title: Combinatorial transcriptional regulation modulates cytoskeletal-mediated dendritic arbor development

status: Public on Oct 10 2017

city: Atlanta

first: Ravi

last: Das

state: Georgia

address: 145 Piedmont Ave SE, Georgia State University,  GA

department: Neuroscience

institute: Georgia State University

summary: Transcription factors (TFs) have emerged as essential cell autonomous mediators of subtype specific dendritogenesis, however, the downstream effectors of these TFs remain largely unknown, as are the cellular events that TFs control to direct morphological change. As dendritic morphology is largely dictated by the organization of the actin and microtubule (MT) cytoskeletons, elucidating TFmediated cytoskeletal regulatory programs is key to understanding molecular control of diverse dendritic morphologies. Previous studies in Drosophila melanogaster have demonstrated that the conserved TFs Cut and Knot exert combinatorial control over aspects of dendritic cytoskeleton development, promoting actin and MTbased arbor morphology, respectively. To investigate transcriptional targets of Cut and/or Knot regulation, we conducted systematic neurogenomic studies, coupled with in vivo genetic screens utilizing multi-fluor cytoskeletal and membrane marker reporters. These analyses identified a host of putative Cut and/or Knot effector molecules and a subset of these putative TF targets converge on modulating dendritic cytoskeletal architecture and are grouped into three major phenotypic categories, based upon neuromorphometric analyses:¬¬ complexity enhancer, complexity shifter, and complexity suppressor. Complexity enhancer genes normally function to promote higher order dendritic growth and branching with variable effects on MT stabilization and F-actin organization, whereas complexity shifter and complexity suppressor genes normally function in regulating proximal-distal branching distribution or in restricting higher order branching complexity, respectively, with spatially restricted impacts on the dendritic cytoskeleton. Collectively, we implicate novel genes and cellular programs by which TFs distinctly and combinatorially govern dendritogenesis via cytoskeletal modulation.

overall_design: Gene expression profiling of control Class I da neurons, Class I da neurons overexpressing Cut (Class I X Cut) or Class I da neurons overexpressing Knot (Class I X Knot), isolated via magnetic bead sorting (using protocols as described in Iyer et al., 2009), was performed at the third instar larval stage of development from independent cell isolations from 40-50 age-matched third instar larvae expressing mCD8::GFP under the control of either GAL4221 driver, in the presence or absence of UAS-Cut (UAS-Cut;Gal4221) or UAS-Knot (UAS-Knot;Gal4221).

first: Surajit

last: Bhattacharya

first: Daniel

last: Cox


title: Long-lived mutants daf-2(e1370) and eat-2 (ad465) expression profilings

status: Public on Nov 20 2017

city: Amsterdam

first: Arwen

last: Gao

address: Meibergdreef 9

country: Netherlands

institute: Academic Medical Center of Amsterdam

summary:
Analysis of gene expression in two long-lived daf-2 mutant (mutation in the insulin/IGF-1 receptor) and eat-2 mutant (caloric restriction model), comparison of gene expression profiles of two long-lived mutants provide novel insight into longevity
Impaired insulin/IGF-1 signaling (IIS) pathway and caloric restriction (CR) are two well-established interventions to prolong lifespan in worm C. elegans. Although many studies using “-omics” approaches have gained informative knowledges on key longevity regulators in either IIS or CR models, few of those investigated the shared regulators between these two longevity interventions and integrated the messages from different –omics studies. In this study, we aimed to identify key pathways and metabolite fingerprints of longevity shared between the two interventions in worms using a multi-omics integration approach. We collected transcriptomics and metabolomics data from two long-lived mutant worm strains, i.e. daf-2 (impaired IIS pathway) and eat-2 (CR model) and compared with N2 strain. We detected many key pathways that were upregulated at the gene expression level in both long-lived mutants, such as defense response and lipid storage, while synthesis of macromolecules and developmental processes were downregulated at the transcript level. From our polar metabolite analysis, we discovered several shared metabolic features between the two long-lived mutants, including glycerol-3P, adenine, xanthine and AMP. In addition, we detected a lowered amino acid pool and two fatty acid species, C18:0 and C17:1, that behaved similarly in both long-lived mutants. After we integrated transcriptomics and metabolomics data based on the annotations in KEGG, our results highlighted a downregulation of pyrimidine metabolism and upregulation of purine metabolism in both long-lived mutants compared to N2 worms. Overall, our findings point towards the existence of shared metabolic pathways that are important for lifespan extension and provide novel insight of potential regulators and metabolic fingerprints for longevity.

overall_design: three worm strains, N2 (Bristol) was used as control/wild-type; together with two long-lived mutants daf-2(e1370) and eat-2(ad465). Both mutants were backcross with N2 strain for three times and sequenced. Culture temperature: 20 C; feeding bacterial strain: E. coli HT115; harvest at young adult phase; 500 worms per biological replicates; 4 replicates per worm strain

middle: W

first: Reuben

middle: L

last: Smith

first: Michel

last: van Weeghel

first: Rashmi

last: Kamble

first: Riekelt

middle: H

last: Houtkooper


title: Extracellular microvesicle microRNAs as predictive biomarkers for targeted therapy in Stage IV cutaneous malignant melanoma

status: Public on Aug 03 2017

city: Stockholm

first: Fernanda

last: Costa Svedman

address: Solnavägen 1

country: Sweden

institute: Karolinska Institute

summary: We analyzed the value of microRNAs (miRNAs) in plasma-derived extracellular microvesicles (EV) as biomarkers for treatment outcome in Stage IV CMM patients receiving MAPK inhibitors (MAPKis).

overall_design: EV miRNAs were extracted from plasma samples from 28 Stage IV CMM patients collected before and during therapy with MAPKis. EV miRNA levels were measured by a quantitative PCR-array and correlated to therapy response and progression-free survival (PFS). Matched plasma samples before and during treatment were obtained from 25 of the 28 patients. MiRNA expression profiling was performed using miRCURY LNA Universal RT miRNA PCR Human panel I (Exiqon, Denmark) covering 372 human miRNAs.  All miRNAs were polyadenylated and reverse transcribed in cDNA in a single reaction step. RNA isolation cDNA synthesis efficiency was examined by the detection of spike-in UniSp2, UniSp4 and UniSp6 to ensure that the quality of the input RNA was sufficiently high for effective amplification. cDNA and Exilent SYBR Green master mix (Exiqon, Denmark) were transferred to qPCR panels preloaded with primers. Amplification was performed in a Lightcycler 480 (Roche). We normalized miRNA expression to a set of miRNAs found to be most stable across conditions defined by the normfinder algorithm

middle: C

last: Svedman

first: Warangkana

last: Lohcharoenkal

first: Matteo

last: Bottai

first: Suzanne

middle: E

last: Brage

first: Enikö

last: Sonkoly

first: Johan

last: Hansson

first: Andor

last: Pivarcsi

first: Hanna

last: Eriksson


title: Frequent Evolution of Copy Number Alterations Following First‑line Treatment with FC(R) is Enriched with TP53 Alterations which Impact Long Term Survival – Results from the CLL8 Trial

status: Public on Aug 25 2017

city: London

first: Jennifer

last: Edelmann

address: Charterhouse Square

department: Centre for Haemato-/Oncology

country: United Kingdom

institute: Barts Cancer Institute

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

summary: To define clonal evolution of somatic copy number alterations (CNAs) in chronic lymphocytic leukemia (CLL), sequential samples of 103 individuals were investigated by SNP-array analysis for appearance of novel CNAs. Patients were enrolled on the CLL8 trial and uniformly received fludarabine, cyclophosphamide +/- rituximab (FC/FCR). Comparing two sequential samples prior to therapy (N=27, a median of 2.9 years apart), CNA evolution occurred in 19% of cases. In contrast, when comparing treatment‑initiation and relapse genomic profiles (a median of 3.6 years apart), CNA evolution was seen in 40% of cases. This suggested association of FC(R) treatment with higher rate of CNA evolution. The only clinical feature significantly associated with CNA evolution was FCR therapy compared with FC (OR=2.806, p=0.024). As this might be related to narrower evolutionary bottlenecks imposed by the more effective FCR therapy, which could execute more selection pressure, we examined matched minimal residual disease data. We found CNA evolution more frequently in cases with CLL cell numbers rapidly receding in early phases of treatment. Finally, we observed frequent rises of TP53 mutant/deficient clones with therapy (N=19, 22%) that were associated with decreased overall survival (p=0.016). These results demonstrated that re-examination of TP53 status upon relapse provides important information.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic peripheral blood samples.
Copy number analysis of Affymetrix® 6.0 arrays was performed for 216 CLL samples. There are also 52 samples from mononuclear cells negative for CD19 which were taken at treatment-initiation and used as references for copy number inference.


title: Long non-coding RNAs have age-dependent diurnal expression that correlates with age-related changes in genome-wide facultative heterochromatin (RNA-Seq data set)

status: Public on Jan 30 2018

city: New Brunswick

first: William

middle: J.

last: Belden

state: NJ

address: 59 Dudley Rd

department: Animal Sciences

country: USA

institute: Rutgers, The State University of New Jersey

type: Expression profiling by high throughput sequencing

type: Non-coding RNA profiling by high throughput sequencing

summary: The circadian rhythm controls timed choreography of gene expression to maintain normal cell physiology and metabolism. The predominant regulatory mechanism of the circadian rhythm is a transcriptional negative feedback loop that facilitates, and is facilitated by, circadian-regulated facultative heterochromatin. The long-term consequence of disrupted diurnal rhythm, or mutations in core clock genes, cause accelerated aging and an increased incidence in age-related diseases. To understand chromatin dynamics underlying age-related changes to circadian transcription, we performed a combined RNA-seq and ChIP-seq at two diurnal time-points for three different age groups. Our analysis focused on uncovering relationships between long non-coding RNA (lncRNA) and age-related changes to heterochromatin. We determined that the core clock genes maintain rhythmic expression regardless of age, but circadian output, including numerous lncRNAs, changes dramatically with age. In addition, there is both diurnal and age-related changes in Histone H3 lysine 9 tri-methylation (H3K9me3) that correlate with the changes in gene expression. Collectively, the data suggest a model where age-related changes in diurnal gene expression occur, in part, due to age-related redistribution of rhythmic facultative heterochromatin. Alterations in heterochromatin appear to be mediated by changes in diurnal lncRNA expression creating an interlocked circadian-chromatin regulatory network that undergoes age-dependent metamorphosis.

overall_design: RNA-seq of zebrafish brain tissues from three different ages (4M, 12M and 20M) at two time points (ZT4 and ZT16)

first: Jinhee

last: Park


title: Comparative expression data between wild-type and ANGPTL4-knockdown MKN28 and MKN28snai1ER cells upon EMT induction

status: Public on Jul 22 2017

city: Singapore

first: Zi Qiang

last: Teo

state: Singapore

address: School of Biological Sciences,

department: SBS

country: Singapore

institute: NTU

summary:
Epithelial-mesenchymal transition (EMT) induced by microenvironment stimuli can be attributed to the transcriptional regulation of epithelial and mesenchymal phenotypes. Here we show how EMT is coordinated with cancer metabolism, an emerging hallmark of tumorigenesis.
To identify molecular drivers of EMT common to all three EMT models, we performed a comparative microarray gene expression analysis.

