis in HTMCs.

overall_design: Oxidative stress induced lncRNAs expression in human trabecular meshwork cells were measured at 2 hours after exposure to doses of 300mM.

first: Wencui

last: Shen


title: Identification of genes involved in sebaceous gland carcinoma of the eyelid

status: Public on Jan 25 2019

city: Toyama

first: Tetsushi

last: Hirano

state: Toyama

address: 2630 sugitani

department: Life Science Research Center

institute: University of Toyama

summary:
Sebaceous gland carcinoma is the frequent malignant tumor of the eyelid. However, there is limited understanding of how altered gene expression of sebaceous gland carcinoma of the eyelid related to the pathogenesis.
In this study, to identify genes involved in sebaceous gland carcinoma of the eyelid, global-scale gene expression analysis was carried out using a GeneChip® system.

overall_design: Total RNA was extracted from sebaceous gland carcinoma of the eyelid and sebaceous adenoma. Quality of the RNA was analyzed using a Bioanalyzer 2100. Gene expression was analyzed by an Affymetrix GeneChip® system with a Human Clariom S array.

first: Tatsuya

last: Yunoki

first: Yoshiaki

last: Tabuchi


title: Inhibition of embryonic HSP-90 function causes variation of cold tolerance in zebrafish

status: Public on Mar 02 2019

city: Hangzhou

first: Jiang

last: Penglei

address: Yuhangtang Road 866

department: School of basic medicine science

institute: Zhejiang University

summary: Accumulating evidence suggests that HSP90 plays roles in modulation of phenotype in vertebrate development, which is closely involved in adaptation and evolution. In this study, we showed that inhibition of embryonic HSP90 function, either by a chemical inhibitor （radicicol） or low conductivity stress, induced variation of cold tolerance in adult zebrafish.

overall_design: Three zebrafish showing significantly increased survival times in cold from radicicol group and three zebrafish from control group were selected for RNA-Seq. Muscle tissue was separated from above mentioned fishes and used as materials for RNA-Seq.

first: Bingshe

last: Han

first: Juntao

last: Luo

first: Penglei

last: Jiang

first: Yan

last: Li

first: Junfang

last: Zhang


title: Systematic transcriptome analysis of white tea based on microarray

status: Public on Dec 07 2018

first: kun

last: luo

state: Beijing

address: Haidian district

institute: Tsinghua university

summary: Emerging in vivo and vitro data suggest that white tea extract (WTE) is capable of favourably modulating metabolic syndrome, especially by ameliorating abnormal lipid metabolism. Microarray-based gene expression profiling was performed in HepG2 cells to analyze the effects of WTE from a systematic perspective. Gene Ontology and pathway analysis revealed that WTE significantly affected pathways related to lipid metabolism. WTE significantly downregulated apolipoprotein B (APOB) and microsomal triglyceride transfer protein (MTTP) expression and thereby reduced the production of very-low-density lipoprotein. In the meanwhile, WTE stimulated low-density lipoprotein-cholesterol (LDL-c) uptake through targeting low-density lipoprotein receptor (LDLR), as a consequence of the activation of sterol regulatory element-binding protein 2 (SREBP2) and peroxisome proliferator-activated receptor δ (PPARδ). Furthermore, WTE significantly downregulated triglycerides synthetic genes and reduced intracellular triglycerides accumulation. Besides, we demonstrated that the tea catechins epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG) are abundant in WTE and contribute to the regulation of cholesterol metabolism related genes, including LDLR, MTTP and APOB. Our findings suggest white tea plays important roles in ameliorating abnormal lipid metabolism in vitro.

overall_design: HepG2 cells were treated with white tea extract (WTE) or DMSO (control group) for 24 hours. Gene expression of different groups were measured by the standard protocol for Agilent DNA chip. KEGG and Reactome analysis were performed to explore WTE functions on hepatic cells.

first: Kun

first: Lan

last: Xie


title: UBC9 knockdown  in bladder cancer T24 cell lines

status: Public on Dec 25 2018

city: Nanning

first: Xiaoliang

address: 22 Shuangyong road

institute: Guangxi Medical University

summary: UBC9 is the sole conjugating enzyme E2 in the sumoylation and plays a pivotal role in maintaining homeostasis and restraining stress reaction. Targeting UBC9 is emerging as a novel strategy for cancer therapy. However, the role of UBC9 in bladder cancer is not clear. Here, we sought to determine the alterations of trancriptome after shRNA-mediated knockdown UBC9 in T24 cell lines．

overall_design: Knockdown of UBC9 was performed in T24 cell lines with controls, respcectively. A total of 6 samples (3 knockdown with 3 controls) were used for RNA sequencing analysis.

first: Qiuyan

last: Wang


title: Identifying circRNA-associated-ceRNA networks in the hippocampus of Aß1-42-induced Alzheimer's disease-like rats using microarray analysis

status: Public on Mar 30 2019

city: Changsha

first: Weijun

last: Peng

address: No.139 Middle Renmin Road

department: The Second Xiangya Hospital

institute: Central South University

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

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus


title: Transcriptome analysis of wild-type and VaWRKY14 overexpressing Arabidopsis

status: Public on Dec 01 2018

city: Wuhan

first: langlang

last: zhang

state: HuBei

address: Cross road of Jiufeng 1 and Guanggu 7 road

institute: Wuhan Botanical Garden, Chinese Academy of Sciences

summary: To investigate the downstream genes of VaWRKY14 during drought stress response in  Arabidopsis, RNA-Seq was carried out on two biological replicates of wild-type and 3 transgenic Arabidopsis lines mixture under normal and drought treatment conditions

overall_design: Examination of gene expression changes after overexpression of VaWRKY14  in  Arabidopsis under normal and drought treatment and identification of VaWRKY14 downstream genes.

first: Langlang

first: Shaohua

first: Haiping

last: Xin


title: Splicing factor Ybx1 mediates persistence of Jak2-mutated neoplasms

city: München

first: Ashokkumar

last: Jayavelu

address: Am Klopferspitz 18

country: Germany

institute: Dept Proteomics and Signal Transduction, MaxPlanck Institute of Biochemistry

summary: Janus kinases (Jak) mediate cytokine, hormone and growth factor responses in hematopoietic cells. Jak2 is one of the most frequently mutated genes in the aging hematopoietic system and in hematopoietic cancers. Mutations in Jak constitutively activate downstream signaling and are drivers of myeloproliferative neoplasms (MPN). In clinical use, Jak-inhibitors have incomplete effects on overall disease burden of Jak2 mutated clones prompting us to investigate the mechanism underlying disease persistence. By in-depth phospho-proteome profiling we here identify proteins involved in mRNA processing as targets of mutant Jak2. Inactivation of the post-translationally modified Jak2-target Ybx1 sensitizes Jak-inhibitor persistent cells to apoptosis and results in RNA mis-splicing, retained intron enrichment and disruption of the transcriptional control of extracellular signal-regulated kinase (ERK) signaling. In combination with pharmacological Jak-inhibition it induces apoptosis in Jak2-dependent murine and primary human cells, leading to in vivo regression of the malignant clones and inducing remission. This identifies and validates a novel cell-intrinsic mechanism how differential protein phosphorylation results in splicing-dependent alterations of Jak2-ERK-signaling and the maintenance of Jak2V617F malignant clones. Therapeutic targeting of Ybx1 dependent ERK-signaling in combination with Jak2-inhibition may eradicate Jak2-mutated cells.

