title: Affymetrix SNP array data for family UNK-129-KW with multiple patients suffering from a lethal form of a primary immunodeficiency.

status: Public on Aug 11 2016

first: Michel

last: Massaad

state: MA

address: One Blackfan Circle

department: Mdicine/Immunology

institute: Boston Children's Hospital

summary: Linkage analysis and Copy Number Variation were performed on DNA isolated from the peripheral blood of the 2 affected male patients, their unaffected parents, and their unaffected 4 male siblings, according to the manufacturer's description. This allowed to narrow down the region of homozygosity specifice to the patients. This approach, in combination with Whole Exome sequencing performed on DNA isolated from the 2 affected patients and their mother, allowed to identify a homozygous missense mutation in the base excision repair enzyme NEIL3 that reduced its enzymatic activity, and a homozygous duplication of exons 48-53 of the LPS Responsive Beige-Like Anchor Protein LRBA that abolished protein expression.

overall_design: Homozygozity mapping was performed with the Affymetrix genome-wide human single nucleotide polymorphism (SNP) array 6.0, and analyzed with Birdsuite version 1.4 and PLINK version 1.07.

middle: J

first: Raif

middle: S

last: Geha

first: Klaus

last: Schmitz

first: Markianos

last: Kyriacos

first: Janet

last: Chou

first: Toshiro

last: Ohsumi


title: Transcriptome profiling of TALEN-mediated LATS2 knockout HeLa-S3 cells

status: Public on Jul 26 2016

city: Suita

first: Daisuke

last: Okuzaki

state: Osaka

address: Yamadaoka 3-1

department: Immunology Frontier Research Center

country: Japan

institute: Osaka univ.

summary: Chromatin modifying activities for construction of appropriate epigenetic landscapes by polycomb repressive complex 2 (PRC2) play an essential role in development and tumorigenesis. However, the spatiotemporal mechanisms by which PRC2 achieves diverse epigenomes for specific tissue or cellular contexts remain poorly understood. Here, we discovered that LATS2 knockout causes dysregulation of PRC2 and subsequent transcriptome changes for differentiation in both mouse and human cells. LATS2 depletion dependent dysregulation of PRC2 also effects H3K4me3 and forms negative feedback loop for maintenance of PRC2. Further analyses reveal that LATS2 on chromatin binds to EZH2 and LATS2 has ability to phosphorylate PRC2 in vitro. These LATS2 dependent H3K27me3 targets are highly induced during neurogenesis, and statistical analysis of glioblastoma multiforme reveals that LATS2-high cases show more dedifferentiated transcriptome and poor prognosis with silencing of H3K27me3 targets. These observations suggest that LATS2-mediated epigenome coordination is pivotal for development and disease, including cancer.

overall_design: Three samples, two cell lines (WT_rep1, WT_rep2, and LATS2 KO) were analyzed by Agilent SurePrint G3 Human Gene Expression 8x60K v1 one color experiments.

first: Kosuke

last: Torigata


title: Human Neonate CD8-T cells are biased towards innate immunity defense mechanisms

status: Public on Jul 25 2016

city: MARSEILLE CEDEX 09

first: Aurelie

last: Bergon

address: parc scientifique de Luminy, case 928

country: France

institute: TAGC INSERM U1090

summary:
To understand better the nature of the poor response of human neonates to intracellular pathogens, we evaluated the transcriptome of neonates as compared to adult naïve CD8-T cells.  A specific transcription signature of the neonatal cells was found, characterized by a lower expression of signalling and CTL functional genes and a high expression of maturation, cell cycle and innate-immunity associated genes.   Functional assays demonstrated that neonatal CD8-T cells undergo homeostatic proliferation, transcribe antimicrobial peptides and produce reactive oxygen species. Master transcription factors were found presumably responsible for this specific signature. Genome wide epigenetic studies showed a corresponding chromatin signature for a number of the differentially expressed genes. Altogether our results show that CD8 neonatal T cells have a particular genetic program with functions within the innate immune response, while still undergoing their maturation process.
Neonates are highly susceptible to infections by intracellular pathogens, which are a major cause of infant morbidity and mortality. CD8-T cells control intracellular pathogens through cytotoxic mechanisms in an antigen-dependent manner. We found that human neonatal CD8-T cells, as compared to adult lymphocytes, had a distinctive pattern of gene transcription, characterized by the lower expression of genes involved in TCR signalling and cytotoxicity and a high expression of genes involved in cell cycle and innate immunity. Functional studies corroborated that neonatal CD8-T cells are less cytotoxic, transcribe antimicrobial peptides and produce reactive oxygen species. These properties could explain the high sensitivity of neonates to intracellular pathogen infections and outline novel functions of neonatal CD8-T cells. PBMC total RNAs from Adult and Neonate subjects were profiled after hybridization with Agilent SurePrint G3 Human GE 8x60K Microarray.

overall_design: CD8-T cells mRNA were extracted from 8 samples including: 4 Adults and 4 Neonates.

first: Ariel

middle: O

last: Galindo-Albarrán

first: Aurélie

first: Béatrice

last: Loriod

first: Hélène

last: Holota

first: Jean

last: Imbert

first: Oscar

middle: H

last: López-Portales

first: Armando

last: Hernández-Mendoza

first: Pierre

last: Ferrier

first: Salvatore

last: Spicuglia

first: Angélica

last: Santana


title: Global transcriptomic changes of either cell cycle arrested parasites or cell cycle re-entered asexual P. falciparum 3D7 parasites.

status: Public on Dec 13 2016

city: Pretoria

first: LynMarie

last: Birkholtz

state: Gauteng

address: c/o Lunnon Road and Heroldt Street, Hatifeld

department: Biochemistry

country: South Africa

institute: University of Pretoria

summary: Parasitic protists, including Plasmodium falciparum malaria parasites, evolved sophisticated biological features to adapt and survive in e.g. mosquito vectors and mammalian hosts. The parasite’s life cycle is extraordinarily controlled, oscillating between quiescent stages (e.g. sporozoites or gametocytes) and stages of intense proliferation. The atypical mode of asexual reproduction in erythrocytes (schizogony: asynchronous nuclear division in the absence of cytokinesis), is clearly divergent from cell division in higher eukaryotes but the mechanisms that control cell cycle progression are poorly understood. Here, depletion of exogenous factors was used to induce reversible cell cycle arrest and allowed transcriptomic investigations of cell cycle control mechanisms operating in the parasite. We show that in early stages of erythrocyte infection, parasites enter a quiescent, G0-like state due to implementation of a G1 restriction point prior to G1/S transition. This quiescence is reversible, with cells making a clear decision to re-engage the proliferation machinery in response to proliferation stimuli. Cell cycle arrest is an adaptive response rather than merely prolongation of the G1 phase, as demonstrated by a distinct transcriptome. The quiescence-proliferation decision-making process in malaria parasites has hallmarks of unique regulatory principles: quiescence is associated with a deregulation of the pre-replicative complex, underlined by transcriptional control of kinases, including PfPK5 as putative functional homologue of the master mammalian cell cycle regulator, CDK1. Cell cycle re-entry is highly coordinated and mediated by a set of early responsive transcripts involving NIMA and Aurora kinases, ApiAP2 transcription factors and calcium signaling. We therefore show that Apicomplexa are able to perform quiescence-proliferation decision-making in a highly coordinated fashion, using atypical cell cycle regulation machinery.

overall_design: Two sets of independent oligonucleotide DNA microarrays were performed to analyze the global transcriptomic changes P. falciparum parasites using either DFMO-arrested parasites or DFMO-arrested parasites followed by putrescine-reversal. DNA microarrays were performed using custom microarray slides that contained 12 468 oligos (60-mer, Agilent Technologies) based on the complete P. falciparum genome. Synchronized ring-stage parasitized erythrocytes (5% hematocrit, 10-15% parasitemia) were incubated with DFMO (IC90) at 37˚C prior to sampling (Arrested time points: A1=21 h post treatment (hpt); A2=29 hpt) or additionally treated after 24 h DFMO pressure with 2 mM putrescine dihydrochloride to induce the re-entry and onset of the cell cycle (Re-entry time points: Re1=27 hpt; Re2=30 hpt and Re3=36 hpt). For each time point, two biological repeats were performed, each with two technical repeats. From 50 ml parasite cultures sourced at specific time points, RNA isolation, cDNA synthesis and dye coupling with Cy3 (reference pool) or Cy5 (samples) were performed as described in van Brummelen, A. C. et al. The Journal of biological chemistry 284, 4635-4646, doi:10.1074/jbc.M807085200 (2009). The slides were scanned using a GenePix™ 4000B scanner.

first: Jandeli

last: Niemand

first: Riette

last: van Biljon

first: Roelof

last: van Wyk

first: Katherine

last: Clark

first: Bianca

last: Verlinden

first: Hilde

last: von Grüning

first: Karen

last: van der Merwe

first: Werner

last: Smidt

first: Annél

last: Smit

first: Janette

last: Reader

first: Teresa

last: Carvalho

first: Heather

last: Painter

first: Manuel

last: Llinás

first: Christian

last: Doerig

first: Lyn-Marié


title: Endothelial DNA methalytion signature in pulmonary arterial hypertension

status: Public on Jul 15 2016

city: Le Plessis Robinson

first: Frédéric

last: Perros

address: 133 Avenue de la Résistance

department: Centre chirurgical Marie Lannelonque

institute: INSERM U999

summary: Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation.

overall_design: DNA was extracted from cultured PEC from patients with idiopathic PAH (n=11), heritable PAH (n=10) and controls (n=18). ). DNA methylation was assessed using the Illumina HumanMethylation450 Assay. After normalization, samples and probes were clustered according to their methylation profile. Differential clusters were functionally analysed using bioinformatics tools.