overall_design: Cells were seeded at a density of 5.25×102 cell/cm2 to allow the formation of individual colonies before indicated treatments. Hypoxia treatments were performed  in hypoxic chamber (Stem cell Technology, USA) purged with 5% CO2 and 95% N2 to obtain O2 concentration at 1% as determined by an O2 sensor. For TGF-β-induced EMT, cells were treated with 10 ng/mL of TGF-β for 2 days. For Snai1-mediated EMT, MKN28Snai1ER/shANGPTL4 and MKN28Snai1ER cells were exposed to 20 ng/mL of 4-hydroxytamoxifen (4-OHT) for 4 days. RNA was extracted from the respective treatments with Trizol following the manufacturer’s protocol. Further sample processing of the RNA was carried out using Applause® WT-Amp ST System (NuGEN), and microarray experiments were performed on GeneChip® Human Gene 1.0 ST arrays according to the manufacturer’s instructions.

first: Ziqiang


title: TYRP1 knock-down in human melanoma cell line (501Mel)

status: Public on Jul 01 2017

city: Rennes

first: Nicolas

last: Mouchet

state: Bretagne

address: 2 Av du Professeur Leon Bernard

department: Institut genetique et developpement de Rennes

country: France

institute: CNRS UMR6290

summary: Efficient TYRP1 knock-down (KD) have been performed in human melanoma cell line expressing a high level of TYRP1 mRNA and protein in order to identify the molecular pathway explaining the decrease of cell proliferation in TYRP1 KD cells.

overall_design: Two non targeting siRNA (NT1 and NT2) and 3 siRNA targeting the ORF sequence of TYRP1 were used. Experiments have been done 3 or 4 times respectively  (( NT1, NT2, TYRP1 A and TYRP1D) and (TYRP1C )). Technical duplicates have been performed to make the batch effect removal accurate.

first: Sebastien

last: Corre

first: David

last: Gilot

first: Marie-Dominique

last: Galibert


title: Stratification of clear cell renal cell carcinoma (ccRCC) genomes by gene-directed copy number alteration (CNA) analysis

status: Public on Jun 09 2017

city: Rostock

first: Dirk

last: Koczan

address: Schillingallee 70

department: Institute for Immunology

country: Germany

institute: University of Rostock

summary: Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) present in 48 clear cell renal cell carcinoma (ccRCC) genomes result in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes are mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs are classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turn out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. Finally, the diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) are successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreases with the number of G3 related gene losses plus the total number of gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

overall_design: clear cell renal cell carcinoma samples (ccRCC) were investigated for copy number alterations using the Affymetrix mapping array Genome-Wide Human SNP 6.0 array. 26 samples were classified as G1 according to Fuhrman tumour grading, 2 were classified as G2 and 20 as G3 grading.

first: Hans-Juergen

last: Thiesen

first: Felix

last: Steinbeck

first: Mathias

last: Maruschke

first: Bjoern

last: Ziems

first: Oliver

last: Hakenberg


title: Copy Number Variation of human hepatocellular carcinoma (HCC) and Cholangiocarcinoma (CCA) from the Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC)

status: Public on Jun 27 2017

city: Bethesda

first: Xin

middle: Wei

last: Wang

state: MD

address: 37 Convent Drive

department: Laboratory of Human Carcinogenesis

institute: National Cancer Institute

summary:
We used Affymetrix SNP6.0 microarray profiling to analyze Copy Number Variation in tumor and paired non-tumor tissue of HCC and CCA patients.
We used copy number data to confirm molecular subgroups of HCC and CCA patients from Thailand

overall_design: For profiling of copy number, tumors and paired non-tumor tissues were profiled separately using Affymetrix Genome-Wide Human SNP Nsp/Sty 6.0 according to the manufacturer's protocol.

first: Wang

last: Xin Wei


title: Gene expression in healthy and lesional psoriatic epidermis from human skin biopsies (laser capture microdissection): set 1

status: Public on Jun 14 2017

city: Lille

first: Denis

middle: A

last: Mogilenko

address: 1 Rue du Professeur Calmette, BP245

institute: INSERM

summary: We performed microarray analysis on laser-microdissected epidermis from healthy volunteers and psoriatic patients to identify genes dysregulated in lesional psoriatic epidermis

overall_design: Epidermis and dermis were obtained from human skin biopsies by laser capture microdissection using Arcturus XT (MDS Analytical Technologies) system, followed by RNA isolation with Arcturus Picopure RNA isolation Kit. 10 ng RNA were amplified with ExpressArt Kit and labeled with One-color microarray-based Gene Expression Analysis Low Input Quick Amp WT Labeling (Agilent Technologies) and hybridized with Human Gene Expression Microarray 8x60K chip (Agilent Technologies). Two sets of samples (3 lesional psoriatic and 2 healthy epidermis samples in set 1 and 3 lesional psoriatic and 3 healthy epidermis samples in set 2, or 3 lesional psoriatic and 2 healthy dermis samples in set 1 and 3 lesional psoriatic and 2 healthy dermis samples in set 2) were processed and normalized separately.

last: Dombrowicz


title: Information-dependent Enrichment Analysis Reveals Time-dependent Transcriptional Regulation of the Estrogen Pathway of Toxicity

status: Public on Jun 05 2017

city: RTP

first: Salil

middle: N

last: Pendse

state: NC

address: 6 Davis Drive

institute: Scitovation

summary: The twenty-first century vision for toxicology involves a transition away from high-dose animal studies to in vitro and computational models (NRC 2007). This transition requires mapping pathways of toxicity  by understanding how in vitro systems respond to chemical perturbation. Uncovering transcription factors/signaling networks responsible for gene expression patterns are essential for defining pathways of toxicity, and ultimately, for determining the chemical modes of action through which a toxicant acts. Traditionally transcription factor identification is achieved via chromatin immunoprecipitation studies and summarized by calculating which transcription factors are statistically associated with up- and downregulated genes. These lists are commonly determined via statistical or fold-change cutoffs, a procedure that is sensitive to statistical power and may not be as useful for determining transcription factor associations. To move away from an arbitrary statistical or fold-change based cutoffs we developed, in the context of the Mapping the Human Toxome project, an enrichment paradigm called Information Dependent Enrichment Analysis (IDEA) to guide identification of the transcription factor network. We used a test case of activation in MCF‑7 cells by 17β estradiol (E2). Using this new approach, we established a time course for transcriptional and functional responses to E2. ERα and ERβ were associated with short-term transcriptional changes in response to E2. Sustained exposure led to recruitment of additional transcription factors and alteration of cell-cycle machinery. TFAP2C and SOX2 were the transcription factors most highly correlated with dose. E2F7, E2F1 and Foxm1, which are involved in cell proliferation, were enriched only at 24h. IDEA should be useful for identifying candidate pathways of toxicity.  IDEA outperforms Gene-set Enrichment Analysis (GSEA) and provides similar results to Weighted Gene Correlation Network Analysis, a platform that helps to identify genes not annotated to pathways.

overall_design: Gene Expression in MCF7 Cells treated with 0.01nM,0.1nM,1nM E2 for 2h,4h,8h,24h measured against time-matched controls


title: Integrated analysis Of Biopsies From Inflammatory Bowel Disease Patients Identifies SAA1 As A Link Between Mucosal Microbes With TH17 And TH22 Cells [diseased subjects]

status: Public on Nov 11 2017

city: Saint Louis

first: Mei San

last: Tang

state: MO

address: 660 S Euclid, Campus Box 8118

department: Pathology & Immunology

institute: Washington University in St Louis

summary: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize the relationships between mucosal T cells, the host tissue environment and microbial communities in IBD patients to identify new therapeutic targets. We identified 26 predictors from our combined data set that were effective in distinguishing between regions of the intestine undergoing active inflammation and regions that were normal. Network analysis on these 26 predictors revealed SAA1 as the most connected node linking the abundance of the genus Bacteroides with the production of IL17 and IL22 by CD4+ T cells. The SAA1-linked microbial and transcriptome interactions were further validated with data from the pediatric IBD RISK cohort. This study identifies expression of SAA1 as an important link between mucosal T cells, microbial communities and their tissue environment in IBD patients. A combination of FACS, gene expression and microbial profiling can distinguish between intestinal inflammatory states in IBD regardless of disease types.

overall_design: We characterized mucosal CD4+ T cells using flow cytometry (FACS), along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from IBD patients. We analyzed these data sets using an integrated framework to identify predictors of inflammatory states and then validated the putative relationship networks by analyzing data from the pediatric RISK cohort.

first: Mei

middle: S

first: Jacqueline

middle: M

last: Leung

first: Uma

last: Gundra

first: P'ng

last: Loke


title: Genotyping data from Phase 2 of the SAMARA study (Supporting a Multi-disciplinary Approach to Researching Atherosclerosis)

status: Public on Nov 01 2017

city: Chapel Hill

first: Jonathan

last: Schisler

address: MBRB, Rm 2340C

department: McAllister Heart Institute

institute: The University of North Carolina at Chapel Hill

summary: Our goal was to measure molecular phenotypes associated with coronary atherosclerosis severity in a geriatric cohort.

overall_design:
106 individual samples from DNA purified from human peripheral blood mononuclear cells analyzed using the Affymetrix Genome-Wide Human 6.0 Array
The sample titles are composed using the following scheme: ID_gender_ancestry_ObsCad_CadClass_CXCL5rank

9 samples are missing CEL files due to hard drive damage and subsequent loss of data.

first: Eleanor

middle: G

last: Hiliard

first: Cam

last: Patterson


title: Affymetrix SNP 6.0 array data for gastric adenocarcinoma and some matched normals

status: Public on Apr 15 2017

city: Boston

first: Steven

last: Schumacher

state: MA

address: 450 Brookline Ave

department: Cancer Biology

institute: Dana-Farber Cancer Institute

summary: Using data from high-density genomic profiling arrays, we investigated the profiles of somatic copy-number aberrations (SCNAs) in 659 gastric adenocarcinomas drawn approximately even numbers of Asian and Western patients with two goals in mind: (1) using the power of our large data set to detect new, and refine existing, regions of significantly recurring SCNAs; (2) determining if there exist fundamental differences in the manifestation of gastric adenocarcinoma in Asian versus Western patients that affect pattern of SCNAs. Among the 83 regions of significant alteration we indeed found some new targets in gastric adenocarcinoma such as the tumor suppressor gene SMARCA4 and proto-oncogene MYB, and additionally refined the boundaries of known significant regions. We found only slight differences in the overall copy number patterns between Asian and Western gastric adenocarcinoma patients indicating that the disease is fundamentally similar in both populations and the divergent clinical outcomes cannot be ascribed to different underlying SCNAs. The 111 copy number profiles contained in this archive are the previously unpublished portion of our study.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from 78 cancer DNAs derived from primary tissues, as well as from DNA obtained from 37 normal DNA samples.
Signal intensities were normalized to raw copy number estimates using the tangent normalization method, as described in Beroukhim R. et al., Nature, 2010. The SNP 6.0 data from this submission were segmented using CBS. Data analysis across samples was performed using this GISTIC 2.0 algorithm (Mermel C. et al., Genome Biology 2011).

