title: The effect of bisphenol A on human prostaspheres derived from primary prostate epithelial cells

status: Public on Nov 05 2014

first: Mario

last: Medvedovic

address: 3223 Eden Av. ML 56

department: Department of Environmental Health

institute: University of Cincinnati

summary: Bisphenol A is an environmental xenoestrogen commonly known as an endocrine disruptor. We previously reported BPA-treated human primary prostate epithelial cell derived prostaspheres had larger size, exhibited clonogenicity, and showed increase in stem cell marker expression. Results reveal the molecular basis of BPA action in human prostate stem-progenitor cells.

overall_design: Human primary prostate epithelial cells from three disease-free Caucasian donors formed prostaspheres from single stem-like cells in matrigel cultures and were treated with 0.1 nM estradiol-17β (E2), 10 nM (B10), 200 nM (B200), and 1000 nM bisphenol A (BPA) for 7 days. The vehicle-treated prostaspheres were used as 'untreated controls'.

first: Hung-Ming

last: Lam

first: Wen-Yang

last: Hu

first: Guang-Bin

last: Shi

first: Yuet-Kin

last: Leung

first: Gail

last: Prins

first: Shuk-Mei

last: Ho


title: Analysis of transcription start sites from nascent RNA identifies a unified architecture of initiation at mammalian promoters and enhancers (GRO-seq)

status: Public on Nov 10 2014

city: Ithaca

first: Leighton

middle: James

last: Core

state: NY

address: 417 Biotechnology Building

department: Moleular Biology and Genetics

country: USA

institute: Cornell University

type: Expression profiling by high throughput sequencing

summary: Despite the conventional distinction between promoters and enhancers, they share many features in mammals, including divergent transcription and similar modes of transcription factor (TF) binding. Here, we examine the architecture of transcription initiation genome-wide through comprehensive mapping of transcription start sites (TSSs) in human lymphoblastoid B-cell (GM12878) and chronic myelogenous leukemic (K562) tier 1, ENCODE cell lines using a nuclear run-on protocol called GRO-cap. This method captures TSSs for both stable and unstable transcripts, thus allowing us to conduct detailed comparisons between thousands of promoters and enhancers in human cells. These analyses reveal a common architecture of initiation at both promoters and enhancers, including tightly spaced (110 bp) divergent initiation that features similar frequencies of core-promoter sequence elements, highly-positioned flanking nucleosomes, and two modes of TF binding. Transcript elongation stability, a feature determined after transcription initiation, provides a more fundamental distinction between promoters and enhancers than the relative abundance of histone modifications and the presence of TFs or coactivators. These results support a unified model of transcription initiation at both promoters and enhancers.

overall_design: We sequenced nascent RNAs purified from run-on sequencing reactions (GRO-seq and PRO-seq) performed in two ENCODE cells lines: K562 and GM12878. We also enriched separate libraries from the same cells for the 5-meG cap associated with transcription start sites (TSSs) in order to produce a comprehensive mapping of nascent TSSs in these cells. This assay is called GRO-cap. We compared these TSSs to those identified in stable RNAs from CAGE assays to generate annotations for all TSSs based on the stability of the resulting transcript.

first: John

middle: T

last: Lis

first: Adam

last: Siepel


title: Association of Prostate Cancer Risk Variants with Gene Expression in Normal and Tumor Tissue

status: Public on Dec 01 2014

city: Boston

first: Kathryn

last: Penney

address: 181 Longwood Ave

department: Medicine

institute: Brigham and Women's Hospital

summary:
Background: Numerous germline genetic variants are associated with prostate cancer risk, but their biological role is not well understood. One possibility is that these variants influence gene expression in prostate tissue. We therefore examined the association of prostate cancer risk variants with the expression of genes nearby and genome-wide. Methods: We generated mRNA expression data for 20,254 genes with the Affymetrix GeneChip Human Gene 1.0 ST microarray from normal prostate (N=160) and prostate tumor (N=264) tissue from participants of the Physicians’ Health Study and Health Professionals Follow-up Study. With linear models, we tested the association of 39 risk variants with nearby genes and all genes, and the association of each variant with canonical pathways using a global test. Results: In addition to confirming previously reported associations, we detected several new significant (p<0.05) associations of variants with the expression of nearby genes including C2orf43, ITGA6, MLPH, CHMP2B, BMPR1B, and MTL5. Genome-wide, four genes (MSMB, NUDT11, NEFM, KLHL33) were significantly associated after accounting for multiple comparisons for each SNP (p<2.5x10-6). Many more genes had a false discovery rate <10%, including SRD5A1 and PSCA, and we observed significant associations with pathways in tumor tissue.
Conclusions: The risk variants were associated with several genes, including promising prostate cancer candidates and lipid metabolism pathways, suggesting mechanisms for their impact on disease. These genes should be further explored in biological and epidemiological studies. Impact: Determining the biological role of these variants can lead to improved understanding of prostate cancer etiology and identify new targets for chemoprevention.

overall_design: 264 prostate tumor and 160 normal prostate tissue samples from the Health Professionals Follow-up Study and Physicians' Health Study Prostate Tumor Cohort. We tested the association of 39 prostate cancer risk variants with Affymetrix gene expression array data. We compared each variant to all nearby genes (500 kb up- and downstream), as well as with all genes and KEGG pathways.

first: Lorelei

last: Mucci


title: miRCURY LNATM microRNA Array (7th Gen) profiling of monocyte-derived osteoclasts and macrophages.

city: Chicago

first: Jezrom

middle: Bokcaerin

last: Self-Fordham

state: IL

address: 801 S Paulina

department: Periodontics

institute: UIC

summary: To examine the miRNA changes that occur during osteoclast differentiation we used the miRCURY LNATM microRNA Array (7th Gen) to profile monocyte-derived osteoclasts and monocyte-derived macrophages. Of the 2046 probes present on the assay, we detected expression of ~400 (20%) miRNAs across all samples.

platform_organism:
Homo sapiens
Human alphaherpesvirus 1
Human alphaherpesvirus 2
Cytomegalovirus
Lymphocryptovirus
Rhadinovirus
JC polyomavirus
Human immunodeficiency virus 1
Merkel cell polyomavirus
Betapolyomavirus hominis
Betapolyomavirus macacae

overall_design: CD14+ monocytes were isolated from the peripheral blood of 4 normal, healthy volunteers and differentiated into osteoclasts or macrophages in vitro. Total RNA was isolated from these cells at 0, 24, 72, 144, and 288 hours of culture. RNA was profiled using the Qiagen miRCURY LNATM microRNA Hi-Power Labelling Kit and miRCURY LNATM microRNA Array (7th Gen).

middle: B

last: Fordham

first: Afsar

middle: R

last: Naqvi

first: Salvador

last: Nares


title: Genome wide TFIIB binding during postnatal and pressure-induced cardiac hypertrophy

status: Public on Nov 17 2014

city: Newark

first: Danish

last: Sayed

state: NJ

address: 185 south orange avenue

department: CBMM

institute: Rutgers-NJMS

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
Purpose: To identify the differential TFIIB bindingl patterns during postnatal cardiac growth, pressure-induced cardiac hypertrophy and adult mouse hearts
Methods: Hearts were extracted from 1-2day old C57 mice, from mice subjecetd to Transaortic coarctation or adult mice. The hearts were sent to Active Motif for TFIIB- ChIP-Seq.
Results: In accordance with previosly published data (Sayed D, et. al. JBC, 2013 Jan 25;288(4):2546-58) with genome wide polII and H3K9ac status during cardiac hypertrophy (GSE50637), Denovo TFIIB recruitment was restricted to speclaized genes with cardiac hypertrophy.