first: Aurélie

last: Hautefort

first: Julie

last: Chesné

first: Jens

last: Preussner

first: Soni

last: Pullamsetti

first: Tost

last: Jorg

first: Looso

last: Mario

first: Fabrice

last: Antigny

first: David

last: Montani

first: Barbara

last: Gired

first: Saadia

last: Eddahibi

first: Jean-Francois

last: Deleuze

last: Seeger

first: Elie

last: Fadel

first: Gerald

last: Simonneau

first: Marc

last: Humbert


title: Age-Related Gene Expression Changes in Prostate Cancer Patients [array]

status: Public on Nov 30 2016

city: Duarte

first: Susan

last: Neuhausen

state: California

address: 1500 E duarte road

department: Population Sciences

country: USA

institute: City of hope

summary: Formalin-fixed, paraffin-embedded (FFPE) from prostate cancer patients

overall_design: Gleason-score matched tumor and adjacent normal samples were collected to compare gene expression differences in early-onset versus late-onset prostate cancer patients

first: Yuan

middle: C

last: Ding


title: Copy number analysis of liver metastases from colorectal cancer

status: Public on Jul 11 2016

city: Oslo

first: Anita

last: Sveen

address: P.O.Box 4953, Nydalen

department: Department of Molecular Oncology

country: Norway

institute: Institute for Cancer Research, Oslo University Hospital

summary: Almost half of all patients diagnosed with colorectal cancer develop liver metastases. The potential role of intra-individual metastatic heterogeneity remains poorly characterized. By high-resolution DNA copy number analyses and a novel approach based on pair-wise genetic distance, we examined the genetic heterogeneity among multiple liver metastatic deposits obtained from 45 patients subject to curative liver resection. We found large variation in intra-individual metastatic heterogeneity. A high level of heterogeneity was associated with poor patient survival. Patients with metachronous metastases who received chemotherapy had significantly more heterogeneity than chemonaïve patients.

overall_design: Genome-wide copy number analysis was performed on fresh frozen tissue samples from 134 liver metastatic deposits and 6 primary tumors from 45 patients with metastatic colorectal cancer using the Affymetrix SNP 6.0 Array

first: Inger

middle: M

last: Løes

first: Sharmini

last: Alagaratnam

first: Stian

last: Knappskog

first: Per

middle: E

last: Lønning

first: Ragnhild

middle: A

last: Lothe


title: Analysis of Sox2-regulated transcriptome in glioma stem cells

status: Public on Nov 04 2016

city: Pamplona

first: Marta

middle: Maria

last: Alonso Roldán

state: Navarra

address: CIMA building , Pio XII 55

department: Dpt of Pediatrics

country: Spain

institute: University Hospital of Navarra

summary: Glioblastoma is the most malignant brain tumor in adults and is associated with poor survival despite multimodal treatments. Glioma stem cells (GSCs) are cells with properties reminiscent from the normal neural stem cells counterparts. They have been postulated to be the culprit of glioma chemo- and radio-resistance ultimately leading to relapse. Understanding the molecular circuits governing the GSC compartment is essential. Sox2, a critical transcription regulator of embryonic and neural stem cell function, is deregulated in GSCs, but the description of the precise molecular pathways regulated by this gene in GSCs remains poorly understood. Results: We performed a genome-wide analysis of Sox2-regulated transcripts in GSCs, using microarray. We identified a total of 135 differentially expressed coding transcripts and 261 non-coding transcripts (B value > 0). Cell adhesion and cell-cell signaling are among the most enriched terms using GO classification. The pathways altered after Sox2 down-modulation includes multiple cellular processes such as aminoacid metabolism and intercellular signaling cascades. We validate the top 5 down regulated coding genes and one of the top 5 up-regulated coding genes. We also defined and classify the set of non-coding transcripts differentially expressed regulated by Sox2 in GSCs, and validated two of them. Conclusions: We present a comprehensive analysis of the transcriptome controlled by Sox2 in GSCs, gaining insights in the understanding of the potential roles of Sox2 in glioblastoma.

overall_design: Sox2 expression was inhibitd in GSC-11 cell line (human glioblastoma neurosphere cell line) using a specific siRNA against human Sox2 (si-Sox2) and a non-targeting control siRNA (si-scramble) (Ambion) in 4 independent experiments

last: Alonso

first: Arlet

last: Acanda


title: Microarray Analysis of DU 145, LNCaP and PC-3 Prostate Cancer Cell Lines upon Docetaxel treatment

status: Public on Jul 21 2016

city: Seattle

first: Robert

last: Moritz

state: Washington

address: 401 Terry Ave Nth

institute: Institute for Systems Biology

summary: We measured the effect of docetaxel treatment to three differentially responsive prostate cancer cell lines, LNCaP, DU145 and PC-3, based on a transcriptional time course response by microarray analysis. These cell lines represent both androgen independent (DU145 and PC-3) and androgen sensitive (LNCaP) cells

overall_design: Hybridized arrays were scanned with Agilent’s dual laser-based scanner. Feature Extraction software version 10.5 (Agilent Technologies) was used to link a feature to a design file and to determine the relative fluorescence intensity between two samples. Dye swap strategy with alternate cy3 and cy5 labeling on docetaxel treated and control groups over four time points was used to have technical replicates and decrease dye bias.

middle: L

first: Chung-Ying

last: Huang

first: Ulrike

last: Kusebauch


title: Molecular features of subtype-specific progression from ductal carcinoma in situ to invasive breast cancer [gene expression data]

status: Public on Jul 07 2016

city: St. Louis

last: Lesurf

state: MO

address: 4444 Forest Park Ave

department: McDonnell Genome Institute

institute: Washington University in St. Louis

summary: Breast cancer consists of at least five main molecular “intrinsic” subtypes, which are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression, and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA and DNA copy number profiles from a total of 59 in situ lesions and 85 invasive tumors, in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

overall_design: One-color design, totaling 105 arrays and 103 unique tissues. Arrays consist of 3 normal controls (1 unique), 46 DCIS lesions (46 unique), and 56 small invasive breast cancers (56 unique).

first: Miriam

middle: R

last: Aure

first: Hanne

last: Mørk

first: Valeria

last: Vitelli

first: Steinar

last: Lundgren

first: Anne-Lise

last: Børresen-Dale

first: Vessela

last: Kristensen

first: Fredrik

last: Wärnberg

first: Michael

last: Hallett

first: Therese

last: Sørlie


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

status: Public on Sep 09 2016

city: Chapel Hill

first: Claire

middle: M.

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: Total RNA was isolated from whole lungs obtained 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

last: Gomez

first: Hong

last: Dang


title: Molecular features of subtype-specific progression from ductal carcinoma in situ to invasive breast cancer

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

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

overall_design: Refer to individual Series


title: Repression of stress-induced LINE-1 expression protects cancer cell populations from lethal drug-exposures [ChIP-Seq]

status: Public on Jun 21 2016

city: Würzburg

first: Claus

middle: Juergen

last: Scholz

address: Josef-Schneider-Str. 2

department: Core Unit SysMed

country: Germany

institute: University Hospital Würzburg

summary: Merkel cell carcinoma is a skin cancer associated with the Merkel cell polyomavirus (MCPyV)  which is found integrated in the genome of the tumor cells. Here 4 MCPyV-positive tumor cell lines (AlDo, LoKe, BroLi and WoWe) were analyzed by comparative gernomic hybridization to define further genetic alterations. Corresponding peripheral blood lymphocytes (PBL) in case of AlDo and LoKe, purified T cells in case of BroLi and Tumor-derived but virus-negative cells of unknown origin (WoWe1)  in case of WoWe served as controls.

overall_design: Comparative genomic hybridization to define amplifications and deletions in the MCC genome.

first: Heike

last: Weber

first: David

last: Schrama

first: Roland

last: Houben


title: Age and estrogen-dependent inflammation in breast adenocarcinoma and normal breast tissue [cohort_2]

status: Public on Jul 01 2016

city: San Francisco

last: Quigley

state: CA

address: 1450 Third St. Room 207

department: Helen Diller Comprehensive Cancer Center

institute: UCSF

summary: Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment.  The relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors, is complex. Low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, but very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue. The molecular impact of these factors on tumor initiation and growth is not well-understood. We modeled the difference in gene expression between 195 breast adenocarcinomas and 195 matched adjacent normal breast tissue samples, using age, body mass index (BMI), and tumor subtype as covariates. Age and BMI were independently associated with inflammation in normal tissue but not tumors. Older patients with ER-positive disease had tumors with higher levels of Estrogen Receptor (ER) signaling compared to adjacent normal tissue and had lower relative levels of tumor macrophage expression. We developed a novel statistic to quantify the rewiring of gene co-expression networks and demonstrate that in ER-positive tumors basal gene networks are rewired even though their expression levels of these genes are not significantly different from those in adjacent normal tissue.  Patient age influences the molecular profile of ER-positive breast tumors. Our data support an immunosuppressive effect of estrogen signaling in the breast tumor microenvironment, suggesting this effect contributes to the greater presence of prognostic and therapeutically relevant immune cells in ER-negative tumors.

overall_design: 296 total samples: 148 breast adenocarcinoma, 148 paired adjacent normal breast tissue


title: Global re-wiring of p53 transcription regulation by the hepatitis B virus X (HBx) protein [Agilent]

status: Public on Jun 22 2016

city: Singapore

first: Thomas

last: Thurnherr

address: 11 Hospital Drive

country: Singapore

institute: NCCS

summary: As HBx has been reported to interact with p53 and alter the recruitment of p53 to its binding sites, we would like to identify p53-associated genes that were deregulated by HBx. We employed whole genome microarray expression profiling to identify genes that were deregulated by HBx protein.

overall_design: HepG2 cells were transduced with recombinant HBx and control adenoviruses 24 hours post seeding. HepG2 cells were treated with UVC (254 nm) irradiation 48 hours postransduction and harvested 24 hours after UV irradiation. Experiements were conducted with three biological replicates.

first: Cheryl

last: Chan

first: Caroline

last: Lee


title: Epigenomic Profiling of Primary Gastric Adenocarcinoma Reveals Super-enhancer Heterogeneity [SNP]

status: Public on Sep 28 2016

first: Aditi

last: Qamra

address: 60 Biopolis Street, Genome, #02-01

institute: GIS

summary: Regulatory elements in cancer remain poorly characterized in primary solid tumors. Here we applied microscale histone modification profiling to delineate the landscape of somatic promoters and super-enhancers in primary gastric adenocarcinoma, analyzing 94 epigenomic  profiles of primary tumors, normal tissues, and cell lines

overall_design:
Genomic DNA extracted from gastric tumors and matched gastric non-malignant (normal) tissues was hybridized on Affymetrix SNP6 genotyping arrays. Normal samples (n=98) from this accession and 25 samples from GSE31168 were used to construct reference models by Affymetrix Genotyping Console 4.2.

Five samples from GSE36138 were also reanalyzed in this study.

Please note that a collective of normal SNP6 profiles were used to construct a reference model, which was used  to normalise the cancer profiles. The copy number changes in the cancer profiles were then detected. The descriptions field contains details about each normal SNP6 profile that used for building the reference model for specified cancer profiles and corresponding processed file name.