Please note that [1] the 'GEW_SNP6_normalized_data_matrix.txt' contains the normalized copy number array data for the 111 samples. Genotype Call (SNP call) data are not provided and are not used in this study.

[2] the 'GEW_SNP6_cbs.seg.txt' contains the segmented data for all 659 samples in our study including the 111 represented here. The segmentation for many of the samples published elsewhere is different. Our study is largely based on segmented data.

[3] The 'GEW_SNP6_tumor_accessions.xlsx' incude the list of accessions and URLs for accessing all of the data (including the 111 novel samples represented here)

first: Byoung

middle: Y

last: Shim

first: Rameen

last: Beroukhim

first: Ramesh

last: Shivdasani

first: Adam

middle: J

last: Bass


title: SNP array data for acute myeloid leukemia samples

status: Public on Apr 10 2017

city: Philadelphia, PA

first: Richard

last: Aplenc

state: PA

address: 3501 Civic Center Blvd

department: Division of Oncology

institute: Children's Hospital of Philadelphia

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

overall_design: Refer to individual Series


title: Affymetrix SNP array data for acute myeloid leukemia samples

summary: Pediatric patients with de novo acute myeloid leukemia. To define genomic architecture, we performed genome-wide copy number abberation analysis in 460 paired diagnostic-remission bone marrow aspirates.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic and remission bone marrow samples.
Copy number aberration analysis of Affymetrix 6.0 SNP arrays (254 sample pairs) and Illumina 2.5M Omni arrays (206 sample pairs) was performed for 460 acute myeloid leukemia samples.
This Series represents the Affymetrix dataset.

first: Soheil

last: Meshinchi


title: Transcriptome profiles of human pre-DC and DC subsets in peripheral blood

status: Public on May 21 2017

first: Kaibo

last: Duan

address: 8A Biomedical Grove, Immunos Building, Level 4

institute: Singapore Immunology Network

summary: Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. Important questions on the origins and differentiation paths of human DC populations remain elusive. Here we combined two high-dimensional technologies, single-cell mRNA sequencing and mass cytometry to define and characterize CD33+CD45RA+ DC precursors (pre-DC) present in human blood. In this study, we showed that a previously understimated pre-DC population shares surface markers with plasmacytoid DC (pDC), but has distinct functional properties that were previously attributed to pDC. Finally, we trace the origin of DCs from BM to peripheral blood and reveal that pre-DC comprise three sub-populations - 1 uncommitted sub-population and 2 lineage-committed sub-populations. The discovery of committed pre-DC populations in present in human peripheral blood confirms the existence of DC as a distinct hematopoietic lineage and opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.

overall_design: Gene expression analysis using total RNA from specific human pre-DC and dendritic cell subsets purified by FACS.

first: Peter

last: See

first: Charles-Antoine

last: Dutetre

first: Michael

last: Poidinger

first: Florent

last: Ginhoux


title: Exposure of bovine oocytes to elevated insulin concentration (0.1 ug/ml) during in vitro maturation changes DNA methylation pattern in Day-8-blastocysts – an epigenetic study.

status: Public on Apr 08 2017

city: Québec City

first: Marc-André

last: Sirard

state: Quebec

address: Offfice 2732, 2440 Hochelaga Blvd.

department: Sciences Animales

country: Canada

institute: Université Laval

type: Methylation profiling by genome tiling array

summary: The aim was to study the potential effect of hyperinsulinemia on  gene expression and differential DNA-methylation of cow embryos by adding 0.1 µg/ml (INS0.1) during in vitro oocyte maturation.

overall_design: In total, 882 abattoir-derived oocytes (equally distributed between treatments (INS0.1) and a control, (INS0)) produced 199 embryos in a period of 8 weeks. Cleavage blastocyst rates were recorded and embryos evaluated for stage and quality grade before individually frozen at -80 °C. 120 of the embryos were used for the methylome analysis, pooled in groups of 10 embryos with a similar distribution of embryos (pools adjusted for quality grade and developmental stage in order to avoid confounding effects in the results due to different embryo characteristics). The experiment was run in four replicates per treatment group.

first: Denise

last: Laskowski

first: Patrice

last: Humblot

first: Ylva

last: Sjunnesson

first: Renée

last: Båge

first: Göran

last: Andersson


title: Expression data from cells sorted from human fetal pancreas

status: Public on Mar 17 2017

city: Paris

first: Raphael

last: Scharfmann

address: 123 bvd Port-Royal

institute: Institut Cochin - Bat. Cassini

summary: Although a large set of data is available concerning organogenesis in animal models, information remains scarce on human organogenesis. In this work, we performed temporal mapping of human fetal pancreatic organogenesis using cell surface markers. We demonstrate that in the human fetal pancreas at 7 weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate either into the acinar, ductal and endocrine lineages. Development towards the acinar lineage is paralleled by a substantial increase in GP2 expression. Conversely, a subset of the multipotent GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, an early marker of endocrine differentiation. Endocrine maturation will progress by up-regulating SUSD2 and lowering ECAD levels. Finally, we show that in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work constitutes a powerful approach to more precisely define intermediate cell population during conversion of multipotent progenitors into the 3 main human pancreatic cell types (acinar, ductal and endocrine) in vivo. As such, the data pave the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.

overall_design: 25 samples in triplicate except Elo at 9WD and GP2m at 11WD that are in duplicate (WD: weeks of development)

first: Cyrille

last: Ramond

first: Nicolas

last: Glaser

first: Claire

last: Berthault

first: Jacqueline

last: Ameri

first: Jeanette

last: Kirkegaard

first: Mattias

last: Hansson

first: Christian

last: Honoré

first: Henrik

last: Semb


title: Analysis of gene expression in colorectal cancer cells with DGKG overexpression

status: Public on Mar 01 2017

city: Sapporo

first: Hiromu

last: Suzuki

state: Hokkaido

address: S1, W17, Chuo-ku

department: Department of Molecular Biology

country: Japan

institute: Sapporo Medical University

summary: To clarify the role of diacylglycerol kinase gamma (DGKG) in colorectal cancer, we carried out a gene expression microarray analysis using HCT116 cells infected with adenoviral vectors which express LacZ, kinase-dead mutant of DGKG (DGKG-KD) or constitutively active form of DGKG (DGKG-CA).

overall_design: HCT116 cells were infected with an adenoviral vector for expressing LacZ, or DGKG-KD or DGKG-CA. Twenty-four hours after infection, total RNA was extracted and gene expression signatures were analyzed.

first: Masahiro

last: Kai


title: Comparison of the RNA expression profiles of CD14+ monocytes from human peripheral blood with derived macrophages (MACs) and osteoclasts (OCs) obtained by exposure with M-CSF and M-CSF/RANKL, respectively, during 5 and 20 days

status: Public on Jul 19 2017

city: Badalona, Barcelona

first: Esteban

last: Ballestar

state: N/A = Not Applicable

address: Ctra de Can Ruti, Camí de les Escoles s/n

country: Spain

institute: Josep Carreras Research Institute (IJC)

summary: The expression profiles of RNA of human CD14+ monocytes were compared with derived macrophages (MACs) and osteoclats (OCs) following M-CSF and M-CSF/RANKL incubation for 5 and 20 days using the SurePrint G3 Human Gene Expression Array (Agilent Technologies, CA, USA). This platform allows the interrogation of >36,000 transcrits and variants per sample. The samples were hybridized in the array following the manufacturer’s instructions.

overall_design: Total RNA isolated by standard procedures from CD14+ cells (total monocytes, MOs) corresponding to three sets of samples of monocytes (MOs) and derived MACs and OCs  following incubation with M-CSF or M-CSF/RANKL for 5 and 20 days.

first: Antonio

last: Garcia-Gomez

first: Tianlu

last: Li

first: Martin

last: Kerick

first: Francesc

last: Català-Moll

first: Natalia

middle: R

last: Comet

first: Javier

last: Rodríguez-Ubreva

first: Lorenzo

last: de la Rica

first: Miguel

last: Branco

last: Martín


title: Expression data from diagnostic samples of diffuse large B-cell lymphomas (DLBCL), follicular lymphoma (FL) and primary and relapsed transformed FL [SNP]

status: Public on Mar 08 2017

city: Aalborg

first: Julie

middle: Støve

last: Bødker

address: Sdr. Skovvej 15

department: Department of Heamatology

country: Denmark

institute: Aalborg University Hospital

summary: Comparison of gene expression profiles from diagnostic samples of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) to a patient case withsamples of primary and relapsed transformed FL.

overall_design: SNP6.0 arrays of saliva, primary and relapsed transformed follicular lymphoma from a patient case.

first: Marianne

middle: T

last: Severinsen

first: Tarec

last: El-Galaly

first: Rasmus

middle: F

last: Brøndum

first: Maria

middle: B

last: Laursen

first: Steffen

last: Falgreen

first: Mette

last: Nyegaard

first: Alexander

last: Schmitz

first: Victor

last: Iver

first: Preben

last: Johansen

first: Lasse

last: Jakobsen

first: Anna

last: Schönherz

first: Hanne

middle: D

last: Rasmussen

first: Linn

last: Reinholdt

last: Bøgsted

first: Karen

last: Dybkær

first: Hans

last: Johnsen


title: Gene expression in healthy and lesional psoriatic epidermis from human skin biopsies (laser capture microdissection): set 2

first: Denis

last: Mogilenko

first: David

last: Dombrowicz


title: Exposure of bovine oocytes to elevated insulin concentration (10 ug/ml) during in vitro maturation changes DNA methylation pattern in Day-8-blastocysts – an epigenetic study.

first: Marc-André

last: Sirard

summary: The aim was to study the potential effect of hyperinsulinemia on  gene expression and differential DNA-methylation of cow embryos by adding 10 µg/ml (INS10) during in vitro oocyte maturation.

overall_design: In total, 882 abattoir-derived oocytes (equally distributed between both treatments (INS10) and a control, (INS0)) produced 199 embryos in a period of 8 weeks. Cleavage blastocyst rates were recorded and embryos evaluated for stage and quality grade before individually frozen at -80 °C. 120 of the embryos were used for the methylome analysis, pooled in groups of 10 embryos with a similar distribution of embryos (pools adjusted for quality grade and developmental stage in order to avoid confounding effects in the results due to different embryo characteristics). The experiment was run in four replicates per treatment group.