first: Maha

last: Abdellatif


title: Analysis of transcription start sites from nascent RNA identifies a unified architecture of initiation at mammalian promoters and enhancers

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

overall_design: Refer to individual Series


title: Transcriptomic profiling of peripheral blood mononuclear cells from healthy individuals

status: Public on Oct 27 2014

city: Madison

first: Heidi

last: Dvinge

state: WI

address: 440 Henry Mall

department: Biomolecular Chemistry

institute: UW-Madison

summary:
Substantial effort is currently devoted to identifying cancer-associated alterations using genomics. Here, we show that standard blood collection procedures rapidly change the transcriptional and post-transcriptional landscapes of hematopoietic cells, resulting in biased activation of specific biological pathways, up-regulation of pseudogenes, antisense RNAs, and unannotated coding isoforms, and RNA surveillance inhibition. Affected genes include common mutational targets and thousands of other genes participating in processes such as chromatin modification, RNA splicing, T and B cell activation, and NF-κB signaling. The majority of published leukemic transcriptomes exhibit signals of this incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes. The effects of sample processing are particularly evident in pan-cancer analyses. We provide biomarkers that detect prolonged incubation of individual samples, and show that keeping blood on ice markedly reduces changes to the transcriptome. In addition to highlighting the potentially confounding effects of technical artifacts in cancer genomics data, our study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors.
This study is complemented by GSE61410: transcriptomic profiling of bone marrow cells from healthy individuals.

overall_design: Peripheral blood mononuclear cells (PBMCs) were isolated from four healthy individuals, following an ex vivo incubation of variable length at either room temperature or on ice. RNA transcriptomes were measured using the Illumina HiSeq.

first: R

last: Bradley

first: H


title: Differential gene expression in renal cortex resulting from SPAK gene disruption

status: Public on Nov 01 2014

city: Baltimore

first: Paul

last: Grimm

state: MD

address: 660 West Redwood Street

department: Physiology

institute: University of Maryland School of Medicine

summary: Poorly defined adaptive processes maintain salt balance when the renal thiazide-sensitive sodium-chloride cotransporter is inhibited, limiting diuretic efficacy. Here, we identify underlying mechanisms in SPAK kinase null mice, which are unable to phospho-activate NCC. Global transcriptional profiling, combined with biochemical, cell biological and physiological phenotyping, identified the gene expression signature of the response, and revealed how it establishes a new adaptive physiology. Salt reabsorption pathways are created by the coordinate induction of a multi-gene transport system, involving solute carriers (Slc26a; Slc4a8; Slc4a9), carbonic anhydrase isoforms, and V-type H+-ATPase subunits in pendrin-positive intercalated cells (PP-IC), and ENaC subunits in principal cells.  A distal nephron remodeling process and induction of Jagged 1-Notch signaling, which expands the cortical connecting tubule with principal cells and replaces acid-secreting α- intercalated cells with PP-IC, is partly responsible. Salt reabsorption is also activated by induction of an alpha-ketoglutarate (α-KG) paracrine signaling system. Coordinate regulation of a multigene α-KG synthesis and transport pathway cause α-KG to be secreted into the pro-urine as the α-KG activated GPCR (Oxgr1) increases on the PP-IC apical surface, allowing paracrine delivery of α-KG to stimulate salt transport. Identification of the integrated compensatory NaCl reabsorption mechanisms provides new insights into thiazide diuretic efficacy.

overall_design: Gene transcrtipt isolated form the renal cortex of 4 SPAK KO and 4 litter-mate WT animals was compared to evaluate differential gene expression with the goal of identifing a nextwork of genes that function cooperatively compensatory to mitigate renal salt loss when the SPAK function is lost.

first: Susan

middle: G

last: Dorsey

middle: A

last: Welling


title: VHL Status Influences Phenotype of Liver Cancers Arising from PTEN Loss

status: Public on Oct 31 2014

city: Nashville

first: Kimryn

last: Rathmell

state: TN

address: 2220 Pierce Ave

institute: Vanderbilt

summary: Background: PTEN loss contributes to the development of many cancers and is associated with both hepatocellular carcinoma and cholangiocarcinoma. The pathogenesis of these malignancies is unclear, but they are speculated to arise from common cellular origins. We explored the influence of secondary effects, like hypoxia signaling, through co-deletion of Pten and Vhl in a murine model.Methods: We used a CreER-linked keratin 18 mouse model to conditionally delete Pten, Vhl or both, evaluating the resultant tumors by histology and gene expression microarray. A cohort of human cholangiocarcinoma samples was evaluated for relationships between HIF-1a expression and clinical outcomes.Results: Both Pten deletion genotypes developed liver tumors, but with differing phenotypes. Pten deletion alone led to large, invasive tumors with widespread hepatosteatosis. Co-deletion of Pten and Vhl resulted in low tumor burden and reduced steatosis. Microarray analysis divided mouse tumors’ respective genotypes by gene expression. This gene expression profile grouped a human tumor cohort according to histologic type with the Pten deletion signature aligning with hepatocellular carcinoma, whereas the Pten; Vhl deletion signature associated with cholangiocarcinomas. In a human cholangiocarcinoma cohort, we observed correlation between HIF-1a expression and overall survival.Conclusions: Pten deletion leads to tumor formation and steatosis in mouse livers. Co-deletion of Vhl and Pten resulted in lower tumor burden with gene expression profiling suggesting a switch from hepatocellular expression features to an expression profile more consistent with cholangiocarinoma. A possible relation between HIF-1a expression and increased overall survival in human cholangiocarcinoma suggests that hypoxia signaling influences tumor phenotype.

overall_design: reference x sample

first: Autumn

middle: J


title: Transcriptomic profiling of bone marrow cells from healthy individuals

summary:
We performed whole-genome transcriptomic profiling of RNA from mononuclear cells from bone marrow aspirates taken from healthy individuals.
This study complements GSE58335: transcriptomic profiling of peripheral blood mononuclear cells from healthy individuals.

overall_design: High-throughput sequencing was done using the Illumina GA IIx. The RNA is from previously published samples (Stirewalt et al., Genes Chromosomes Cancer, 2008, PMID:17910043)

first: M

last: McIntosh


title: Interstrain differences in the severity of liver injury induced by a choline- and folate-deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism.

status: Public on Oct 16 2014

city: Jefferson

first: Volodymyr

last: Tryndyak

address: 3900 NCTR Rd

department: Division of Biochemical Toxicology

institute: US-FDA National Center for Toxicological Research

summary: Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and developed countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD. The goals of this study were to compare the magnitude of interindividual differences in the severity of liver injury induced by methyl-donor deficiency among individual inbred strains of mice and to investigate the underlying mechanisms associated with the variability. Feeding mice a choline- and folate-deficient diet for 12 wk caused liver injury similar to NAFLD. The magnitude of liver injury varied among the strains, with the order of sensitivity being A/J ≈ C57BL/6J ≈ C3H/HeJ < 129S1/SvImJ ≈ CAST/EiJ < PWK/PhJ < WSB/EiJ. The interstrain variability in severity of NAFLD liver damage was associated with dysregulation of genes involved in lipid metabolism, primarily with a down-regulation of the peroxisome proliferator receptor α (PPARα)-regulated lipid catabolic pathway genes. Markers of oxidative stress and oxidative stress-induced DNA damage were also elevated in the livers but were not correlated with severity of liver damage. These findings suggest that the PPARα-regulated metabolism network is one of the key mechanisms determining interstrain susceptibility and severity of NAFLD in mice.