overall_design: Examination of Ybx1 mRNA processing and splicing events in BaF3 V617F cells with shNT, sh1Ybx1 and sh2Ybx1

first: Florian

last: Heidel

first: Matthias

last: Mann

first: Ashok Kumar


title: Distinct Hippocampal Expression Profiles of Long Non-coding RNAs in an Alzheimer’s Disease Model

status: Public on Mar 29 2019

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

summary: In the present study, we applied microarray technology to analyse the expression profiles of lncRNAs and messenger RNAs (mRNAs) in the hippocampus of rats in a validated AD model. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological roles and potential signalling pathways of these differentially expressed lncRNAs.

overall_design: Hippocampal lncRNA and mRNA profiles of the AD group and the control group. Each group included 3 hippocampal tissue which were submitted to microarray analysis according to the Agilent One-Color Microarray-Based Gene Expression Analysis protocol (Agilent Technology).

first: Zhe


title: Systems Analysis of the Human Pulmonary Arterial Hypertension Lung Transcriptome

status: Public on Dec 23 2018

city: Indianapolis

first: Robert

last: Stearman

state: IN

address: 950 W Walnut St

department: Medicine/Pulmonary

institute: Indiana Univeristy School of Medicine

summary:
Rationale:
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary artery pressure and vascular resistance, typically leading to right heart failure and death. Current therapies improve quality of life of the patients but have a modest effect on long-term survival. A detailed transcriptomics and systems biology view of the PAH lung is expected to provide new testable hypotheses for exploring novel treatments.

Objectives:
Complete transcriptomics analysis of PAH and control lung tissue to develop disease-specific and clinical data/tissue pathology gene expression classifiers from expression datasets. Gene expression data were integrated into pathway analyses.

Methods:
Gene expression microarray data was collected from 58 PAH and 25 control lung tissues. The strength of the dataset and its derived disease classifier was validated using multiple approaches. Pathways and upstream regulators analyses was completed with standard and novel graphical approaches.

Measurements and Main Results:
The PAH lung dataset identified expression patterns specific to PAH subtypes, clinical parameters, and lung pathology variables. Pathway analyses indicate the important global role tumor necrosis factor and transforming growth factor signaling pathways. In addition, novel upstream regulators and insight into the cellular and innate immune responses driving PAH were identified. Finally, WNT-signaling pathways may be a major determinant underlying the observed sex differences in PAH.

Conclusion:
This study provides a transcriptional framework for the PAH-diseased lung, supported by previously reported findings, and will be a valuable resource to PAH research community. Our investigation revealed novel potential targets and pathways amenable to further study in a variety of experimental systems.


title: Gene expression analysis of head and neck squamous cell carcinoma (HNSCC) cell lines.

status: Public on Nov 15 2018

first: Curtis

last: Pickering

state: TX

address: 1515 Holcombe Blvd

department: Head and Neck Surgery

institute: The University of Texas MD Anderson Cancer Center

summary: Human cancer cell lines are the most frequently used preclinical models in the study of cancer biology and the development of therapeutics. Although anatomically diverse, human papillomavirus (HPV)-driven cancers have a common etiology and similar mutations that overlap with but are distinct from those found in HPV-negative cancers. Building on prior studies that have characterized subsets of head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESC) cell lines separately, we performed genomic, viral gene expression, and viral integration analyses on 74 cell lines that include all readily-available HPV-positive (9 HNSCC, 8 CESC) and CESC (8 HPV-positive, 2 HPV-negative) cell lines and 55 HPV-negative HNSCC cell lines. We used over 700 human tumors for comparison. Mutation patterns in the cell lines were similar to those of human tumors. We confirmed HPV viral protein and mRNA expression in the HPV-positive cell lines. We found HPV types in three CESC cell lines that are distinct from those previously reported. We found that cell lines and tumors had similar patterns of viral gene expression; there were few sites of recurrent HPV integration. As seen in tumors, HPV integration did appear to alter host gene expression in cell lines. The HPV-positive cell lines had higher levels of p16 and lower levels of Rb protein expression than did the HPV-negative lines. Although the number of HPV-positive cell lines is limited, our results suggest that these cell lines represent suitable models for studying HNSCC and CESC, both of which are common and lethal.

overall_design:
RNAseq from individual cell lines grown under standard tissue culture conditions.

***Pleaes note that the raw sequence data cannot be provided due to these being old cell lines without proper consents. Please contact the submitter for the sequence data***

middle: R

first: Faye

last: Johnson

first: Jeffrey

middle: N

last: Myers


title: RNA-binding protein WDR43 binds prevalently to open chromatin and promotes gene transcription

status: Public on Feb 08 2019

city: Rochester

first: jinlong

last: lu

state: NY

address: 213 Hutchinson Hall

institute: University of Rochester

summary: The intricate regulation of transcription underlies cellular differentiation and development. However, the general relevance of RNA-binding proteins (RBPs) in polymerase (Pol) II transcription is less understood. Here we revealed that WDR43, a novel chromatin-bound RBP, promotes transcription and is essential for self-renewal of embryonic stem cells (ESCs) and early embryonic development. WDR43 binds to promoter-associated non-coding and nascent RNAs, localizes at thousands of gene promoters and enhancers, and interacts with the Pol II transcription machinery. Recombinant WDR43 directly promotes transcription and the release of elongation factor P-TEFb in vitro. Depletion of WDR43 in ESCs leads to global defects in Pol II pause release and mRNA expression. These results demonstrate that WDR43 maintains high-level expression of pluripotency programs by modulating Pol II activity and transcription elongation. To extend these findings, we demonstrated widespread co-occupancy of open chromatin by multiple RBPs, suggesting an unforeseen role for RBPs in transcription control

overall_design: Expression profiling by high throughput sequencing and genome occupancy profiling by high throughput sequencing. chrTAP-seq for WDR43.