first: Denise

last: Laskowski

first: Patrice

last: Humblot

first: Ylva

last: Sjunnesson

first: Renée

last: Båge

first: Göran

last: Andersson


title: Human hepatocellular carcinoma (HCC) and Cholangiocarcinoma (CCA) from Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC)

first: Xin

last: Wang

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


title: Influence of hexafluoro-2-propanol (HFIP) on lipopolysaccharides-induced inflammation in human microvascular endothelial cells of the lung

status: Public on Mar 14 2017

city: Zurich

first: Beatrice

last: Beck-Schimmer

address: Winterthurerstrasse 190

department: Institute of Physiology

country: Switzerland

institute: University of Zurich

summary:
Hexafluoro-2-propanol (HFIP), a water-soluble primary metabolite of the volatile anesthetic sevoflurane, has recently been shown to have favorable properties, improving overall survival in a chronic model of murine peritonitis. The mechanisms of protection provided by HFIP are currently unknown.
We therefore performed a gene expression analysis in an in vitro model of endotoxin-induced endothelial cell injury to gain insight into involved molecular mechanisms. Pathway analysis was subsequently performed using the GeneGo Metacore Framework.

overall_design: Human microvascular endothelial cells (HMVEC) were stimulated with 20mcg/mL lipopolysaccharides (LPS) to induce an inflammatory response. Hexafluoro-2-propanol (HFIP) was added to the cell culture medium containing LPS (phosphate-buffered saline, PBS, in controls) for a time period of 6 hours at a concentration of 8mmol/L. After 6 hous, total RNA from HMVEC was extracted and genome-wide RNA levels were assessed. In total, twelve samples with LPS- or PBS-stimulated HMVEC, from which six samples were treated with HFIP, were hybridized on microarrays . One sample of the LPS+HFIP group was lost due to technical reasons (hybridization procedure).

first: Martin

last: Urner

first: Inge

middle: K

last: Herrmann

first: Melanie

last: Hasler

first: Roman

last: Schimmer

first: Christa

last: Booy

first: Birgit

last: Z’graggen

first: Hubert

last: Rehrauer

last: Schläpfer

first: Fabian

last: Aigner

first: Richard

last: Minshall

first: Wendelin

last: Stark


title: Expression data of Hematopoietic progenitor and stem cells after 18h of culture with or without extracellular vesicles secreted by AFT stromal cells

city: Barcelona

first: Gregoire

last: Stik

state: select a state

address: 88 Dr Aiguader

institute: CRG

summary:
Hematopoietic progenitor and stem cells from bone marrow have been sorted by FACS (LSK, Lineage -, Sca1 + and cKit +) and co-culture during 18h without cytokines with or without extracellular vesicles (EV) secreted by AFT stromal cells.
We used microarray to detail the modification of gene expression level of LSK cells after contact with AFT Evs

overall_design: 3 conditions were analysed for gene expression by microarrays. LSK cells after cell sorting, LSK cells cultured 18h without EV and LSK cells cultured 18h with EVs derived from AFT cells. For each conditions 5 biological replicates have been used

first: Stik

last: Gregoire

first: Durand

last: Charles


title: Involvement of β-defensin 130 (DEFB130) in the macrophage microbicidal mechanisms for killing Plasmodium falciparum

status: Public on Feb 10 2017

city: Obihiro

first: Ryo

last: Takano

address: Inada-cho

department: National Research Center for Protozoan Diseases

institute: Obihiro University of Agriculture and Veterinary Medicine

summary: Understanding the molecular defense mechanism of macrophages and identifying their effector molecules against malarial parasites may provide important clues for the discovery of new therapies. To analyze the immunological responses of malarial parasite-induced macrophages, we used DNA microarray technology to examine the gene profile of differentiated macrophages phagocytizing Plasmodium falciparum-parasitized erythrocytes (iRBCs). The transcriptional gene profile of macrophages in response to iRBCs represented 168 down-regulated genes, which were mainly involved in the cellular immune response, and 216 upregulated genes, which were involved in cellular proteolysis, growth, and adhesion. Importantly, the specific upregulation of β-defensin 130 (DEFB130) in these macrophages suggested a possible role for DEFB130 in malarial parasite elimination. Strikingly, differentiated macrophages phagocytizing iRBCs exhibited an increase in intracellular DEFB130 levels and DEFB130 appeared to accumulate at the site of iRBC engulfment. Furthermore, DEFB130 synthetic peptide exhibited a modest toxic effect on P. falciparum in vitro and P. yoelii in vivo, unlike scrambled DEFB130 peptide, which showed no antiplasmodial activity. Our data broaden our knowledge of the immunological response of macrophages to iRBCs and shed light on a new target for therapeutic intervention.

overall_design: Human monocyte-derived macrophages were co-cultured with plasmodium falciparum-infected erythrocytes (iRBCs), saponin-treated iRBCs, or non-infected erythrocytes (RBCs).

first: Mohamad

last: Terkawi


title: Exposure of bovine oocytes to insulin concentration (0.1 and 10 ug/ml) during in vitro maturation changes DNA methylation pattern in Day-8-blastocysts - an epigenetic study

first: Marc-André

last: Sirard


title: Gene expression profiling of A549 human lung cancer cell line treated with allosteric inhibitors targeting atypical PKCs

status: Public on Jan 17 2017

city: Frankfurt am Main

first: Jose

middle: M.

last: Arencibia

address: Theodor-Stern-Kai 7

department: Medizinische Klinik I

institute: Universitätsklinikum Frankfurt

summary: There is a current and ongoing need for improved cancer therapies. It is anticipated that future personalized cancer treatment will involve combinations of selective targeted drugs. A number of protein kinases, including members of the AGC group of kinases such as atypical protein kinase C (PKCi and PKCz) are validated drug targets. The regulation of many AGC protein kinases is mediated by a pocket in the small lobe of the kinase domain, the PIF-pocket. We developed a new compound class and provide biochemical and crystallography data showing that such compounds bind to the PIF-pocket and allosterically inhibit aPKC activity. We demonstrated that a representative compound, PS432, is a selective inhibitor in vivo. PS432, inhibited the proliferation of cancer cell lines more potently than ATM, a PKCi inhibitor in clinical trials, whereas PS432 had only minor effects on PNT1A cells. Analysis of the transcriptome by microarray and the proteome by SILAC indicated that the major effects of PS432 were on the cell cycle, while FACS indicated an accumulation of cells in the G1-G0 phase. PS432 significantly inhibited the growth of A549 tumor xenografts at 2.5 mg/kg/day without significant side effects. PS432 chemical class has good pharmacological properties and is orally available. Notably, PS432 had synergistic effects with a proteasome and with PI3-kinase inhibitors. The data indicates that derivatives from this new chemical class have potential for application in combination therapies in future personalized cancer treatments.

overall_design: Analysis of gene expression changes in A549 cells after treatment with allosteric inhibitors targeting atypical PKCs.

first: Ricardo

last: Biondi


title: Differences prevailing in bovine in vitro produced blastocysts in the view of their post-transfer phenotypes three days ahead of implantation

status: Public on Mar 23 2017

summary: Embryo transfer is largely used in cattle and classically performed at D7 (or D8) using unsorted D7 (or D8) blastocysts produced in vivo, or in vitro in defined media without serum or feeders. Outdated systems including serum and co-culture were however of interest for research purposes. We thus wondered whether embryos that would form a blastocoel at different times after fertilisation (D6 to D8) and stay in culture for up to 2 additional days (D6+1, D6+2, D7+1) would equally develop in vivo after temporary transfer to oestrus-synchronised recipients. Globally alike, those that survived up to D18 reached primitive streak stages and elongated to filamentous sizes similarly to in vivo (D18) or in vitro controls (classical D7-T7). Recovery rate differed between D6 and D8 embryos that were immediately transferred (58 vs 25% in D6-T6 vs D8-T8). With a reduced but intermediate survival (33%), the D6 embryos that stayed 2 more days in culture produced 7 times more IFN-tau at D18 than the immediately transferred D6 embryos. At the end of the culture, D6+2 embryos also displayed the higher number of differences with the D6 blastocysts. A “+1” phenotype emerged from the D6+1 and D7+1 embryos, that shared a larger gene set enrichment than the blastocysts they derived from, possible sign of a similar adaption to the in vitro environment. To the best of our knowledge, this is the first time that this culture system (B2, serum, co-culture) is used to study its impacts on the embryonic transcriptome prior to transfer. Initially reputed as beneficial to produce more expanding and hatching blastocysts, this culture system generated blastocysts that all dissembled in vivo developed ones (D7). Despite a loss of 40 to 60% in the two weeks after ET, no dying (vs surviving) signature was detectable in any of the transferred groups (D6, D6+2, D7+1, D8); was it rather a matter of developmental “pause”? Whether molecular differences prevailing to transfer partly reflected those induced by unfavourable conditions (or diapause) was therefore assessed.

overall_design: After in vitro fertilization, bovine zygotes were cultured in batch of 25 embryos in 50 µl drops, at 39°C with 5% O2, 5% CO2 and 90% N2 until blastocoel formed at day 6 (condition “6”) or day 8 (condition “8”). One and two days after day 6, early formed blastocysts were also collected, not as “day 8 forming ones” but as “cultured 1 or 2 more days” (condition “6+1 and 6+2”). One days after day 7, early formed blastocysts were also collected, not as “day 8 forming ones” but as “cultured 1 more day” (condition “7+1”)

first: I

last: Hue

last: Dufort

first: A

last: Vitorino Carvalho

first: D

last: Laloe

first: S

last: Degrelle

first: C

last: Viebahn

first: M-A


title: Transcriptional profiling of subcutaneous adipose tissue of morbidly obese subjects before and after 2 years of bariatric surgery.

status: Public on Mar 16 2017

city: Malaga

first: Eduardo

last: García-Fuentes

state: Malaga

address: Plaza del Hospital Civil s/n

institute: Instituto de Investigación Biomédica de Málaga (IBIMA)/Hospital Regional Universitario, Málaga, Spain.

summary: Transcriptional profiling of subcutaneous adipose tissue before and after 2 years of bariatric surgery. This type of surgery produce a masive weight loss in morbidly obese subjects, and improve the comorbidities associated to obesity. Goal was to determine the effects of bariatric surgery on the gene expression of subcutaneous adipose tissue.

overall_design: Prospective study in morbidly obese subjects: before and after bariatric surgery. Biological replicates: 8 morbidly obese women before bariatric surgery, and the same subjects  (n=8) 2 years after bariatric surgery.

first: Juan

last: Gonzalez-Plaza

first: Carolina

last: Gutierrez-Repiso

first: Sara

last: Garcia-Serrano

first: Francisca

last: Rodriguez-Pacheco

first: Lourdes

last: Garrido-Sanchez

first: Concepcion

last: Santiago-Fernandez

last: Garcia-Arnes

first: Francisco

last: Moreno-Ruiz

first: Alberto

last: Rodriguez-Cañete

last: Garcia-Fuentes


title: Parallel SNP and CGH arrays of cytogenetic normal MDS patients and detection of alterations present in CD3+ T cells and bone marrow cells

status: Public on Jan 01 2017

city: Badalona

first: Mar

last: Mallo

address: Ctra de Can Ruti, s/n, camí de les escoles. Edifici IMPPC

institute: Josep Carreras Leukaemia Research Institute

summary: Fifty per cent of myelodysplastic syndromes has a normal karyotype. Genomic microarray allows the detection of alterations in this subset of cases. There to different types of genomic arrays: CGH and SNP array. In this study we want to compare both platforms and check the ability