overall_design: Male A/J, C3H/HeJ and WSB/EiJ inbred mice were maintained on either control or choline- and folate-deficient (CFD) diets for 12 weeks. Gene expression profiles in the livers from control mice and mice fed a CFD-diet were investigated.

first: Aline

last: de Conti

first: Tao

last: Han

first: James

middle: C

last: Fuscoe

first: Ivan

last: Rusyn

first: Frederick

last: Beland

first: Igor

middle: P

last: Pogribny


title: Pituitary Gene Expression Profiles of Growing Beef Steers Grazing High versus Low Endophyte-Infected Tall Fescue Grass

status: Public on Oct 23 2014

city: Lexington

last: Matthews

state: Ky

address: 207 W.P. Garrigus Buidling

department: Animal and Food Sciences

institute: University of Kentucky

summary: Neotyphodium coenophialum is an endophytic fungus that infects most tall fescue (Festuca arundinacea) pastures that are commonly used in animal grazing systems in the United States. Beef cattle grazing such pastures are impaired in health and production performance, resulting in a large economic loss in US food-animal production systems. Based on clinical and biochemical blood analyte profiles, hepatic targeted gene and protein analyses, and hepatic transcriptomic profiling, microarray analysis using the BovGene-1_0-v1 array (Affymetrix) was conducted to determine if grazing endophyte-infected tall fescue pastures affects pituitary gene expression profiles of growing beef steers. The specific overall hypothesis tested was that grazing high endophyte-infected pasture would alter the pituitary genomic expression profiles of the same growing steers, especially genes involved in production and secretion of prolactin, growth hormone, thyroid stimulating hormone, and adrenocorticotropic hormone.

overall_design: Sixteen steers were assigned to graze either a low toxic endophyte tall fescue-mixed grass (LE treatment, 5.7 ha, n = 8) or a high toxic endophyte infected tall fescue (HE treatment, 5.7 ha, n = 8) pasture located in the University of Kentucky Agricultural Research Center. All steers had ad libitum access to fresh water, an industry standard mineral-vitamin supplement, and grazed respective pastures for 89 to 105 days. Whole pituitaries were collected for RNA extraction and microarray analysis.

first: J

last: Hegge

first: K

middle: L

last: Cerny

first: P

last: Bridges


title: Gene expression profiles of patients with schizophrenia, bipolar disorder and healthy controls

status: Public on Oct 11 2014

city: São Paulo

first: Renato

middle: David

last: Puga

state: São Paulo

address: Dr Ovidio Pires de Campos,785

department: Instituto de Psiquiatria

country: Brazil

institute: Universidade de São Paulo

summary: Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions, with a lifetime prevalence of about 1%. Both disorders have a neurodevelopment component, with onset of symptoms occurring most frequently during late adolescence or early adulthood. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. These gene expression profiles were used to identify the molecular mechanisms that differentiate SZ and BP from healthy controls but also that distinguish both from healthy individuals. They were also used to expand an analysis from an experiment that searched molecular alterations in human induced pluripotent stem cells derived from fibroblasts from control subject and individual with schizophrenia and further differentiated to neuron to identify genes relevant for the development of schizophrenia (GSE62105).

overall_design: Brain tissue (frontal cortex) from 30 healthy controls, 29 bipolar disorder patients and 29 schizophrenia patients were analyzed. The reference is an in-house pool of RNA extracted from 15 human cell lines.

first: Angelica

last: de Baumont

first: Mariana

last: Maschietto

first: Leandro

last: Lima

first: Ana

last: Tahira

first: Daniel

last: Mariani

first: Dirce

middle: M

last: Carraro

first: Eloisa

middle: H

last: Olivieri

first: Alex

last: Fiorini

first: Luiz

last: Barreta

first: Joana

last: Palha

first: Paulo

last: Belmonte-de-Abreu

first: Carlos

last: Filho

first: Helena

last: Brentani


title: Co-expression network analysis from genes involved with neural-differentiation shows specific pattern in patients with schizophrenia

status: Public on Oct 09 2014

summary: Schizophrenia is a severe and debilitating neuropsychiatric disorder with the involvement of genetic and environmental factors contributing to its pathogenesis. The specific role of the brain cell types in the disease remains uncovered due to the difficulties in accessing diseased tissue. This study analysed molecular alterations in human induced pluripotent stem cells (hiPSCs) derived from fibroblasts from control subject and individual with schizophrenia and further differentiated to neuron to identify genes relevant for the development of schizophrenia. We identified 228 genes that are involved with metabolic processes, signal transduction, nervous system development, regulation of neurogenesis and neuronal differentiation. These genes were analysed in expression microarrays of post-mortem brain tissue (frontal cortex) of additional patients with schizophrenia and normal individuals revealing only six common genes: CACNA1E, CEBPB, DUX4, EDNRA, SPHK1 and SPRY4 (GSE62191). Furthermore, a co-expression network analysis of the 228 genes revealed a non-conserved module enriched for genes associated with oxidative stress and negative regulation of cell differentiation as involved with schizophrenia. This study supports the relevance of using cellular approaches to dissect molecular aspects of neurogenesis with impact in the schizophrenic brain.

overall_design: Biopsies of primary human fibroblasts from a 48-year-old woman with DSM-IVTR schizophrenia defined as treatment-resistant under clozapine treatment (SZCP) were collected in parallel with a control subject (CON) negative for any major lifetime DSM-IVTR diagnosis. Fibroblasts underwent primary culture procedures to generate hiPSCs and were subsequently differentiated into neuron precursor cells (NPCs). Samples generation and culture conditions are described in Paulsen et al. (2011). Five replicates of expression microarray experiments using a reference design, where test sample (NPC) is derived from reference sample (hiPSC).

first: Bruna

middle: S

last: Paulsen

first: Henrique

last: Vieira

last: Krepischi

first: Stevens

last: Rehen


title: Identification of copy number variation using aCGH in Chinese chicken breeds

status: Public on Oct 10 2014

city: zhengzhou

first: ruili

last: han

address: 95 wenhua road

country: China

institute: henan agriculture university

type: Genome variation profiling by genome tiling array

summary:
CNV plays an important role in the chicken genomic studies,it is imperative need to investigate the extent and pattern of CNVs using array comparative genomic hybridization (aCGH) in chinese chicken breeds for future studies associating phenotype to genome architecture.
we describe systematic and genome-wide analysis of CNVs loci in five Chinese indigenous chicken breeds were evaluated by aCGH.

overall_design: 5 Chinese native chicken were detected using ANKA broiler as reference.

first: Han

last: Ruili

first: Kang

last: Xiangtao


title: Genome-wide analysis of mRNA expression alterations in Stage III-IV high-grade serous ovarian cancer patients exhibiting clinically defined differences in ascites volume (high volume ascites versus low volume ascites)

status: Public on Oct 01 2014

city: Toronto

first: carl

last: virtanen

state: Ontario

address: 101 College St

department: Princess Margaret Genomics Centre

country: Canada

institute: University Health Network

summary: Microarrays were used to examine gene expression changes in the surgical resections of high-grade serous ovarian cancer patients exhibiting clinically distinct levels of ascites volume.  The present studies primary aim was to determine if there is a molecular gene expression  difference between the patients presenting at time of surgery when high volumes ascites cases were compared to those with low volume ascites. The secondary aim was to determine what relevance this difference, if found, has to previously discovered molecular sub-types of high grade serous ovarian cancer.

overall_design: Total RNA obtained from snap-frozen stage III-IV high-grade serous ovarian cancer patients presenting with low volume (<=200 cc) or high volume (>=1000 cc) ascites volume.