The 'readme_re-analysis.txt' contains the details about the re-analyzed samples (e.g. sample characteristics, sample-to-file association etc.).

first: Ooi

middle: W

last: Fong

first: Patrick

last: Tan


title: Affymetrix SNP array data for myelodysplastic syndromes samples

status: Public on May 24 2016

first: Matt

last: Walter

address: 4940 parkview

department: oncology

institute: washington university in st.louis school of medicine

summary:
Traditional response criteria in MDS and AML are based on bone marrow morphology and may not accurately reflect tumor burden in patients treated with hypomethylating agents. We used massively parallel sequencing of serial bone marrow samples to monitor MDS and AML tumor burden during treatment with epigenetic therapy (decitabine and panobinostat). Serial bone marrow samples (and skin as a source of normal DNA) from 25 MDS and AML patients were sequenced . We observed that responders, including those in complete remission (CR), can have persistent measurable tumor burden for at least one year without disease progression. Using an ultra-sensitive barcode sequencing approach, we detected extremely rare mutations  months to years prior to disease relapse. While patients can live with persistent clonal hematopoiesis in a CR or stable disease, ultimately we find evidence that expansion of a rare subclone can drive relapse or progression. Digital sequencing provides an alternative measure of tumor burden and disease response which may augment traditional clinical response criteria in patients treated with hypomethylating agents and its use should be explored in future clinical trials.
BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. The Philadelphia chromosome, encoding BCR-ABL1, is the defining lesion of chronic myelogenous leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL) cases. To define oncogenic lesions that cooperate with BCR-ABL1 to induce ALL, we performed genome-wide analysis of leukemic samples from 23 CML cases and 304 ALL cases, including 43 BCR-ABL1 B-ALL cases. IKZF1 (encoding the transcription factor Ikaros) was deleted in 83.7% of BCR-ABL1 B-ALL cases, but not in chronic phase CML. Deletion of IKZF1 was also identified as an acquired lesion in lymphoid blast crisis of CML. The IKZF1 deletions resulted in haploinsufficiency, expression of a dominant negative Ikaros isoform or the complete loss of Ikaros expression. Sequencing of IKZF1 deletion breakpoints suggested that aberrant V(D)J recombination is responsible for the deletions. These findings suggest that genetic lesions resulting in the loss of Ikaros function are a key event in the development of BCR-ABL1 ALL.

overall_design:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or skin tissue samples.
Copy number analysis of Affymetrix  genome wide SNP 6.0 arrays was performed for MDS 7 patients, each patient has skin, bone marrow tumor at pre-study and last. skin DNA was used as references for copy number inference (therefore there are only 14 data columns in the processed data file; no processed data for the skin samples).

first: Geoffrey

last: Uy

first: Eric

last: Duncavage

first: Jin

last: Shao

first: Matthew


title: Affymetrix SNP array data for Ovarian Cancer Samples

city: Vancouver

first: Kelsie

last: Thu

state: British Columbia

address: 675 West 10th Avenue

country: Canada

institute: BC Cancer Research Centre

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

summary: This study aimed to generate a new panel of comprehensively, genomically characterized high-grade serous ovarian carcinoma (HGSOC) cell line and xenograft models. Multidimensional genomic data were generated and compared between cell lines/xenografts and the tumours they were derived from, indicating the cell lines/xenografts are highly similar to their patient-matched tumours. Cell line/xenograft data were also compared to TCGA ovarian tumours to show the cell lines are good models of clinical HGSOC.

overall_design: Affymetrix SNP 6 arrays were performed according to the manufacturer's instructions on genomic DNA extracted from i) tumour cells purified from ovarian tumour ascites, ii) established cell lines, iii) patient derived xenografts, and iv) lymphoblast lines. Evaluation of the similarity in copy number/methylation/gene expression/mutational profiles of cell lines/tumours/xenografts was performed.

first: Adi

middle: F

last: Gazdar


title: Genome wide association study on neuropathy in multiple myeloma

status: Public on Jun 01 2016

city: Rotterdam

first: Mark

last: van Duin

address: Wytemaweg 80

country: Netherlands

institute: Erasmus MC

summary:
Performing GWAS on multiple myeloma in relation to the development of the toxicity neuropathy. This set was used as validation set.
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 therapy prior to autologous stem-cell transplantation and conducted validation in an independent cohort of 116 MM patients. We identified one previously unreported BiPN risk locus at 21q22.3 (rs2839629, PKNOX1; OR = 0.53, 95% CI: [0.40-0.69]). PKNOX1 is known to regulate MCP-1, a potent mediator of chemotherapy-induced peripheral neuropathy. rs2839629 is in strong linkage disequilibrium ( r2 = 0.87) with rs915854, localized 6.5kb centromeric to CBS encoding 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:
Each patient of both IFM and HOVON cohorts was genotyped using the Affymetrix SNP6.0 Human DNA chip (Affymetrix, Santa Clara, CA) according to manufacturer’s instructions (Affymetrix, Santa Clara, CA). The HOVON65 samples were genotyped using CRLMM v2 resulting in a call rate higher than 95%. Unannotated SNPs according to the hg19 na32 SNP6 Affymetrix annotations (n= 130) along with SNPs from MT and sexual chromosomes (n= 37,326) were not considered in the study. To perform GWAS in the IFM cohort, we used stringent criteria to select a total of 370,605 SNPs from the 872,166 SNPs available onto the array. A SNP was analysed if an AA or BB genotype was present in more than 5% of patients, if its genotype was determined in at least 95% of the patients and if the Hardy-Weinberg rule was not rejected. Statistical analyses were performed using SNPTEST v2.5.11. Firstly, we compared 370,605 genotypes from 155 IFM patients with neuropathy (grade >= 2) after bortezomib exposure to 314 control patients treated with bortezomib who did not develop neuropathy (grade 0-1). Secondly, we performed a validation in the HOVON 65/GMMG-HD4cohort for the highest associated SNPs as identified in the discovery cohort. We compared 41 bortezomib-treated patients with neuropathy (grade >= 2) with 75 bortezomib-treated controls who did not develop neuropathy. We applied a one-sided logistic regression with 10,000 label swapping permutations to correct for multiple testing in order to confirm BiPN association in this independent cohort.
This set was used as a validation set. An independent dataset was used for discovery [GSE65777].

first: Rowan

last: Kuiper


title: Effect of FSH on granulosa cell expression in cow.

status: Public on May 01 2016

city: Québec City

first: Marc-André

last: Sirard

state: Quebec

address: Offfice 2732, 2440 Hochelaga Blvd.

department: Sciences Animales

institute: Université Laval

summary: FSH signaling is well known to lead to steroidogenesis, cellular proliferation, and follicular growth. The development of global transcriptomic allows to expand our understanding of the FSH effect on several additional functions of granulosa cells and to better understand how it controls or prevents several differentiation events in granulosa cells from medium size follicles

overall_design: Two-condition experiment, CTR vs. FSH treated bovine granulosa cells. Biological replicates: 4 control replicates, 4 treated replicates. Experiments done in dye-swap.

first: Anne-Laure

last: Nivet

first: Isabelle

last: Dufort

last: Gilbert

first: Marc-Andre


title: caArray_orkin-0038: Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling

status: Public on Jun 17 2016

city: Rockville

first: Mervi

last: Heiskanen

state: MD

address: 9609 Medical Center Drive, 1W378

department: CBIIT

institute: NCI

summary: Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias.

overall_design:
orkin-00383
Assay Type: Gene Expression
Provider: Affymetrix
Array Designs: HG-U133A
Organism: Homo sapiens (ncbitax)
Tissue Sites:
Material Types: total_RNA, synthetic_RNA, organism_part, whole_organism
Disease States: Down Syndrome; Transient Myeloproliferative Disorder, non Down Syndrome; Acute Megakaryoblastic Leukemia, Down Syndrome; Acute Megakaryoblastic Leukemia, non Down Syndrome; Acute Myeloid Leukemia, Down Syndrome; Acute Myeloid Leukemia


title: Copy number variation in melanoma biopsy specimens

status: Public on Apr 22 2016

city: Dayton

first: Michael

last: Markey

state: OH

address: 3640 Colonel Glenn Hwy.

department: Biochemistry and Molecular Biology

institute: Wright State Unviersity

summary: Melanoma is the least common form of skin cancer, but accounts for the most deaths.  Dermatopathologists face difficult diganostic determinations with a subset of ambiguous melanoma cases.  Copy number variation in melanoma can serve as an additional biomarker to distinguish melanoma from benign melanocytic lesions.

overall_design: Affymetrix SNP6.0 microarrays were performed according to the manufacturer's directions  with gDNA isolated from FFPE melanocytic lesions and melanomas taken originally as biopsies.

middle: P


title: Copy number variation analysis of hepatic metastases from uveal melanoma

status: Public on May 18 2016

city: Liverpool

first: Sarah

last: Coupland

address: 6th Floor Duncan Building, Daulby Street

department: Molecular and Clinical Cancer Medicine

country: United Kingdom

institute: University of Liverpool

summary: Metastatic uveal melanoma (MUM) is chemoresistant and usually fatal within one year of diagnosis. There is an urgent need to better understand disease pathogenesis, in order to determine key drivers of the metastatic process that could be effectively targeted by therapy. Gene copy number variations occurring in a rare cohort of 13 metastatic and six matched primary, formalin-fixed, paraffin-embedded uveal melanoma samples were identified using the Affymetrix Genome-Wide Human SNP 6.0 Array. Gross chromosomal abnormalities commonly seen in primary UM and associated with the development of metastasis were observed in the MUMs. The most common CNVs were gene amplifications on chromosome 8q, especially in the region 8q24.3. Interestingly, deletions on chromosome 3 were detected at a lower frequency. Genomic profiles of PUM-MUM pairs varied in their degree of similarity and complexity. No genes were altered being unique to either all PUMs or all MUMs of the pairs, but 135 gene CNVs were consistently shared. Of these genes, 125 were amplifications located on chr. 8q24.3. Five genes in the region 8q24.3 and two genes on chromosome 3 were selected for validation by immunohistochemistry because of their known function in cancer (BCL6, C-MYC, E2F5, PTP4A3, SNAI2, and WISP1), or known importance in UM pathology (BAP1). The functional effect of these CNVs on protein expression was confirmed; amplified genes showed increased expression and deleted genes reduced expression. To conclude, our data demonstrate frequent amplification of chromosome 8q in MUMs, suggesting that genes facilitating the expansion of UM in the metastatic niche occur in this region. Furthermore, validation of a range of amplified 8q genes at the protein level strongly indicates the CNVs may be functional and, contribute to MUM biology.

