title: Expression data in HK-2 cells following exposure to Nnm_ld

overall_design:
Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to a low dose of Nnm or a control over 24 hrs or 48 hrs. Three biological replicates per compound/time-point.


title: Expression data in HK-2 cells following exposure to Fk

status: Public on Dec 31 2015

city: Dublin

first: Peadar

last: O'Gaora

address: Belfield

country: Ireland

institute: UCD

summary:
Background: The development of a new drug from candidate to market is a complex process requiring vast resources of time, money and personnel. The rate of failure in the development pipeline is enormous, leading to wasted resources that could have been better employed on alternative candidates. The requirement for early stage prediction of toxicity is, then, of paramount importance to expedite the introduction of new therapies to clinical practice. To date, most transcriptomics efforts to solve this problem have applied Support Vector Machine techniques to data derived from in vivo studies in rats.

Results: We applied a toxicogenomics approach to determine whether known renal toxicants could be identified as such from their effects on the transcriptome of the human renal proximal tubular epithelial cell line, HK-2. Based on clustering of differentially expressed genes, we identified 3 toxicity groups within the set of compounds. We used Random Forest to generate a classifier to accurately place compounds in groups.  The classifier is based on a signature biomarker comprising 21 genes identified by Random Forest and could differentiate between the groups with high accuracy. Furthermore, we could correctly classify external samples from a dataset exhibiting a marked ‘batch effect'.

Conclusions: No toxicity-associated gene expression alterations could be identified across a set of toxic compounds. Random Forest is a suitable technique for the classification of compounds into toxicity groups. Using a measure of differential expression rather than expression level per se generates a robust classifier that can potentially be applied in a platform-independent manner.

overall_design:
Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to Fk or control over 12 hrs or 48 hrs. Three biological replicates per compound/time-point.

first: Leonhard

middle: N

last: Gruber

first: Mohamed

middle: R

last: Daha

first: Michael

middle: P

last: Ryan


title: Expression data in HK-2 cells following exposure to Kbr_hd

summary:
Background: The development of a new drug from candidate to market is a complex process requiring vast resources of time, money and personnel. The rate of failure in the development pipeline is enormous, leading to wasted resources that could have been better employed on alternative candidates. The requirement for early stage prediction of toxicity is, then, of paramount importance to expedite the introduction of new therapies to clinical practice. To date, most transcriptomics efforts to solve this problem have applied Support Vector Machine techniques to data derived from in vivo studies in rats.

Results: We applied a toxicogenomics approach to determine whether known renal toxicants could be identified as such from their effects on the transcriptome of the human renal proximal tubular epithelial cell line, HK-2. Based on clustering of differentially expressed genes, we identified 3 toxicity groups within the set of compounds. We used Random Forest to generate a classifier to accurately place compounds in groups.  The classifier is based on a signature biomarker comprising 21 genes identified by Random Forest and could differentiate between the groups with high accuracy. Furthermore, we could correctly classify external samples from a dataset exhibiting a marked ‘batch effect’.

Conclusions: No toxicity-associated gene expression alterations could be identified across a set of toxic compounds. Random Forest is a suitable technique for the classification of compounds into toxicity groups. Using a measure of differential expression rather than expression level per se generates a robust classifier that can potentially be applied in a platform-independent manner.

overall_design:
Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to a high dose of Kbr or a control over 24 hrs or 48 hrs. Three biological replicates per compound/time-point.


title: Expression data in HK-2 cells following exposure to Aa_ld

overall_design:
Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to a low dose of Aa or a control over 24 hrs or 48 hrs. Three biological replicates per compound/time-point.


title: Expression data from miR-224 expressing cells versus control cells

city: Singapore

first: Yu

last: Wang

address: 11 Hospital Drive

department: Biochemistry

country: Singapore

institute: National University of Singapore

summary: miR-224 is up-regulated in hepatocelluar carcinoma. We mimicked mir-224 over-expression by transfecting 50 nM of miR-224 precursor molecules or control oligos into HCT116 cells with low miR-224 endogenous levels

overall_design: Cells were harvested 24 hours post transfection. Expression profiling was performed on three pairs of miR-224 or control transfected cells from three independent experiments

first: Wang

last: Yu


title: Gene signature of the post-Chernobyl papillary thyroid cancer

city: Warsaw

first: Michal

last: Swierniak

address: Banacha 2C

department: Centre of New Technologies

country: Poland

institute: University of Warsaw

summary:
Thyroid gland is among the most sensitive organs to ionizing radiation. Whether low-dose radiation-induced papillary thyroid cancer (PTC) differs from sporadic PTC is yet unknown.
We used microarrays to identify gene signature of radiation-induced papillary thyroid carcinomas

overall_design: To identify molecular differences between radiation-induced (Exposed to Chernobyl Radiation, ECR) and sporadic PTC, we investigated 65 childhood/young adult PTC samples using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus). The PTC samples were from patients born either before (33 ECR cases) or at least 9 months after (32 non-ECR cases) the Chernobyl catastrophe. Multofactoral analyses were performed in order to define some additional factors that could have impact on the gene expression profile. Morover the microarray data were validated with the QPCR reaction and exon arrays.

first: Barbara

last: Jarzab


title: Expression data in HK-2 cells following exposure to Aa_hd

overall_design:
Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to a high dose of Aa or a control over 24 hrs or 48 hrs. Three biological replicates per compound/time-point.


title: Expression data in HK-2 cells following exposure to CsA (external  dataset 2)

overall_design:
Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to CsA or control over 12 hrs or 48 hrs. Three biological replicates per compound/time-point.


title: Expression data in HK-2 cells following exposure to CsA

overall_design:
Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to CsA or control over 12 hrs, 24 hrs, or 48 hrs. Three biological replicates per compound/time-point.


title: Expression data in HK-2 cells following exposure to CdCl

overall_design:
Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to CdCl or control over 12 hrs or 48 hrs. Three biological replicates per compound/time-point.


title: Expression data in HK-2 cells following exposure to CsA (external dataset 1)


title: Expression data from four stage of hUC-MSCs

status: Public on Dec 30 2015

city: Chongqing

first: xiaoqin

last: zhou

address: Zhongshan Er Road

country: China

institute: Children's hospital of Chongqing medical university

summary:
hUC-MSCs exhibit the biological characteristics and potential for neural differentiation.The different gene involved in the neural differentiation were not clear.
We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during the process of neural differentiation.

overall_design: Human umbilical cord derived mesenchymal stem cells were induced in vitro, RNA extraction and hybridization on Affymetrix microarrays were performed on the cells at successive four stages. We sought to obtain the gene expresssion pattern in the four stage of hUC-MSCs.

first: Zhou

last: Xiaoqin

first: Gu

last: Jialu


title: High-resolution transcriptome analysis reveals neuropathic pain gene-expression signatures in spinal microglia after nerve injury

city: Seoul

first: Seog Bae

last: Oh

address: 101 Daehakro, Jongno-Ku

country: South Korea

institute: Seoul National University

summary:
Microglia activation contributes to the development of neuropathic pain.
To identify changes of microglial gene expression during their activation after peripheral nerve injury, we employed microarray analysis of individually collected pools of 10 spinal microglia cells

overall_design: After the L4 SNT, spinal cords of mice were used for microarray experiments at POD1 and POD7. Six biologically independent hybridizations were performed for each condition. cDNA was synthesized from pooled ten microglia which were collected from three spinal cord slices of an individual mouse and then used for each microarray chip.

first: Heejin

last: Jeong

first: Young-Ji

first: Kihwan

last: Lee

first: Yong

middle: H

last: Kim

first: Yunsin

first: Minho

last: Kang

first: Bao-Chun

last: Jiang

first: Young

middle: I

last: Yeom

first: Long-Jun

last: Wu

first: Junhyong

first: Seog

middle: B

first: Yong-Jing

last: Gao


title: The ETS transcription factor Elf5 drives lung metastasis in luminal breast cancer via recruitment of Gr-1+CD11b+ myeloid derived suppressor cells [chronic]

city: Sydney

first: Daniel

last: Roden

state: NSW

address: 384 Victoria Street

country: Australia

institute: Garvan Institute

summary: Elf5 expression in mammary progenitor cells regulates a cell fate decision that establishes the alveolar cell lineage. In luminal breast cancer cells, increased Elf5 expression suppressed estrogen receptor and FoxA1 expression and was implicated in the acquisition of resistance to the cytostatic effects of antiestrogen therapy. We show that in the PyMT model of luminal breast cancer, increased Elf5 expression drives lung metastasis by recruiting myeloid-‐derived suppressor cells, and that this activity overcomes the epithelializing influence of Elf5. Breast cancer expression signatures identify a similar process in humans, and increased Elf5 immunohistochemical staining predicts poor prognosis in the luminal A subgroup. Thus Elf5 may promote escape from hormonal therapy and drive metastasis in luminal breast cancer.

overall_design: Gene expression analysis of wild-type PyMT mammary tumors, mammary tumors from chronic (8 weeks) Elf5 dox induced expression (EGFP+ sorted) with control comparison (EGFP- sorted), and Elf5/EGFP+ lung metastasis

first: David

last: GallegoOrtega

first: Anita

last: Ledger

middle: L

first: Christina

last: Cho

first: Stephanie

last: Allerdice

first: Heather

middle: J

first: Fatima

last: Valdes-Mora

first: Adelaide

last: Young

first: Brian

middle: Y

first: Warren

last: Kaplan

first: Robert

last: Salomon

first: Catherine

last: Piggin

last: Rabinovich

first: Ewan

last: Millar

first: Samantha

last: Oakes

first: Tatyana

last: Chtanova

first: Alexander

last: Swarbrick

first: Matthew

last: Naylor

first: Sandra

last: O'Toole

first: Julia

middle: M

last: Gee

first: Ian

last: Ellis

first: Susan

last: Clark

first: Christopher

last: Ormandy


title: Gene expression changes in HK-2 cells following exposure to nephrotoxic compounds

first: Peadar

last: O'Gaora

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

overall_design:
Refer to individual Series

Aa: Aristolochic acid
CdCl: Cadmium chloride
CsA: Cyclosporine A
Di: Diquat dibromide
Fk:  FK506
KBr: Potassium bromate
Nnm: N-Nitrosomorpholine
Ota: Ochratoxin
Ra: Rapamycin
hd: High dose
ld: Low dose


title: The ETS transcription factor Elf5 drives lung metastasis in luminal breast cancer via recruitment of Gr-1+CD11b+ myeloid derived suppressor cells

first: Daniel

last: Roden

overall_design: Refer to individual Series


title: The ETS transcription factor Elf5 drives lung metastasis in luminal breast cancer via recruitment of Gr-1+CD11b+ myeloid derived suppressor cells [acute]

overall_design: Gene expression analysis of acute (1 week) Elf5 dox induced expression (EGFP+ sorted) with control comparison (EGFP- sorted)

first: David

last: GallegoOrtega

first: Anita

last: Ledger

first: Christina

last: Cho

first: Stephanie

last: Allerdice

first: Heather

last: Lee

first: Fatima

last: Valdes-Mora

first: Adelaide

last: Young


title: Expression data in HK-2 cells following exposure to Di

overall_design:
Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to Di or control over 12 hrs or 48 hrs. Three biological replicates per compound/time-point.