first: Xianju

last: Bi

first: Yanhui

last: Xu

first: Tong

first: Xinmin

first: Wenzhi

last: LI

first: Kaili

first: Ge

last: Zhan

first: Zhongyang

last: Wu

first: Yafei

last: Yin

first: Wen

last: Shao

first: J

middle: Y

last: Lu

first: Liang

first: Jicheng

last: Zhao

first: Jiawei

first: Jie

first: Guohong

first: Pilong

first: Xiaohua

last: Shen


title: Distinct Adaptive Mechanisms Drive Recovery from Aneuploidy Caused by Loss of the Ulp2 SUMO Protease

status: Public on Nov 13 2018

city: New Haven

first: Hong-Yeoul

last: Ryu

address: 266 Whitney Ave

institute: Yale

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

overall_design: Refer to individual Series


title: Distinct Adaptive Mechanisms Drive Recovery from Aneuploidy Caused by Loss of the Ulp2 SUMO Protease [RNA-seq]

summary: In response to acute loss of the Ulp2 SUMO-specific protease, yeast become disomic for chromosome I (ChrI) and ChrXII. Here we report that ChrI disomy, which creates an adaptive advantage in part by increasing the dosage of the Ccr4 deadenylase, was eliminated by extended passaging. Loss of aneuploidy is often accompanied by mutations in essential SUMO-ligating enzymes, which reduced polySUMO-conjugate accumulation. The mRNA levels for almost all ribosomal proteins increases transiently upon initial loss of Ulp2, but elevated Ccr4 levels limit excess ribosome formation. Notably, extended passaging leads to increased levels of many small nucleolar RNAs (snoRNAs) involved in ribosome biogenesis, and higher dosage of three linked ChrXII snoRNA genes suppressed ChrXII disomy in ulp2Δ cells. Our data reveal that aneuploidy allows rapid adaptation to Ulp2 loss, but long-term adaptation restores euploidy. Cellular evolution restores homeostasis through countervailing mutations in SUMO-modification pathways and regulatory shifts in ribosome biogenesis.

overall_design: In these comparisons, the ulp2Δ cells either carried a WT ULP2 plasmid or empty vector and were passaged for 50 or 500 generations. mRNA profiles of them were generated by sequencing, in triplicate, using Illumina HiSeq 2500 .

first: Mark

last: Hochstrasser


title: Haemopedia: Mouse Haematopoietic Gene Expression

status: Public on Nov 29 2018

city: Parkville

first: Carolyn

last: de Graaf

address: 1G Royal Parade

country: Australia

institute: Walter and Eliza Hall Institute

summary: Database of gene expression in different haematopoietic cell types at haemosphere.org.

overall_design: Comparison of gene expression in different haematopoietic cell types.

first: Jarny

last: Choi

first: Tracey

last: Baldwin


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA207]

status: Public on Oct 31 2018

city: Tempe

first: Ben

last: Readhead

state: AZ

address: 797 E. Tyler Street

institute: ASU-Banner Neurodegenerative Disease Research Center

summary: Integration of in silico and in vitro approaches to design and conduct transcriptomic drug screening in patient-derived neural cells, in order to survey novel pathologies and points of intervention in schizophrenia.

overall_design: Here we compare the transcriptional responses of eight commonly used cancer cell lines (CCLs) directly to that of human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs) from twelve individuals with SZ and twelve controls across 135 drugs, generating over 4,300 unique drug-response transcriptional signatures.

first: Kristen

last: Brennand


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA205]


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA206]


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA204]


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA203]


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA104]


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA103]


title: Conventional and neo-antigenic peptides naturally processed and presented by beta cells are targeted by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors

status: Public on Aug 02 2018

city: Bruxelles

first: Decio

middle: Laks

last: Eizirik

address: Route de Lennik 808

department: Faculté de Médecine

country: Belgium

institute: Université Libre de Bruxelles

summary: Human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes. However, their target epitopes have not been demonstrated to be naturally processed and presented by β cells. We therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Preproinsulin yielded multiple previously described HLA-A2-restricted epitopes. Secretogranin V (SCG5/7B2), proconvertase-2, urocortin-3 and the insulin gene enhancer protein ISL-1 were identified as novel β-cell antigens, which were processed into HLA-A2-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. HLA-A2-bound neo-epitopes were also represented and originated from an alternative mRNA splice isoform (SCG5-009) and from an islet amyloid polypeptide transpeptidation product. This first description of the β-cell HLA peptidome opens new avenues to understand the antigen processing pathways employed by β cells and provides a valuable tool for developing T-cell biomarkers and tolerogenic vaccination strategies.

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

first: Jean-Valery

last: Turatsinze


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA105]


title: Establishment and characterization of CRISPR/Cas9-mediated Merlin/NF2 knockout human mesothelial cell line Met-5A

status: Public on Jun 20 2018

city: Nagoya

first: Akinobu

last: Ota

state: Aichi

address: 1-1 Yazakokarimata

department: Food and Nutritional Environment

institute: Kinjo Gakuin University

summary: To investigate the effect of NF2 on gene expression, we have employed whole genome microarray expression profiling using MeT-5A cells.

overall_design: The MeT-5A cells were plated at 80% confluence and cultured for 24 hours in vitro.

first: Sivasundaram

last: Karnan


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA101]


title: Next Generation Sequencing of ovarian CA-MSC & MSC Transcriptomes

status: Public on Aug 17 2018

city: Melbourne

first: Elizabeth

middle: Louise

last: Christie

state: Victoria

address: 305 Grattan St

institute: Peter MacCallum Cancer Centre

summary: Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes,  promote tumor cell growth,  increase cancer ‘stemness’ and  chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression.  Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs.    Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation.  Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes,  promote tumor cell growth,  increase cancer ‘stemness’ and  chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression.  Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs.    Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation.

overall_design: mRNA profiles of 4 normal omental MSCs and 10 ovarian CA-MSCs using Illumina TruSeq RNA Sample Preparation kit and Illumina HiSeq 100bp PE sequencing.

first: Lan

last: Coffman

first: Alex

middle: T

last: Pearson

first: Leonard

last: Frisbie

first: Zackary

last: Freeman

first: David

last: Bowtell

first: Ronald

last: Buckanovich


title: Histone variant macroH2A1 rewires carbohydrate and lipid metabolism of hepatocellular carcinoma cells towards cancer stem cells

status: Public on Jul 21 2018

city: S. Giovanni Rotondo (FG)

first: Tommaso

last: Mazza

address: Viale Cappuccini, 1

institute: IRCCS Casa Sollievo della Sofferenza

summary: We recently described the phenotype of HepG2 and Huh-7 hepatocellular carcinoma cells deleted for histone variant macroH2A1, which acquire cancer stem cell phenotype (Lo Re O et al., Hepatology 2017, PMID: 28913935). We found that short hairpin RNA-mediated macroH2A1 knockdown induces acquisition of CSC-like features, including the growth of significantly larger and less differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to chemotherapeutic agents, and stem-like metabolic changes consistent with enhanced hypoxic responses and increased glycolysis. As macroH2A1 is a potent transcriptional modifier we asked how KD of this histone variant might affect patterns of gene expression, and whether we could identify potential mechanistic links to the observed in vitro and in vivo HCC phenotypes. We obtained and validated an RNA-Seq dataset (Borghesan M et al., Cancer Res 2016, PMID: 26772755; Lo Re O et al., Hepatology 2017, PMID: 28913935), to conduct an unbiased comparison of the transcriptional profiles of HepG2 macroH2A1 KD cells and controls. Using a cut-off of 2 fold change, assessment of differentially expressed genes for macroH2A1 KD versus CTL showed no transcriptional overlap between the different HepG2 cell lines. Considering all differentially-expressed genes, there was significant enrichment (–log(p-value) > 1.3) in several functions and pathways that regulate pluripotency of human embryonic stem cells.