overall_design: 19 samples in total: 13 metastatic uveal melanoma (MUMs) and in six cases their paired primary UM (PUMs)

first: Conni

last: McCarthy

first: Helen

last: Kalirai

last: Lake

first: Andrew

last: Dodson

first: Bertil

last: Damato


title: Paired Breast Adenocarcinoma and Adjacent Normal tissue

first: David

last: Quigley


title: T-bet recruits P-TEFb to super-enhancers to regulate T helper cell differentiation (Agilent 1)

status: Public on Jun 08 2016

city: London

first: Richard

last: Jenner

address: 72 Huntley Street

department: Cancer Biology

institute: UCL Cancer Institute

summary:
The transcription factor T-bet induces differentiation of CD4+ T cells into the Th1 lineage and also allows for a degree of functional plasticity. Here, we show that T-bet acts through super-enhancers to recruit the elongation factor P-TEFb. Th1-specific genes are poised for activation in Th2 cells and P-TEFb recruitment activates transcriptional elongation. T-bet also induces extensive P-TEFb binding at super-enhancers, where it acts to stimulate enhancer RNA transcription. P-TEFb inhibition selectively blocks activation of lineage-specific genes and reverses Th1-associated retinitis pathology. T-bet-mediated recruitment of P-TEFb to super-enhancers at otherwise poised genes provides a model for how lineage-specifying factors promote differentiation towards specific cell fates whilst maintaining a degree of functional plasticity.
Transcriptional profiling of human Th1 and Th2 cells

overall_design: Two-condition experiment, unstimulated or reactivated Th1 and Th2 cells vs. universal reference. Biological replicates: 3

first: Catherine

last: Evans

first: Arnulf

last: Hertweck


title: Influence of ATM-mediated DNA damage response on genomic variation in human induced pluripotent stem cells (Affymetrix CNV)

status: Public on Mar 29 2016

city: Rochester

first: Hu

last: Li

state: MN

address: 200 First Street, Gonda Building G19-408

department: Molecular Pharmacology & Experimental Therapeutics

institute: Mayo Clinic

summary: Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors.

overall_design: We isolated genomic DNA from Ataxia-telangiectasia (A-T) iPSC cells derived from patient fibroblasts virus and episomal vectors, coresponding fibroblasts, normal human fibroblast derived iPSCcells,  for hybridization to the Affymetrix Genome-Wide Human SNP 6.0 Array.

first: Junjie

last: Lu

first: Paul

last: Lerou


title: Affymetrix SNP array data for HNSCC samples

city: Kansas City

first: Sufi

last: Thomas

state: Kansas

address: 3901 Rainbow Blvd

department: Otolaryngology

institute: KUMC

summary: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved HNSCC samples.

overall_design: Copy number analysis of Affymetrix 500K SNP arrays was performed for 11 HNSCC samples, which were used as references for copy number inference.

first: Levi

middle: G

last: Ledgerwood

first: Dhruv

last: Kumar

first: Agda

middle: K

last: Eterovic

first: Jo

last: Wick

first: Ken

last: Chen

first: Hao

last: Zhao

first: Loubna

last: Tazi

first: Pradip

last: Manna

first: Spencer

last: Kerley

first: Radhika

last: Joshi

first: Lin

last: Wang

first: Simion

middle: I

last: Chiosea

first: James

middle: D

last: Garnett

first: Terance

middle: T

last: Tsue

first: Jeremy

last: Chien

first: Gordon

middle: B

last: Mills

first: Jennifer

last: Grandi


title: Toll-like Receptor 6 and Connective Tissue Growth Factor are significantly upregulated in mitomycin-C treated urothelial carcinoma cells under hydrostatic pressure stimulation

status: Public on Mar 21 2016

city: New Taipei

first: Chih-Cheng

address: No 2, Ln 59, Jian-Cheng Rd, Sijhih Dist

country: Taiwan

institute: Sijhih Cathay General Hospital

summary: Urothelial carcinoma (UC) is the most common histologic subtype of bladder cancer. The administration of mitomycin C (MMC) into bladder after transurethral resection of the bladder tumor (TURBT) is a common treatment strategy for preventing recurrence after surgery. We previously applied hydrostatic pressure combined with MMC in UC cells and found that hydrostatic pressure synergistically enhanced MMC-induced UC cell apoptosis via the Fas/FasL pathways. To understand the alteration of gene expressions in UC cells caused by hydrostatic pressure and MMC, oligonucleotide microarray was used to explore all of the differentially expressed genes. After bioinformatics analysis and gene annotation, Toll-like receptor 6 (TLR6) and connective tissue growth factor (CTGF) showed significant up-regulation among altered genes, and their expressions with each treatment of UC cells were validated by quantitative real-time PCR (qPCR). We conclude that under treatment with MMC and hydrostatic pressure, UC cells showed increasing apoptosis via extrinsic pathways through upregulation of TLR6 and CTGF.

overall_design: BFTC905 cells, a UC cell line, were cultured in the presence of 10 μg/ml of MMC for 2.5 hours. The MMC-treated cells were then incubated in a well-designed hydrostatic bioreactor for 10 kPa pressure treatment in duplicate or were cultured as usual to be used as control sets.

first: Shao-Kuan

first: Chih-Ang

last: Chung

first: Yu-Che

last: Cheng

first: Chi-Jung

last: Huang

first: Wen-Yih

first: Ruoh-Chyu

last: Ruaan

first: Chuan

last: Li

first: Chia-Wen

last: Tsao

first: Wei-Wen

last: Hu


title: Genome-wide LOH and DNA copy number alteration in HPV-neg OSCC and their associations with disease-specific survival

status: Public on Mar 23 2016

first: Chu

last: Chen

address: 1100 Fairview Ave. N, PO Box 19024, M/S M5-C800

department: PHS

institute: Fred Hutchinson Cancer Research Center

summary:
Oral squamous cell carcinoma (OSCC) is associated with high case-fatality. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we examined paired DNA from peripheral blood and tumor cells to assess genome-wide LOH and DNA copy number alteration (CNA) and their associations with risk factors, tumor characteristics, and disease-specific mortality among 75 patients with HPV-negative OSCC.
We found a highly heterogeneous and complex genomic landscape of HPV-negative tumors, and identified regions in 4q, 8p, 9p, and 11q that seem to play an important role in oral cancer biology and survival from this disease.

overall_design: We used Affymetrix 6.0 SNP arrays to test paired DNA from peripheral blood and tumor cells isolated by laser capture microdissection from 75 patients with HPV-negative OSCC. Peripheral blood DNA is used as reference for CNA to LOH.

first: Yuzheng

last: Zhang

first: Melissa

middle: M

last: Loomis

last: Upton

first: Pawadee

last: Lohavanichbutr

first: John

last: Houck

first: David

last: Doody

first: Eduardo

last: Mendez

first: Neal

last: Futran

first: Stephen

last: Schwartz

first: Pei


title: Affymetrix SNP array data for B-lineage acute lymphoblastic leukemia

status: Public on Mar 01 2016

city: Rome

first: Monica

last: Messina

address: Via Benevento 26

department: Department of Cellular Biotechnologies and Hematology

country: Italy

institute: Sapienza University

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

summary:
To shed light on the molecular bases of B-lineage acute lymphoblastic leukemia lacking known rearrangements (B-NEG ALL) and the differences between children and adults, we analyzed 168 B-NEG ALLs - including children, adolescents/young adults (AYA) and adults by genome-wide technologies, namely Next-generation sequencing and copy number aberration (CNA).
Affymetrix SNP array analysis was performed according to the manufacturer's directions on DNA extracted from bone marrow sampled at diagnosis and paired germline DNA extracted from peripheral blood/bone marrow at complete remission or saliva.

overall_design: Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 13 B-NEG ALL samples and their paired normal (non-tumoral) DNA samples, included in the discovery panel, processed in the same experiment and deposited.

first: M


title: Notch1 Signaling Regulates the Aggressiveness of Differentiated Thyroid Cancer and Inhibits SERPINE1 Expression

city: Madison

first: Brian

last: Johnson

state: WI

address: 1400 University Ave

department: Oncology

institute: UW-Madison

summary: To identify novel down-stream effectors of Notch1 signaling, we have employed cDNA microarray expression profiling as a discovery platform.   Human follicualr thyroid carcinoma cell line FTC236 was engineered with tet-on inducible system to establish a stable cell line.  The stable cell line FTC236-Notch1 showed robust inducibility with doxycycline, which triggers the expression of Notch1 intracellular domain (NICD).  The mRNA samples from FTC236-Notch1 cells with or without doxycline treamtment were analyzed in this assay.  Top 50 gene sequences were identified as of the most significance which distinguished between doxycycline treated samples and control samples.   Expression of SERPINE1, a down-regulated gene duing Notch1 activation from this signature, was quantified in the same RNA samples by real-time PCR.  The protein level was further confirmed by Western blot that restoration of NICD inhibits the expression of SERPINE1.

overall_design: NICD induced gene expression in human follicular thyroid cancer cell line was measured at 48 hours after exposure to doses of 0, and 1 ug/mL of doxycycline.  Three independent experiments were performed at separate time.

first: Xiao-Min

last: Yu

first: Herbert


title: Affymetrix Genome-Wide Human SNP Array 6.0 data for Type II Enteropathy-associated T-cell lymphoma

status: Public on Mar 03 2016

first: Sanjanaa

last: Nagarajan

state: Singapore

department: Department of Medical Sciences

institute: National Cancer Centre Singapore

summary: Type II Enteropathy-associated T-cell lymphoma (Type II EATL) is an aggressive intestinal T-cell lymphoma with poor prognosis and has not been molecularly profiled. Through targeted amplicon sequencing, we identified a large portion of Type II EATL samples that harbor mutations in the STAT5B, JAK3 and GNAI2 genes. Genome-wide DNA copy number profiling of Type II EATL tumors and matched normal samples was performed to determine copy-number changes in this disease.

overall_design: Affymetrix SNP6 arrays were performed according to the manufacturer's directions on gDNA extracted from 4 tumors and 4 matched whole blood samples.

first: Maarja

last: Nairismägi

first: Choon

last: Ong


title: Type II Enteropathy-associated T-cell lymphoma

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

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

overall_design: Refer to individual Series


title: Effect of bone marrow-specific aryl hydrocarbon receptor (Ahr) gene knockout on expression profiles of hematopoietic stem cells from young and old mice.