first: Leonhard

last: Gruber

first: Mohamed

last: Daha

first: Michael

last: Ryan


title: Identification of negative feedback regulators in response to acute activation of BCR-ABL1 kinase signaling in MLL-AF4 and E2A-PBX1 acute lymphoblastic leukemia

status: Public on Dec 29 2015

city: San Francisco

first: Huimin

last: Geng

state: CA

address: 513 Parnassus Ave., MSB HSW 1201

department: Department of Laboratory Medicine

country: USA

institute: UCSF

summary: Human B cell lineage acute lymphoblastic leukemia (ALL) cells carrying MLL-AF4 (SEM; BEL) and E2A-PBX1 (697) gene rearrangements were transduced with the mouse ecotropic receptor to permit subsequent entry of retroviral BCR-ABL1 GFP and GFP empty vectors (EV) pseudotyped with murine ecotropic envelope. GFP expression was measured by flow cytometry. Transductions with BCR-ABL1 GFP and GFP empty vectors (EV) were performed in the presence and absence of 2 mmol/l Imatinib (TKI). Washout of Imatinib in one series of experiments is indicated with an arrow. To study gene expression changes in MLL-AF4 and E2A-PBX1 B cell lineage ALL cells that were transduced with empty vectors (EV), BCR-ABL1 GFP in the presence of Imatinib (BCR-ABL1 OFF), washout of Imatinib (BCR-ABL1 ON) and subsequent re-addition of Imatinib, microarray analyses were performed.

overall_design: Three ALL cell lines (SEM, BEL and 696) were tranduced with BCR-ABL1 GFP and GFP empty vectors (EV) in the presence and absence of 2 mmol/l Imatinib, then washout of Imatinib, and then subsequent re-addition of Imatinib

first: Markus

last: Muschen


title: Comparison of osteocyte-enriched bone from DMP1 cre Mbtps1 knockout mice with littermate controls.

city: Rensselaer

first: Sridar

middle: V

last: Chittur

state: NY

address: One Discovery Drive, CRC 342G

department: Center for Functional Genomics

institute: SUNY-University at Albany

summary: Purpose of arrays were to determine what the effect of deletion of Mbtps1 gene was on gene expression of osteocytes in bone in vivo.  DMP1 cre driver was used to delete the Mbtps1 gene in osteocytes and osteoblasts in bone.  We then isolated osteocyte enriched bone particles from 40 week old male mice to determine the effect of this deletion on gene expression.  We have previously shown that Mbtps1 is needed for transcription of Phex, DMP1, and MEPE genes in osteoblasts in culture.  Arrays showed these genes were reduced as expected in osteocytes in vivo.  Controls represent osteocyte enriched bone from 40 week old littermates.  Also, as expected, Mbtps1 expression was reduced in these knockout mice

overall_design: 4 control mice and 3 knock out mice were used in the analysis

first: Jeffrey

last: Gorski


title: Gene profiling of Tregs across inbred strains.

status: Public on Dec 23 2015

city: Boston

first: CBDM

last: Lab

state: MA

address: 77 Avenue Louis Pasteur

department: Microbiology and Immunobiology

institute: Harvard Medical School

summary: Gene-profiling of Tregs across inbred strains. There is a wide inter-individual range in the frequency of FoxP3+ Treg cells, but little is known about the underlying genetic or epigenetic mechanisms. We explored this issue accross inbred strains of mice. During this study, we established the gene expression profiles of Treg cells from the various inbred strains of mice.

overall_design: For each inbred strain of mice, CD4+ TCRb+ CD25hi Treg cells (50k)  from 9w old male (Jackson laboratory) were double sorted into Trizol. For BM Treg, cells were triple-sorted. Top 50% among CD25high cells were selected to ensure high Foxp3+ purity (over 99%). 2 biological replicates per condition. RNA was amplified, labeled and hybridized to Affymetrix Mouse Gene 1.0 ST Arrays (Expression Analysis).

first: Fabien

last: Depis

first: Diane

last: Mathis

first: Christophe

last: Benoist


title: Marked alterations of neutrophil functions during sepsis-induced immunosuppression

status: Public on Dec 28 2015

city: Lyon

first: Julien

last: Textoris

address: Hôpital Edouard herriot - Pavillon P; 5 place d'Arsonval

department: Medical Diagnostic Discovery Department (MD3)

country: France

institute: bioMérieux

summary:
Background: Severe septic syndromes deeply impair innate and adaptive immunity. While neutrophils represent the first line of defense against infection, little is known about their phenotype and functions during sepsis-induced immunosuppression. The objective of this study was thus to perform for the first time a global evaluation of neutrophil alterations in immunosuppressed septic patients based on phenotypic, functional and transcriptomic studies. In addition, the potential association of these parameters and deleterious outcomes was assessed.
Methods: Peripheral blood was collected from 9 septic shock patients at D3-4 and D6-8 presenting with features of sepsis-induced immunosuppression and compared to 8 healthy controls.
Results: In order to get on overview of potential neutrophil alterations after sepsis, we performed transcriptomic analyses on purified neutrophils from 9 septic shock patients and 8 healthy volunteers. For each time point, comparisons were made between patients and controls. Venn diagrams indicated that 364 up-regulated genes and 328 down-regulated genes were common between the two analyses (Supplementary Tables 1 and 2). Interestingly, most of the differentially expressed genes are involved in cell maturation (CD177), apoptosis (STK4, Caspase 8), cell recruitment and chemotaxis (CD44, TPST, MMP9, CREB1), and antimicrobial properties (ARG1, STOM, ADAM9, CD63, YKL40) of neutrophils.
Conclusions: The aim of the current study was to perform an extensive investigation of neutrophil alterations during sepsis-induced immunosuppression through phenotypic, functional and transcriptomic studies. Notably, transcriptomic study on purified neutrophils revealed differentially expressed genes between septic patients and healthy volunteers.

first: Julie

last: Demaret

first: Fabienne

last: Venet

first: Arnaud

last: Friggeri

first: Marie-Angélique

last: Cazalis

first: Jonathan

last: Plassais

first: Laurent

last: Jallades

last: Malcus

first: Françoise

last: Poitevin-Later

first: Alain

last: Lepape

first: Guillaume

last: Monneret


title: Gene expression profiling in 38 JMML patients and 9 healthy donors (Validation cohort)

city: padova

first: silvia

last: bresolin

state: padova

address: via giustiniani 3

department: department of women's and children's health

country: Italy

institute: università di padova

summary:
Juvenile myelomonocytic leukemia (JMML) is a very rare and aggressive stem cell disease that mainly occurs in young children. RAS activation constitutes the core component of oncogenic signaling. In addition, the leukemic blasts of a quarter of JMML patients present with monosomy 7 (-7), whereas more than half of the patients show enhanced age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care. This results in an event-free survival of 50 - 60%, indicating that novel molecular driven therapeutic options are urgently needed. Using gene expression profiling in an extensive series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression.
Interestingly, LIN28B overexpression was significantly correlated with higher HbF levels whereas patients with -7 seldom showed enhanced LIN28B expression. In line with LIN28B’s role as mediator of fetal hematopoiesis, this explains the biology behind the observation that patients with -7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7 microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Finally, high LIN28B expression was associated with poor clinical outcome in our JMML patient series, but not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified LIN28B as a crucial molecular player at the heart of a novel fetal-like subgroup in JMML.

overall_design: Gene expression was measured on Affymetrix in 38 JMML patients and 9 healthy donors in a validation cohort.

first: Silvia

last: Bresolin


title: In vitro effect of the integrine LAMA4 on motility and cluster formation of human chondrocytes

status: Public on Dec 22 2015

city: Graz

first: Karin

last: Wagner

state: Styria

address: Stiftingtalstrasse 24

department: Molecular Biology

country: Austria

institute: Medical University Graz

summary:
Background: Cluster formation of hypertrophic chondrocytes is a sign of late stage osteoarthritis. In vitro chondrocytes have the ability to migrate on scaffolds. Important for motility issues in cartilage are integrines, part of the extracellular matrix, important for locomotory stimuli. The integrine Laminin4 is highly present in hypertrophic clusters of chondrocytes. We were interested if a blockade of LAMA4 is leading to less cluster formation.

Methods: Human chondrocytes were cultured in a 2D matrixgel model and treated with different concentrations of a monoclonal anti-LAMA4-antibody.Migration habits were analysed using the cellobserver technique. An array analysis was performed before and after anti-LAMA4 treatment. The data set was screened for possible motility relevant genes. F-actin staining was performed to document cytoskeletal changes.

Results: Anti-LAMA4 treatment reduced significantly the rate of cluster formation in human chondrocytes. Cells changed their surface promoting fewer extensions. Genes for motility and migration associated processes were differentially expressed by anti-LAMA4 treatment.