overall_design: Profiling the transcriptome of hepatocellular carcinoma cells HepG2 knocked-down for macroH2A1 using RNA-Seq.

first: Manlio

last: Vinciguerra


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA106]


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA201]


title: Total RNA-seq in a primary T-ALL patient cohort

status: Public on Sep 11 2018

city: Ghent

first: Karen

last: Verboom

address: De Pintelaan 185

department: Pediatrics and Genetics

institute: Ghent University

summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer resulting from malignant transformation of T-cell precursors. Several oncogenes, including the ‘T-cell leukemia homeobox 1’ TLX1 (HOX11) transcription factor, have been identified as early driver events that cooperate with other genetic aberrations in leukemic transformation of progenitor T-cells. The TLX1 controlled transcriptome in T-ALL has been investigated extensively in the past in terms of protein-coding genes, but remains unexplored thus far at the level of long non-coding RNAs (lncRNAs), the latter renown as well-established versatile and key players implicated in various cancer hallmarks. In this study, we present the first extensive analysis of the TLX1 regulated transcriptome focusing on lncRNA expression patterns. We present an integrative analysis of polyA and total RNA sequencing of ALL-SIL lymphoblasts with perturbed TLX1 expression and a primary T-ALL patient cohort (including 5 TLX1+ and 12 TLX3+ cases). We expanded our initially presented dataset of TLX1 and H3K27ac ChIP data in ALL-SIL cells (Durinck et al., Leukemia, 2015) with H3K4me1, H3K4me3, and ATAC-seq data to accurately define (super-) enhancer marked lncRNAs and assigned potential functional annotations to candidate TLX1-controlled lncRNAs through an in silico guilt-by-association approach. Our study paves the way for further functional analysis of selected lncRNAs as potential novel therapeutic targets for a precision medicine approach in the context of T-ALL.

overall_design: total RNA-seq data was generated for a primary T-ALL patient cohort

first: Wouter

last: Van Loocke

first: Pieter-Jan

last: Volders

first: Bieke

last: Decaesteker

first: Jean

last: Soulier

first: Pieter

last: Van Vlierberghe

first: Jo

last: Vandesompele

first: Frank

last: Speleman

first: Kaat

last: Durinck


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA202]

first: Ben

last: Readhead

first: Kristen

last: Brennand


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA102]


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA107]


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [MSA108]


title: Functional characterizations of the Hippo pathway effectors YAP and TAZ

status: Public on May 25 2018

city: La Jolla

first: Bing

last: Ren

address: 9500 Gilman Dr., CMM-East, Admin Area/Rm 2071

institute: University of California, San Diego School of Medicine

summary: The Hippo pathway plays an important role in regulating tissue homeostasis, and its effectors YAP and TAZ are responsible for mediating the vast majority of its physiological functions. Although YAP and TAZ are thought to be largely redundant and similarly regulated by Hippo signaling, they have developmental, structural, and physiological differences which suggest there may be differences in their regulation and downstream functions. To better understand the functions of YAP and TAZ in the Hippo pathway, we generated knockout cells and evaluated them in response to many conditions and stimuli. Here, we used RNA-seq to identify and compare differences in the transcriptional profiles between the YAP and TAZ.

overall_design: The overall goal is to examine expression changes under baseline starvation condtions and in response to LPA stimulation. mRNA profiles of wild type (WT), YAP KO, TAZ KO, and YAP/TAZ-dKO HEK293A cells were generated using deep sequencing with three biological replicates.

first: Steven

last: Plouffe

first: Yunjiang

last: Qiu


title: Metabolic reprogramming of Kaposi’s sarcoma associated herpes virus infected B-cells in hypoxia

status: Public on May 19 2018

city: Philadelphia

first: Rajnish

middle: Kumar

last: Singh

state: Pennsylvania

address: 202B Johnson Pavilion 3610 Hamilton walk

department: Otorhinolaryngology

institute: University of Pennsylvania

summary: We report differential gene expression in BJAB-KSHV/BJAB cells treated with Cobalt chloride/BJAB-KSHV cells treated with Cobalt Chloride compared to BJAB cells

overall_design: Differential gene expression in KSHV positive cells growing under hypoxic conditions

first: Erle

middle: S

last: Robertson


title: T-ALL


title: Gene expression of L3 parvalbumin neurons in the DLPFC comparing schizophrenia with unaffected subjects

status: Public on Jul 01 2018

city: Pittsburgh

first: David

last: Lewis

state: PA

address: 3811 O'Hara St

department: Psychiatry and Neuroscience

institute: University of Pittsburgh

summary:
Schizophrenia is associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction is manifest as cognitive deficits that appear to arise from disturbances in gamma frequency oscillations.
These oscillations are generated in DLPFC layer 3 via reciprocal connections between pyramidal cells and parvalbumin (PV)-containing interneurons. The density of cortical PV neurons is not altered in schizophrenia, but expression levels of several transcripts involved in PV cell function, including PV, are lower in the disease.

overall_design: We combined a novel immunohistochemical approach, laser microdissection, and microarray profiling to analyze the transcriptome of DLPFC layer 3 PV cells in 36 matched pairs of schizophrenia and unaffected comparison subjects.

first: John

last: Enwright

first: Zhiguang

last: Huo

first: Dominique

last: Arion

middle: P

last: Corradi

first: George

last: Tseng


title: MiRNAs expression in supernatant after ultraviolet irradiation

status: Public on Mar 07 2018

city: Nanjing

first: Ni

state: Jiangsu

address: 300 Guangzhou Rd

department: Department of Dermatology

institute: The First Affiliated Hospital of Nanjing Medical University

summary: To investigate the mechanism of radiation induced bystander effect, we explored miRNAs expression in supernatant of human skin fibroblasts after culturing for 24h post UV irradiation. Primary human skin fibroblasts were obtained from healthy volunteers by means of a foreskin circumcision. Human skin fibroblasts was irradiated with 20J/cm2 UVA or 60mJ/cm2 UVB. Expression of miRNAs were tested by microarray between radiation and control samples.

overall_design: Radiation-induced miRNA expression in supernatant of human skin fibroblasts was measured at 24 hours after exposure to doses of 20J/cm2 UVA or 60mJ/cm2 UVB.

last: Ni

first: Yanling

last: Tao


title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia [RNA-seq]

overall_design: RNA-sequencing from


title: Human embryonic stem cell, chimpanzee induced pluripotent stem cell, orangutan induced pluripotent stem cell, rhesus embryonic stem cell, and their derived cortical organoid RNA-seq

status: Public on May 31 2018

city: Boston

first: Andrew

middle: Ryan

last: Field

state: MA

address: 45 Shattuck St

department: BCMP

institute: Harvard Medical School

summary: We compared a 5 week time course of cortical organoid differentiation across human, chimpanzee, orangutan, and rhesus using bulk RNAseq. In addition, single cell RNAseq was performed on a subset of time points from human cells in weeks 0, 1, 2, and 5.