first: Carl

last: Virtanen

first: Tomer

last: Feigenberg

first: Ted

last: Brown


title: Chronic Bisphenol A and Genistein Exposure in MCF7 cells

status: Public on Sep 01 2014

city: Columbus

first: Craig

middle: Joseph

last: Burd

state: OH

address: 460 W. 12th Ave. Rm 920 BRT

department: Molecular Genetics

institute: The Ohio State University

summary: Exposures to environmental endocrine disruptors is growing and human contact in industrialized countries has become signficant and constant.  We studied the effect of chronic exposure to two endocrine disrupting compound, bisphenol A and genistein, in an in vitro cell culture system. MCF7 cells were cultured for greater than 70 passages under normal (MCF7-F) conditions or with the addition of 50 nM BPA (MCF7-B) or GEN (MCF7-G).  We performed transcriptome analysis of the all three cell lines in the absence of any estrogenic compounds and in the presence of 10 nM estradiol for 3 hours.

overall_design: The MCF7-F, B, G cell lines were starved of all estrogenic compounds by culturing the cells for 72 hours in phenol red free DMEM containing 5% charcoal/dextran treated FBS.  Cells were then treated with either ethanol vehicle or 10 nM 17b-estradiol for 3 hours.  Total RNA was harvested and utilized for whole genome analysis on the Affymetrix Human Trascriptome Array 2.0.  The experiment was performed in duplicate

first: Andrea

last: Patterson

first: Xiaokui

last: Mo


title: CTCR-OV03/CTCR-OV04 ovarian cancer

city: Pieve Emanuele

first: Charlotte

middle: K Y

last: Ng

state: MI

address: Via Rita Montalcini 4

department: Biomedical Sciences

country: Italy

institute: Humanitas University

summary:
High-grade serous ovarian cancer (HGSOC) exhibits significant genomic heterogeneity within a patient at presentation. Recent work has suggested that this heterogeneity is linked to the development of resistance and disease progression in that chemotherapy selects for minor resistant subclones embodied in presentation disease leading to short progression-free survival and resistant relapse. Cell line models support this by showing that relapse is not an immediate descendant of presentation disease, but so far no immediate clinical evidence has been provided that convincingly demonstrates the origin of relapse. It is further still unclear what evolutionary processes shape the mutational landscape of HGSOC in vivo and to what extent the degree of genomic heterogeneity impacts a patient's clinical outcome. We address these questions by inferring evolutionary trees of metastatic disease from structural variations between 138 cancer samples obtained from 17 patients undergoing neoadjuvant chemotherapy for HGSOC. Using novel phylogenetic methods, we quantify genomic changes in the course of chemotherapy and the degree of clonal expansion and show that these indices determine patient outcome with high accuracy. We demonstrate that relapse is indeed a minor subclone of presentation disease by verifying that the focal NF1 deletion of a relapse case was already present at biopsy. By leveraging the information contained in the evolutionary trees, we unveil the etiology of genetic heterogeneity and the tumorigenic potential of HGSOC cell populations.
This is the first comprehensive study showing the origin, strength and effect of genetic heterogeneity in HGSOC in a clinical setting. In addition to its immediate clinical significance, it strengthens previous statements that single sample biopsies are seemingly insufficient to predict disease progression and stresses the importance of establishing multiple sampling as a routine approach in the clinic.

overall_design: Clinical data and tissue samples were collected on the prospective CTCR-OV03 and CTCR-OV04 clinical studies designed to identify biomarkers of heterogeneity.

middle: K

first: Susanna

last: Cooke

first: James

middle: D

last: Brenton


title: Transcriptomic analysis of human cybrid cell lines harboring increasing levels of the mitochondrial DNA (mtDNA) 3243A>G mutation

status: Public on Sep 02 2014

city: Philadelphia

first: Douglas

last: Wallace

state: PA

address: 3501 Civic Center Blvd

department: Center for Mitochondrial and Epigenomic Medicine

institute: The Children's Hospital of Philadelphia

summary: Mitochondria generate signals of adaptation that regulate nuclear genes expression via retrograde signaling.  But this phenomenon is complexified when qualitatively different mitochondria and mitochondrial DNA (mtDNA) coexist within cells.  Although this cellular state of heteroplasmy leads to divergent phenotypes clinically, its consequences on cellular function and the cellular transcriptome are unknown.  To interrogate this phenomenon, we generated somatic cell cybrids harboring increasing levels of a common mtDNA mutation (tRNALeu(UUR) 3243A>G) and mapped the resulting cellular phenotypes and transcriptional profiles across the complete range of heteroplasmy.  Small increases in mutant mtDNAs caused relatively modest defect in mitochondrial oxidative capacity, but resulted in sharp transitions in mitochondrial ultrastructure and in the nuclear and mitochondrial transcriptomes, with the critical functional threshold corresponding to the induction of epigenetic regulatory systems.  Principal component analysis underscores how each heteroplasmy level occupies a different "transcriptional space", with low levels heteroplasmy (20-30%) producing a dose-response linear progression in one direction, and mutationload of 50, 60 and 90% producing changes in the opposite direction.  Hence, subtle changes in mitochondrial energetics can act through the epigenome to generate the phenotypes of the common “complex” diseases.

overall_design: Cells were generated by transferring the wildtype (3243A) and mutant (3243G) mtDNAs from a heteroplasmic 3243A>G patient’s lymphoblastoid cell line into 143B(TK-) mtDNA-deficient (ρo) cells and selected for transmitochondrial cybrids.  Subsequent mtDNA depletion, reamplification, and cloning (Wiseman and Attardi, 1978) resulted in a series of stable cybrids harboring approximately 0, 20, 30, 50, 60, 90, and 100% 3243G mutant mtDNAs. Total RNA extracted from each cell line was then extracted, depleted of rRNA, and measured in sequenced in triplicates.

first: Martin

last: Picard

first: Jiangwen

last: Zhang

first: Saege

last: Hancock

first: Olga

last: Derbeneva

first: Ryan

last: Golhar

first: Pawel

last: Golik

first: Sean

last: O'Hearn

first: Shawn

middle: E

last: Levy

first: Prasanth

last: Potluri

first: Maria

last: Lvova

first: Antonio

last: Davilla

first: Chun

last: Lin

first: Juan

last: Perin

first: Eric

middle: F

last: Rappaport

first: Hakon

last: Hakonarson

first: Ian

last: Trounce

first: Vincent

last: Procaccio


title: Gene expression profiles of HMEC-1 after exposure to the chemotherapeutic drugs bleomycin and cisplatin with untreated samples as control

status: Public on Oct 22 2014

city: Groningen

first: Jourik

last: Gietema

address: Hanzeplein 1

department: Medical Oncology

country: Netherlands

institute: UMCG

summary:
Chemotherapy-related endothelial damage contributes to the early development of cardiovascular morbidity in testicular cancer patients. We aimed to identify relevant mechanisms of and search for candidate biomarkers for this endothelial damage.
Human micro-vascular endothelial cells (HMEC-1) were exposed to bleomycin or cisplatin with untreated samples as control. 18k cDNA microarrays were used. Gene expression differences were analysed at single gene level and in gene sets clustered in biological pathways and validated by qRT-PCR. Protein levels of a candidate biomarker were measured in testicular cancer patient plasma before, during and after bleomycin-etoposide-cisplatin chemotherapy, and related to endothelial damage biomarkers (von Willebrand Factor (vWF), high-sensitivity C-Reactive Protein (hsCRP)).
Microarray data identified several genes with highly differential expression; e.g. Growth Differentiation Factor 15 (GDF-15), Activating Transcription Factor 3 (ATF3) and Amphiregulin (AREG). Pathway analysis revealed strong associations with ‘p53’ and ‘Diabetes Mellitus’ gene sets. Based on known function, we measured GDF-15 protein levels in 41 testicular patients during clinical follow-up. Pre-chemotherapy GDF-15 levels equalled controls. Throughout chemotherapy GDF-15, vWF and hsCRP levels increased, and were correlated at different time-points.
An unbiased approach in a preclinical model revealed genes related to chemotherapy-induced endothelial damage, like GDF-15. The increases in plasma GDF-15 levels in testicular cancer patients during chemotherapy and its association with vWF and hsCRP suggest that GDF-15 is a potentially useful biomarker related to endothelial damage.