status: Public on Jun 30 2016

last: Welle

state: NY

address: 601 Elmwood Avenue

institute: University of Rochester

summary: As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from bone marrow restricted conditional Ahr-knockout and AhR floxed mice. HSC from young-adult (8 wk old) cAhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in Ahr-KO mice. Aged cAhR-KO mice (18 months old) also displayed alterations in peripheral white blood cell counts, serial repopulation potential and levels of ROS in bone marrow cells, consistent with previous observations on the role of AhR in the hematopoietic system.

overall_design: 22 samples: 5 young Ahr knockout, 6 old Ahr knockout, 5 young floxed Ahr, 6 old floxed Ahr

first: Kameshwar

last: Singh

first: Thomas

last: Gasiewicz


title: ROCK1 KD in U87 cells

status: Public on Jan 28 2016

city: Birmingham

last: Turan

address: University of Birmingham, Edgbaston

institute: University of Birmingham

summary:
ROCK1 KD in U87 cells
Samples were collected at 24h or 48h after siRNA ROCK1 transfection or control siRNA (NSC) in U87 cells

overall_design: 3 replicates for control and 3 replicates for ROCK1 KD in U87 cells at 24h.

first: Philipp

last: Antczak

first: Neil

last: Hotchin

first: Francesco

last: Falciani


title: Genome-wide association and epistatic studies in sporadic medullary and juvenile papillary thyroid carcinomas

status: Public on Feb 01 2016

city: Valencia

first: Joaquin

last: Dopazo

state: Valencia

address: Eduardo Primo Yúfera, 3

department: Systems Biology

institute: Centro de Investigacion Principe Felipe

summary: Although many genetic studies on thyroid cancers using different approaches have been conducted, just a few loci have been systematically associated. Given the difficulties to obtain single-loci associations this work focuses on the study of epistatic interactions that could help to understand the genetic architecture of complex diseases and explain new heritable components of genetic risk. To our knowledge, this is the first genome-wide epistatic screening for epistasis ever performed in thyroid cancer. Here, we analyzed both sporadic medullary thyroid cancer (sMTC) and juvenile papillary thyroid cancer (PTC) patients. We have identified two significant epistatic gene interactions in sMTC (CHFR-AC016582.2 and C8orf37-RNU1-55P) and three in juvenile PTC (RP11-648k4.2-DIO1, RP11-648k4.2-DMGDH and RP11-648k4.2-LOXL1). Interestingly, each interacting gene pair included a non-coding RNA, providing thus support to the relevance that these elements are increasingly gaining to explain cancer development and progression. Overall, this study contributes to the understanding of the genetic basis of thyroid cancer susceptibility in two different case scenarios such as sMTC and juvenile PTC. It opens further ways of knowledge of new heritable components of genetic risk to disease through association and statistical viewpoints.

overall_design: DNA derived from peripheral blood was hybridized to Affymetrix Genome-Wide Human SNP 6.0 arrays. Two different series of patients were recruited, one with 66 sporadic medullary thyroid cancer (sMTC) patients, with no family history suggestive of MEN 2. The second group compiled 30 juvenile patients with PTC (under 18 years of age) with no history of head and neck irradiation. Additionally, 129 healthy controls comprising unselected, unrelated, race, age, and sex-matched individuals without previous thyroid-related disease history were recruited.

first: Marta

last: Bleda

first: Luz

last: Garcia-Alonso

first: Ignacio

last: Medina

first: Cristina

middle: Y

last: Gonzalez

first: Raquel

last: Fernandez

first: Rocio

last: Nuñez-Torres

first: Berta

last: Luzon-Toro

first: Ana

last: Torroglosa

first: Martina

last: Marba

first: Maria

last: del Valle Enguix-Riego

first: David

last: Montaner

first: Guillermo

last: Antiñolo

first: Salud

last: Borrego


title: Real-time quantitative PCR analysis of male rat fed either Lard based or Corn Oil based high fat diet and their female offspring

status: Public on Jan 21 2016

city: Washington

first: Lu

last: Jin

address: 3970 Reservoir Rd NW

institute: Georgetown University

summary: Sperm cells from Sprague Dawley male rats fed different high fat diets (lard or corn oil based) and their 50-days-old female offspring mammary gland were used to perfom this array

overall_design: qPCR miRNA expression profiling. Sperm cells and mammary gland cells were harvested from male rats and their female offspring respectivly, as indicated in the summary. Equal amount total RNA from each animal was pooled prior to miRNA expression analysis.

first: Camile

middle: C

last: Fontelles


title: Affymetrix SNP array data from BM-CD138+, obtained from newly diagnosed Multiple Myeloma patients  [response to VTD therapy]

status: Public on Dec 31 2015

city: Bologna

first: Carolina

last: Terragna

address: Via Massarenti, 9

department: Department of Experimental, Diagnostic and Specialty Medicine - DIMES

institute: Institute of Hematology "L.A.Seràgnoli"

summary: The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is an early and deep tumour burden reduction; this characterizes and defines the complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC derived from MM patients who achieved CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy.  One hundred and eighteen MM primary tumours obtained from homogeneously treated patients were globally profiled both for gene expression and for single nucleotide polymorphism genotype. Genomic results were used to obtain a predictor of sensitivity to VTD induction therapy, as well as to describe both the transcription and the genomic profile of PC derived from patients with MM who will respond optimally to primary induction therapy.  By analysing the gene profiles of CR patients, we identified a 5-gene signature predicting CR with an overall median accuracy of 75% (range: 72%-85%). In addition, we highlighted the differential expression of a series of genes, whose deregulation, accordingly to their reported functions, might explain the CR patients’ sensitivity to VTD therapy. We also showed that a small copy number loss, covering 606Kb on chromosome 1p22.1 was the most significantly associated with CR patients.  The study provides insights into the genomic landscape of PC obtained from newly diagnosed MM patients achieving CR after VTD and shows that patients might be accurately stratified according to their sensitivity to VTD.

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic CD138+ cell fractions obtained from bone marrow samples.

first: Flores

middle: A

last: Dico

first: Marina

last: Martello


title: Affymetrix SNP6.0 array data for EBF1-PDGFRB rearranged acute lymphoblastic leukemia

status: Public on Apr 05 2016

city: Newcastle upon Tyne

first: Claire

middle: Joanne

last: Schwab

state: Tyne and Wear

address: Level 5, Sir James Spence Institute, Queen Victoria Rd

department: Northern Institute for Cancer Research

institute: Newcastle University

summary: The EBF1-PDGFRB gene fusion accounts for <1% B-cell precursor acute lymphoblastic leukaemia and occurs within the Philadelphia-like ALL subtype. We performed Affymetrix SNP 6.0 array was undertaken patients who tested positive for EBF1-PDGFRB rearrangement by FISH and/or RT-PCR.

overall_design: We performed Affymetrix SNP 6.0 array on genomic DNA extracted from bone marrow samples taken at diagnosis in 9 patients, at relapse in one patient and at remission in one patient.

first: Christine

last: Harrison


title: Co-expression networks in generation of induced pluripotent stem cells

city: Los Angeles

first: Giovanni

last: Coppola

address: 1524 Gonda, 695 Charles Young Drive South

department: Psychiatry and Neurology

institute: UCLA

summary: We developed an adenoviral vector, in which Yamanaka’s four reprogramming factors (RFs) were controlled by individual CMV promoters in a single cassette (Ad-GFP-SOcMK). This permitted coordinated expression of RFs (SOX2, OCT3/4, c-MYC and KLF4) in a cell for a transient period of time, synchronizing the reprogramming process with the majority of transduced cells assuming induced pluripotent stem cell (iPSC)-like characteristics as early as 3 days. These reprogrammed cells resembled human ES cells with regard to morphology, biomarker expression, and could be differentiated into cells of the germ layers in vitro and in vivo. These iPSC-like cells, however, failed to expand into larger iPSC colonies. The short and synchronized reprogramming process allowed us to study global transcription changes within short time intervals. Weighted Gene Co-Expression Network analysis (WGCNA) identified sixteen large gene co-expression modules, each including members of gene ontology categories involved in cell differentiation and development. In particular, the brown module contained a significant number of ES cell marker genes, whereas the turquoise module contained cell-cycle related genes that were downregulated in contrast to upregulation in human ESCs. Strong coordinated expression of all 4 RFs via adenoviral transduction may constrain stochastic processes and lead to silencing of genes important for cellular proliferation.

overall_design: Cells were dedifferentiated and gene expression assessed at 13 timepoints

first: Sharan

last: Paul

first: Lance

last: Pflieger

first: Warunee

last: Dansithong

first: Fuying

last: Gao

first: Stefan-M

last: Pulst


title: Expression profiles of normal hematopoietic stem and progenitor cells and acute myeloid leukemia sub-populations

status: Public on Jan 04 2016

city: Stanford

first: Andrew

last: Gentles

address: 1201 Welch Road

institute: Stanford University

summary: Acute Myeloid Leukemia AML is a cancer in which the process of normal cell hematopoietic differentiation is disrupted. Evidence exists that AML comprises a hierarchy with leukemic stem cells giving rise to more differentiated, but immature and functionally incompetent populations. The similarity of these AML subpopulations to normal stages of hematopoietic differentiation has not been dissected comprehensively at the transcriptional level. Here we introduce Normal Memory Analysis (NorMA), a data analysis method that extracts from omic data the remnants of the healthy normal-like phenotype. Applying NorMA to gene expression data from AML uncovered a wealth of information in the normal-like component of data: the normal hematopoietic memory of AML tumor cells. We found significant variation within the patient population, and we found strong association of this normal hematopoietic memory with survival. We found that undifferentiated NorMA phenotype has significantly worse survival than differentiated NorMA phenotype, showing that the NorMA classification of tumors captures a biologically meaningful stratification of patients, with highly significant survival association. Patients with NorMA phenotype in the undifferentiated Hematopoietic Stem Cell HSC stage had the worst survival, with median survival time under 6 months. We further found significant survival differences between tumor groups with differentiated NorMA phenotype, depending on their hematopoietic path: AML patients with NorMA phenotype in megakaryocyte-erythroid progenitor MEP stage had significantly better survival than those with NorMA phenotype in granulocyte-macrophage progenitor GMP stage. Thus NorMA produced a stratification of AML cohorts by differentiation stage, with significant outcome differences. It also provided clean molecular signatures for these stages. NorMA can be used in many other contexts, to explore for example the tumor cell of origin, or disease predisposition.