Conclusion: LAMA4 blockade leads to less cluster formation in human chondrocytes in vitro. Anti-LAMA4 treatment suppresses filopodia expression, a possible explanation for less clustering. Interestingly anti-LAMA4 treatment seams to support a more milieu of earlier OA

overall_design: human chondrocytes were analysed untreated, IL-1 treated and 2A3 antibody treated

first: F

middle: C

last: Moazedi-Fuerst


title: Histone deacetylase inhibitors antagonize distinct pathways to suppress tumorigenesis of embryonal rhabdomyosarcoma.

status: Public on Dec 21 2015

city: Seattle

first: James

middle: William

last: MacDonald

state: WA

address: 4225 Roosevelt Way NE

department: Environmental and Occupational Health Sciences

institute: University of Washington

summary: Embryonal rhabdomyosarcoma (ERMS) is the most common soft tissue cancer in children and is characterized by myogenic differentiation arrest. The prognosis of patients with relapsed or metastatic disease remains poor.  ERMS genomes show few recurrent mutations, suggesting that other molecular mechanisms such as epigenetic regulation might play major role in driving ERMS tumor biology. In this study, we have demonstrated the diverse roles of HDACs in the pathogenesis of ERMS by characterizing effects of HDAC inhibitors, trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA; also known as vorinostat) in vitro and in vivo. TSA and SAHA suppress ERMS tumor growth and progression by inducing myogenic differentiation as well as reducing the self-renewal and migratory capacity of ERMS cells.

overall_design: To identify candidate genes that are differentially regulated in histone deacetylase inhibitor-treated embryonal rhabdomyosarcoma, a gene expression profiling study using the Affymetrix Human Gene 2.0 microarray platform and ingenuity pathway analysis of differentially expressed genes were performed on RD and 381T cells treated with trichostatin A or dimethyl sulfoxide (treatment vehicle).

first: Terra

last: Vleeshouwer-Neumann

first: Michael

last: Phelps

first: Theo

middle: K

last: Bammler

middle: W

first: Isaac

last: Jenkins

first: Eleanor

last: Chen


title: Pervasive polymorphic imprinted methylation in the human placenta

city: Vancouver

first: Wendy

last: Robinson

state: BC

address: 950 W 28th Ave

department: Medical Genetics

country: Canada

institute: University of British Columbia

type: Methylation profiling by genome tiling array

summary: The maternal and paternal copies of the genome are both required for mammalian development and this is primarily due to imprinted genes, those that are mono-allelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilisation.  There are a large number of germline DMRs that have not yet been associated with imprinting and their function in development is unknown.  In this study, we developed a genome-wide approach to identify novel imprinted DMRs, specifically in the human placenta, and investigated the dynamics of imprinted DMRs during development in somatic and extra-embryonic tissues.  DNA methylation was evaluated using the Illumina HumanMethylation450 array in 116 human tissue samples, publically available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas.  43 known and 101 novel imprinted DMRs were identified in the human placenta, by comparing methylation between diandric and digynic triploids and female and male gametes.  72 novel DMRs showed a pattern consistent with placental-specific imprinting and this mono-allelic methylation was entirely maternal in origin.  Strikingly, these DMRs exhibited polymorphic imprinted methylation specifically in placenta.  These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation

overall_design: For the identification of imprinted DMRs in the placenta, chorionic villous samples from 5 diandric and 5 digynic triploids pregnancies were assayed, along with a pooled sample of complete hydatiform moles (CHM). Placental chorionic villous samples (n=63) included 29 control pregnancies delivered at term, while the remaining 34 were delivered preterm or miscarried, or had abnormal MSS results,  IUGR or LOPET.  The preterm births were associated with one or more of: preterm labour, premature rupture of membranes (PROM), chorioamnionitis, placental abruption, and incompetent cervix.  All samples were determined to be chromosomally normal using standard karyotyping or comparative genome hybridization, as previously described (Robinson et al. 2010).  Two to four independent sites were taken from each placenta and after DNA extraction from chorionic villous, the DNA was pooled before being utilized in this study.  Thirty-three fetal tissues, including brain (n=8), spinal cord (n=7), muscle (n=9), and kidney (n=9) were collected from second trimester foetuses, as previously described (Price et al. 2012).  Adult female whole blood samples (n=10) were collected from control women.  Extra-embryonic cell types (n=19), including cord blood (embryonic), cord, amniotic membrane, chorionic membrane, 1st, 2nd and 3rd trimester trophoblast and mesenchyme, and decidua (maternal), were isolated from control placental samples.

first: Courtney

last: Hanna

first: Maria

middle: S

last: Peñaherrera

first: Heba

last: Saadeh

first: Simon

last: Andrews

first: Deborah

middle: E

last: McFadden

first: Gavin

last: Kelsey


title: The homeobox transcription factor Nkx2-1 regulates microRNAs controlling downstream gene silencing in lung epithelial cells (mRNA)

first: Joshua

middle: David

last: Campbell

address: 72 East Concord St.

institute: Boston University

summary: Cell-specific gene expression is achieved by a combination of mechanisms including transcriptional and post-transcriptional regulation. The transcription factor Nkx2-1, essential for lung cell differentiation, mainly acts in transcriptional activation but can directly or indirectly repress gene expression. microRNAs are a class of small non-coding RNA that control one of the major mechanisms of gene repression. To identify miRNAs regulated by Nkx2-1 that may mediate its repressing effects, we knocked-down Nkx2-1 in mouse lung epithelial cell lines and systematically identified targets by genome-wide miR and mRNA expression analyses. Nkx2-1 controls expression of miRs known to contribute to lung cell differentiation in development and disease and others not previously described. Amongst the significantly altered miRs, the mir-106a-363 cluster, miR-1195, miR-378, and miR-346 are directly correlated with the levels of Nkx2-1, whereas miR-200c/b, miR-221, and miR- 222 are inversely correlated. These miRNAs are expressed in embryonic lung at day E11.5, and/or E19.5 determined by in-situ hybridization. Expression of predicted targets of mir-1195, mir-346 and miR-200c and mir-221/222 were evaluated by mRNA expression microarrays in Nkx2-1 knockdown cells identifying those anti-correlated to the corresponding miRNA expression. Genes regulated by mir-1195, Cyp2s1 and Map3k2, by mir-346, Klf6, and miR-200c, Myb, Nfib, and Six1, were validated by qRT-PCR. Inhibition of mir-1195 confirms the inverse correlation of this miRNA with its putative targets Cyp2s1 and Map3k2. This miRNA-mRNA expression analysis identifies potential paths of Nkx2-1 mediated gene repression, and contributes to the understanding of gene regulation in lung epithelial differentiation and development.

overall_design: Nkx2-1 mRNA was knocked down in lung epithelial cells using a lentivirus expressing a shRNA targeting Nkx2-1 (n=3) and compared to empty vector controls (n=3).

first: Jean-Bosco

last: Tagne

first: Omar

last: Mohtar

middle: D

first: Meenakshi

last: Lakshminarayanan

first: Jingshu

last: Huang

first: Anne

last: Hinds

first: Jining

last: Lu

last: Ramirez


title: A Systems Approach to Understanding Human Rhinovirus and Influenza Virus Infection

first: Richard

last: Gelinas

address: 401 Terry Avenue North

institute: Institute for Systems Biology

summary:
Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Despite modest advances in the diagnosis and treatment of infections by these viruses, novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild.
In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days.  From these data, we constructed a transcriptional regulatory network model that revealed shared and unique host responses to these viral infections such that after a lag of 4-8 hours, most cell host responses were similar for both viruses, while divergent host cell responses appeared after 24-48 hours. The similarities and differences in gene expression after epithelial infection of rhinovirus, influenza virus, or both viruses together revealed qualitative and quantitative differences in innate immune activation and regulation. These differences help explain the generally mild outcome of rhinovirus infections compared to influenza infections which can be much more severe.

overall_design: Human bronchial epithelial cells (BEAS-2B) were infected with rhinovirus, influenza virus or both viruses and RNAs were then profiled at 10 time points (2, 4, 6, 8, 12, 24, 26, 48, 60 and 72hrs)

first: Taek-Kyun

last: Kim

first: Anjali

last: Bheda-Malge

first: Yakang

last: Lin

first: Koti

last: Sreekrishna

first: Rachel

last: Adams

first: Mike

first: Charles

last: Bascom

first: Jay

middle: P

last: Tiesman

first: Robert

last: Isfort


title: Insulator dysfunction and oncogene activation in IDH mutant gliomas

city: Jerusalem

first: Yotam

last: Drier

state: Israel

address: Faculty of Medicine, The Hebrew University, Ein Kerem

department: Immunology and Cancer Research

country: Israel

institute: The Hebrew University of Jerusalem

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Gain-of-function IDH mutations define major clinical and prognostic classes of gliomas. Mutant IDH protein produces a novel onco-metabolite, 2-hydroxyglutarate (2-HG), that interferes with iron-dependent hydroxylase enzymes, including the TET family of 5'-methylcytosine hydroxylases. TET enzymes are critical for the dynamic regulation of DNA methylation. IDH mutant gliomas thus manifest a CpG island methylator phenotype (G-CIMP), though the functional significance of this altered epigenetic state remains unclear. Here we show that IDH1 mutant gliomas exhibit hyper-methylation at CTCF binding sites, leading to reduced binding of this methylation-sensitive insulator protein. Loss of CTCF binding is associated with a loss of insulation between topological domains and aberrant gene activation. We specifically demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to aberrantly interact with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Treatment of IDH mutant gliomaspheres with demethylating agent partially restores insulator function and reduces PDGFRA expression. Conversely, CRISPR-mediated disruption of the CTCF binding sequence in IDH wildtype gliomaspheres induces PDGFRA expression and increases proliferation. Our study suggests that IDH mutations promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression.

overall_design:
CTCF occupancy characterization and histone H3K27 acetylation profiling in IDH1 mutant and wild-type glioma patient specimens and culture models.

ChIP-seq raw data is to be made available through dbGaP (controlled access) due to patient privacy concerns.

first: William

middle: A

last: Flavahan

first: Bradley

last: Bernstein


title: Comprehensive genomic analysis identify novel subtypes and targets of triple-negative breast cancer

city: Houston

first: Suzanne

last: Fuqua

state: Texas

address: 1 Baylor Plaza

institute: Baylor College of Medicine


title: Comprehensive genomic analysis identify novel subtypes and targets of triple-negative breast cancer (67 not triple-negative tumors)

summary:
Recent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
We identified and confirmed four distinct, stable TNBC subtypes: (1) Luminal-AR (LAR); 2) Mesenchymal (MES); 3) Basal-Like Immune-Suppressed (BLIS), and 4) Basal-Like Immune-Activated (BLIA).

overall_design: RNA profiling analyses were conducted on 198 TNBC tumors (ER-negativity defined as Allred Scale value ≤2) with >50% cellularity (discovery set: n=84; validation set: n=114)  and 67 not triple-negative tumors.

first: Matthew

last: Burstein

first: Anna

last: Tsimelzon

first: Susan

middle: G

last: Hilsenbeck

first: Graham

last: Poage

first: Kyle

last: Covington

first: Jenny

last: Chang

first: C

last: Osborne

first: Gordon

last: Mills

first: Ching

last: Lau

first: Powel

middle: H

last: Brown


title: The homeobox transcription factor Nkx2-1 regulates microRNAs controlling downstream gene silencing in lung epithelial cells

first: Joshua

last: Campbell

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

platform_organism:
Mus musculus
synthetic construct


title: Metabolic stress is a barrier to Epstein-Barr virus mediated B-cell immortalization

status: Public on Dec 19 2015

city: Durham

first: Karyn

last: Mcfadden

state: NC

address: 213 Research Drive

department: MGM

institute: Duke

summary:
Early after infection, Epstein-Barr Virus (EBV) induces a transient period of hyper-proliferation that is suppressed by the activation of the DNA damage response and a G1/S phase growth arrest. This growth arrest prevents long-term outgrowth of the majority of infected cells. We developed a method to isolate and characterize infected cells that arrest after this early burst of proliferation.
We used microarray analysis to uncover changes in gene expression that could  give us a better understanding of the pathways that attenuate immortalization.