overall_design: In an acute-exposure setting, HMEC-1 were left untreated as controls or were treated with 0.3 (IC50 (concentration inhibiting cell survival by 50%)) or 1.5 ug/mL (IC90) bleomycin and 2.6 (IC50) and 12.9 uM (IC90) cisplatin for 6, 24 and 48 hours. In a chronic-exposure setting, lower doses were administrated (IC10; bleomycin 0.06 ug/mL or cisplatin 0.52 uM) two times a week; cells were collected for analysis at day 30. Administration of cisplatin had to be withheld at the 7th administration because of considerable cell dead, but was continued at full dose thereafter. Bleomycin could be administrated without disruption. Total RNA was isolated from HMEC-1 and pooled for each time point and drug concentration from 2 independent experiments.

first: Renske

last: Altena

first: Rudolf

last: Fehrmann

first: Hink

last: Boer

first: Elisabeth

last: de Vries

first: Coby

last: Meijer


title: Identification of Novel Virulence-related Genes in Burkholderia pseudomallei by Comparing Gene Expression Profiles in Two Mice Model Through Microarray

status: Public on Sep 12 2014

city: Maung

first: THANATCHAPORN

last: BARTPHO

state: Khon Kaen

address: 123 Mitthaphap

department: Microbiology

country: Thailand

institute: Meliodosis Research Center, Faculty of Medicine, Khon Kaen University

summary: The gene expression profiles were investigated and compared in spleen, lungs and liver of susceptible (BALB/c) and resistant (C57BL/6) hosts to identify genes participated in survival and virulence functions encoded in the B. pseudomallei genome. Subsequently, genes with unknown function and located with virulence gene clusters or suspected to be transcription regulator were selected for a novel virulence gene investigation

sample_organism:
Burkholderia pseudomallei
Burkholderia pseudomallei K96243

platform_organism:
Burkholderia mallei
Burkholderia pseudomallei

overall_design:
DNA microarray was used to compare gene expression profiles of B. pseudomallei 1909a in spleen, lung and liver of infection-susceptible BALB/c mice (Th2 prototype) and infection-resistant C57BL/6 mice, (Th1 prototype) during an acute infection. The gene expression profile of B. pseudomallei in culture medium at mid-log phase was used to identify genes that expressed higher or lower in vivo when compared to the in vitro gene profile
KEYWORDS: Gene expression

first: Sunisa

last: Chirakul

first: Tanatchaporn

last: Bartpho

first: Thidathip

last: Wongsurawat

first: Suwimol

last: Taweechaisupapong

first: Nitsara

last: Karoonuthaisiri

first: Adel

last: Talaat

first: Surasakdi

last: Wongratanacheewin

first: Robert

last: Ernst

first: Rasana

middle: W

last: Sermswan


title: Expression data of genome-length HCV RNA-replicating OL8(3.5Y) cells and OL8(3.5Y)-derived ribavirin-resistant cells

status: Public on Aug 30 2014

city: Okayama

first: Shinya

last: Satoh

address: 2-5-1 Shikata-cho Kita-ku

country: Japan

institute: Okayama University

summary:
Ribavirin (RBV) is a potential partner of interferon-based therapy and recently approved therapy using direct acting antivirals for patients with chronic hepatitis C, However, the precise mechanisms undelying RBV action against hepatitis C virus (HCV) replication are not yet understood. To clarify this point, we established RBV-resistant cell lines from RBV-sensitive HCV RNA-replicating cell line, OL8(3.5Y), and characterized their features.
We used  microarrays to compare the gene expression pattern between OL8(3.5Y) cells and three RBV-resistant cells and identified genes commonly altered by more than four-fold among RBV-resistant cells compared with the OL8(3.5Y) cells.

overall_design: Growing cells  from RBV-sensitive OL8(3.5Y) and three RBV-resistant cell lines were used for RNA extraction and hybridization on Affymetrix microarrays.

first: Nobuyuki

last: Kato


title: Pig experiment Sterksel early antibiotics/stress

city: Wageningen

first: Dirkjan

last: Schokker

address: Droevendaalsesteeg 1

department: Wageningen Livestock Research

institute: Wageningen UR

summary: Impact of antibiotics (T2) or antibiotics in combination with stress (T3) in early life on intestinal functioning in pigs on 8, 55, 176 days in jejunum and ileum (blood only day 8) and control pigs (T1)

overall_design: 4 pools consisting of 16 animals were generated per time-point (day 8, 55, 176 after birth) per treatment (T1;control, T2; antibiotics, T3; antibiotics+stress)

first: S

last: Vastenhouw

first: M

last: Smits

first: J

last: Rebel


title: Central Role of ULK1 in Type I Interferon Signaling

status: Public on Aug 26 2014

city: Berlin

first: Pawel

last: Lisowski

address: Hannoversche Str. 28

country: Germany

institute: Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association

summary: We provide evidence that the Unc-51-like kinase 1 (ULK1) is phosphorylated and activated during engagement of the Type I IFN receptor. Our studies demonstrate that the function of ULK1 controls expression of key interferon stimulated genes (ISGs) that mediate important biological functions, including anti-viral and antineoplastic responses.

overall_design: Total RNA was isolated from untreated and IFNβ-treated Ulk1/2+/+ and Ulk1/2-/- mouse embryonic fibroblasts (MEFs). Cells were treated for 6 hours with or without mouse IFNβ (2500 IU/ml).

first: Diana

last: Saleiro

first: Leonidas

last: Platanias


title: Cross-platform toxicogenomics for the prediction of nongenotoxic hepatocarcinogenesis in rat

status: Public on Aug 18 2014

city: Basel

first: Jonathan

last: Moggs

address: Fabrikstrasse 2

country: Switzerland

institute: Novartis

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

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

platform_organism:
Mus musculus
Rattus norvegicus

overall_design: Refer to individual Series


title: Effect of Helicobacter pylori on ATM-dependent DNA damage responses [biopsy]

status: Public on Aug 23 2014

city: Yufu

first: Katsuhiro

last: Hanada

state: Oita

address: 1-1 Idaigaoka, Hasama-machi

department: Faculty of Medicine

institute: Oita University

summary:
Carcinogenic bacteria, Helicobacter pylori, induce DNA double-strand breaks in infected host cells, while ATM-dependent DNA damage responses in host cells suppress genome instabilities caused by DNA breakages, which resulting in the suppression of H. pylori-induced gastric cancers.
Although Helicobacter pylori infection is etiologically related to the inflammation-related malignancy, gastric cancers, it role in the molecular pathogenesis of disease remains unclear. In vitro studies have suggested the infection may cause breaks in double-stranded DNA. We used microarray analysis of H. pylori-infected human gastric biopsies to investigate the effect of H. pylori on gene expression genes involved in DNA repair and DNA damage response. Micro-array analysis and immunohistochemistory showed that ATM (ataxia-telangiectasia mutated) was upregulated in H. pylori gastritis but down regulated in the premalignant lesion, intestinal metaplasia. Studies in gastric cancer cell lines showed that H. pylori-infection induced activation of ATM and formation of γ-H2AX.  γ-H2AX formation was present following infection with bout cag pathogenicity island (PAI)- positive and negative strains but more robust with cag PAI positive strains consistent with the fact that both cag PAI positive negative strains are associated with gastric cancer but the risk is higher with cag PAI positive strains.  Eradication of H. pylori infection is associated with a reduction in cancer risk even in the most high risk populations.  These data provide a plausible molecular mechanism for a direct bacterial-host interaction increasing cancer risk.