overall_design: Expression profiles of 104 normal and leukemic populations were obtained using Affymetrix microarrays

first: Bo

last: Dai


title: The effect of short-chain fatty acids (SCFAs) on human monocyte-derived dendritic cells (DCs)

status: Public on Dec 28 2015

city: Copenhagen N

first: Thomas

last: Litman

state: Outside the US or Canada

address: Blegdamsvej 3C

department: ISIM

country: Denmark

institute: University of Copenhagen

summary:
We investigated the influence of SCFAs on human, monocyte derived DCs that represent a reliable in vitro model to study circulating DCs, one of the key regulators of our immune system. We studied the individual effect exerted by SCFA, the main metabolic end-products of fermentation by anaerobic bacteria in the gut, on the gene expression of immature and mature DC, exploring the potential of circulating bacterial metabolites to directly influence immune system cells. We found that SCFAs have little effect on the transcriptome of immature DC, whereas the transcriptome of mature DC was highly perturbed especially by butyrate and propionate. Our findings show an overall down-regulation of LPS-induced inflammatory responses and provide new insights into host-microbiome interactions.
In this dataset, we include the expression data obtained from immature and matured (via lipopolysaccharide, LPS) human monocyte-derived dendritic cells untreated and treated with 1mM of acetate, butyrate, or propionate.

overall_design: Monocyte-derived dendritic cells were obtained from three different donors. We treated 1*10^6 cells with 1mM of acetate, or 1mM of butyrate, or 1mM of propionate. We purified total RNA from each treatment and pooled equal amounts of RNA from each donor for each treatment. We obtained 8 samples, including two controls: the immature dendritic cells and the matured (via lipopolysaccharide, LPS) dendritic cells.

first: Claudia

last: Nastasi

first: Anders

last: Woetmann


title: Human Papillary thyroid cancer cell line, BCPAP control vs. miR-146b-5p mimic transfected

status: Public on Dec 17 2015

city: Kaohsiung

first: Chen

middle: Kai

last: Chou

address: No.123, Dapi Rd., Niaosong Dist

institute: Chang Gung Memorial Hospital-Kaohsiung Medical Center

summary: Transcriptional profiling of human papillary thyroid cancer cells comparing control untreated BCPAP cells with BCPAP cells transfected with miR-145b-5p mimic.

overall_design: Two-condition experiment, BCPAP cells vs. miR-146b-5p transfexted BCPAP cells. Biological replicates: 1 control sample, 1 transfected sample.

first: Chen-Kai


title: Role of interferon-alpha in the activation of tubular epithelial cell in lupus nephritis (LN)

status: Public on Dec 15 2015

city: Bari

first: Fabio

last: Sallustio

state: Bari

address: Piazza G. Cesare N°11

institute: University of Bari

summary: Plasmacytoid dendritic cells (pDCs) play a key role in the activation of the autoimmune response in LN. Recently we demonstrated that these cells infiltrate the kidney of patients with LN at tubulointerstitial level. The pDCs are the main producers of IFN-alpha, whose effects on the renal tubule are poorly understood. The aim of the study was to investigate the effects of INF-alpha in renal epithelial cells (RPTEC). We investigated the effect of IFN-alpha on  the whole-genome gene expression profile in RPTEC cells,. Genomic analysis showed that after stimulation, 108 genes are up-regulated and only 7 are down-regulated, with a fold-change> 2. The Gene Set Enrichment analysis confirmed that  IFN-alpha induced the pathway of  antigen presentation and the inflammatory signaling in RPTEC. Among the up-regulated genes involved in these pathways, there were HLA-I, the ubiquitins (FBXO6 and DTX3L) and the immunoproteasome subunits LMP7. We performed the validation of these genes by real time PCR and citometry experiments on RPTEC stimulated with IFN-alpha. Immunohistochemical analysis of LMP7 and MXA protein, specific marker of IFN-alpha, showed a significant upregulatation of both proteins in renal biopsies of patients with LN class IV compared to class I. Confocal microscopy showed the colocalization of LMP7-MXA  in tubular epithelium of patients with LN class IV and activation of inflammatory signaling via NF-kB in the MXA+ tubules. Our data suggested that inhibition of INF-alpha pathways could represent a novel therapeutic strategy to reduce renal tubular damage in patients with LN.

overall_design: To identify genes specifically modulated by INF-alpha in RPTEC,  we stimulated 3 different cell clones with 100U/ml INF-alpha  for 48 hours and compared their whole-genome gene expression profiles with that from 3 RPTEC clones cultured without stimuli.

first: Cesira

last: Cafiero

first: Giuseppe

last: Castellano


title: Development of gene expression signatures for knockdown of synthetic lethal gene

status: Public on Dec 12 2015

city: Chuo-ku

first: Takashi

last: Kohno

state: Tokyo

address: 1-1, Tsukiji 5-chome

institute: National Cancer Center Research Institute

summary: We performed genome-wide expression profiling analysis to define the genes underlying the synthetic-lethal relationship between CBP and p300. We extracted 1,936 genes whose expression levels changed >2-fold upon p300-knockdown (KD) in CBP-KO cells, or upon CBP-KD in p300-KO cells, but not in either KD in wild-type cells

overall_design: Gene expression profile in human lung H1299, H1299 CBP KO, H1299 p300KO cells was measured at 48 hours after transfection of siNT, siCBP or sip300.  Two independent experiments were performed at each time (48 hours).

first: Hideaki

last: Ogiwara


title: Generation of a monoclonal antibody recognizing the CEACAM glycan structure and inhibiting adhesion using cancer tissue-originated spheroid as an antigen

status: Public on Dec 30 2015

city: Kyoto

first: Masahiro

last: Inoue

state: Kyoto

address: Med-Pharm Collaboration Bldg 503, Shimoadachi-cho 46, Sakyou-ku, Kyoto, 606-8304, Japan

department: Clinical Bio-resource Research and Development

institute: Kyoto Univ Graduate School of Medicine

summary: Spheroids cultured directly from tumours can better reflect in vivo tumour characteristics than two-dimensional monolayer culture or three-dimensional culture of established cell lines. In this study, we generated antibodies by directly immunizing mice with cancer tissue-originated spheroids from colorectal cancer. We performed phenotypic screening via recognition of the surface of the spheroids and inhibition of their adhesion to extracellular matrices to identify a monoclonal antibody, clone 5G2. The antibody inhibited cell migration in two-dimensional culture and promoted cell detachment. Western blotting and immunohistochemistry detected the 5G2 signal in many colorectal cancer spheroids, as well as patient tumours, but the signal was reduced in various cell lines. The expression pattern also changed when spheroids were cultured in two-dimensional conditions. We found that 5G2 recognized the N-glycan structure, including Lea and Lec, and their major carrier proteins were CEACAM5 and CEACAM6. Translocation of integrin 4 from the lateral membrane to the extracellular matrix contact interface in the spheroids was delayed by pre-incubation with 5G2. Thus, cancer tissue-originated spheroids can be a useful antigen for generating novel anti-cancer antibodies as the glycan structure is lost in cell lines but retained in cancer tissue-originated spheroids.

overall_design: Gene expression was compared in cancer tissue-originated spheroids (CTOSs) under floating conditions, under gel embeded conditions, CTOS-derived xenograft tumors, and corresponding microdissected patient tumors. One experiment was performed for each sample.


title: C3A Cells: Exposure vs Control [one-channel arrays]

status: Public on Dec 09 2015

city: Amsterdam

first: Jessica

last: Legradi

address: De Boelelaan 1087

department: IVM

institute: VU Amsterdam

summary: Gene expression profiles comparing FCCP, CCCP, Dinoterb, Benzoapyrene, TCP, Medium control, 0,1% DMSO in C3A cells

overall_design: C3A cells were exposed for 2 hours to substances, 6 replicate wells per concentration were pooled. Total RNA was extracted using RNeasy Mini Kit (QUIAGEN, Product 74104, Hombrechtikon, Switzerland). Quality of extracted RNA was checked via the Nanodrop 1000 spectraphotomoeter V3.7, as well as running the samples on a 1.5% agarose gel. cDNA was generated and labeled with Cy3 or Cy5-CTP using the low RNA input linear amplification kit (Perkin-Elmer). Total RNA was reverse transcribed to cDNA using RNasin® Plus RNAse Inhibitor (N2611), M-MLV Reverse transcriptase (RNase H Minus, Point Mutant) (M3682),  5x Buffer (M3682) and random primer  (C1181) from Promega AG (product number in brackets) (Promega AG, Dübendorf, Switzerland). For Microarray analysis Agilent SurePrint G3 Human Gene Expression Microarrays (8x60K) were used. Each treatment consisted of two biological replicates, the control consisted of three biological replicates.

first: Alessa

last: Hawliczek-Ignarski


title: Transcriptomics of circulating human eosinophils

status: Public on Dec 10 2015

city: Illkirch

first: Doulaye

last: Dembele

address: 1 rue Laurent Fries

department: Biopuces

institute: IGBMC

summary: Global expression pattern in eosinophils in various conditions such as eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis.

overall_design: Eosinophil were isolated from peripheral blood by FACS from 4 hypereosinophilic conditions: eosinophilic asthma (4 replicates), hypereosinophilic dermatological diseases (3 replicates), parasitosis (3 replicates) and pulmonary aspergillosis (4 replicates).

first: Cindy

last: Barnig

first: Ghada

last: Alsaleh

first: Nicolas

last: Jung

last: Dembélé

first: Nicodème

last: Paul

first: Anh

last: Poirot

first: Béatrice

last: Uring-Lambert

first: Philippe

last: Georgel

first: Fréderic

last: de~Blay

first: Seiamak

last: Bahram


title: Mode of toxic action assignment of chemicals


title: Transcriptome profiling of bovine inner cell mass and trophectoderm derived from in vivo generated blastocysts

status: Public on Dec 02 2015

city: Québec City

first: Marc-André

last: Sirard

address: Offfice 2732, 2440 Hochelaga Blvd.

department: Sciences Animales

institute: Université Laval

summary: This study describes the generation and analysis of the transcriptional profile of bovine inner cell mass (ICM) and trophectoderm (TE), obtained from in vivo developed embryos by using a bovine-embryo specific array (EmbryoGENE) containing 37,238 probes.

overall_design: Four replicates of bovine inner cell mass (ICM) and four replicates of trophectoderm (TE), obtained from in vivo developed embryos recolted at day 7.5 post-insemination. TE was used as reference (control). The hybridization were done in a dye-swap design.