sample_organism:
Macaca mulatta
Pan troglodytes
Pongo abelii
Homo sapiens

overall_design: Bulk RNAseq of hESCs, ch-iPSCs, or-iPSCs, rhESCs, and each of 6 time points corresponding to weeks 0, 1, 2, 3, 4, and 5 during cortical organoid differentiation. Single cell RNAseq of human ESCs, week 1, week 2, and week 5 organoids.

middle: M

last: Jacobs

first: Ian

last: Fiddes

first: Alex

last: Phillips

first: Andrea

last: Reyes-Ortiz

first: Erin

last: LaMontagne

first: Lila

last: Whitehead

first: Vincent

last: Meng

first: Jimi

last: Rosenkrantz

first: Max

last: Hauessler

first: Sol

last: Katzman

first: Sofie

last: Salama

last: Haussler


title: The DNA methylation profile of liver tumors in C3H mice and identification of differentially methylated regions involved in the regulation of tumorigenic genes

status: Public on Apr 04 2018

city: Tsukuba

first: Keiko

last: Nohara

address: 16-2 Onogawa

department: Center for Health and Environmental Risk Research

institute: National Institute for Environmental Studies

type: Methylation profiling by high throughput sequencing

summary:
Background: C3H mice have been frequently used in cancer studies as animal models  of spontaneous liver tumors and chemically induced hepatocellular carcinoma (HCC).  Epigenetic modifications, including DNA methylation, are among pivotal control  mechanisms of gene expression leading to carcinogenesis. Although information on  somatic mutations in liver tumors of C3H mice is available, epigenetic aspects are yet  to be clarified.
Methods: We performed next generation sequencing-based analysis of DNA  methylation and microarray analysis of gene expression to explore genes regulated by  DNA methylation. Overlaying these data, we selected cancer-related genes whose  expressions are inversely correlated with DNA methylation levels in the associated  differentially methylated regions (DMRs) located around transcription start sites (TSSs)  (promoter DMRs). We further assessed mutuality of the selected genes for expression  and DNA methylation in human HCC using the Cancer Genome Atlas (TCGA)  database.
Results: We obtained data on genome-wide DNA methylation profiles in the normal  and tumor livers of C3H mice. We identified promoter DMRs of genes which are  reported to be related to cancer and whose expressions are inversely correlated with  the DNA methylation, including Mst1r, Slpi and Extl1. The association between DNA  methylation and gene expression was confirmed using a DNA methylation inhibitor 5-  aza-2'-deoxycytidine (5-aza-dC) in Hepa1c1c7 cells and Hepa1-6 cells.  Overexpression of Mst1r in Hepa1c1c7 cells illuminated a novel downstream pathway  via IL-33 upregulation. Database search indicated that gene expressions of Mstr1 and  Slpi are upregulated and the TSS upstream regions are hypomethylated also in human  HCC. These results suggest that DMRs, including those of Mst1r and Slpi, are  involved in liver tumorigenesis in C3H mice, and also possibly in human HCC.
Conclusions: Our study clarified genome wide DNA methylation landscape of C3H  mice. The data provide useful information for further epigenetic studies of mice models  of HCC. The present study particularly proposed novel DNA methylation-regulated  pathways for Mst1r and Slpi, which may be applied not only to mouse HCC but also to  human HCC.

overall_design: Examination of 6 mice liver DNA methylation modifications (normal liver tissue 3 samples vs liver tumor tissue 3 samples)


title: Comparative transcriptomics in two extreme neopterans reveal general trends in the evolution of modern insects

status: Public on Jun 05 2018

city: Barcelona

first: Guillem

last: Ylla

state: Catalonia

address: Passeig Marítim de la Barceloneta, 37

country: Spain

institute: Institute of Evolutionary Biology

summary: The success of neopteran insects, with 1 million species described, is associated with developmental innovations like the holometaboly and the evolution from short to long germ-band embryogenesis. To unveil the mechanisms underlining these innovations, we compared gene expression during the ontogeny of two extreme neopterans, the cockroach Blattella germanica (polyneopteran, hemimetabolan and short germ-band species), and the fly Drosophila melanogaster (endopterygote, holometabolan and long germ-band species). Results revealed that genes associated with metamorphosis are predominantly expressed in late nymphal stages in B. germanica and in early-mid embryo in D. melanogaster. In B. germanica the maternal to zygotic transition (MZT) concentrates early in embryogenesis, when juvenile hormone factors are significantly expressed. In D. melanogaster, the MZT extends throughout embryogenesis, during which juvenile hormone factors appear unimportant. These differences possibly reflect broad trends in the evolution of development within neopterans, related to the germ-band type and the metamorphosis mode.

overall_design: For each chosen developmental stage of Blattella germanica (Non-fertilized eggs, Embryos day 0, 1, 2, 6, 13, Nymphs 1, 3, 5, 6 and Adult females), 2 pools of specimens were obtained, the mRNAs fraction was isolated by Poly-A and the cDNA sequenced.

first: Xavier

last: Belles

first: M

middle: D

last: Piulachs


title: Genes and mechanisms regulated by androgens as possible contributors to the male excess observed in autism

status: Public on Feb 01 2018

city: Illkirch

first: Angélique

last: Quartier

address: 1, rue Laurent Fries

institute: IGBMC

overall_design: Refer to individual Series


title: Genes and mechanisms regulated by androgens as possible contributors to the male excess observed in autism [LNCaP]

summary: We optimized ChIP-sequencing protocole and anti-androgen receptor (AR) antibodies on human prostate cancer cell line (LNCaP) after either DMSO (solvent) or DHT 100nM 4 hours treatment.

overall_design: Examination of AR IP sequences with 2 anti-AR antibodies (commercial N-20 from SantaCruz or homemade 3279.4) after DMSO or DHT 100nM treatment by deep sequencing using Illumina HiSeq 2500

first: Bernard

last: Jost

first: Stéphanie

last: Le Gras

first: Amélie

last: Piton


title: Genes and pathways regulated by androgens as possible contributors to the male excess observed in autism [RNA-Seq]

summary: We analyzed androgens effects on human neural stem cells (hNSCs) by RNA-sequencing after either DMSO (solvent), DHT 100nM, 10nM, Testosterone 100nM, 10nM, R1881 1nM or retinoic acid 1µM 24 hours treatment in order to find the role of androgen receptor (AR) during brain development.

overall_design: Examination of DHT 100nM, 10nM, Testosterone 100nM, 10nM and R1881 1 nM (and retinoic acid 1µM) regulated genes in hNSCs by generating mRNA profiles of DMSO (3 or 4 technical replicates within the 3 biological replicates batches 1, 2 and 3: 10 samples in total) and DHT 100nM (natural metabolite of testosterone, AR agonist, 3 technical replicates within the 3 biological replicate batches 1, 2 and 3: 9 samples in total), DHT 10nM (3 technical replicate of 1 biological serie batch 1), Testosterone 100nM (3 technical replicate of 1 biological serie batch 1), Testosterone 10nM (3 technical replicate of 1 biological serie batch 1), R1881 1nM (3 technical replicate of 1 biological serie batch 1), retinoic acid (3 technical replicate of 1 biological serie batch 1) 24 hours treated hNSCs by deep sequencing using Illumina HiSeq 2500

first: Céline

last: Keime


title: Gene expression signatures of highly metastatic gallbladder cancer cells

status: Public on Nov 09 2017

city: Shanghai

first: Huaifeng

last: Li

address: NO.1665, kongjiang road, Shanghai, China

department: general surgery

institute: Xinhua hospital affiliated to Shanghai jiaotong university, school of medicine

summary: Liver invasion and metastasis often occur in gallbladder cancer (GBC). We established a liver metastasis mouse model using NOZ cells for two round intrasplenic injection. We acquired a highly metastatic subclone of NOZ cells, we named it LiM2-NOZ(second-round liver metastasis NOZ) cells. Then we characterized the long noncoding RNAs (lncRNAs) and mRNAs that differentially expressed in NOZ and LiM2-NOZ cells.