overall_design: To identify tumor suppressors affected by H. pylori-infection, microarray screening was used to compare the gene expression profiles of gastric mucosa obtained from individuals with H. pylori-gastritis and with intestinal metaplasia with tissue from uninfected controls.

first: Yoshio

last: Yamaoka


title: Cross-platform toxicogenomics for the prediction of nongenotoxic hepatocarcinogenesis in rat (protein)

summary: In this study we performed microarray-based molecular profiling of liver samples from Wistar rats exposed to genotoxic carcinogens (GC), nongenotoxic carcinogens (NGC) or non-hepatocarcinogens (NC) for up to 14 days. In contrast to previous toxicogenomics studies aimed at the inference of molecular signatures for assessing the potential and mode of compound carcinogenicity, we considered multi-level omics data. Besides evaluating the predictive power of signatures observed on individual biological levels, such as mRNA, miRNA and protein expression, we also introduced novel feature representations which capture putative molecular interactions or pathway alterations by integrating expression profiles across platforms interrogating different biological levels.

overall_design: Male Wistar rats were treated by oral gavage with the eight nongenotoxic hepatocarcinogens Phenobarbital sodium (PB), Piperonylbutoxide (PBO), Dehydroepiandrosterone (DHEA), Acetamide (AA), Methapyrilene HCl (MPy), Methylcarbamate (Mcarb), Diethylstilbestrol (DES) and Ethionine (ETH), the two genotoxic carcinogens C.I Direct Black (CIDB) and dimethylnitrosamine (DMN), the two non-hepatocarcinogens Cefuroxime (CFX) and Nifedipine (Nif), and the three compounds with undefined carcinogenic class Cyproterone acetate (CPA), Thioacetamid (TAA) and Wy-14643 (Wy). Depending on the administered compound, livers were taken after 3, 7, or 14 days for histopathological evaluation. From the five animals per treatment group three animals were selected based on the histopathological findings and subjected to molecular profiling using Affymetrix RG-230A arrays (mRNA expression), Agilent G4473A arrays (miRNA expression) and Zeptosens ZeptoMARK reverse arrays (protein expression).

first: Michael

last: Römer

first: Heidrun

last: Ellinger-Ziegelbauer

first: Johannes

last: Eichner


title: p53 shapes genome-wide changes in small non-coding RNA expression during the human DNA damage response

status: Public on Aug 15 2014

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 box 602

department: Department of Human Genetics

country: Belgium

institute: KU Leuven

type: Non-coding RNA profiling by high throughput sequencing

summary: Small RNA-seq on MCF10A, HCT116 and HCT116p53-/- cell lines after induction of DNA damage (5 Gy Irradiation).

overall_design: Small RNA-seq on MCF10A, HCT116 and HCT116p53-/- at 4 and 24 hours after induction of DNA damage (5 Gy Irradiation), done in duplicate with respective control (0 hour) using illumina Genome Analyzer IIx

first: Hiro

last: Hattori

first: Madan

last: Babu

first: Ashok

last: Venkitaraman


title: Cross-tissue methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease neuropathology

status: Public on Aug 17 2014

city: London

first: Leonard

last: Schalkwyk

address: De Crespigny Park

department: IOP-SGDP

country: United Kingdom

institute: King's College London

summary: Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from three independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease.

overall_design: For the first (discovery) stage of our analysis, we used multiple tissues from donors (N = 122) archived in the MRC London Brainbank for Neurodegenerative Disease. From each donor, we isolated genomic DNA from four brain regions (EC, superior temporal gyrus (STG), prefrontal cortex (PFC) and CER) and, where available, from whole blood obtained pre-mortem.  Our analyses focused on identifying differentially methylated positions (DMPs) associated with Braak staging, a standardized measure of neurofibrillary tangle burden determined at autopsy.

first: Katie

last: Lunnon

first: Rebecca

last: Smith

first: Eilis

last: Hannon

first: Philip

last: De Jager

first: Gyan

last: Srivastava

first: Manuela

last: Volta

first: Claire

last: Troakes

first: Safa

last: Al-Sarraj

first: Joe

last: Burrage

first: Ruby

last: Macdonald

first: Daniel

last: Condliffe

first: Lorna

last: Harries

first: Pavel

last: Katsel

first: Vahram

last: Haroutunian

first: Zachary

last: Kaminsky

first: Catharine

last: Joachim

first: John

last: Powell

first: Simon

last: Lovestone

first: David

last: Bennett

last: Mill


title: Effect of Helicobacter pylori on ATM-dependent DNA damage responses

first: Katsuhiro

last: Hanada

first: Yoshio

last: Yamaoka


title: Rat hypothalamus: Methimazole (MMI)-saline vs MMI-T3

status: Public on Jul 31 2014

city: Aberdeen

first: Perry

last: Barrett

address: Greenburn Road, Bucksburn

department: Rowett Institute for Nutrition and Health

institute: University of Aberdeen

summary: Sprague Dawley rats rendered hypothyroid with 22 days of MMI treatment with half the receiving T3 injection on day 21. Rats killed 24h later and hypothalamic tissue recovered.

overall_design: Two condition experiment MMI vs MMI-T3  hypothalami 4 replicates per treatment

first: Annika

last: Herwig

first: Claus-Dieter

last: Mayer


title: Whole genome expression analysis of a skin biopsy from two individuals with ectodermal dysplasia features associated with hearing loss in GRHL2

status: Public on Aug 11 2014

first: Venu

middle: Madhav

last: Pullabhatla

address: Great Maze Pond

department: Guy's Hospital

institute: Biomedical Research Centre

summary: Whole-genome expression microarray analysis was performed using RNA extracted from skin biopsies sampled from two related and affected individuals as well as 4 pooled, healthy controls. The hypothesis was that the downstream effects of the inherited GRHL2 missense mutation in the two siblings would be evident by enriched pathways and processess linked to the cutaneous roles of the grainyhead like-2 protein. Functional analysis of the results identified a multitude of enriched gene ontology (GO) processes, pathways, networks and disease-associated transcripts related to the function of GRHL2 in the affected individuals' samples compared to controls. Results provide important information about significantly up-regulated and down-regulated GO networks, pathways and processes involved in epithelial morphogenesis .

overall_design: Total RNA extracted from two skin biopsies from each of the affected individuals was compared to skin biopsies from 4 pooled, healthy controls.

last: McGrath


title: Pervasive effects of an endophytic fungus on host genetic and phenotypic expression in a tropical tree (part 3)

status: Public on Aug 12 2014

city: Panama

first: Luis

last: Mejia

address: Roosvelt Ave. Tupper Building – 401

department: Smithsonian Tropical Research Institute

country: Panama

institute: Smithsonian Institution

summary: Inoculation of endophyte-free (E-) Theobroma cacao leaves with Colletotrichum tropicale (E+), the dominant foliar fungal endophyte in healthy T. cacao, induced significant changes in the expression of hundreds of host genes. Further, E+ leaves exhibit enhanced pathogen resistance, increased lignin and cellulose content, reduced maximum rates of photosynthesis (Amax), and enrichment of nitrogen-15 and carbon-13 isotopes that all correspond to the changes in expression of specific functional genes in related pathways. Moreover, a cacao gene highly up-regulated in E+ leaves increases pathogen resistance apart from any direct endophyte effects. Thus, benefits of increased pathogen resistance in E+ plants are partially due to enhanced induction of intrinsic host defense pathways, and potential costs include reduced photosynthetic capacity and endophyte metabolism of host tissues. Similar effects are likely to be properties of most plant-endophyte interactions, suggesting general relevance to the design and interpretation of studies of genetic and phenotypic expression in plants.