overall_design: Human PBMCs were labeled with CellTrace Violet and infected with the B95-8 strain of EBV. At 4 days post-infection, the cells were labeled with a second proliferation dye, CFSE. Cells that proliferated  are called PP and those that initially proliferated and then arrested are called PA. Total mRNA was isolated from sorted PA and PP cells using an RNeasy kit . The RNA was processed using an Ambion MessageAmp Premier Package and hybridized to a Human Genome U133 Plus. 2.0 Chip by the Duke Center for Genomic and Computational Biology Microarray Core. The  resultant CEL files were RMA normalized (Partek) and the data was analyzed with GenePattern  and GSEA v2.

last: McFadden

first: Micah

last: Luftig


title: NFAT-dependent IL-2 and IL-23 produced by DC are key regulators of pathogenic   TH17-mediated lung inflammation

first: Michael

last: Poidinger

address: #04-06, 8A Biomedical Grove

department: Bioinformatics

institute: Singapore Immunology Network

summary: Calcineurin/NFAT/IL-2 signaling pathway is activated in dendritic cells (DC) upon encounter of β glucan, the main component of the fungal cell wall, raising the question about the role of NFAT-regulated genes in DC biology in vivo. To directly assess the function of IL-2 secreted by DC, we analyzed mice lacking of IL-2 in the DC lineage, CD4-expressing cells and with complete deletion of IL-2 in the germ line in a mouse model of pulmonary fungal infection. Here we found that specifically the loss of IL-2 in DC resulted in increased mice mortality upon the fungus Aspergillus fumigatus challenge and expansion of Th17 cells in the lung. We demonstrated that only CD103+DC were able to release IL-2 in acute phase of pulmonary Aspergillosis through the Ca2+-Calcineurin-NFAT signaling. We also found that NFAT mediates IL-23 transcription in lung DC, where IL-2 results essential in restraining the priming of a pathogenic infiltrating IL-17+Sca1+CD90+CD4+ cell with stem cell like properties. Thus, IL-2 and IL-23 secreted by DC in the lung have an antagonistic relationship on the Th17 differentiation program with IL-2 inducing T cell differentiation and IL-23 inducing a stem cell like molecular signature to Th17 cells upon Aspergillus challenge. DC-Il2-/- then confer the Th17 stemness, releasing IL-23 in response to the fungus contributing to the development of a Th17 cell effector population, particularly pathogenic in infection.

overall_design: D1 cells with no treatment, or treatment with different fungal types or antigens at 1, 4 and 6 hours, in triplicate, with the 3 untreated samples at 1hr also including techincal repeats

first: Teresa

last: Zelante

first: Alicia

last: Wong

first: Jan

last: Fric

first: Hock

last: Tay

first: Francesca

last: Zolezzi

first: Paola

middle: R

last: Castagnoli

first: Josephine

last: Lum


title: Changes in transcriptome during excisional cutaneous murine wound healing

city: Moscow

first: Evgeniy

last: Riabenko

address: 9 Institutskiy per.

department: Department of Control and Applied Mathematics

country: Russia

institute: Moscow Institute of Physics and Technology

summary:
Using microarray analysis, we explored the differences in gene expression in wounded and intact skin using murine model. Injured skin samples were examined at days 1 and 4 post injury.
The results provide the detailed molecular profile of the the genetic response to injury.

overall_design: Two full-thickness dermal wounds were made on the opposite sides of the midline of each mouse using a 4 mm punch biopsy instrument. Wounds were made through the epidermis, dermis, and subcutaneous tissue layers while leaving the fascia intact. At a specified time point after the wounding (1 and 4 days), mice were sacrificed by carbon dioxide inhalation. The wounds and surrounding tissues or intact skin samples were removed with an 8 mm biopsy punch.

first: A

last: Kostarnoy

first: P

last: Gancheva

first: E

first: D

last: Maltseva

last: Sakharov


title: Global gene expression in response to genetic and growth factor manipulation of TWIST1 expression and function

city: Jupiter

first: Siddaraju

middle: Valagerehalli

last: Boregowda

state: Florida

address: 130 Scripps Way

department: Molecular Medicine

institute: Scripps Florida

summary:
In addition to their stem/progenitor properties, mesenchymal stem cells (MSCs) also exhibit various effector functions  potent effector (angiogenic, anti-inflammatory, immune-modulatory) functions that are largely  paracrine in nature. It is widely believed that effector functions underlie most of the therapeutic  potential of MSCs and are independent of their stem/progenitor properties. Here we demonstrate  that stem/progenitor and effector functions are coordinately regulated at the cellular level by the  transcription factor Twist1 and specified within populations according to a hierarchical model.  We further show that manipulation of Twist1 levels by genetic approaches or by exposure to  widely used culture supplements including fibroblast growth factor 2 (Ffg2) and interferon  gamma (IFN-gamma) alters MSC efficacy in cell-based and in vivo assays in a predictable  manner. Thus, by mechanistically linking stem/progenitor and effector functions our studies  provide a unifying framework in the form of an MSC hierarchy that models the functional  complexity of populations. Using this framework, we developed a Clinical Indications  Prediction (CLIP) scale that predicts how donor-to-donor heterogeneity and culture conditions  impact the therapeutic efficacy of MSC populations for different disease indications.
We used microarrays to detail the global gene expression in response to genetic and growth factor manipulation of TWIST1 expression and function.

overall_design: Mesenchymal stem cells at subconfluent culture in growth media (CONTROL), or supplemented with FGF2 (20 ng/ml) (FGF2), trasfected with scrambled (SCRAMBLED) or TWIST1 siRNA (TWIST1) were used for RNA extraction and hybridization on Affimentrix microarrays. We pooled three independently extracted RNA samples per group.

first: Veena

last: Krishnappa

first: Christopher

middle: L

last: Haga

first: Luis

last: Ortiz

first: Donald

last: Phinney


title: Gene expression profile of collagen VI deficient human fibroblasts

status: Public on Dec 18 2015

city: Barcelona

first: Susana

last: Kalko

state: BARCELONA

address: c/Rosello 153

department: Bioinformatics Platform

country: Spain

institute: IDIBAPS

summary: In order to gain insight into the molecular pathogenesis of collagen VI defects we have performed gene expression microarray analysis of dermal fibroblasts. We have compared the transcriptome of fibroblasts, treated or untreated with ascorbic acid, from UCMD patients (n = 6) and aged-matched healthy children (n = 5).

overall_design: We analysed the gene expression profile of fibroblasts obtained from healthy control and ucmd children (23 in total). RNA was extracted and processed for further hybridization on Affymetrix microarrays (Affymetrix® Human Genome U219 Array Plate)

first: Cecilia

last: Jimenez Mallebrera


title: Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences

city: L'Hospitalet del Llobregat

first: Sebastian

last: Moran

state: Barcelona

address: Av. Gran Via de l'Hospitalet, 199-203

department: PEBC

institute: IDIBELL

summary: DNA methylation is the most well-known epigenetic mark and CpG methylation is critical for many cellular processes and human disorders. Cancer has highlighted the relevance of an aberrant DNA methylation landscape, including promoter CpG island hypermethylation-associated silencing of tumor suppressor genes and the presence of DNA hypomethylation blocks, but an altered DNA methylome is also now evident in other pathologies. However, progresses in delivering complete DNA methylation maps are compromised by the high price and labor and interpretation-consuming aspects of the single nucleotide methods nowadays used for whole genome bisulfite sequencing analyses. Following the success of the industry-leading HumanMethylation450 BeadChip (Infinium) methylation microarray that assess close to 450,000 CpG sites (450K), we have biologically and technically validated the newly developed MethylationEPIC BeadChip (Infinium) microarray that covers over 850,000 CpG methylation sites (850K). The 850K microarray contains >90% of the original 450K methylation sites, but add new 350,000 CpGs located in enhancers regions identified by the ENCODE and FANTOM5 projects. Herein, we show that the 850K DNA methylation array demonstrates high reproducibility for the previously analyzed CpG sites included in the 450K microarray; it is consistent among technical replicates; it is reliable in the matched study of fresh frozen vs formalin-fixed paraffin-embeded samples; and it is useful for both 5-methylcytosine and 5-hydroxymethylcytosine determination. The provided validation milestones highlights the value of the MethylationEPIC BeadChip as an informative and useful tool for the analyses of the DNA methylation profile of the human genome.

overall_design: DNA was quantified by Quant-iT PicoGreen dsDNA Reagent (Invitrogen) and the integrity was analyzed in a 1.3% agarose gel. Bisulfite conversion of 600 ng of each sample was perform according to the manufacturer's recommendation for Illumina Infinium Assay. Effective bisulphite conversion was checked for three controls that were converted simultaneously with the samples. 4 ul of bisulfite converted DNA were used to hybridize on Infinium HumanMethylation 450 BeadChip, following Illumina Infinium HD Methylation protocol. Chip analysis was performed using Illumina HiScan SQ fluorescent scanner. The intensities of the images are extracted using GenomeStudio (2011.2) Methylation module (1.8.5) software. Methylation score of each CpG is represented as beta value.

first: Manel

last: Esteller


title: A Novel Human Leiomyoma Tissue Derived Matrix for Cell Culture Studies

city: Oulu

first: Pirjo

last: Åström

address: Aapistie 5A

country: Finland

institute: University of Oulu

summary:
The composition of the matrix molecules is important in in vitro cell culture experiments of e.g. human cancer invasion and vessel formation. Currently, the mouse Engelbreth-Holm-Swarm (EHS) sarcoma -derived products, such as Matrigel®, are the most commonly used tumor microenvironment mimicking (TMEM) matrices for experimental studies. However, since Matrigel® is non-human in origin, its molecular composition does not accurately simulate human TMEM and we expect myogel to be more natural environment for human cancer cells. The environment may have crucial impact on cell behavior and gene expression.
The gene expression of the cells growing on top of myogel compared to those growing on top of plastic were sought for potential differencies.