overall_design: Three independent NOZ and three independent LiM2-NOZ cells were used

first: Yingbin

last: Liu

first: Yunpeng

last: Jin

first: Yang

last: Yang


title: Upregulation of inflammation-related genes in the blood of Huntington’s patients

status: Public on Sep 15 2017

city: Berlin

first: Josef

last: Priller

address: Charitéplatz 1

department: Department of Neuropsychiatry

institute: Charité - Universitätsmedizin Berlin

summary: Blood is a very accessible tissue and as such constitutes a useful source of clinical markers. While it is obvious that metabolic disorders leave a clear mark in blood, it is not so clear whether this is the case for neurodegenerative diseases of the brain. Markers for neurodegenerative diseases are potentially useful to advance our understanding of the mechanisms involved in these diseases but are nearly impossible to obtain from living patients. To find whether altered gene expression could be found in blood of patients with a neurodegenerative disease, we collected blood samples from patients of Huntington’s disease (HD) and analysed their differences versus controls in terms of gene expression by RNA-seq analysis. We observed significant differential expression of a set of genes, with genes upregulated in patients enriched in immune response related functions and inflammatory response. We conclude that it is possible to detect changes in the expression of RNAs in blood from patients of HD and that this reflects the inflammatory pathology associated to the disease.

overall_design:
RNA-seq profiles of blood taken from normal controls and Huntington's disease patients
Please note that the 'readme' spreadsheet in the 'HTT.fpkm_v2.xls' contains data processing and column header details.

first: Miguel

last: Andrade-Navarro

first: Katja

last: Muehlenberg

first: Eike

last: Spruth

first: Nancy

last: Mah

first: Adrián

last: González-López

first: Matthew

last: Huska

first: Enrique

last: Muro

first: Jean-Fred

last: Fontaine

first: Vyacheslav

last: Amstislavskiy

first: Alexei

last: Soldatov

first: Wilfried

last: Nietfeld

first: Erich

middle: E

last: Wanker


title: Motif Variation Regulates the Affinity Landscape and Epigenetic State of the MyoD Cistrome

status: Public on Jan 02 2018

city: Ottawa

first: Theodore

last: Perkins

state: ON

address: 501 Smyth Rd.

department: Cellular and Molecular Medicine

institute: Ottawa Hospital Research Institute

summary: The cis-regulatory code is the cellular lexicon by which the transcriptional machinery converts sequence information within cis-regulatory modules (CRMs) into gene expression output. Tissue-specific transcription factors such as MyoD orchestrate gene expression programs by binding to short DNA motifs called E-boxes within their target CRMs to modulate chromatin state and to fine-tune gene expression output. Despite extensive research, how the relatively short and ubiquitously distributed E-box motifs contribute to binding specificity, assembly and the functional output of the transcriptional machinery remains poorly understood. Here, we have carried out an integrative analysis of the relationship between MyoD occupancy, nucleosome positioning, CRMs-associated histone marks and motif sequences within the myogenic CRMs in differentiating muscle cells. Our data suggests that variant sequences within MyoD-binding motifs and their multiplicity within the CRMs, as well as the spatial arrangement of the motifs, in combination confer binding affinity of MyoD, nucleosome occupancy and the epigenetic state of the myogenic CRMs. Our comparative genomic analysis of single nucleotide polymorphism (SNPs) across publically available data from 17 strains of laboratory mice suggests that variant sequences within MyoD-bound motifs, but not their genome-wide counterparts, are under selection. Taken together, our data suggests that variant sequences within MyoD-binding motifs are retained and have functional role to confer a dynamic range of affinities, enabling MyoD to establish a broad spectrum of activity across myogenic CRMs.

overall_design: Genome-wide binding of MyoD and the association with gene expression and histones in Myotubes

first: Michael

middle: A

last: Rudnicki

first: Vahab

last: Soleimani


title: Genes and mechanisms regulated by androgens as possible contributors to the male excess observed in autism [hNSCs]

first: Angélique

last: Quartier

summary: We analyzed androgen receptor (AR) target genes on human neural stem cells (hNSCs) by ChIP-sequencing of AR IP after either DMSO (solvent), Testosterone 100nM, DHT 10 or 100nM 4 hours treatment in order to find the role of AR during brain development.

overall_design: Examination of AR IP sequences after DMSO (1 technical replicate), Testosterone 100nM (AR agonist, 2 technical replicates), DHT 10nM (AR agonist, natural metabolite of testosterone, 2 technical replicates) or DHT 100nM treatment by deep sequencing using Illumina HiSeq 2500

first: Bernard

last: Jost

first: Stéphanie

last: Le Gras

first: Amélie

last: Piton


title: Cooperative binding of Oct4, Sox2, and Klf4 with stage-specific transcription factors orchestrates reprogramming [RNA-seq]

status: Public on Jan 19 2017

city: Los Angeles

first: Kathrin

last: Plath

address: 615 Charles E. Young Drive South

department: Biological Chemistry

institute: UCLA

summary: Oct4, Sox2, Klf4, and cMyc (OSKM) reprogram somatic cells to pluripotency. To gain a mechanistic understanding of their function, we mapped OSKM-binding, stage-specific transcription-factors (TFs), and chromatin-states in discrete reprogramming stages and performed loss- and gain-of-function experiments. We found that early in reprogramming OSK extensively bind somatic-enhancers and initiate their decommissioning by recruiting Hdac1. Concurrently, OSK engage other sites, including specific pluripotency-enhancers, and induce the relocation of somatic TFs to these sites and away from somatic-enhancers, extending somatic-enhancer decommissioning genome-wide. Pluripotency-enhancer selection early in reprogramming occurs predominantly at sites with high OSK-motif densities and requires collaborative binding by OSK. Most pluripotency-enhancers are selected later and occupied by OS and stage-specific-TFs like Esrrb. Overexpression of stage-specific-TFs influences reprogramming efficiency by changing OSK-occupancy, somatic-enhancer decommissioning, and pluripotency-enhancer selection. We propose that collaborative interactions among OSK and with stage-specific-TFs direct both somatic-enhancer decommissioning and pluripotency-enhancer selection, which drives the enhancer reorganization underlying reprogramming

overall_design: RNA-seq

first: Constantinos

last: Chronis

first: Petko

last: Fiziec

first: Bernadett

last: Papp

first: Stefan

last: Butz

first: Giancarlo

last: Bonora

first: Shan

last: Sabri

first: Jason

last: Ernst


title: Gene expression of L3 and L5 pyramidal neurons in the DLPFC comparing schizophrenia from bipolar major depressive disorders and unaffected subjects.