overall_design:
This was a time course experiment, which objective was to assess gene expression changes in leaves of Theobroma cacao due to inoculation with endophyte Colletotrichum tropicale, over a period of two weeks. Three un-inoculated T. cacao leaves (E-) were collected at time 0, just prior to inoculation, and four T. cacao leaves inoculated with C. tropicale (E+) were collected at 3, 7, and 14 dpi, each leaf from a different plant. Sampled leaves were of developmental stage C-D (Mejía et al. 2012).
Mejía, L.C., Guiltinan, M., J. , Shi, Z., Landherr, L., and Maximova, S., N. (2012). Expression of Designed Antimicrobial Peptides in Theobroma cacao L. Trees Reduces Leaf Necrosis Caused by Phytophthora spp, in Small Wonders: Peptides for Disease Control. American Chemical Society), 379-395.

first: Edward

middle: A

last: Herre

first: Jed

last: Sparks

first: Klaus

last: Winter

first: Milton

middle: N

last: Garcia

first: Sunshine

last: Van Bael

first: Joe

last: Stitt

first: Zi

last: Shi

first: Yufan

last: Zhang

first: Mark

last: Guiltinan

first: Siela

last: Maximova


title: Vibrio vulnificus : biofilm cells vs. planktonic cells

status: Public on Jul 26 2014

city: Seoul

first: Jin Hwan

last: Park

address: Gwanak-ro 599

country: South Korea

institute: Seoul National University

summary: The profiles of transcripts from the planktonic cells and biofilm cells of V. vulnificus were compared by using a V. vulnificus whole-genome microarray

overall_design:
Two-condition experiment,  planktonic cells vs. biofilm cells. Biological replicates: 3 control, 3 experimental, independently grown and harvested. One replicate per array.
For transcriptome analysis, the V. vulnificus whole genome TwinChip, manufactured and kindly provided by the 21C Frontier Microbial Genomics and Applications Center (Daejeon, South Korea), was used.

first: Jin

first: Sang

last: Choi


title: Expression data from Panc1 pancreatic epithelial cells

status: Public on Aug 01 2014

city: Rochester

first: Raul

last: Urrutia

address: 200 1st Street SW

department: Biochemistry & Molecular Biology

institute: Mayo Clinic

summary:
Krüppel-like factors (KLFs) are a group of master regulators of gene expression conserved from flies to human.  However, scant information is available on either the mechanisms or functional impact of the coupling of KLF proteins to chromatin remodeling machines, a deterministic step in transcriptional regulation.  In the current study, we use genome-wide analyses of chromatin immunoprecipitation (ChIP-on-Chip) and Affymetrix-based expression profiling to gain insight into how the KLF11, a human transcription factor involved in tumor suppression and metabolic diseases, works by coupling to three co-factor groups: the Sin3-histone deacetylase system, WD40-domain containing proteins, and the HP1-histone methyltransferase system.
We utilized genome-wide expression analysis of wild type KLF11 and three mutants that disrupt KLF11-chromatin machinery interactions to examine the relationship of the transcription factor and chromatin systems in the regulation of gene networks.

overall_design: Panc1 epithelial cells were plated at a density of 1x10^6 cells/100mm dish and transduced with empty vector, KLF11, KLF11-A347S, KLF11-486, or KLF11-EAPP adenovirus at an MOI of 150.  RNA was prepared as previously described from pooled biological triplicates.

first: Urrutia

last: Raul

first: Calvo

last: Ezequiel


title: Expression data from DOX(doxorubicin) -treated wild type or CHIP knockout C57BL/6J mice at day 5

status: Public on Jul 23 2014

city: beijing

first: zhang

middle: yun

last: long

state: beijing

address: No.10 Xitoutiao, You An Men

department: Department of Physiology and Pathophysiology,

institute: School of Basic Medical Sciences, Capital Medical University

summary:
The clinical application of doxorubicin as a broad-spectrum anti-tumor antibiotic is limited greatly by its cardiotoxicity. Various mechanisms have been studied, but little is known about whether genes or pathways relevant with energy metabolism contributes to doxorubicin-induced cardiomyopathy or not.
We used microarrays to detail the global expression profiling of acute cardiomyopathy induced by doxorubicin in wild type or CHIP knockout C57BL/6J mice and discovered distinct classes of changed genes during this process.

overall_design: The whole hearts were selected for RNA extraction and hybridization on Affymetrix microarrays at day 5 after a single intraperitoneal injection of doxorubicin at a dose of 15 mg/kg.

first: Hui-Hua

last: Li

first: Yun-Long

first: Wen-jun


title: Transcriptional analyses of wheat responses to the necrotrophic effector SnTox3

status: Public on Jul 25 2014

city: Canberra

first: Britta

last: Winterberg

state: ACT

address: Linnaeus Way, Bldg.134

department: Plant Sciences

country: Australia

institute: The Australian National University

summary: Wheat (Triticum aestivum) was infiltrated with the Stagonospora nodorum effector protein SnTox3 to identify differentially regulated genes.

overall_design: SnTox3 was isolated from P. pastoris expression strains, purified and infiltrated into the susceptible wheat line BG220. Samples were collected 6, 12, 24 and 48 hours post infiltration (hpi) in biological triplicates. Total RNA was isolated and used for microarray analysis with the Affymetrix GeneChip Wheat Genome Array following the manufactures instructions. Resulting data were analysed using the Partek Genomics Suite.


title: Re-replication generates whole-chromosomal instability and anueploidy

city: San Francisco

first: Stacey

last: Hanlon

state: California

address: 600 16th Street Genentech Hall S376

department: Biochemistry and Biophysics

institute: University of California, San Francisco

summary: Aneuploidy, a hallmark of cancer, often arises from whole-chromosomal instability (W-CIN).   Many cancers exhibiting W-CIN, however, show no direct insult to the mitotic proteins that ensure proper segregation of chromosomes.  This has stimulated interest in identifying defects in non-mitotic processes that might disrupt chromosome behavior in mitosis.  Here we show in Saccharomyces cerevisiae that transient re-replication of centromeric DNA, due to deregulation of replication initiation proteins, greatly induces aneuploidy of the rereplicated chromosome.  Some of this aneuploidy appears to arise from simple missegregation of both sister chromatids to one daughter cell, indicating that centromeric re-replication can disrupt proper centromere function during mitosis.  Another source of aneuploidy appears to be the generation of an extra sister chromatid via homologous recombination, suggesting that centromeric rereplication can trigger breakage and repair events that expand chromosome numbers while preserving chromosome structure.  Given the emerging connections between the deregulation of replication initiation proteins and oncogenesis, our findings offer the possibility of a new non-mitotic source of aneuploidy that may be relevant to cancer.

overall_design: Diploid strains containing a re-replicating locus were induced to re-replicate through a centromere.  This compilation includes the analysis of the re-replication, as well as the copy-number determination of alleged aneuploid colonies from various backgrounds.  Series contains a total of 194 copy number hybridizations and 8 re-replication profile hybridizations. Note that the VALUE field reported for all of the sample tables in this series are the log2 of the normalized Cy3/Cy5 ratio. To convert these into usable copy number profiles raise 2 to the indicated VALUE.