overall_design: 90 000 HSC-3 cells were cultured in 6-well plates (three replicates) with and without myogel coating. The RNA samples were pooled and the changes in gene expressions were analyzed.

first: Tuula

last: Salo

first: Meeri

last: Sutinen

first: Elias

last: Sundquist

first: Nilva

last: Cervigne

first: Carine

last: Ervolino de Oliveira

first: Saad

last: Ullah Akram

first: Steffen

last: Ohlmeier

first: Ehsanul

last: Hoque Apu

first: Fumi

last: Suomi

first: Lauri

last: Eklund

last: Juusela

first: Carolina

last: Cavalcante Bitu

first: Johanna

last: Korvala

first: Ricardo

last: Coletta


title: Patterns of DNA methylation in human fetal and adult liver

city: Providence

first: Jennifer

middle: Ann

last: Sanders

state: RI

address: 593 Eddy Street

department: Pediatric Endocrinology

institute: Rhode Island Hospital

summary: DNA methylation is an important epigenetic control mechanism that has been shown to be associated with gene silencing through the course of development, maturation and aging.  However, only limited data are available regarding the relationship between methylation and gene expression in human development.  We analyzed the methylomes and transcriptomes of three human fetal liver samples (gestational age 20-22 weeks) and three adult human liver samples.  Genes whose expression differed between fetal and adult numbered 7,673. Adult overexpression was associated with metabolic pathways and, in particular, cytochrome P450 enzymes while fetal overexpression reflected enrichment for DNA replication and repair.  Analysis for DNA methylation using the Illumina Infinium 450K HumanMethylation BeadChip showed that 42% of the quality filtered 426,154 methylation sites differed significantly between adult and fetal tissue (q≤0.05).  Differences were small; 69% of the significant sites differed in their mean methylation beta value by ≤0.2.  There was a trend among all sites toward higher methylation in the adult samples with the most frequent difference in beta being 0.1.  Characterization of the relationship between methylation and expression revealed a clear difference between fetus and adult.  Methylation of genes overexpressed in fetal liver showed the same pattern as seen for genes that were similarly expressed in fetal and adult liver.  In contrast, adult overexpressed genes showed fetal hypermethylation that differed from the similarly expressed genes.  An examination of gene region-specific methylation showed that sites proximal to the transcription start site or within the first exon with a significant fetal-adult difference in beta (>0.2) showed an inverse relationship with gene expression.  Nearly half of the CpGs in human liver show a significant difference in methylation comparing fetal and adult samples.  Sites proximal to the transcription start site or within the first exon that show a transition from hypermethylation in the fetus to hypomethylation or intermediate methylation in the adult are associated with inverse changes in gene expression.  In contrast, increases in methylation going from fetal to adult are not associated with fetal-to-adult decreased expression.  These findings indicate fundamentally different roles for and/or regulation of DNA methylation in human fetal and adult liver.

overall_design: Bisulphite converted DNA from triplicate adult and fetal human liver were hybridized to Illumino 450K HumanMethylation BeadChip Arrays

first: Susan

middle: M

last: Huse

first: Philip

last: Gruppuso


title: Gene expression profiling of human neuroblastoma cell line BE(2)-C with inducible KDM4C expression

city: Augusta

first: Justin

last: Choi

state: GA

address: 1410 Laney Walker Blvd.

department: Cancer Center

institute: Georgia Regents University

summary: The microarray gene expression profiling reveals that the histone H3 demethylase KDM4C transcriptionally activates the serine-glycine pathway, stress responses and genes in control of cell-cycle progression.

overall_design: Affymetrix microarray assays were performed according to the manufacturer's directions on total RNA isolated from three independent samples of BE(2)-C_tetoff_KDM4C cells cultured in the presence or absence of doxycycline for 6 days.

first: Han-Fei

last: Ding

first: Jane


title: The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defense in skeletal muscles

status: Public on Dec 16 2015

city: Illkirch

first: Doulaye

last: Dembele

address: 1 rue Laurent Fries

department: Biopuces

institute: IGBMC

summary: Transcriptional microarray analysis was conducted on gastrocnemius muscle of control and PGC-1β(i)skm-/- mice one week after the last tamoxifen administration using the Affymetrix Mouse Gene 1.0 ST.

overall_design: each sample represent a pool of 3 different mice.

first: Thanuja

last: Ramamoorthy

first: Gilles

last: Laverny

first: Anna-Isabel

last: Schlagowski

first: Joffrey

last: Zoll

first: Nadia

last: Messaddeq

first: Jean-Marc

last: Bornert

first: Salvatore

last: Panza

first: Arnaud

last: Ferry

first: Bernard

last: Geny

first: Daniel

last: Metzger


title: NSD1 Mutations Generate a Genome-Wide DNA Methylation Signature

city: Toronto

first: Rosanna

last: Weksberg

state: Ontario

address: 555 University Ave.

department: Genetics and Genome Biology

institute: The Hospital for Sick Children

summary: Sotos syndrome (SS) represents an important human model system for the study of epigenetic regulation; it is an overgrowth/intellectual disability syndrome caused by mutations in a histone methyltransferase, NSD1. As layered epigenetic modifications are often interdependent, we propose that pathogenic NSD1 mutations have a genome-wide impact on the most stable epigenetic mark, DNA methylation (DNAm). By interrogating DNAm in SS patients, we identify a genome-wide, highly significant NSD1+/- specific signature that differentiates pathogenic NSD1 mutations from controls, benign NSD1 variants and the clinically overlapping Weaver syndrome.  Validation studies of independent cohorts of SS and controls assigned 100% of these samples correctly.  This highly specific and sensitive NSD1+/- specific signature encompasses genes that function in cellular morphogenesis and neuronal differentiation, reflecting cardinal features of the SS phenotype. The identification of SS-specific genome-wide DNAm alterations will facilitate both the elucidation of the molecular pathophysiology of SS and the development of improved diagnostic testing.

overall_design: Bisulphite converted DNA from 122 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip array.

first: Sanaa

last: Choufani

first: Andrei

last: Turinsky


title: Genome-wide DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer's disease

city: New York

first: Andrew

last: Sharp

address: 1470 Madison Av

department: Genetics and Genomic Sciences

institute: Icahn School of Medicine at Mount Sinai

summary: Recent work has identified roles for environmental, genetic and epigenetic factors in AD risk. Motivated by suspected roles for epigenetic modifications in AD, we performed a genome-wide screen of DNA methylation using the Illumina Infinium HumanMethylation450 array platform on bulk tissue samples from the superior temporal gyrus (STG) of AD cases and non-demented controls. We paired a sliding window approach with linear models that account for age, gender, ethnicity, and estimated cellular proportions (neuronal vs. glial), to characterize AD-associated differentially methylated regions (DMRs).

overall_design: Whole DNA was extracted from STG tissue dissections collected from deceased individuals with and without Alzheimers Disease. DNA was bisulfite converted and global DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.

first: Corey

middle: T

last: Watson

first: Panos

last: Roussos

first: Paras

last: Garg

first: Vahram

last: Haroutunian

middle: J


title: The obese fetal transcriptome

status: Public on Dec 17 2015

city: Medford

first: Heather

middle: C

last: Wick

address: 161 College Ave

department: Department of Computer Science

institute: Tufts University

summary:
The objective of this study was to identify the tissue expression patterns and biological pathways enriched in term cord blood fetal RNA of obese women compared to lean
In fetuses of obese women, 683 differentially regulated genes were identified.

overall_design: This was a prospective whole genome microarray study comparing umbilical cord blood samples collected from eight obese women and eight lean women at term who underwent prelabor cesarean delivery. A functional annotation tool was used to compare tissue expression patterns in cord blood samples from obese and lean women. Pathways analysis software identified physiological systems, molecular and cellular functions, and upstream regulators that were significantly differentially regulated in fetuses of obese women compared to lean.

first: Andrea

last: Edlow

first: Lisa

last: Hui

first: Diana

last: Bianchi


title: Sumoylation-deficient bone marrow derived dendritic cells transcriptomic analysis after LPS stimulation

status: Public on Dec 14 2015

city: Paris

first: Adrien

last: Decque

address: 28 rue du Docteur Roux

institute: Institut Pasteur

summary: Bone marrow derived dendritic cells were generated from Ubc9[fl;-] and Ubc9[+/+] mice. After in vitro derivation in the presence of GM-CSF, dendritic cells were treated with tamoxifen for four days to cause CreERT2 activation, and induce Ubc9 floxed allele deletion. This allowed comparative transcriptomic analysis of Ubc9[+/+] and Ubc9[-/-] dendritic cells unstimulated or stimulated with 10ng/ml LPS for one hour and six hours.

overall_design: Three biological replicates of each conditions were used. Analyzed bone marrow derived dendritic cells were Ubc9 WT or Ubc9 KO. Cells were left unstimulated or stimulated with LPS 10 ng/ml for one hour and six hours.


title: Comparison of the DNA methylation profiles of CD14+ monocytes from human peripheral blood with DCs and MACs obtained by exposure with GM-CSF/IL-4 and GM-CSF, respectively, and with mature DCs and MACs after LPS exposure

status: Public on Dec 11 2015

city: Badalona, Barcelona

first: Esteban

last: Ballestar

state: N/A = Not Applicable

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

institute: Josep Carreras Research Institute (IJC)

summary:
Comparison of the DNA methylation profiles of CD14+ monocytes from human peripheral blood with derived dendritic cells (DCs) and macrophages (MACs) obtained by exposure with GM-CSF/IL-4 and GM-CSF, respectively, and with mature DCs and MACs after lipopolysaccharide (LPS) exposure
The methylation profiles of bisulfite-modified DNA of human CD14+ monocytes were compared with derived immature dendritic cells (iDCs) and macrophages (iMACs) following GM-CSF/IL-4  and GM-CSF incubation, and then activation/maturation with lypopolysaccharyde (LPS) using the Infinium HumanMethylation450 BeadChips (Illumina, Inc., San Diego, CA,). This platform allows the interrogation of >485,000 methylation sites per sample at single-nucleotide resolution, and comprises an average of 17 CpG sites per gene in the 99% of RefSeq genes. 96% of CpG islands are covered, with additional coverage in CpG island shores and the regions flanking them. The samples were hybridized in the array following the manufacturer’s instructions.