status: Public on Apr 04 2017

first: David

last: Lewis

summary:
Impairments in certain cognitive processes (e.g., working memory) are typically most pronounced in schizophrenia (SZ), intermediate in bipolar disorder (BP) and least in major depressive disorder (MDD).
Given that working memory depends, in part, on neural circuitry that includes pyramidal neurons in layer 3 (L3) and layer 5 (L5) of the dorsolateral prefrontal cortex (DLPFC), we sought to determine if transcriptome alterations in these neurons were shared or distinctive for each diagnosis.

overall_design: We collected brain specimens (n=76) with SZ (n=19; 6 had schizoaffective disorder), BP (n=19; all had bipolar 1 disorder) or MDD (n=19) and UC subjects (n=19) which were matched as tetrads for sex and as closely as possible for age. Each subject has 2 technique replicates.

first: Dominique

last: Arion

first: John

middle: F

last: Enwright

last: Corradi

first: Zhiguang

last: Huo

first: George

last: Tseng


title: Cooperative binding of Oct4, Sox2, and Klf4 with stage-specific transcription factors orchestrates reprogramming

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


title: The gastrula transition reorganizes replication origin selection in Caenorhabditis elegans

status: Public on Jan 22 2017

city: Montpellier

first: Hervé

last: Seitz

address: 141 rue de la Cardonille

department: IGH (UMR 9002)

institute: CNRS

type: Genome variation profiling by genome tiling array

summary: Some features underlying replication origin activation in metazoan cells have been identified, but little is known about their regulation during metazoan development. Using the nascent strand purification method, we identified replication origins throughout Caenorhabditis elegans embryonic development and found that the origin repertoire is thoroughly reorganized after gastrulation onset. During the pluripotent embryonic stages (pre-gastrula), potential cruciform structures and open chromatin are determinant factors to establish replication origins. The enrichment of replication origins in transcription factor binding sites and their presence inside promoters of highly transcribed genes, particularly operons, argue that transcriptional activity contributes to replication initiation before gastrulation. After the gastrula transition, when differentiation programs are set in the embryos, origins are particularly selected at enhancers, in the vicinity of CGI-like sequences, and non-coding genes. Our findings suggest that origin selection coordinates replication initiation with transcriptional programs during metazoan development.

overall_design:
3 replicates for pre-gastrula embryos and 3 for mixed embryos are analyzed. A replicate of L1 negative control is used for identification of the specific signal by subtracting it from the samples, and RNase treated control is generated as a technical control for the procedure used to identify replication origins.

Please note that [1] a description of each data column (in the processed data *txt files) is provided in the 'readme.txt' and [2] the column 'M.norm.minus.neg.w5' contains the data that forms the basis of this study's conclusion.

first: Marta

last: Rodriguez-Martinez

first: Natalia

last: Pinzon

first: Charles

last: Ghommidh

first: Emmanuelle

last: Beyne

first: Christelle

last: Cayrou

first: Marcel

last: Méchali


title: Comparison of transcriptomic profiles of Pseudomonas protegens H78 and its (p)ppGpp0 relA/spoT mutant

status: Public on Feb 27 2017

first: Xianqing

last: Huang

address: DongChuan RD, Minhang District

department: School of Life Sciences and Biotechnology

institute: Shanghai Jiao Tong University

summary: Transcriptomic profiles of  Pseudomonas protegens H78 and its (p)ppGpp0 relA/spoT mutant, which were grown to the late exponential phase (OD600 = 5.0 to 6.0) in the KMB media at 28 °C, were assessed by deep sequencing (RNA-seq) on Illumina 2500.

overall_design: Two bacterial strains, Pseudomonas protegens H78 wild type strain and its (p)ppGpp0 mutant strain, each was replicated three times.


title: Cooperative binding of Oct4, Sox2, and Klf4 with stage-specific transcription factors orchestrates reprogramming [ATAC-seq]

first: Kathrin

last: Plath

overall_design: Examination of 9 different histone modifications, 1 histone variant, the histone H3, 10 transcription factors and 3epigenetic regulators in 4 cell types.

first: Constantinos

last: Chronis

first: Petko

last: Fiziec

first: Bernadett

last: Papp

first: Stefan

last: Butz

last: Bonora


title: CSF pQTL study in the Japanese population [genotyping Q17]

status: Public on Dec 30 2016

city: Kodaira

first: Daimei

last: Sasayama

address: 4-1-1 Ogawahigashi-machi

institute: National Center of Neurology and Psychiatry

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

summary: Cerebrospinal fluid (CSF) is virtually the only one accessible source of proteins derived from the central nervous system (CNS) of living humans and possibly reflects the pathophysiology of a variety of neuropsychiatric diseases. However, little is known regarding the genetic basis of variation in protein levels of human CSF. We examined CSF levels of 1,126 proteins in 133 subjects and performed genome-wide association analysis of 514,227 single nucleotide polymorphisms (SNPs) to detect protein quantitative trait loci (pQTLs). Spearman’s correlation was used to identify association between genotypes of SNPs and protein levels. A total of 421 cis and 25 trans SNP-protein pairs were significantly correlated at a false discovery rate (FDR) of less than 0.01 (nominal P < 7.66 x 10 −9). Cis-only analysis revealed additional 580 significant cis SNP-protein pairs with FDR < 0.01 (nominal P < 2.13 x 10 −5). pQTL SNPs were more likely, compared to non-pQLT SNPs, to be disease/trait-associated variants identified by previous genome-wide association studies. The present findings suggest that genetic variations play a major role in the regulation of protein expression in the CNS. The obtained database will serve as a valuable resource for future neuropsychiatric research.

overall_design: CSF levels of 1,126 proteins in 133 subjects were examined. Genome-wide association analysis was performed to detect protein quantitative trait loci (pQTLs) affecting CSF protein levels.

first: Kotaro

last: Hattori

first: Shintaro

last: Ogawa

first: Yuki

last: Yokota

first: Ryo

last: Matsumura

first: Toshiya

last: Teraishi

first: Hiroaki

last: Hori

first: Miho

last: Ota

first: Sumiko

last: Yoshida

first: Hiroshi

last: Kunugi


title: CSF pQTL study in the Japanese population [somascan]


title: Cooperative binding of Oct4, Sox2, and Klf4 with stage-specific transcription factors orchestrates reprogramming [ChIP-seq]

first: Giancarlo

first: Shan

last: Sabri

first: Jason

last: Ernst


title: RNA-Chromatin Interactome Reveals Enhancer-Promoter Connectivity in 3D Genome

status: Public on Aug 29 2017

city: San Diego

first: Bing

last: Zhou

state: CALIFORNIA

address: 9500 Gilman Drive

institute: University of California San Diego

summary: High eukaryotic genomes are populated with enhancers, but it has been a major challenge in defining specific enhancer-promoter relationship. Enhancers can also be divided into typical and super-enhancers, yet their functional distinctions remain to be understood. Here, we report a strategy to capture in situ Global RNA Interactions with DNA by deep sequencing (GRID-seq). By deducing general RNA background on chromatin, we unexpectedly detect a highly selective set of RNAs (including both lncRNAs and protein-coding pre-mRNAs) decorated on enhancers, particularly super-enhancers. Based on the origins of those RNAs and functional perturbation of enhancer activities, we are able to infer global enhancer-promoter connectivity, which is significantly beyond the traditional framework. These findings provide a functional RNA-chromatin interactome in 3D genome.