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from bone marrow or peripheral blood and, in some cases, also lymphocytes CD3 isolated from peripheral blood samples.
Copy number analyses of Affymetrix 6.0 SNP arrays were performed for 22 MDS with normal karyotype. There are also 7 samples from lymphocytes CD3 isolated from peripheral blood, which were used as germ-line DNA (control).

first: Francesc

last: Solé

first: Sabrina

last: Classen

first: Brigitte

last: Royer-Pokora


title: SNP profiles of 50 HB tumors

status: Public on Jan 30 2017

city: Houston

first: Toni-Ann

last: Mistretta

state: TX

address: 1 Baylor Plaza, BCM 315

department: Pathology

institute: Baylor College of Medicine

summary: Hepatoblastoma (HB) is the most common liver cancer in children, but few pre-treatment tumors have been molecularly profiled. Consequently, there are no validated prognostic or therapeutic biomarkers for HB patients. We report on molecular analysis of 88 clinically-annotated HB tumors. This analysis pointed to three risk-stratifying molecular subtypes—low, intermediate and high risk—that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways. High-risk tumors are characterized by high NFE2L2 activity and LIN28B, HMGA2, SALL4 and AFP expression, low let-7 expression and HNF1A activity, and high coordinated expression of oncofetal proteins and stem cell markers. Tests on a 35 HB validation set supported these genes as prognostic biomarkers.

overall_design: 88 clinically-annotated frozen pre-clinical HB specimens with corresponding surgical pathology reports were included in the study (Table S1) following histological review. Specimens and clinical annotation were obtained from the COG Tumor Biospecimen Bank in Columbus, Ohio, the Pediatric Oncology Group Hepatoblastoma Biology Study P9346, and Texas-based institutions, under IRB-approved protocols. Whole exome sequencing (WES) was performed on 35 tumors for which matching normal DNA – either a blood sample or tumor-adjacent normal liver – was available (Table S2). Targeted sequencing of the CTNNB1 and NFE2L2 genes and the TERT promoter was completed on all 88 tumors. DNA from 47 HBs, including all 35 samples subjected to WES, was also analyzed by SNP array. RNA and miRNA expression profiling were performed on 50 and 57 tumors, respectively.

first: Pavel

last: Sumazin

first: Yidong

last: Chen

first: Lisa

last: Treviño

first: Stephen

last: Sarabia

first: Oliver

last: Hampton

first: Kayuri

last: Patel

first: Barry

last: Zorman

first: Patrick

last: Thompson

first: Andras

last: Heczey

first: Sarah

last: Comerford

first: David

last: Wheeler

first: Murali

last: Chintagumpala

first: Rebecka

last: Meyers

first: Dinesh

last: Rakheja

first: Milton

last: Finegold

first: Gail

last: Tomlinson

first: D

middle: W

last: Parsons

first: Dolores

last: López-Terrada


title: Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells [GenomeWideSNP_6]

status: Public on Dec 31 2016

city: Berlin

first: Lars

last: Bullinger

address: Augustenburger Platz 1

department: Hematology, Oncology and Tumorimmunology

institute: Charité

summary: Inhibition of the HSP90 chaperone results in depletion of many signaling proteins that drive tumorigenesis, such as downstream effectors of KRAS, the most commonly mutated human oncogene. As a consequence, several small-molecule HSP90 inhibitors are being evaluated in clinical trials as anticancer agents. To prospectively identify mechanisms through which HSP90-dependent cancer cells evade pharmacologic HSP90 blockade, we generated multiple mutant KRAS-driven cancer cell lines with acquired resistance to the purine-scaffold HSP90 inhibitor PU-H71. All cell lines retained dependence on HSP90 function, as evidenced by sensitivity to short hairpin RNA-mediated suppression of HSP90AA1 or HSP90AB1 (also called HSP90α and HSP90β, respectively), and exhibited two types of genomic alterations that interfere with the effects of PU-H71 on cell viability and proliferation: (i) a Y142N missense mutation in the ATP-binding domain of HSP90α that co-occurred with amplification of the HSP90AA1 locus, (ii) genomic amplification and overexpression of the ABCB1 gene encoding the MDR1 drug efflux pump. In support of a functional role for these alterations, exogenous expression of HSP90α Y142N conferred PU-H71 resistance to HSP90-dependent cells, and pharmacologic MDR1 inhibition with tariquidar or lowering ABCB1 expression restored sensitivity to PU-H71 in ABCB1-amplified cells. Finally, comparison with structurally distinct HSP90 inhibitors currently in clinical development revealed that PU-H71 resistance could be overcome, in part, by ganetespib (also known as STA9090) but not tanespimycin (also known as 17-AAG). Together, these data identify potential mechanisms of acquired resistance to small molecules targeting HSP90 that may warrant proactive screening for additional HSP90 inhibitors or rational combination therapies.

overall_design: SNP arrays were profiled in PU-H71-sensitive and resistant A549, MDA-MB-231 and SW480 cell lines.

first: Arefeh

last: Rouhi

first: Stefan

last: Fröhling

first: Claudia

last: Scholl


title: Regulated gene expression for breast cancer cells treated with NLC-Citral for 48 hours

city: Serdang

first: Noraini

last: Nordin

state: selangor

address: Animal Tissue Culture Lab

department: Cell Biology

country: Malaysia

institute: University Putra Malaysia

summary: To further develop our gene expression study, we have employed the microrarray expression to study the regulate gene expression on breast cancer cells after 48 hours of treatments

overall_design: The regulated genes in different pathways were measured at 48 hours post treatment (NLC-Citral) as compared to the control treatments (Citral, or NLC-Blank).

first: Noorjahan

last: Alitheen


title: microRNA expression profiling among WTX low human gastric cancer tissues and matched adjacent WTX high normal gastric mucosa

status: Public on Feb 15 2017

city: Tianjin

first: Shan

last: Gao

address: No 94, weijin road

country: China

institute: Nankai University

summary: Comparing to matched normal mucosa, WTX was lost in most of human gastric cancers (Zhang et al., 2016). We analyzed the microRNA expression profiling among WTX low human colorectal cancer tissues and matched adjacent WTX high normal colorectal mucosa. The aimed to identify the unique signature of miRNAs which related to WTX loss in human colorectal cancers.

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus
Human gammaherpesvirus 8
Macacine gammaherpesvirus 4
Betapolyomavirus macacae

overall_design: We performed microRNA expression profiling on 5 patients who were WTX low in gastric cancers and WTX high in matched normal mucosa samples.

first: Qingling

last: Zhang

first: Guifang

last: Zhu

first: Huilin

last: Niu

first: Qiming

last: Wang


title: Comparative gene expression profiling of cutaneous B cell lymphomas

first: Anne

last: Janin

address: 1 Av C Vellefaux

institute: University Paris 7, INSERM, APHP

summary: The oncogenic microRNA 17-92 cluster is involved in the lymphomagenesis of nodal and systemic B cell lymphomas, but has not been studied so far in primary cutaneous B cell lymphomas. We performed the quantitative analysis of miR-17-92 cluster and its paralogs miR-106a-363 and miR-106b-25 in 22 primary cutaneous diffuse large B-cell lymphomas-leg type (PCLBCL-LT) and 22 primary cutaneous follicle center lymphomas (PCFCL). Mir-20a and miR-106a were overexpressed in PCLBCL-LT compared to PCFCL. Multivariate Cox analysis showed that higher miR-20a and miR-20b were associated with poorer disease-free survival and poorer overall survival, independently of histological type. Gene expression profiling showed underexpression of 8 candidate target genes of miR-20a, miR-20b and miR-106a in PCLBCL-LT compared to PCFCL. Among the candidate target genes, PTEN, NCOA3 and CAPRIN2 were confirmed to be underexpressed in PCLBCL-LT using quantitative RT-PCR of laser-microdissected tumor cells. In multivariate Cox analysis, lower PTEN mRNA expression level was associated with poorer disease-free survival, independently of the histological type. Altogether, this molecular and bioinformatics study of patients’ skin biopsy samples showed that the oncogenic miR-17-92 cluster is involved in cutaneous B cell lymphoma progression, and that the down-regulation of its target gene PTEN is associated with poorer disease-free survival.

overall_design: 10 skin samples from patients were analyzed. 6 were PCLBCL-leg type and 4 PCFCL.

first: Maxime

last: Battistella

first: Martha

last: Romero

first: Luis

last: Castro Vega

first: Guillaume

last: Gapihan

first: Fatiha

last: Bouhidel

first: Hervé

last: Bachelez

first: Jean-Paul

last: Feugeas


title: Differentiated Demographic Histories and Local Adaptations between Sherpas and Tibetans

city: Shanghai

first: Chao

address: 320 Yueyang Road

institute: Partner Institute for Computational Biology (PICB)

summary: To revisit and address four major unresolved issues regarding prehistory, especially the Neolithic history of Sherpas and Tibetans and their hypoxic adaptation: (i) whether they are two genetically different ethnic groups; (ii) whether population substructures exist in either of the two groups; (iii) how long they have diverged from their ancestral group and when the two separated groups started to re-contact by population admixture; and (iv) whether the two groups share major high-altitude adaptation mechanisms. The careful and systematical analysis of these newly sequenced genomes, together with available genotyping data can provide further insight into the genetic origins of Sherpas and Tibetans and uncover their different adaptive mechanisms.

overall_design: We generate or collect genome-wide data in 111 Sherpas (Tibet and Nepal) and 177 Tibetans (Tibet and Qinghai), and analyze these together with available data from present-day human populations. This current dataset includes 65 Chinese Sherpas and 18 Tibetans. To obtain the genotypes for other samples that collected in our analysis, please refer to  Peng et al, MBE 2011, Xu et al, MBE 2011, Lou et al, AJHG 2016, Simonson et al, Since 2010, Lu et al, AJHG 2016 and Jeong et al, Nat Comm 2014; and contact the corresponding authors of the above publications.

first: Yan

last: Lu

first: Haiyi

last: Lou

first: Shuhua

last: Xu


title: Genomic copy number variations in the genomes of leukocytes predict prostate cancer clinical outcomes

status: Public on Feb 09 2017

city: Pittsburgh

first: Shuchang

last: Liu

state: Pennsylvania

address: 130 De Soto Street

institute: University of Pittsburgh

summary: Accurate prediction of prostate cancer clinical courses remains elusive. In this study, we performed whole genome copy number analysis on leukocytes of 273 prostate cancer patients using Affymetrix SNP6.0 chip. Copy number variations (CNV) were found across all chromosomes of the human genome. An average of 152 CNV fragments per genome was identified in the leukocytes from prostate cancer patients. The size distributions of CNV in the genome of leukocytes were highly correlative with prostate cancer aggressiveness. A prostate cancer outcome prediction model was developed based on large size ratio of CNV from the leukocyte genomes. This prediction model generated an average prediction rate of 75.2%, with sensitivity of 77.3% and specificity of 69.0% for prostate cancer recurrence. When combined with Nomogram and the status of fusion transcripts, the average prediction rate was improved to 82.5% with sensitivity of 84.8% and specificity of 78.2%. In addition, the leukocyte prediction model was 62.6% accurate in predicting short prostate specific antigen doubling time. When combined with Gleason’s grade, Nomogram and the status of fusion transcripts, the prediction model generated a correct prediction rate of 77.5% with 73.7% sensitivity and 80.1% specificity. To our knowledge, this is the first study showing that CNVs in leukocyte genomes are predictive of clinical outcomes of a human malignancy.