overall_design: Total DNA isolated by standard procedures from CD14+ cells (total monocytes, MOs) corresponding to three sets of samples of monocytes (MOs), derived immature DCs and MACs (iDCS and iMACS) and activated/mature DCs and MACs following incubation with LPS (mDCS and mMACs)

first: Roser

last: Vento-Tormo

first: Javier

last: Rodríguez-Ubreva

first: Carlos

last: Company

first: Lorenzo

last: de la Rica

first: Jose

last: Urquiza

first: Biola

last: Javierre

first: Radhakrishnan

last: Sabarinathan

first: Ana

last: Luque

first: Manel

last: Esteller

first: Josep

last: Aran

first: Damiana

last: Álvarez-Errico


title: Role of macrophages in colitis

status: Public on Dec 10 2015

city: Atlanta

first: Timothy

last: Denning

address: 100 Piedmont Ave.

department: Center for Inflammation Immunity & Infection

institute: Georgia State University Institute for Biomedical Sciences

summary: The goal of this project is to identify genes preferentially expressed in inflammatory macrophages as compared with control macrophages.

overall_design: inflammatory macrophage vs. control macrophage


title: Gene expression profiling of tumor cells and M2 macrophages from WT mice and mice with deletion of integrin beta3 in macrophage lineage cells (b3KOM)

city: Saint Louis

first: Katherine

last: Weilbaecher

state: Missouri

address: 660 South Euclid Avenue

department: Department of Medicine

institute: Washington University in St. Louis

summary: To better understand the impact of integrin beta3 signaling in myeloid cells on the tumor microenvironment, we compared the gene expression profiles of FACS isolated GFP+ PyMT-BO1 MFP tumor cells and also M2 TAMs (CD11b+Gr1-F4/80+CD206+) from tumor tissue of WT mice and b3ΚΟΜ mice.

overall_design: PyMT-BO1-GFP-Luc tumor cells (100,000) were injected into mammary fat pad (MFP) tissue from WT and b3KOM mice. PyMT-BO1-GFP-Luc cells and CD206hi tumor-associated macrophages (TAMs) were FACS-sorted from day 10 MFP tumor tissue. FACS-sorted cells directly used for RNA extraction and hybridization on Affymetrix microarrays.

first: Xinming

last: Su

first: Kirsten

last: Roomp

first: Jochen

last: Schneider

middle: N


title: Revealing different roles of the mTOR-targets S6K1 and S6K2 in breast cancer by expression profiling and structural analysis

status: Public on Dec 09 2015

city: Linköping

first: Patrik

last: Lundström

address: Campus Valla

department: Physics, Chemistry and Biology

country: Sweden

institute: Linköping University

summary: Expression profiles of ZR751 breast cancer cells after downregulation of S6K1, S6K2 and S6K1+S6K2.

overall_design: Triplicates of control, S6K1siRNA, S6K2siRNA and S6K1+S6K2siRNA, in total twelve samples.

first: Elin

last: Karlsson

first: Ivana

last: Magić

first: Josefine

last: Bostner

first: Christine

last: Dyrager

first: Fredrik

last: Lysholm

first: Anna-Lotta

last: Hallbeck

first: Olle

last: Stål


title: Comprehensive genomic analysis identify novel subtypes and targets of triple-negative breast cancer (198 TNBC tumors)

city: Houston

first: Suzanne

last: Fuqua

address: 1 Baylor Plaza

institute: Baylor College of Medicine

summary:
Recent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
We identified and confirmed four distinct, stable TNBC subtypes: (1) Luminal-AR (LAR); 2) Mesenchymal (MES); 3) Basal-Like Immune-Suppressed (BLIS), and 4) Basal-Like Immune-Activated (BLIA).

overall_design: RNA profiling analysis was conducted on 198 TNBC tumors (ER-negativity defined as Allred Scale value ≤2) with >50% cellularity (discovery set: n=84; validation set: n=114)

first: Matthew

last: Burstein

first: Anna

last: Tsimelzon

first: Susan

last: Hilsenbeck

first: Graham

last: Poage

first: Kyle

last: Covington

first: Jenny

last: Chang

first: C

middle: K

last: Osborne

first: Gordon

middle: B

last: Mills

first: Ching

last: Lau

first: Powel

last: Brown


title: Identification of genes associated with breast cancer micrometastatic disease in bone marrow disseminated tumor cells (DTCs)

city: saint louis

first: chidananda

last: Mudalagiriyappa

address: 4940 Parkview Pl.

department: Surgery

institute: washington university in saint louis

summary: In this study, we assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer

overall_design: In this dataset, Primary breast tissue from stage II or III breast cancer patients were included in the analysis. This study allowed the identification of novel gene expression patterns associated with the presence of DTCs BM by IHC and supports the concept of epithelial to mesenchymal transition transition  (EMT) of DTCs present in the BM .

first: Chidananda

last: Siddappa

first: Mark

last: Watson

first: Sreeraj

last: Pillai

first: Rebecca

last: Aft


title: IL-4 orchestrates STAT6-mediated DNA demethylation leading to dendritic cell differentiation

status: Public on Dec 12 2015

first: Esteban

last: Ballestar

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

overall_design: Refer to individual Series


title: Global gene expression profiling of FOP- or resFOP-iMSCs treated by several ligands

city: Kyoto

first: Makoto

last: Ikeya

address: 53 kawahara-cho, shogoin

department: Center for iPS Cell Research and Application(CiRA)

country: Japan

institute: Kyoto University

summary:
Analyzed differentially expressed genes  among FOP- or resFOP-iMSCs treated by several ligands:
Activin-A, 100 ng/mL; BMP-7, 100 ng/mL; TGF-B3, 10 ng/mL

overall_design: Comparison of gene expressions among  FOP- or resFOP-iMSCs treated 16h by several ligands

first: J

last: Toguchida

first: M


title: Comparison of mouse macrophages and reproductive tract epithelial cells at baseline and in an inflammatory milieu mimicking a Chlamydia genital tract infection

city: New Haven

first: Raymond

middle: Morris

last: Johnson

state: CT

department: Med/Infectious Diseases

institute: Yale University

summary: Chlamydia trachomatis urogenital serovars are intracellular bacteria that parasitize human reproductive tract epithelium.  As the principal cell type supporting bacterial replication, epithelial cells are central to Chlamydia immunobiology initially as sentries and innate defenders, and subsequently as collaborators in adaptive immunity-mediated bacterial clearance.  In asymptomatic individuals who do not seek medical care a decisive struggle between C. trachomatis and host defenses occurs at the epithelial interface.  For this study we modeled the immunobiology of epithelial cells and macrophages lining healthy genital mucosa and inflamed/infected mucosa during the transition from innate to adaptive immunity.  Upper reproductive tract epithelial cell line responses were compared to bone marrow-derived macrophages utilizing gene expression microarray technology.  Those comparisons showed minor differences in the intrinsic innate defenses of macrophages and epithelial cells.  Major lineage-specific differences in immunobiology relate to epithelial collaboration with adaptive immunity including an epithelial requirement for inflammatory cytokines to express MHC class II molecules, and a paucity and imbalance between costimulatory and coinhibitory ligands on epithelial cells that potentially limits sterilizing immunity (replication termination) to Chlamydia-specific T cells activated with limited or unconventional second signals.

overall_design:
2 mouse reproductive tract epithelial cell lines compared to bone marrow macrophages untreated vs. treated with inflammatory supernatant (4 replicates each).
Contributor: The Indiana University Center for Medical Genomics- Jeanette McClintick


title: Identification of genes involved in apoptosis-induced by cold atmospheric pressure plasma in human lymphoma U937 cells

status: Public on Dec 15 2015

city: Toyama

first: Yoshiaki

last: Tabuchi

state: Toyama

address: 2630 Sugitani

department: Life Science Research Center

institute: University of Toyama

summary:
Cold atmospheric pressure plasma (CAP) is known as a source of biologically active agents, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recent medical investigations have focused on applying CAP to cancer treatment. There is also growing evidence that exposure of cells to CAP or CAP-activated medium induces apoptosis in cancer cells, and ROS and/or RNS are considered to be effective agents to CAP-induced apoptosis. More recently, we demonstrated that Ar-CAP or Ar containing 2.5 % of N2 (Ar-N2-CAP) significantly induced apoptosis in human lymphoma U937 cells. However, a detailed molecular mechanism underling the induction of apoptosis by CAP in cancer cells is unclear.
In the present study, to identify genes involved in the induction of apoptosis by CAP in human lymphoma U937 cells, global-scale gene expression analysis was performed using a GeneChip® system.

overall_design: Human lymphoma U937 cells were treated with Ar-CAP or Ar-N2-CAP. Total RNA samples were prepared from the cells, and quality of the RNA was analyzed using a Bioanalyzer 2100. Gene expression was analyzed by an Affymetrix GeneChip® system with a Human Genome U133-plus 2.0 array. Sample preparation for array hybridization was carried out as described in the manufacturer’s instructions.

first: Hidefumi

last: Uchiyama

first: Tatsuya

last: Yunoki


title: Evaluation of Inter-Batch Differences in Stem-Cell Derived Neurons

city: Chicago

first: Wei

last: Zhang

state: IL

address: 680 N. Lake Shore Drive, Suite 1400

institute: Northwestern University

summary: Genome wide DNA methylation profiling of Neurons derived from human induced pluripotent stem cells (iCell Neurons) at different time points were abtained by the Infinium HumanMethylation450 BeadChip (450K array) Kit (WG-314-1002), which interrogates >480,000 CpG sites in the human genome.In total, 36 samples were profiled using the 450K arrays.

overall_design: 1 ug purified DNA from each timepoint was submitted to the University of Chicago Genomics Core where it was converted with the EZ-96 DNA Methylation™ Kit (Deep Well Format), as per manufacturer's protocol, followed by array analysis using the Infinium HumanMethylation450 BeadChip (450K array) Kit (WG-314-1002), which interrogates >480,000 CpG sites in the human genome.

middle: E

last: Dolan


title: Integrated analysis of genome-wide DNA methylation and gene expression profiles identifies potential novel biomarkers of rectal cancer [methylation]

status: Public on Dec 02 2015

city: Harbin

first: Jiufeng

last: Wei

address: Yiyuan street

institute: the Fourth Affiliated Hospital of Harbin Medical University

summary:
DNA methylation was suggested as the promising biomarker for rectal cancer diagnosis. However, it remains a great challenge to search for the optimal methylation biomarkers to obtain ideal diagnostic performance. We aimed to identify new molecular markers for rectal cancer by evaluating their epigenomic and transcriptomic profiles. Genome-wide methylation analysis revealed 18568 probes with significant methylation differences between the six rectal cancer and paired normal samples. Transcriptome profiling presented 773 low-expressed and 1,161 over-expressed genes. After merging the DNA methylation with gene expression data, we identified a panel of 36 genes with an inverse correlation between methylation and gene expression levels. A genome-wide DNA methylation approach merged with array-based gene expression profiles allowed identifying a number of novel, epigenetically regulated candidate tumor-related genes in rectal carcinogenesis, which can be a good strategy to discover optimal DNA methylation diagnostic panels.
Genome wide DNA methylation profiling of paired rectal cancers and adjacent normal tissues. The Illumina Human Methylation 450K BeadChip was used to obtain DNA methylation profiles across approximately 485,000 CpGs in all samples. Samples included six pairs of rectal cancers and adjacent normal tissues.