first: Sayyed

last: Hosseini

first: Isabelle

last: Dufort

first: Caballero

last: Julieta

first: Fariba

last: Moulavi

first: Hamid

middle: R

last: Ghanaei

first: Marc


title: C3A Cells: Exposure vs Control [two-channel arrays]

first: Jessica

last: Legradi

summary: Gene expression profiles comparing FCCP, CCCP, 6OH-BDE47, Ethylenglycol, TCP, PCP, Aniline, chloroaniline, DMSO in C3A cells

overall_design: C3A cells were exposed for 2 hours to substances, 6 replicate wells per concentration were pooled. Total RNA was extracted using RNeasy Mini Kit (QUIAGEN, Product 74104, Hombrechtikon, Switzerland). Quality of extracted RNA was checked via the Nanodrop 1000 spectraphotomoeter V3.7, as well as running the samples on a 1.5% agarose gel. cDNA was generated and labeled with Cy3 or Cy5-CTP using the low RNA input linear amplification kit (Perkin-Elmer). Total RNA was reverse transcribed to cDNA using RNasin® Plus RNAse Inhibitor (N2611), M-MLV Reverse transcriptase (RNase H Minus, Point Mutant) (M3682),  5x Buffer (M3682) and random primer  (C1181) from Promega AG (product number in brackets) (Promega AG, Dübendorf, Switzerland). For Microarray analysis Agilent SurePrint G3 Human Gene Expression Microarrays (8x60K) were used. Each treatment and controls consisted of three biological replicates.

first: Alessa

last: Hawliczek-Ignarski


title: Effect of rBC2LCN 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: We show a recombinant lectin probe, rBC2LCN, is a new tool for fluorescence-based imaging and flow cytometry analysis of human pluripotent stem cells, as an alternative to conventional pluripotent maker antibodies. Live or fixed colonies of both human embryonic stem cells and induced pluripotent stem cells were visualized using fluoresceinated rBC2LCN. Fluoresceinated rBC2LCN also separated live pluripotent stem cells from mixed cell population by flow cytometry.

overall_design: Induced gene expression in human ES cells was measured at 3 days treatment of rBC2LCN lectin. WA01 (H1) cells were treated with 1, 10 and 100 ug/ml of rBC2LCN or 1 of FITC-rBC2LCN for three days. Two independent experiments were performed at each treatment experiment. Samples of human ES cells (KhES-1 and 3), human iPS cells (201B7 and 253G1) and HDF in each conventional culture condition were used for outgroup examples.

first: Yasuko

last: Onuma


title: Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia

status: Public on Dec 01 2015

city: Nantes

first: Karim

last: Si-Tayeb

address: 8,quai Moncousu

institute: l'institut du thorax, UMR INSERM1087 / CNRS6291, IRS-UN

summary: Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. We aimed to validate urine-sample-derived human induced pluripotent stem cells (UhiPSCs) as an appropriate tool to model PCSK9-mediated ADH and FHBL. To achieve our goal, urine-sample-derived somatic cells were reprogrammed into hiPSCs by using episomal vectors. UhiPSC were efficiently differentiated into hepatocyte-like cells (HLCs). Compared to control cells, cells originally derived AQ3 from an individual with ADH (HLC-S127R) secreted less PCSK9 in the media (−38.5%; P=0.038) and had a 71% decrease (P<0.001) of low-density lipoprotein (LDL) uptake, whereas cells originally derived from an individual with FHBL (HLC-R104C/V114A) displayed a strong decrease in PCSK9 secretion (−89.7%; P<0.001) and had a 106% increase (P=0.0104) of LDL uptake. Pravastatin treatment significantly enhanced LDL receptor (LDLR) and PCSK9 mRNA gene expression, as well as PCSK9 secretion and LDL uptake in both control and S127R HLCs. Pravastatin treatment of multiple clones led to an average increase of LDL uptake of 2.19±0.77-fold in HLC-S127R compared to 1.38±0.49 fold in control HLCs (P<0.01), in line with the good response to statin treatment of individuals carrying the S127R mutation (mean LDL cholesterol reduction=60.4%, n=5). In conclusion, urine samples provide an attractive and convenient source of somatic cells for reprogramming and hepatocyte differentiation, but also a powerful tool to further decipher PCSK9 mutations and function.

overall_design: Gene expression of untreated cells in culture was performed. 2 samples are from a healthy donor, 2 samples are from a patient carrying the PCSK9 S127R GOF mutation, 3 samples are hiPS reprogrammed from the healthy donor's cells and 3 samples are hiPS reprogrammed from patient's cells.


title: A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency (Family B)

status: Public on Nov 25 2015

city: Boston

first: Raif

middle: S.

last: Geha

state: MA

address: 1 Blackfan Circle, Karp 10

department: Division of Immunology

institute: Boston Children's Hospital

summary:
Affymetrix 6.0 SNP data for haplotype comparison of patients from two different families sharing the same homozygous mutation in TFRC, to determine if the families were related to each other
Peripheral blood was used for patients who had no history of hematopoietic stem cell transplant (HSCT). Fibroblasts cell lines were used as a source of DNA for the individual who received HSCT.

overall_design: Genomic DNA from 3 subjects (2 from Family A, 1 from Family B in duplicate) was genotyped at 909,622 single nucleotide polymorphisms (SNPs) on the Genome-Wide Human SNP 6.0 Array (Affymetrix).

first: Haifa

middle: H

last: Jabara

first: Steven

middle: E

last: Boyden

first: Janet

last: Chou

first: Narayanaswamy

last: Ramesh

first: Michel

middle: J

last: Massaad

first: Halli

last: Benson

first: Wayne

last: Bainter

first: David

last: Fraulino

first: Fedik

last: Rahimov

first: Colin

last: Sieff

first: Zhi-Jian

last: Liu

first: Salem

last: Alshemmari

first: Basel

last: Al-Ramadi

first: Hasan

last: Al-Dhekri

first: Rand

last: Arnaout

first: Mohammad

last: Abu-Shukair

first: Anant

last: Vatsayan

first: Eli

last: Silver

first: Sanjay

last: Ahuja

first: E

last: Davies

first: Martha

last: Sola-Visner

first: Toshiro

last: Ohsumi

first: Nancy

last: Andrews

first: Luigi

last: Notarangelo

first: Mark

last: Fleming

first: Waleed

last: Al-Herz

first: Louis

last: Kunkel

middle: S


title: GENE TARGETS OF PALMITATE, OLEATE AND THEIR MIXTURE IN CULTURED LHCN-M2 MYOTUBES

city: Barcelona

first: Anna

middle: Maria

last: Gómez Foix

address: Diagonal 643

department: Bioquímica i Biologia Molecular

institute: Universitat de Barcelona

summary: A global transcriptomic study enables investigating human skeletal muscle gene targets of palmitate versus oleate and the capacity of oleate to alter palmitate-effects.

overall_design: LHCN-M2 myotubes were treated with 0.5 mM palmitate, 0.5 mM oleate or 0.25 mM palmitate plus 0.25 mM oleate (mixture) or not (controls) for 16 h. Changes in gene expression were analyzed by DNA microarray. The experimental design was a loop with 4 biological replicates.

last: Gómez-Foix

first: Maria

last: Guitart


title: A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency (Family A)

first: Raif

last: Geha

summary:
Affymetrix 6.0 SNP data for genome-wide linkage scans of a consanguineous Kuwaiti family with a combined immunodeficiency
Peripheral blood or saliva were used for patients who had no history of hematopoietic stem cell transplant (HSCT). Fibroblasts cell lines were used as a source of DNA for individuals who received HSCT.

overall_design: Genomic DNA from 32 subjects (5 affected and 27 unaffected) from Family A was genotyped at 909,622 single nucleotide polymorphisms (SNPs) on the Genome-Wide Human SNP 6.0 Array (Affymetrix).

first: Haifa

last: Jabara

first: Steven

last: Boyden

first: Janet

last: Chou

first: Narayanaswamy

last: Ramesh

first: Michel

last: Massaad

first: Halli

last: Benson

first: Wayne

last: Bainter

first: David

last: Fraulino

first: Fedik

last: Rahimov

first: Colin

last: Sieff

first: Zhi-Jian

last: Liu

first: Salem

last: Alshemmari

first: Basel

middle: K

last: Al-Ramadi

last: Al-Dhekri

middle: G


title: A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency

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

overall_design: Refer to individual Series


title: Next generation sequencing reveals the diversity and population-genetic properties of cattle CNVs

status: Public on Nov 04 2015

city: Beltsville

first: Derek

middle: Martens

last: Bickhart

address: Building 005, Rm 318, BARC-West 10300 Baltimore Ave

department: BARC

institute: USDA ARS

type: Genome variation profiling by genome tiling array

summary: Structural and functional impacts of copy number variations (CNVs) on livestock genomes are not yet well understood. In this study, we have identified 1853 CNV regions (CNVRs) using population-scale sequencing data generated from 75 cattle of 8 breeds (Holstein, Angus, Jersey, Limousin, Romagnola, Brahman, Gir and Nelore). Individual genome sequence coverage ranged from 4 to 30 fold, with a mean of 11.8 fold. A total of 3.1% (87.5 Mb) of the cattle genome is predicted to be copy number variable, representing a substantial increase over the previous estimates (~2%). This dataset was highly correlated with array CGH data (r2 = 0.761) and was validated to be accurate with an estimated 12% false positive rate and a 19% false negative rate based on qPCR and array CGH, respectively. Hundreds of CNVs were found to be either breed specific or differentially variable across breeds, including the RICTOR gene in dairy breeds and the PNPLA3 gene in the beef breeds. In contrast, clusters of the PRP and PAG genes are duplicated in all sequenced animals, implicating that subfunctionalization, neofunctionalization or overdominance play a role in diversifying these fertility related genes. Further population-genetic analyses based on CNVs revealed the population structures of these taurine and indicine breeds and uncovered hundreds of positively selected CNV candidates near important functional genes. These CNV results provide a new glimpse of diverse selections during cattle speciation, domestication, breed formation, and recent genetic improvement.

overall_design: 25 animals were analyzed using a custom Nimblegen aCGH chip with 2.1 million probes. The reference animal chosen was L1 Dominette, a Hereford cow of European ancestry. The array was subjected to a dye-swap with the reference sample to test probe intensity fidelity. Single channel intensity data from the array was used in a digital aCGH analysis to compare aCGH copy number estimates to copy number estimates derived from sequence data. Briefly, the reference signal from all analyzed arrays was collected and a median signal intensity was calculated from probe intensities within the BTF3 gene. The copy number of the reference animal was then inferred by division of single channel probe intensities with the median intensity of the BTF3 gene. Next, test sample intensities were normalized by taking the log2 ratio of the test intensity divided by the normalized reference copy number for the probe. CN values derived from sequence data were also normalized in this fashion by taking the log2 of the ratio of NGS CN divided by aCGH reference copy number.