overall_design:
Prostate cancer samples were obtained from University of Pittsburgh Medical Center Tissue Bank. These samples were collected from 1998-2012. 273 buffy coat samples from prostate cancer patients were analyzed.
Among these samples, 143 samples were followed at least 90 months, 35 patients were non-recurrent for 90 months or more, 55 patients experiencing recurrence with short PSADT (PSA doubling time <4 months), and 53 patients experiencing recurrence with long PSADT (PSA doubling time >15 months) after radical prostatectomy.

first: Jian-Hua

last: Luo

middle: P

last: Yu


title: Characterisation of the genomic landscape of CRLF2 deregulated acute lymphoblastic leukaemia

status: Public on Feb 24 2017

city: Newcastle upon Tyne

first: Lisa

last: Russell

address: Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Level 6, Herschel Building, Brewery Lane

institute: Newcastle University

summary:
Deregulated expression of the type I cytokine receptor, CRLF2 (CRLF2-d), is observed in 5-15% of B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), is associated with activation of the JAK/STAT pathway and has an inferior outcome compared to those with good risk cytogenetics. We aimed to determine the clinical and genetic landscape of CRLF2-d ALL using genomic approaches including karyotyping, fluorescence in situ hybridisation, whole genome and whole exome sequencing. The clinical and demographic features of CRLF2-d patients were characteristic of BCP-ALL. Patients with IGH-CRLF2 were older than those with P2RY8-CRLF2 (4yrs v 14yrs, p<0.001), while the incidence of CRLF2-d among Down syndrome patients was high (31%). CRLF2-d co-occurred with established primary chromosomal rearrangements but the majority (72%) had B-other ALL. The copy number alteration (CNA) profile was similar to B-other ALL, although CRLF2-d patients harboured higher frequencies of IKZF1 (43% v 23%) and BTG1 deletions (15% v 2%). There were differences in the CNA profile between IGH-CRLF2 and P2RY8-CRLF2 patients: deletions of IKZF1 (71% v 33% p<0.001), BTG1 (31% v 9%, p=0.004) and ADD3 (46% v 13%, p=0.008). A novel gene fusion, USP9X-DDX3X was discovered in 18% of CRLF2-d ALL. Pathway analysis of the mutational profile revealed novel involvement of the focal adhesion pathway. In conclusion, CRLF2-d defines a discrete subtype of B-other ALL, characterised by a distinctive profile of cooperating abnormalities, which drive leukaemogenesis in conjunction with CRLF2-d. Although the functional relevance of many of these abnormalities are unknown, they likely activate alternative pathways, which may represent novel therapeutic targets.
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or remission bone marrow.

overall_design: DNA copy number analysis of 26 acute lymphoblastic leukaemia samples (11 diagnostic only, 15 matched diagnostic and remission samples) was perform using the Affymetrix Genome-Wide Human SNP6.0 Array.

first: L


title: Patterns of Copy-Number Loss in Gastric Adenocarcinoma

city: Singapore

first: Ioana

last: Cutcutache

address: 8 College Rd

department: Centre for Computational Biology

institute: Duke-NUS

summary: Genome-wide DNA copy number profiling of gastric tumors and matched non-maligant samples to determine patterns of copy-number loss. Other samples included in this study can be found under accession number GSE31168.

overall_design: Affymetrix SNP6 arrays were performed according to the manufacturer's instructions on DNA extracted from 14 tumors and 14 matched non-malignant samples.

first: Steven

last: Rozen

first: Patrick

last: Tan


title: A Curcumin-Based CBP HAT Inhibitor Modulates the Transcription Functions of Tumor Suppressor p53

status: Public on Nov 24 2016

city: New York

first: Zichen

last: Wang

state: NY

address: 1468 Madison Ave

department: Pharmacological Sciences

institute: Icahn School of Medicine at Mount Sinai

summary: Coactivator CREB-binding protein (CBP) regulates the transcription program of p53, which orchestrates cellular responses to a wide-range of stress conditions that cause genomic instability. Given the ability of CBP to regulate transcription by multiple mechanisms, the biological significance of its acetylation-directed functions may not be fully clear. The present study demonstrates the development of a curcumin-derived modulator of CBP histone acetyl-transferase (HAT) activity, CM354, which inhibits acetylation of p53 on lysine 382, acetylation of histone H3K27 and autoacetylation of CBP. These epigenetic changes are concomitant with downregulation of p53 and CBP functions, which facilitate the presence of histone methyl transferase, Enhancer of zeste homolog 2 (EZH2), on CDKNI1A/p21 promoter, thereby, enhancing the level of trimethylation on H3K27. Treatment with CM354 results in the activation of PARP and the abrogation of cellular growth. Genome-wide network analysis depicts that CM354 could alter cell-fate by enrichment of chromatin H3K27 methylation and activation of the polycomb group of proteins. Though previously reported HAT inhibitors act at higher concentrations and lack cell permeability, the present study shows the impact of modulating endogenous CBP HAT activity on chromatin landscape and p53 functions.

overall_design: Gene expression in human U2OS cell lines after treatment of CM354 (1.5uM), Doxorubicin (300ng/ml), the combination of the two drugs, as well as the untreated control was measured. Each condition is performed in duplicates.

first: Avi

last: Ma'ayan

first: Shiraz

last: Mujtaba


title: Gene expression in blood of obese pediatric patients

status: Public on Sep 30 2016

city: Krakow

first: Marcin

last: Piechota

address: Smetna 12

department: Molecular Neuropharmacology

country: Poland

institute: Institute of Pharmacology PAS

summary:
Differences between groups of children with obesity and healthy controls.
The objective of the study was to identify new molecular markers of hypertension in obese pediatric patients. A total of 12 children with obesity and 20 healthy children were enrolled in the study. The whole genome expression was assessed in leukocytes using GeneChip® Human Gene 1.0 ST microarray.

overall_design: Microarray comparison of genome expression in blood mononuclear cells between two groups of children (obese, healthy).

first: S

last: Skoczen


title: Gene profiling of the zone of altered morphology of choriodecidua overlying the cervix before labor in preterm samples

status: Public on Nov 25 2016

city: Paris

first: Céline

last: Méhats

address: 24 rue du Faubourg St jacques

institute: Inserm

summary: To characterize the molecular signature of the choriodecidua remodeling in third trimestry of pregnancy before labour, we have employed whole genome microarray expression profiling. Fetal membranes were collected from women undergoing a emergency cesarean delivery before term (before 32 weeks of gestation and between 33-35 weeks of gestation), for preeclampsia and/or in utero growth retardation. During surgery, a Kocher's forceps was placed on membranes overlying the cervix and the area surrounding the forceps was dissected in the operating room under sterile conditions, the site, pinched by the forceps, being discarded. Fetal membranes in a remote zone were also sampled. Isolated RNAs were hybridized to the Aligent SurePrint G3 Human GE 8x60K Microarray.

overall_design: Microarray analysis was conducted on four distincts groups overlying the cervix and remote from the cervix before 32 weeks of gestation (XPZ) or between 33 and 35 weeks of gestation (PZ) composed of three pools for the XPZ samples and two pools for the PZ samples, each pool consisted of three samples from three different women.

first: Louis

last: Marcellin

first: Sébastien

last: Jacques


title: Effect of FGFC on human embryonic stem cells

city: Tsukuba

first: Yuzuru

last: Ito

state: Ibaraki

address: Central 6, Higashi 1-1-1

department: Biotechnology Research Institute for Drug Discovery

institute: National Institute of Advanced Industrial Science and Technology (AIST)

summary: Fibroblast growth factors (FGFs) are essential for maintaining self-renewal in human embryonic stem cells and induced pluripotent stem cells. Recombinant basic FGF (bFGF or FGF2) is conventionally used to culture pluripotent stem cells; however, because of bFGF instability, repeated addition of fresh bFGF into the culture medium is required in order to maintain its concentration. In this study, we demonstrate that a heat-stable chimeric variant of FGF, FGFC, can be successfully used for maintaining human pluripotent stem cells. FGFC is a chimeric protein composed of human FGF1 and FGF2 domains that exhibits higher thermal stability and protease resistance than do both FGF1 and FGF2. Both human embryonic stem cells and induced pluripotent stem cells were maintained in ordinary culture medium containing FGFC instead of FGF2. Comparison of cells grown in FGFC with those grown in conventional FGF2 media, showed no significant differences in terms of the expression of pluripotency markers, global gene expression, karyotype, or differentiation potential into the three germ lineages. We therefore propose FGFC, as an effective alternative to FGF2, for maintenance of human pluripotent stem cells.

overall_design: Gene expressions in human ES and iPS cells were measured at 4-50 days cultured with FGFC, in place of bFGF.

first: Yasuko

last: Onuma


title: Impact of IL-27 on hepatocyte antiviral gene expression and function

status: Public on Nov 09 2016

city: Oxford

first: Timothy

last: Hinks

state: United Kingdom

address: John Radcliffe Hospital, Headley Way, Oxford

department: NDM Experimental Medicine - New College

institute: University of  Oxford

summary:
IL-27 has been shown to play a role in modulating functions of diverse cell types like Th1, Th2, NK and B cells demonstrating both pro and anti-inflammatory roles. It is also capable of inducing STAT1, STAT3 and ISG's. To investigate the role of IL-27 on hepatocytes, Huh7.5 cells were treated with Il-27 and analysed the differentially expressed genes by microarray analysis.
Microarray analysis showed that the upregulated genes belonged to antigen presentation and DNA replication pathways and involved strong upregulation of CXCL-10 a gene associated with liver inflammation.

overall_design: 28 Huh7.5 Samples stimulated with IFNA, IL10, IL17, IL22, IL27 and IL28 for 24 and 72 hrs.

first: Narayan

last: Ramamurthy

first: Sara

last: Boninsegna

first: Rebecca

last: Adams

first: Natasha

last: Sahgal

first: Helen

last: Lockstone

first: Dilair

last: Baban

first: Emanuele

last: Marchi

first: Paul

last: Klenerman


title: Lung cell responses to wood combustion aerosols

status: Public on Jan 13 2017

city: Munich

first: Sebastian

last: Oeder

address: Biedersteinerstr. 29

department: Center for Allergy and Environment (ZAUM)

institute: Technische Universität München

summary: Human A549 lung epithelial cells were exposed directly at the air-liquid interphase towards combustion aerosols of wood burning. The goal was to compare the responses towards different wood and burning conditions. Beech log woods were burnt in a modern masonry heater, soft wood pellets were burnt in a pellet boiler.