sample_organism:
Drosophila melanogaster
Homo sapiens
Mus musculus

overall_design: Exploration of global RNA-chromatin interactions in 3 cell types of 3 species

first: Xiao

last: Li

first: Liang

last: Chen

first: Lantao

last: Gou

first: Hairi

first: Xiang-Dong

last: Fu


title: miRNA-Seq of human placenta: spontaneous preterm birth in the presence of intra-amniotic infection/inflammation and controls

status: Public on Jun 14 2016

city: Columbus

first: William

middle: Edward

last: Ackerman IV

state: Ohio

address: N521 Doan Hall, 410 West 10th Avenue

department: Obstetrics and Gynecology

institute: The Ohio State University

summary: Using RNA-sequencing (RNA-Seq and miRNA-Seq), we analyzed paired villous trophoblast and decidual basalis transcriptomes of 15 women pregnant with singleton gestations grouped as follows: (1) spontaneous preterm birth (PTB) in the setting of amniocentesis-proven intra-amniotic infection (IAI) and histological chorioamnionits (n=5; GA median [range]: 26 [25-31] weeks); (2) spontaneous idiopathic preterm birth (iPTB, n=5, GA: 32 [30-33] weeks); and (3) term normal pregnancy, that delivered a heathy infant by cesarean section in the absence of labor (n=5; GA: 39 [38-39] weeks).

overall_design:
The primary goal of this study was to identify differentially expressed transcripts and illuminate molecular mechanisms distinguishing IAI-associated PTBs from spontaneous PTBs in the absence of IAI. We further compared iPTB specimens to term specimens to determine genes differentially regulated with advancing gestational age and following spontaneous PTB without IAI. Finally, we determined transcripts selectively expressed in either the villous trophoblast or decidua basalis in each clinical context.

Raw data for this series are not available because consent forms do not allow for public access to raw data.

last: Ackerman

first: Catalin

last: Buhimschi


title: CSF pQTL study in the Japanese population

first: Daimei

last: Sasayama

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


title: RNA-Seq Analysis of Dose-Dependent TCDD-Elicited Hepatic Gene Expression in Male Mice

status: Public on Feb 28 2017

city: East Lansing

first: Timothy

last: Zacharewski

state: Michigan

address: 603 Wilson Road

department: BMB

institute: Michigan State University

summary: Dose-dependent hepatic gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the liver of C57BL/6 male mice.

overall_design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle

first: Kelly

last: Fader

first: Rance

last: Nault


title: Genome-wide analysis of gene expression in Lobosphaera incisa under nitrogen starvation and different light intensities

status: Public on May 01 2017

city: Paris

first: Olivier

last: Vallon

address: 13 rue Pierre et Marie Curie

department: UMR CNRS 7141

institute: University of Paris, Institut de Biologie Physico-Chimique (IBPC)

summary: Lobosphaera incisa is an oleaginous green microalga and a target organism of high biotechnological interest because it is the richest known plant source of arachidonic acid (ARA), a pharmaceutically and nutraceutically valuable omega-6 long-chain polyunsaturated fatty acid. ARA is deposited in considerable amounts in storage lipid triacylglycerols, most profoundly when L. incisa is exposed to nitrogen starvation. To get insights into genome-wide gene expression in L. incisa under nitrogen starvation, the whole transcriptome was sequenced by RNA-Seq. Total RNA was isolated under four growth conditions: exponential growth (control) and growth in nitrogen-depleted medium for 12 or 72 hours at normal or high light intensities. Statistical and differential gene expression analyses were conducted by comparing the various samples. The results of this study were used to identify patterns of gene regulation with special emphasis on genes involved in fatty acid and lipid metabolism.

overall_design: Total RNA sequencing of cells grown under four conditions: one control and three nitrogen starvation conditions; for each condition two biological replicate samples were sequenced, each in four technical replicates (32 samples in total)

first: Nicolas

middle: J

last: Tourasse

first: Inna

last: Khozin-Goldberg

first: Sammy

last: Boussiba

first: Stefan

last: Leu


title: Loss of HDAC-mediated repression and gain of NF-kB activation underlies cytokine induction in ARID1A and PIK3CA mutation-driven ovarian cancer

status: Public on Sep 15 2016

first: Falong

last: Lu

state: Massachusetts

address: 200 Longwood Ave, WAB 159

department: Program of Cellular and Molecular Medicine

institute: Boston Children's Hospital / HHMI

summary: ARID1A is frequently mutated in ovarian clear-cell carcinoma (OCCC) and often co-exists with activating mutations of PIK3CA. Although induction of pro-inflammatory cytokines has been observed in this cancer, the mechanism by which the two mutations synergistically activate cytokine genes remains elusive. Here we established an in vitro model of OCCC by introducing ARID1A knock-down and mutant PIK3CA in a normal human ovarian epithelial cell line, which resulted in cell transformation and cytokine gene induction. We demonstrate that loss of ARID1A impairs the recruitment of the Sin3A-HDAC complex, while PIK3CA mutation releases RelA from IkB, leading to cytokine gene activation. We show that an NF-kB inhibitor partly attenuates proliferation of OCCC and improves the efficacy of carboplatin both in cell culture and a mouse model. Our study thus reveals the mechanistic link between ARID1A/PIK3CA mutations and cytokine gene induction in OCCC, and suggests NF-kB inhibition can be a potential therapeutic option.

overall_design: Examine transcriptome and chromatin accessibility differences between human WT ovarian cells and cells with single or double mutations.

first: Minchul

last: Kim

first: Yi

last: Zhang


title: Measurement of inter-individual variability in gene expression in mouse neutrophils

status: Public on Sep 21 2016

first: Hervé

last: Seitz

summary: We extracted RNA from C57BL/6 mouse neutrophils to measure inter-individual variability in gene expression. 5 of the 10 blood samples were analyzed separately, the other 5 were pooled then split into 5 technical replicates to measure technical variability. We could then measure inter-individual variability in gene expression and compare it to the amplitude of miRNA-guided repression by miR-223.

overall_design: 5 samples were from individual mice (samples #1, 3, 5, 9 and 10) and 5 samples were from the pooled blood of the other five mice (samples #2, 4, 6, 7 and 8).

first: Natalia

last: Pinzón

first: Blaise

last: Li

first: Laura

last: Martinez

first: Anna

last: Sergeeva

first: Jessy

last: Presumey

first: Florence

last: Apparailly