first: George


title: Affymetrix SNP6 array data for NLPHL- and PMBCL-derived cell lines

status: Public on Oct 12 2015

city: Vancouver

first: Christian

last: Steidl

state: BC

address: 675 W 10th Avenue

department: Lymphoid Cancer Research

institute: BC Cancer Agency

summary:
We previously identified rearrangements involving CIITA, the master transcriptional regulator of MHC class II expression, as common mutational events in PMBCL and cHL. In order to inform on the prevalence and different types of structural genomic aberrations affecting CIITA in PMBCL and HL we performed high-resolution copy number analysis.
Affymetrix SNP6 arrays were performed according to the manufacturer's instructions on DNA extracted from cell lines.

overall_design: Copy number analysis of Affymetrix SNP6 arrays was performed for 1 NLPHL- and 3 PMBCL-derived cell lines.


title: Gene expression profiles of prostate cancer cell line with or without HDAC inihbitors

city: Nagoya

first: Shinya

last: Sato

address: kawasumi1, mizuho-ku

institute: Nagoya City University

summary: Histone deacetylase (HDAC) inibitors suppress cell proliferation of prostate cancer, but the detailed mechanisms are unknown. Moreover, HDAC includes 18 family members, namely HDAC1-11 and SIRT1-7, and differences of effects on prostate cancer proliferation among these enzymes are also unknown. Thus, we clarified differences of gene expression between prostate cancer cell line (LNCaP) treated with pan-HDAC inhibitors (TSA and OBP-801) or selective HDAC inhibitor (NCC-149, HDAC8-specific inhibitor)using cDNA microarray.

overall_design: LNCaP treated with TSA (1μM), NCC149 (2μM), OBP-801 (200nM) or DMSO for 24hrs, RNA was extracted from cells, and cDNA array was performed.


title: Combination testing using a single MSH5 variant alongside HLA haplotypes improves coeliac disease risk prediction in the Polish population

status: Public on Oct 15 2015

city: Warszawa

first: Krzysztof

last: Goryca

address: Banacha 2c

department: CeNT

country: Poland

institute: Uniwersytet Warszawski

summary:
Background. Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification of potential coeliac disease (CD) patients. We intended to identify new genetic variants associated with CD in the Polish population that would improve CD risk prediction when used alongside HLA haplotype analysis.
Results. Association analysis using four HLA-tagging SNPs showed that, as was found in other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, and HLA-DQ2.5/DQ8) were found at higher frequencies in CD patients than in healthy control individuals in the Polish population. Both CD-associated SNPs discovered by GWAS were found in the CD susceptibility region, confirming the previously-determined association of the major histocompatibility (MHC) region with CD pathogenesis. The two most significant SNPs from the GWAS were rs9272346 (HLA-dependent; localized within 1 Kb of DQA1) and rs3130484 (HLA-independent; mapped to MSH5). Specificity of CD prediction using the four HLA-tagging SNPs achieved 92.9%, but sensitivity was only 45.5%. However, when a testing combination of the HLA-tagging SNPs and the MSH5 SNP was used, specificity decreased to 80%, and sensitivity increased to 74%.

overall_design: DNA samples of 336 CD and 264 unrelated healthy controls were used to create DNA pools (9 and 6, respectively) for a genome wide association study (GWAS). GWAS findings were validated with individual HLA tag singlenucleotide polymorphism (SNP) typing of 473 patients and 714 healthy controls.

first: Agnieszka

last: Paziewska

first: Bozena

last: Cukrowska

first: Michalina

last: Dabrowska

first: Magdalena

last: Piatkowska

first: Anna

last: Kluska

first: Michal

last: Mikula

first: Jakub

last: Karczmarski

first: Beata

last: Oralewska

last: Rybak

first: Jerzy

last: Socha

first: Aneta

last: Balabas

first: Natalia

last: Zeber-Lubecka

first: Filip

last: Ambrozkiewicz

first: Ewa

last: Konopka

first: Ilona

last: Trojanowska

first: Malgorzata

last: Zagroba

last: Szperl

last: Ostrowski


title: Diversity in Modulation of Interferon Stimulated Genes by Dobrava, Kurkino, and Sochi Genotypes of Dobrava-Belgrade Hantavirus in comparison to Tula Virus

status: Public on Nov 01 2015

city: Berlin

first: Daniel

last: Bourquain

state: Berlin

address: Seestraße 10

department: Centre for Biological Threats and Special Pathogens 1

institute: Robert Koch Institute

summary: We used an in vitro model to study the impact of hantavirus infection on the cellular gene expression profile. To do so, A549 cells were infected with pathogenic DOBV genotypes Dobrava, Kurkino, and Sochi and less-pathogenic TULV . A549 cells were chosen because of their high susceptibility towards hantavirus infection and because many fundamental studies on hantavirus biology and on host gene expression changes following infection have been performed with this cell line. Cells were infected at a high multiplicity of infection of 5 focus forming units (FFU) per cell to guarantee uniform infection of all cells. Total RNA from infected and mock-infected control cells was isolated at 12 h post infection. This point of time was chosen to allow enough time for establishment of infection and progression to early viral gene expression but to avoid the risk of missing gene expression changes associated with the onset of the cellular innate immune response towards infection. The distinct modulation of cellular transcription of A549 cells was analyzed by means of a whole genome cRNA microarray. All experiments were performed in duplicate using RNA samples from two independently infected cell cultures for each analysis. To compare the gene expression profiles, ratios were calculated by dividing the merged normalized signal intensities of infected samples by mock-control signal intensities. Genes that exhibited a ≥2-fold change (FC) in gene expression  and signal intensities that were significantly above the background with p-values ≤ 0.01 were chosen for further analysis. The successful infection of A549 cells with all viruses and the uniform progression of infection were confirmed by immunofluorescence microscopy of cells infected in parallel. At 12 h post infection with each virus nearly all cells were infected without showing cytopathic effects. Since different clinical courses are caused by infection with distinct DOBV genotypes, genotype-specific regulation of cellular transcripts were investigated that may be crucial for pathogenesis in vitro. Selected infection regulated candidates were verified by qPCR at different time points after infection.

overall_design: We analyzed the gene expression profile of A549 cells wich were either mock-infected or infected with Dobrava Virus (DOBV) Dobrava, Kurkino or Sochi, or with Tula Virus (TULV) at a multiplicity of infection of 5. Experiments were performed in duplicate. At 12 h post infection total RNA was isolated from infected cells and used for microarray analysis.

first: Peter

middle: T

last: Witkowski

first: Katrin

last: Bankov

first: Brita

last: Auste

first: Andreas

last: Nitsche

first: Piotr

middle: W

last: Dabrowski

first: Detlev

last: Krüger

first: Lars

last: Schaade


title: Effect of a JAK inhibitor on gene expression of HUT78 cell line

status: Public on Oct 31 2015

city: Santander

first: Nerea

last: Martinez

address: Avda Cardenal Herrera Oria

institute: IDIVAL

summary: Developing targeted therapy for cutaneous T cell lymphoma (CTCL) patients still requires actionable mutated genes and deregulated pathways to be identified. There is increasing evidence that activating mutations in JAK genes and deregulated JAK/STAT signaling are important mechanisms involved in multiple B and T cell malignancies, including CTCL. Therefore, in this study we focused on studying the mutational status of JAK1, JAK2 and JAK3 genes in a series of human CTCL lesions and cell lines using next-generation sequencing (NGS). We found that 7 of 48 (14.7%) of the analyzed cases harbored mutations in the JAK1 and JAK3 genes that mainly affected the pseudokinase domain of the corresponding proteins. On the basis of these results, we used a specific JAK inhibitor (INCB018424) in a series of CTCL cell lines with deregulated JAK/STAT activity. Treatment of CTCL cells with INCB018424 resulted in dose-dependent reduction of activated STAT expression, diminished cell viability, and increased apoptosis. We also studied global changes in gene expression in cells with mutated JAK1 and JAK3 proteins treated with INCB018424 and identified multiple genes that were differentially regulated by JAK/STAT signaling, such as FGF20 (upregulated) and EGR1 (downregulated). Thus, our results show that the detection of deregulated JAK/STAT signaling in CTCL lesions via JAK mutations or other surrogate markers may serve to indicate the clinical use of JAK/STAT inhibitors.

overall_design: 3 replicates of cells treated with DMSO or JAKi during 30 min and 3h


title: Affymetrix SNP array data for long time/short time survivors

status: Public on Oct 07 2015

city: New York

first: Douglas

last: Levine

address: 1275 York Ave.

department: Surgery

institute: MSKCC

summary:
Ovarian cancer is the seventh-most common cancer and the eight-most common cause of death from cancer in woman. Some women with ovarian cancer survive a long time (> 10yrs). We want to know if there’s a genetic difference between these long survivors and the broader population of interest.
Affymetrix SNP arrays were performed according to the manufacturer's directions on sample DNA.

overall_design: Copy number analysis of Affymetrix SNP arrays was performed for 12 short time and 12 long time OVCA survivor samples.

first: Anil

last: Sood


title: NF-kB activation confers a prolonged event-free-survival in newly diagnosed myeloma patients harboring t(4;14) treated with bortezomib.

status: Public on Sep 15 2015

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)

summary:
NF-kB pathway activation is the hallmark of hematological malignancies.
In multiple myeloma (MM), a large variety of genomic alterations leading to either inactivation of repressor such as TRAF3, CYLD or cIAP1/2 or amplification of activators such as CD40 or NIK collectively contribute to frequently deregulate NF-kB signaling.
In order to evaluate the prognostic impact of NF-kB mutations in MM, we performed a comprehensive analysis of a panel of newly diagnosed patients with cIAP1/2 biallelic deletion. We found that all patients have dysregulated NF-kB pathway and the majority of them presented t(4;14).
Then we analyzed clinical outcome of 37 MM at presentation with t(4;14) and treated with bortezomib according to their NF-kB status. We showed that increase of NF-kB activity confers prolonged event-free survival.
Altogether, our data suggest that NF-kB activation resulting from NF-kB mutations (ie cIAP1/2 deletion) or other mechanisms improves outcome of t(4;14)-positive MM treated with bortezomib.

overall_design:
NF-kB pathway examined for 34 myeloma patients with high resolution genome-wide chip

SUBMITTER_COMMENT: Relevant clinical data are included in the original paper, please read the article.

first: Florence

last: Magrangeas

first: Hervé

last: Avet-Loiseau

first: Loïc

last: Campion

first: Catherine

last: Guérin

first: Philippe

last: Moreau

first: Nikhil

last: Munshi

first: Stéphane

last: Minvielle