overall_design: The lung cells were exposed 3 times to each combustion aerosol (beech or pellet). The duration of the exposure was 4h. The cells were seeded into transwell-inserts 24h before exposure. Within each exposure 3 transwell-inserts were exposed to the complete aerosol and 3 transwell-inserts were exposed to clean air. Effects in the aerosol-treated cells were referenced against the corresponding clean air controls (from the same day).

first: Jeroen

last: Buters

first: Renate

last: Effner


title: Integrated Analysis of Genome-Wide DNA Copy Number and Gene Expression with Patient Outcomes in Esophageal Adenocarcinoma [Copy Number]

status: Public on Nov 01 2016

city: Boston

first: Tony

middle: Edward

last: Godfrey

state: Massachusetts

address: 700 Albany Street

department: Surgery

institute: Boston University

type: Genome binding/occupancy profiling by SNP array

summary: Esophageal adenocarcinoma (EAC) is now the most common esophageal malignancy in the United States with >15,000 new cases per year. Prognosis for patients with EAC is poor due to both late diagnosis and early metastasis to lymph nodes. The goal of this study was to perform an integrated analysis of genome-wide DNA copy number changes, gene expression and patient clinical data in order to identify events and genes associated with clinical endpoints or that may play a key role in EAC development and therefore provide potential therapeutic targets. Specifically, we report on a series of 116 EAC specimens studied using Affymetrix SNP 6.0 and U133 Plus 2 GeneChip arrays plus additional cohorts of 73 and 114 EAC patients whose tumors were analyzed using Affymetrix StyI 250K arrays and fluorescence in-situ hybridization (FISH) respectively.  Integration of this genomic data with clinical information and outcomes  enabled identification of copy number changes and coordinate gene expression events that are associated with patient prognosis, that validate known or suspected oncogenes and tumor suppressor genes and that also facilitate identification of novel, putative driver genes in large regions of copy number gain and loss. These findings add to our understanding of the basic biology of EAC and provide a guide for development of novel prognostic tools and therapies.

overall_design: Copy number analysis of Affymetrix 250K Sty (n=73) and SNP6.0 arrays (n=116) was performed for 189 esophageal adenocarcinoma samples. There are also 72 samples from normal squamous esophageal epithelium, which were used as references for copy number inference for the 250K Sty array data and 15 samples from white blood cells used as references for copy number inference for the SNP6.0 array data.

first: Santhoshi

last: Bandla


title: Copy number variant (CNV) and Single nucleotide polymorphism (SNP) of UCLA hESC lines

status: Public on Dec 15 2016

city: Los Angeles

first: Kathrin

last: Plath

state: CA

address: 615 Charles E. Young Drive South

institute: University of California, Los Angeles

summary: Female human ESC-lines can carry active X-chromosomes (Xa) or an XIST-RNA- coated inactive X-chromosome (Xi XIST+ ). Additionally, many ESC-lines have abnormal X-chromosome-inactivation (XCI)-states where the Xi no longer expresses XIST-RNA and has transcriptionally active regions (eroded Xi=Xe). The fate of each XCI-state upon differentiation is unclear because individual lines often contain a mixture of XCI-states. Here, we established homogeneous XiXa, XeXa, and XaXa ESC-lines. We found that these lines were unable to initiate XIST-expression and X-chromosome- wide silencing upon differentiation indicating that the ESC XCI-state is maintained in differentiated cells. Consequently, differentiated XeXa and XaXa cells displayed higher levels of X-linked gene-expression than XiXa cells. Although global transcriptional compensation between X-chromosomes and autosomes is not required for female ESC-differentiation, the degree of X-chromosome- silencing influences differentiation efficiencies. Our data suggest that the Xi XIST+ Xa state is inherent to human ESCs and that all other XCI-states, including XaXa, are abnormal and arise during ESC-derivation or maintenance.

overall_design: Genomic DNA from ESC lines and differentiated cardiomyocyte derivatives was extracted according to standard protocols. Genomic stability was analyzed on an Affymetrix genome-wide SNP 6.0 array as per manufacturers instructions at the UCLA microarray core. The analysis was performed as described (Greenman et al., 2010).

first: Sanjeet

last: Patel

first: Giancarlo

last: Bonora

first: Rachel

last: Kim

first: Constantinos

last: Chronis

first: Anna

last: Sahakyan

first: Justin

last: Langerman

first: Sorel

last: Fitz-Gibbon

first: Liudmilla

last: Rubbi

first: Rhys

last: Skelton

first: Reza

last: Ardehali

first: Matteo

last: Pellegrini

first: William

last: Lowry

first: Amander

last: Clark


title: The self-renewal of gastric cancer stem cells is regulated by a specific collaboration between the microenvironment and the genetic condition.

city: Daejeon

first: sujin

last: Baek

address: Gwahank-ro 125

department: MGRC

country: South Korea

institute: KRIBB

summary: Because cancer stem cells already had genetic and epigenetic alterations which can affect the self-renewal, we tried to characterize genetic and epigenetic changes of the gastric cancer stem cells. To do this, we performed SNP array, MBD sequencing and RNA sequencing.

overall_design: copy number alteration profiles of Normal tissue and gastric cancer stem cell were generated by SNP6.0 Array, in three patients(csc1,csc2,csc3).

first: Sae-Ock

last: Oh

first: Seon-Young

first: Su-Jin


title: Differential responses of choroidal melanocytes and uveal melanoma cells to low oxygen conditions

status: Public on Sep 10 2016

city: Quebec City

first: Solange

last: Landreville

address: 1050 chemin Sainte-Foy, Room H2-02

department: Ophthalmology

institute: Université Laval

summary:
PURPOSE: Tissue culture is traditionally performed at atmospheric oxygen concentration (21%), which induces hyperoxic stress, as endogenous physiologic oxygen tension found in tissues varies between 2% and 9%. This discrepancy may lead to misinterpretation of results and may explain why effects observed in vitro cannot always be reproduced in vivo and vice versa. Only a few studies have been conducted in low physiologic oxygen conditions to understand the development and differentiation of cells from the eye.
METHODS: The aim of this study was to investigate the growth and gene expression profile of melanocytes from the choroid permanently exposed to 21% (hyperoxic) or 3% (physiologic) oxygen with proliferation assays and DNA microarray. The cellular behavior of the melanocytes was then compared to that of cancer cells.
RESULTS: The gross morphology and melanin content of choroidal melanocytes changed slightly when they were exposed to 3% O2, and the doubling time was statistically significantly faster. There was an increase in the percentage of choroidal melanocytes in the active phases of the cell cycle as observed by using the proliferation marker Ki67. The caveolin-1 senescence marker was not increased in choroidal melanocytes or uveal melanoma cells grown in hyperoxia. In comparison, the morphology of the uveal melanoma cells was similar between the two oxygen levels, and the doubling time was slower at 3% O2. Surprisingly, gene expression profiling of the choroidal melanocytes did not reveal a large list of transcripts considerably dysregulated between the two oxygen concentrations; only the lactate transporter monocarboxylate transporter (MCT4) was statistically significantly upregulated at 3% O2.
CONCLUSIONS: This study showed that the oxygen concentration must be tightly controlled in experimental settings, because it influences the subsequent cellular behavior of human choroidal melanocytes.

overall_design: Three primary cultures of choroidal melanocytes cultured at two percentages of oxygen are analyzed by gene profiling.

first: Cindy

last: Weidmann

first: Jade

last: Pomerleau

first: Laurence

last: Trudel-Vandal


title: Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia [neutrophils]

status: Public on Sep 09 2016

city: Chapel Hill

first: Claire

last: Doerschuk

state: NC

address: Marsico Hall 7205 CB#7248

department: Marsico Lung Institute

institute: University of North Carolina at Chapel Hill

summary:
The transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs.
These studies tested the role of Nrf2 during pneumonia induced by Streptococcus pneumoniae (SP) at 24 hours in mice and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils.

overall_design: Lung neutrophils were isolated from wildtype (WT) and Nrf2 null mice 24 hours after intratracheal instillation of Streptococcus pneumoniae (SP) or an equivalent volume of phosphate-buffered saline (PBS).  Gene expression was profiled using Affymetrix Mouse Gene 2.1 ST arrays (Santa Clara, CA, USA).

first: John

middle: C

last: Gomez

first: Hong

last: Dang


title: Insights into the combined action of SAHA (vorinostat) and Mithramycin A in Sézary cells through gene expression profiling

status: Public on Dec 12 2016

city: MARSEILLE

first: CHELBI

last: RABIE

address: Parc Scientifique et Technologique de Luminy, 163 avenue de Luminy, Case 906, 13288 Marseille cedex 9

institute: CIML

summary:
Suberoyl Anilide Hydroxamic Acid (SAHA), also named under Vorinostat, is an inhibitor of class I and II histone deacetylases (HDACi) approved by the USA Food and Drug Administration (FDA) for the treatment of advanced and refractory cutaneous T-cell lymphomas (CTCL). Its limited efficacy led to its use in various combination therapies. Given that SAHA modifies the expression of many genes under control of Sp1 (or Sp3) transcription factors, we investigated here its association to the FDA-approved anticancer antibiotic Mithramycin (MitA), a direct inhibitor of the binding of Sp1 family factors to GC-rich DNA promoters. We found that MitA alone, similar to SAHA, efficiently induced the apoptotic death of peripheral blood lymphocytes from Sézary syndrome (SS) patients while the two drugs in combination demonstrated a synergistic effect that could even overcome the resistance to MitA used in mono-treatment. A deep analysis of gene expression profiling suggested that SAHA and MitA, either independently or synergistically, counteracted many intertwined pro-survival pathways mis-regulated in SS cells as TCR, Notch1, mTOR, PI3K/Akt, JAK/STAT and b-catenin pathways, as well as the resistance of these tumors to intrinsic and extrinsic apoptosis. This analysis also suggested that SAHA/MitA combined treatment might efficiently oppose to the abnormal adhesion, migration and invasive properties of SS cells, in addition their immunosuppressive behavior. Finally, from a mechanistic point of view, our observations strongly support a major role of additive or synergistic epigenetic modifications in the combined effect of the two drugs, with a rather limited contribution of Sp1 (or Sp3)-mediated transcriptional regulation.
Peripheral blood tumor cells from Sézary patients were expanded in vitro and treated with SAHA and/or MitA previous to RNA isolation and Microarray processing. Deep analysis of gene expression profiling suggested that SAHA and Mithramycin A (MitA), either independently or synergistically, counteracted many interwined pro-survival pathways mis-regulated in Sézary cells, as well as abnormal adhesion, invasion and invasive properties. Data also favored additive or synergistic epigenetic modifications in the combined effect of the two drugs.

overall_design: Total RNAs were extracted from 48 samples corresponding to 4 patients, 4 treatments (no drug, SAHA, MitA, SAHA+MitA) and three biological replicates.