overall_design: Bisulphite converted DNA from the 12 samples were hybridised to the Illumina Human Methylation 450K BeadChip

first: Ming

last: Liu


title: Methylation data and effect of JAK3 inhibition on human MO-to-DC and MO-to-MAC differentiation

summary:
Comparison of the DNA methylation profiles of CD14+ monocytes from human peripheral blood with derived dendritic cells (DCs) and macrophages (MACs) obtained by exposure with GM-CSF/IL-4 and GM-CSF, respectively. Effects on the methylation profiles of DCs and MACs of JAK3 inhibitor PF-956980
The methylation profiles of bisulfite-modified DNA of human CD14+ monocytes were compared with derived dendritic cells (DCs), macrophages (MACs) following GM-CSF/IL-4  and GM-CSF incubation, and DC and MAC samples incubated with JAK3 inhibitor PF-956980 using the Infinium HumanMethylation450 BeadChips (Illumina, Inc., San Diego, CA,). This platform allows the interrogation of >485,000 methylation sites per sample at single-nucleotide resolution, and comprises an average of 17 CpG sites per gene in the 99% of RefSeq genes. 96% of CpG islands are covered, with additional coverage in CpG island shores and the regions flanking them. The samples were hybridized in the array following the manufacturer’s instructions.

overall_design: Total DNA isolated by standard procedures from CD14+ cells (total monocytes, MOs) corresponding to three sets of samples of monocytes (MOs), derived DCs and MACs (DCs and iMACs; DMSO as these samples were differentiated in the absence of JAK3 inhibitors) and DCs and MACs differentiated in the presence of JAK3 inhibitor PF-956980.

first: Roser

last: Vento-Tormo

first: Carlos

last: Company

first: Javier

last: Rodríguez-Ubreva

first: Lorenzo

last: de la Rica

first: Jose

last: Urquiza

first: Biola

last: Javierre

first: Radhakrishnan

last: Sabarinathan

first: Ana

last: Luque

first: Manel

last: Esteller

first: Josep

last: Aran

first: Damiana

last: Álvarez-Errico


title: Stem cell-derived immature human dorsal root ganglia neurons to identify peripheral neurotoxicants

city: Cologne

first: Agapios

last: Sachinidis

state: NRW

address: Robert-Kochstr. 39

department: Institute of Neurophysiology

country: Germany

institute: University of Cologne

summary: Safety sciences and the identification chemical hazard have been seen as one of the most immediate practical applications of human pluripotent stem cell technology. Protocols for the generation of many desirable human cell types have been developed, but optimization of neuronal models for toxicological use has been astonishingly slow, and the wide, clinically- important field of peripheral neurotoxicity is still largely unexplored. Here, a 2-step protocol to generate large lots of identical peripheral human neuronal precursors was characterized and adapted to the measurement of peripheral neurotoxicity. High content imaging allowed an unbiased assessment of cell morphology and viability. The computational quantification of neurite growth as functional parameter highly sensitive to disturbances by toxicants was used as endpoint reflecting specific neurotoxicity. The differentiation of cells towards dorsal root ganglia neurons was tracked in relation to a large background data set based on gene expression microarrays. On this basis, a peripheral neurotoxicity (PeriTox) test was developed as first toxicological assay that harnesses the potential of human pluripotent stem cells to generate cell types/tissues that are not otherwise available for prediction of human systemic organ toxicity. Testing of more than 30 chemicals showed that human neurotoxicants, as well as neurite growth enhancers, were correctly identified. Various classes of chemotherapeutics causing human peripheral neuropathies were identified, while they were missed when tested on human central neurons. The PeriTox-test established here shows the potential of human stem cells for clinically-relevant safety testing of drugs in use and of new emerging candidates.

overall_design: Undifferentiated human embryonic stem cells (hESCs) (4 control samples) were differentiated by a specific differentiation protocol for 8 days and subsequently cryopreserved. After thawing cells were further differentiated for 1, 4  and 7 days(called as  immature dorsal root ganglia neurons (iDRG) (for each time point 4 samples) .  RNA was analysed by Human Genome U133 plus 2.0 microarrays (Human Genome U133 plus 2.0 microarrays). At day 1 after thawing immature human dorsal root ganglia neurons were obtained and several neurotoxicants have been tested for their toxicity potential.

first: Lisa

last: Hoelting

first: Marcel

last: Leist


title: Expression data from human mast cell progenitors and mature basophils

status: Public on Dec 01 2015

city: Solna

first: Joakim

middle: S

last: Dahlin

address: CMM, Visionsgatan 18

department: Department of Medicine, Solna

institute: Karolinska Institutet

summary:
CD34+ CD117+ cells in human peripheral blood have mast cell-forming capacity. We have identified highly committed mast cell progenitors as Lin- CD34+ CD117 intermediate/high FcεRI+ cells.
To explore the gene expression profile of the highly committed mast cell progenitors, we performed whole-transcriptome microarray analyses of the cells and compared them with mature basophils.

overall_design: Mast cell progenitors and mature basophils from human blood were isolated from 3 subjects using fluorescence-activated cell sorting and whole-transcriptome microarray analyses were performed.

first: Jenny

last: Hallgren


title: Intestinal epithelial cells from Crohn's Disease patients

city: Erlangen

first: Rocío

last: López Posadas

address: TRC, Schwabachanlage 12

department: Medicine Clinic 1

institute: University of Erlangen-Nuremberg

summary:
Inflammatory Bowel Diseases are associated with marked alterations of IECs with a subsequent loss of barrier function.
To identify alterations in signaling pathways in intestinal epithelium upon inflammation, we analyzed the transcriptome of IECs from patients suffering from Crohn’s disease.

overall_design: Intestinal epithelial cells were isolated from the terminal ileum of Crohn´s Disease patients (4 uninflamed and 5 inflamed areas). RNA was isolated and subjected to Affymetrix gene chip analysis

first: Claudia

last: Günther

first: Stefania

last: Vetrano

first: Silvio

last: Danese

first: Christoph

last: Becker


title: Impact of SNPs on methylation readouts by Illumina HM450K Array. Methylation profiles in European and Asian populations

status: Public on Dec 03 2015

city: Gliwice

first: Aleksandra

last: Pfeifer

address: Wybrzeze Armii Krajowej 15

institute: MSC Memorial Cancer Center and Institute of Oncology

summary: We performed a comparative study of European and Asian populations using Illumina HM450K. We found that the majority of Infinium probes, which differentiated two examined groups, had SNPs in their target sequence. We investigated the impact of those SNPs on methylation readouts by Illumina HM450K Array. Our study clearly demonstrates that SNP variation existing in the genome, if not accounted for, may lead to false interpretation of the methylation signal differences suggested by some of the Illumina Infinium probes.

overall_design: Human B-lymphocyte cell lines representing Caucasian from Georgia (n=18), further referred to as Europeans and Chinese from Bejing, further referred to as East Asians (n=18) populations were used in the study. All lines were derived from unrelated healthy adults males.

first: Patrycja

last: Daca-Roszak

first: Jadwiga

last: Zebracka-Gala

first: Dagmara

last: Rusinek

last: Szybinska

first: Barbara

last: Jarzab

first: Michal

last: Witt

first: Ewa

last: Zietkiewicz


title: HOXA5 counteracts stem cell traits by inhibiting Wnt signaling

status: Public on Dec 13 2015

city: Lausanne

first: Paloma

last: Ordóñez

address: Station 19

department: Swiss Experimental Cancer Research Institute

country: Switzerland

institute: École Polytechnique Fédérale de Lausanne

summary:
Here we identify HOXA5 as an important repressor of intestinal stem cell fate in vivo and identify a reciprocal feedback between HOXA5 and Wnt signaling. HOXA5 is suppressed by the Wnt pathway to maintain stemness and becomes active only outside the intestinal crypt where it inhibits Wnt signaling to enforce differentiation. In colon cancer, HOXA5 is down-regulated and its re-expression induces loss of the cancer stem cell phenotype preventing tumor progression and metastasis. Tumor regression by HOXA5 induction can be triggered by retinoids, which represents a tangible means to treat colon cancer by eliminating cancer stem cells.
We use microarrays to identify HOXA5 signature in SW480 human colon carcinoma cell line

overall_design: RNA was obtained from SW480 cells, transduced with HOXA5 OE or HOXA5 KD. Hybridization was performed on Affymetrix microarrays.

last: Ordonez-Moran

first: Joerg

last: Huelsken


title: Gene expression profile of OECM1 overexpression let-7i

city: Taipei

first: Tsai-Tsen

last: Liao

state: State...

address: No.201, Sec.2, Shih-Pai Rd. Peitou, Taipei, Taiwan, 11221, R.O.C

country: Taiwan

institute: Institute of Clinical Medicine

summary: Expression of let-7i results in transcriptome alteractions in head and neck cancer cell line, OECM1.

overall_design: To investigate the role of let-7i on OECM1 cells, we screened the differentially expressed genes of OECM1-mCherry (as control), OECM1-let-7i (as let-7i overexpression cell line).

first: Muh-Hwa

last: Yang


title: Expression data from UKRV-Mel-15a melanoma-derived clones resistant to cytolysis mediated by Melan-A/MART1 (26-35) cytotoxic T lymphocytes (CTL).

city: Berlin

first: Frédéric

last: Ebstein

address: Charité Platz 1/Virchowweg 6

department: Institut für Biochemie

institute: Charité Universitätsmedizin Berlin

summary: Efficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to impaired expression of IFN-γ-inducible components of the antigen presentation machinery and consequent inefficient processing of HLA-dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that repeated short-term co-cultures of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-1 (26-35)-specific CTL led to the generation of clones resistant to CTL-mediated cell death. To determine which of the UPS components and its associated pathways was responsible for CTL escape; three UKRV-Mel-15a clones were subjected to microarray gene expression analysis.

overall_design: Three UKRV-Mel-15a-derived melanoma clones were isolated following three repeated short-term exposures to Melan-A/MART (26-35) CTL and  harvested for RNA extraction and hybridization on Affymetrix microarrays.