first: Ramy

last: Ragheb

first: Rabie

last: Chelbi

first: Nathalie

last: Bonnet

first: Thérèse

last: Le Treut

first: Pascale

last: Poulin

last: Beaufils

first: Jean

last: Gabert

first: Béatrice

last: Loriod

first: Pascal

last: Rihet

first: Regis

last: Costello

first: Brigitte

last: Kahn-Perlès


title: Gene profiling of the zone of altered morphology of choriodecidua overlying the cervix before labor

first: Céline

last: Méhats

summary: To characterize the molecular signature of the choriodecidua remodeling in late pregnancy befour labour, we have employed whole genome microarray expression profiling to identify genes that sign for fetal membranes remodeling. Fetal membranes were collected from healthy women, after an uncomplicated pregnancy, undergoing a planned cesarean delivery at term, for feto-pelvic disproportion or scarred uterus. During surgery, a Kocher's forceps was placed on membranes overlying the cervix and the swelling area surrounding the forceps was dissected in the operating room under sterile conditions, the site, pinched by the forceps, being discarded. Fetal membranes in a remote zone were also sampled. Isolated RNAs were hybridized to the Aligent SurePrint G3 Human GE 8x60K Microarray. Two independent bio-analyses singularize  a signature in the zone of altered morphology for Graft vs Host Disease and leukocyte activation, arguing for a focal loss of maternal-fetal tolerance. This was further confirmed by flow cytometry, electron microscopy, and immuhistochemistry analyses.

overall_design: Microarray analysis was conducted on three distinct groups of three paired sets of zone of altered morphology and intact morphology from nine pregnant women in total. These women were delivered at term by cesarean sectionfor feto-pelvic disproportion or scarred uterus, after an uncomplicated pregnancy.

first: Louis

last: Marcellin

first: Sébastien

last: Jacques


title: Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia

first: Claire

last: Doerschuk

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

overall_design: Refer to individual Series


title: A Genome-Wide Search for Greek and Jewish Admixture in the Kashmiri Population

status: Public on Aug 16 2016

city: Salt Lake City

first: Lynn

last: Jorde

state: UT

department: Human Genetics

institute: University of Utah

summary: The Kashmiri population is an ethno-linguistic group that resides in the Kashmir Valley in northern India. A longstanding hypothesis is that this population derives ancestry from Jewish and/or Greek sources. There is historical and archaeological evidence of ancient Greek presence in India and Kashmir. Further, some historical accounts suggest ancient Hebrew ancestry as well. To date, it has not been determined whether signatures of Greek or Jewish admixture can be detected in the Kashmiri population. Using genome-wide genotyping and admixture detection methods, we determined there are no significant or substantial signs of Greek or Jewish admixture in modern-day Kashmiris. The ancestry of Kashmiri Tibetans was also determined, which showed signs of admixture with populations from northern India and west Eurasia. These results contribute to our understanding of the existing population structure in northern India and its surrounding geographical areas.

overall_design: DNA was collected from 15 Kashmiri individuals from the Kashmir Valley who provided written consent. The families of these individuals have resided in the Kashmir Valley for at least three generations and have no history of marriages outside of the valley or to a non-Kashmiri. Sixteen Kashmiri Tibetans from Srinagar, India, who have Tibetan ancestry and now practice Islam, were also genotyped. We performed further genotyping on a previously undescribed population of 32 first- and second-generation Tibetan exiles in McLeod Ganj, which included two individuals from the Tibetan Children’s Village, to serve as population references. These individuals were then genotyped for single nucleotide polymorphisms (SNPs) using the Affymetrix Genome-Wide Human SNP Array 6.0.

first: Jonathan

last: Downie

first: Tsewang

last: Tashi

first: Felipe

last: Lorenzo

first: Julie

middle: E

last: Feusier

first: Hyder

last: Mir

first: Josef

last: Prchal

first: Parvaiz

middle: A

last: Koul


title: A Genome Wide Association Study Reveals Genetic Predisposition for Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma by Variation in the PREP1-CBS locus.

status: Public on Nov 23 2016

city: Saint Herblain

first: Wilfried

last: Gouraud

address: bd Jacques Monod

department: Integrated Center of Oncology René Gauducheau

institute: ICO (Integrated Center of Oncology Nantes)

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

summary: We performed a genome-wide association study using Affymetrix HD-SNP arrays 6.0 to identify risk variants for developing bortezomib-induced peripheral neuropathy (BiPN) in 469 multiple myeloma (MM) patients who received bortezomib-dexamethasone (VD) induction therapy prior to autologous stem-cell transplantation (ASCT) and conducted validation in an independent cohort of 114 MM patients. We identified one previously unreported gene locus associated with BiPN at 21q22.3 (rs2839629, PKNOX1; OR = 1.89, P= 6.47 x 10-7). PKNOX1 is known to regulate expression of MCP-1, a potent mediator of chemotherapy-induced peripheral neuropathy. rs2839629 is in strong linkage disequilibrium (LD, r2 = 0.87) with rs915854, localized 6.5kb centromeric to CBS encoding an endogenous H2S-producing enzyme. CBS-H2S signalling pathway is implicated in the pathogenesis of a variety of neurodegenerative and inflammatory disorders, and specifically in neuropathy models. Our data provide conclusive evidence for genetic susceptibility to BiPN in MM and new potential targets in neuro-protective strategies of treatment.

overall_design: Identify risk variants for developing bortezomib-induced peripheral neuropathy (BiPN) within a cohort of 469 MM patients by means of genome wide association study, validation in an independent cohort of 114 MM patients

first: Florence

last: Magrangeas

first: Rowan

last: Kuiper

first: Hervé

last: Avet-Loiseau

first: Catherine

last: Guérin-Charbonnel

first: Alexandre

last: Aussem

first: Haytham

last: Elghazel

first: Jérôme

last: Suhard

first: Henri

last: Der Sakissian

first: Michel

last: Attal

first: Pieter

last: Sonneveld

first: Charles

last: Dumontet

first: Philippe

last: Moreau

first: Mark

last: van Duin

first: Loïc

last: Campion

first: Stéphane

last: Minvielle


title: Relapsed diffuse large B-cell lymphoma present different genomic patterns of alterations between early and late relapses

status: Public on Sep 26 2016

city: Vandoeuvre-lès-Nancy

first: Sebastien

last: Hergalant

address: Faculté de Médecine. 9 avenue de la forêt de Haye

department: Bioinformatics

institute: INSERM

summary: Despite major advances in first-line treatment, a significant proportion of patients with diffuse large B-cell lymphoma (DLBCL) will experience treatment failure. Time of relapse is a major prognostic parameter in this context, with a particularly poor prognosis for early relapse. Our purpose was to determine genomic alterations associated with early-relapsed (ER) and late-relapsed (LR) DLBCLs, using high resolution array-based comparative genomic hybridization and integrating structural abnormalities and gene expression of 39 samples from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) study. ER and LR DLBCLs present a similar landscape of large copy number variations (CNVs), with an average 14.89 and 16.11 CNVs per sample, respectively (p=0.81). Deletions of CDKN2A/B (28%) and IBTK (23%) were frequent events in relapsed DLBCLs. We identified 56 protein-coding genes and 25 long non-coding RNAs with significantly differential CNVs distribution between ER and LR DLBCLs with a false discovery rate < 0.05. In ER DLBCLs, genetic abnormalities were related to regulation of transcription, cell cycle and apoptosis, with duplications of histone H1T (31%), deletions of DIABLO (26%), PTMS (21%) and CK2B (15%). In LR DLBCLs, genetic aberrations were related to immune response, with alterations of IgHV (40%), IgKV (15%), and deletions of B2M (20%) and CD58 (10%), regulation of cell proliferation, with duplications of HES1 and DVL3 (25% and 20%, respectively) and regulation of transcription, with MTERF4 deletions (20%). This study provides new insights into the genetic abnormalities in relapsed DLBCLs. Dysregulation of cell cycle, apoptosis and gene transcription may indicate targeted therapy.

overall_design: Comparative study of CNVs in 19 early- and 20 late-relapsed DLBCLs

first: J

last: Broséus

first: S

first: G

last: Ramstein

first: C

last: Gisselbrecht

last: Thieblemont

first: R

last: Houlgatte


title: Expression data from mononuclear cells from bone marrow and peripheral blood of leukemia patient samples

status: Public on Sep 17 2016

city: Portland

first: Byung

last: Park

state: Oregon

address: 3181 SW Sam Jackson Park Rd. CR145

institute: Oregon Health & Science University

summary:
Gene expression analysis was conducted using a GeneChip® Human Genome U133(HG–U133A & B) array with more than 39,000 transcripts
Cytokines, growth factors, and their receptors are known to play important roles in cell survival, proliferation, differentiation and immune response in normal and cancer cells. Substantial evidence indicates that deregulation of growth factor and cytokine signaling contributes to leukemogenesis through aberrant activation of kinase-driven signaling pathways. In order to identify cytokine/growth factor receptors that are critical for leukemia cell growth, we established a novel functional RNAi-based screen targeting 188 non-kinase cytokine/growth factor receptors and associated proteins that are highly expressed in hematopoietic malignancies.
In AML 46884 is missing for Set A and 103855 is missing for Set B and in T-ALL 52570 Set A is missing because of sample size limitation.

overall_design: Gene expression profiling was done using mononuclear cells from bone marrow and peripheral blood of 141 leukemia patient samples including AML (N=38), precursor B-cell acute lymphoblastic leukemia (B-ALL; N=17), T-cell acute lymphoblastic leukemia (T-ALL; N=13), chronic lymphocytic leukemia (CLL; N=41), chronic myeloid leukemia (CML; N=22)), and myelodysplastic syndrome (MDS; N=10).

first: Rita

middle: M

last: Braziel

first: Guang

last: Fan

first: Anupriya

last: Agarwal


title: Expression data from three rice lines (1-control, 1-transgenic and 1-negative segregant) throughout generations and under salt stress

status: Public on Aug 03 2016

city: Lisbon

middle: Maria

last: Batista

address: Av Padre Cruz

department: Food safety and nutrition

country: Portugal

institute: Instituto Nacional de Saude Dr. Ricardo Jorge

summary:
The approval of genetically modified (GM) crops is preceded by years of intensive research to demonstrate safety to humans and environment. We recently showed that in vitro culture stress is the major factor influencing proteomic differences of GM vs. non-GM plants. This made us question the number of generations needed to erase such memory. We also wondered about the relevance of alterations promoted by transgenesis as compared to environment-induced ones.
Here we followed three rice lines (1-control- C, 1-transgenic- Ta and 1-negative segregant- NSb) throughout eight generations after transgenesis, and further analyzed their response to salinity stress on the F6 generation.

overall_design: Three pools of 10 whole fifteen days-old rice seedlings (Oryza sativa L. ssp. japonica cv. Nipponbare) were selected from each line at F4, F6 and F8 generations. Because salinity stress was imposed on half of the seedlings (C, Ta and NSb) in F6 generation, from this generation onwards we worked with six rice lines (C, Csalt, Ta, Tasalt, NSb, NSbsalt).

first: Cátia

last: Fonseca

first: Sébastien

last: Planchon

first: Sónia

last: Negrão

first: Jenny

last: Renaut

first: Maria

last: Oliveira