first: Martin

last: Keller

first: Peter

last: Kloetzel

first: Ulrike

last: Seifert


title: A PTIP-PA1 subcomplex promotes transcription for IgH class-switching independently from the associated MLL3/MLL4 methyltransferase complex

city: Copenhagen N

first: Laura

middle: Maarit

last: Pikkupeura

address: Ole Maaloes vej 5

department: BRIC

country: Denmark

institute: University of Copenhagen

summary: Class-switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B cell genome. Transcription at the immunoglobulin heavy-chain (Igh) locus targets CSRassociated DNA damage and is promoted by the BRCT domain-containing PTIP protein. Although PTIP is a unique component of the MLL3/MLL4 chromatin-modifying complex, the mechanisms for how PTIP promotes transcription remain unclear. Here we dissect the minimal structural requirements of PTIP and its different protein complexes using quantitative proteomics in primary lymphocytes. We find that PTIP functions in transcription and CSR separately from its association with the MLL3/MLL4 complex and from its localization to sites of DNA damage. We identify a tandem BRCT domain of PTIP that is sufficient for CSR and identify PA1 as its main functional protein partner. Collectively, we provide genetic and biochemical evidence that a PTIP-PA1 subcomplex functions independently from the MLL3/MLL4 complex to mediate transcription during CSR. These results further our understanding of how multi-functional chromatin-modifying complexes are organized by subcomplexes that harbor unique and distinct activities.

overall_design: Genome-wide analysis of histone modifications in PA1-WT and -KO mouse activated B cells

first: Linda

last: Starnes

first: Dan

last: Su

first: Brian

last: Weinert

first: Margarida

middle: A

last: Santos

first: Andreas

last: Mund

first: Rebeca

last: Soria

first: Young-Wook

last: Cho

first: Irina

last: Pozdnyakova

first: Martina

last: Højfeldt

first: Andrea

last: Vala

first: Wenjing

first: Blanca

last: López-Méndez

first: Ji-Eun

last: Lee

first: Weiqun

last: Peng

first: Joan

last: Yuan

first: Kai

last: Ge

first: Guillermo

last: Montoya

first: André

last: Nussenzweig

first: Chunaram

last: Choudhary

first: Jeremy

last: Daniel


title: Establishment of tractable human iPSC-based models for the study and targeting of glioma initiation (Methlyation)

city: La Jolla

first: Robert

last: Morey

state: CA

address: 2880 Torrey Pines Scenic Dr

department: Pathology

institute: UCSD

summary: Gliomas can originate upon transformation of adult Neural Progenitor Cells (NPCs) to Tumor Initiating Cells (TICs). Studies on human Glioma TICs (GTICs) have focused on the use of primary tumors from which GTICs could be isolated. Therefore investigations on the driver events underlying NPC transformation and human glioma initiation remain limited to the use of human embryonic material. Here we report on the development of strategies for the modeling of human gliomagenesis based on the use of human induced Pluripotent Stem Cells (hiPSCs). Transformation of hiPSC-derived NPCs (iNPCs) by defined genetic alterations led to the establishment of tractable human GTIC models suitable for studying the early steps of gliomagenesis as well as for screening studies. Dysregulation of PI3K, MAPK and p53 signaling in iNPCs led to the acquisition of functional GTIC properties. In vivo transplantation led to the formation of highly aggressive, infiltrative and heterogeneous tumors upon limited dilutions and secondary transplantation, faithfully recapitulating gliomagenesis. Metabolic modulation by chemical approaches compromised GTIC viability. Pilot screening of 101 anti-cancer compounds identified 3 molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results demonstrate the potential of hiPSCs for the functional testing of putative driver mutations underlying human tumorigenesis and pave new avenues for the development of personalized cancer therapeutics.

overall_design: Bisulphite converted DNAs of four cells lines, wild-type neural progenitor cells, neural progenitor cells with P53 knockdown, neural progenitor cells with P53 knockdown and inhibition of the PI3K and MAPK signaling pathways, and NS27Z +B AB0789 (Glioma Stem Cells) were  hybridised to the Illumina Infinium HumanMethylation 450K Beadchip.

first: Louise

last: Laurent

first: Ignacio

last: Sancho-Martinez

first: Juan

middle: I

last: Belmonte


title: Extensive alopecia areata is reversed by IL-23 cytokine antagonism

status: Public on Dec 08 2015

city: New York

first: Mayte

last: Suarez-Farinas

state: NY

address: One Gustave L. Levy Place, Box 1077

department: Population Health Science and Policy

institute: Icahn School of Medicine at Mount Sinai

summary: Alopecia areata (AA) is a prevalent disease associated with major emotional distress, and lacks effective, safe therapeutics for patients with extensive hair loss. This is the first report of hair regrowth with specific cytokine antagonism, in three patients with extensive hair loss ranging from 40% scalp involvement to alopecia universalis. Ustekinumab, an IL-12/23p40 antagonist that is highly effective in psoriasis, showed impressive ability to induce hair regrowth, coupled with suppression of inflammatory pathways and upregulation of hair keratins. Our report suggests that extensive AA is reversible using targeted treatments, opening the door for specific cytokine antagonism for this debilitating disease.

overall_design: We evaluated hair regrowth in three AA patients at 20 weeks after treatment with 3 subcutaneous doses of 90mg ustekinumab given at weeks 0, 4, and 16. Skin biopsies of lesional and non-lesional scalp (when available) were taken at baseline (week 0) and at week 20. We also obtained biopsies from three healthy individuals.

first: Emma

last: Guttman

first: Maria

last: Suprun


title: Gene expresssion profiles of cancer of the appendix

city: Winston-Salem

first: Lance

middle: David

last: Miller

state: North Carolina

address: Medical Center Blvd

department: Cancer Biology

institute: Wake Forest School of Medicine

summary: Appendiceal cancer patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often demonstrate an unpredictable variability in survival outcomes. Biomarkers predictive of CRS/HIPEC efficacy could better guide treatment decisions. In this study we hypothesized that variation in the transcriptional programming of appendiceal tumors might distinguish molecular subtypes with differential outcomes after CRS/HIPEC. The goal of this study was to investigate the potential of a prognostic gene signature to discriminate patients with favorable and unfavorable outcomes in a “discovery” set of patient (the original tumor series (n=24)), and confirm its prognostic value in a second “validation” series (the validation cohort (n=39)).

overall_design: Total RNA isolated from 24 appendiceal tumors (the original tumor series) and 39 appendiceal tumors (the valdiation series) were profiled on Affymetrix U133A GeneChips and Affymetrix U219 GeneAtlas Array Strips, respectively.

middle: D

first: Jeff

middle: W

last: Chou

first: Edward

last: Levine


title: Epigenome analysis of adipose tissue DNA from MZ twins discordant for BMI

city: Helsinki

first: Khadeeja

last: Ismail

state: Helsinki

address: Mannerheimintie 172

department: Department of Public Health

institute: University of Helsinki

summary: Genome wide DNA methylation profiling of adipose tissue of MZ twins discordant and concordant for BMI. The Illumina Infinium 450k Human DNA methylation Beadchip  was used to obtain DNA methylation profiles across approximately 485,000 CpGs. Samples included 24 pairs discordant  and  11 pairs concordant for BMI.

overall_design: Bisulphite converted DNA from the 70 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.

first: Kirsi

last: Pietiläinen

first: Miina

last: Ollikainen


title: Integrated analysis of genome-wide DNA methylation and gene expression profiles identifies potential novel biomarkers of rectal cancer

first: Jiufeng

last: Wei

country: China

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

overall_design: Refer to individual Series


title: DNA Methylation Patterns Associated with Fatigue in Primary Sjögren’s Syndrome

status: Public on Dec 04 2015

city: Uppsala

first: Juliana

last: Imgenberg-Kreuz

address: Husargatan 3

department: Medical Sciences

institute: Uppsala University

summary:
Genome-wide analysis of DNA methylation profiles from patients with Sjögren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array.
Background  Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary Sjögren’s syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS.  Methods  48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array.

overall_design: Case-case study including Sjögren's patients with high fatigue (n=24) and patients with low fatigue levels (n=24)

first: Katrine

last: Norheim


title: Rosemary polyphenols induce unfolded protein response and changes in cholesterol metabolism in colon cancer cells

city: Madrid

first: Alberto

last: Valdés

state: Madrid

address: C\Nicolás Cabrera, 9

department: Bioactividad y Análisis de Alimentos

institute: Instituto de Investigación en Ciencias de la Alimentación

summary:
Several studies have demonstrated that rosemary polyphenols exert changes in the lipid metabolism in adipose and hepatic cells. However, limited information is available about their effect on the lipids metabolism in cancer cells.
To improve our limited knowledge on this issue, a Foodomics approach is applied to study the effects of a polyphenol-enriched supercritical rosemary extract and carnosic acid on the transcriptome and cholesterol metabolism in HT-29 colon cancer cells.

overall_design: Transcriptome analysis of RNA samples from HT-29 colon cancer cells untreated or treated with rosemary extract and carnosic acid for 24 hours. Three biological replicates were included in the experiment.

first: Giuseppe

last: Sullini

first: Elena

last: Ibáñez

first: Alejandro

last: Cifuentes

first: Virginia

last: García-Cañas


title: Expression data from short-term mouse embryonic stem cell exposure Assay

city: stockholm

first: ying

last: sun

address: Tomtebodavagen 23

department: Personalized Healthcare and biomarkers

institute: AstraZeneca

summary:
In vitro prediction of developmental toxicity during early discovery phases of drug development has the potential to guide decision-making toward prioritizing candidate drugs that are less likely to later show teratogenicity in vivo. Such screening would reduce animal use in preclinical studies, including full-scale regulatory reproductive toxicology. we evaluate an assay format based on short-term toxicogenomic responses in pluripotent embryonic stem cells (ESC). We exposed attached undifferentiated cells of the mouse ESC cell line R1 for 6h to 10 known teratogenic and 9 non-teratogenic pharmaceutical drugs .
We used microarry to access genome-wide gene expression response and identify gene signatures to classify teratogens and non-teratogens.

overall_design: In total sixty samples treated by 20 compounds (including one solvent compound, 10 teratogen compounds and 9 non-teratogen compounds and triplicates for each)  are performed by microarray expriment,

first: Ying

last: Sun

first: Måns

last: Jergil

first: Kenneth

last: Stockling

first: Heike

last: Hellmold

first: Lennart

last: Dencker

first: Anne-Lee

last: Gustafson

first: Hugh

last: Salter

first: Michael

last: Stigson