first: Joachim

middle: J


title: Expression data for Male Fischer 344 rat exposed to nickel subsulfide

status: Public on Jul 19 2014

city: Raleigh

first: Alina

last: Efremenko

state: North Carolina

address: 6 Davis Dr

institute: The Hamner Institutes for Health Sciences

summary: To provide insights into the mode of action for Ni3S2 lung carcinogenicity by examining gene expression changes in target cells after inhalation exposure. Gene expression changes were determined in micro-dissected lung broncho-alveolar cells from Fischer F344 rats following inhalation of Ni3S2 at 0.0, 0.04, 0.08, 0.15, and 0.60 mg/m3 (0.03, 0.06, 0.11, and 0.44 mg Ni/m3) for one and four weeks (6 hours per day, 5 days per week). Results:  Broncho-alveolar lavage fluid evaluation and lung histopathology provided evidence of inflammation only at the two highest concentrations, which were similar to those tested in the 2-year bioassay.  The number of statistically significant up- and down-regulated genes decreased markedly from one to four weeks of exposure, suggesting adaptation.  Cell signal pathway enrichment at both time-points primarily reflected responses to toxicity, including inflammatory and proliferative signaling. While proliferative signaling was up-regulated at both time points, some inflammatory signaling reversed from down-regulation at 1 week to up-regulation at 4 weeks. Conclusions:  These results support a mode of action for Ni3S2 carcinogenicity driven by chronic toxicity, inflammation and proliferation, leading to mis-replication, rather than by direct genotoxicity.  Benchmark dose (BMD) analysis identified the lowest pathway transcriptional BMD exposure concentration as 0.026 mg Ni/m3, for apoptosis/survival signaling.  When conducted on the basis of lung Ni concentration the lowest pathway BMD was 0.64 µg Ni/g lung, for immune/inflammatory signaling. Implications:  These highly conservative BMDs could be used to derive a point of departure in a nonlinear risk assessment for Ni3S2 toxicity and carcinogenicity.

middle: Y


title: Characterization of Functional Methylomes by Different Methods to Identify Novel Disease Associated Variants

city: Quebec

first: Frederic

last: Guenard

address: 2440, Hochelage blvd

institute: Laval University

type: Methylation profiling by genome tiling array

summary: Identification of CpG sites associated to plasma TG levels

overall_design: Bisulphite converted DNA from 24 visceral adipose tissue (VAT) samples were hybridised to the Illumina Infinium HumanMethylation450 Beadchip. Contributor: the Multiple Tissue Human Expression Resource Consortium

first: Fiona

last: Allum

first: Xiaojian

last: Shao

first: Frédéric

last: Guénard

first: Marie-Michelle

last: Simon

first: Stephan

last: Busche

first: Maxime

last: Caron

first: John

last: Lambourne

first: Julie

last: Lessard

first: Karolina

last: Tandre

first: Åsa

last: Hedman

first: Tony

last: Kwan

first: Lars

last: Rönnblom

first: Timothy

last: Spector

first: André

last: Tchernof

first: Simon

last: Marceau

last: Lathrop

first: Marie-Claude

last: Vohl

first: Tomi

last: Pastinen

first: Elin

last: Grundberg


title: Development of peptidomimetic inhibitors of the ERG gene fusion product in prostate cancer

status: Public on Jul 15 2014

city: Ann Arbor

first: Xiaoju

last: Wang

address: 1500 E. Medical Center Drive

institute: University of Michigan


title: C1q elicited macrophage gene expression

status: Public on Jul 10 2014

city: Notre Dame

first: Erliang

last: Zeng

state: IN

address: 384 Fitzpatrick Hall

institute: University of Notre Dame

summary: We have data from a previous microarray experiment which shows that C1q elicits macrophages to express genes important for clearance of dead (apoptotic) cells. In this experiment we want to determine the signaling mechanism by which C1q is turning on macrophage gene expression.  For our control (sample 1-3) we heated C1q to denature it so it is inactive. We also want to know which portion of C1q is responsible for activation the macrophage so we generated C1qtails (samples 4-5). We also have macrophages treated with the whole C1q molecule (7-9). And finally we have a cell line (J774) treated with C1q but does not activate the cells (samples 10-12).

overall_design: Bone marrow derived macrophages or J774 cells were adhered to heat inactivated C1q, C1q tails or C1q for 18 hours. Cells were harvested and RNA was isolated and converted to double stranded cDNA and subsequently labeled and hybridized onto NimbleGen mouse gene expression array [100718_MM9_EXP] using Nimblegen Hybridization system 4 according to manufacturer’s instructions (Roche)

first: M

last: Galvan

first: D

last: Foreman

first: E

first: J

last: Tan

first: S

last: Bohlson


title: Comparative Analysis of Neonatal versus Adult Brain in Unilateral Brain Injury Mice Model Revealing Genes Involved in High Compensatory Motor Functional Recovery Mechanism

city: Tsukuba

first: RANDEEP

last: RAKWAL

state: Ibaraki

address: 1-1-1 Tennodai

department: Institute of Health and Sport Sciences

institute: University of Tsukuba

summary: Previously, while studying the development, especially of corticospinal neurons, it was concluded that the main compensatory mechanism after unilateral brain injury in rat at neonatal stage was due to in part by nonlesioned ipsilateral corticospinal neurons that escaped selection by axonal elimination or neuronal apoptosis (Yoshikawa et al., 2011, Dev Neuroscience). However, above result suggesting compensatory mechanism in neonate brain could not be correlated with high functional recovery. Therefore, we asked - what is the difference among neonate and adult in context of functional recovery and mechanism/s therein, especially focused on the corticospinal neurons? Toward this goal, in the present study, we have utilized a unilateral brain injury mice model and compared motor functional recovery mechanism post-neonatal brain injury (hereafter termed, NBI) with adult brain injury (hereafter termed, ABI). Three analyses were perfomed: i) quantitative behavioral analysis of the forelimb movements using the ladder walking test, where the corticospinal system has been suggested to play an important role ii) a neuroanatomical retrogradely tracing analysis of unlesioned side corticospinal neurons; and iii) differentially global gene expressions profiling in the unlesioned-side neocortex (rostral from bregma) in NBI and ABI using a high-throughput DNA microarray approach on a 8x60 K whole genome Agilent DNA chip using a two-color (Cy3/Cy5) dye-swap approach. Behavioral data confirmed the higher recovery ability in NBI over ABI is related to non-lesional frontal neocoetex including rostral caudal forelimb area. With a overall aim to unravel the underlying molecular events, in the present study a first inventory of the differential expressed gene expressions genome-wide in the NBI and ABI model mice has been provided.

overall_design: The neonatal (n=20) and adult (n=12) left hemidecortication animals were made to perform the ladder rung walking test after 4, 8, and 12 weeks of lesion creation. The control animals (n=9) did the same test postnatal 8-12 weeks. The hemidecortication animal model was perfomed at postnatal day 7 (NBI group) and postnatal 8-12 weeks (ABI group). In the NBI and ABI groups, we decided to aspirate area of left cerebral cortex including the sensorimotor cortex (SMC). In order to confirm different motor functional mechanism between NBI and ABI, the right side neocortex (rostral from bregma) was individually ground to a very fine powder with liquid N2 t prepare teh samples for DNA microarray analysis.

first: Akira

last: Yoshikawa

first: Tomoya

last: Nakamachi

first: Junko

last: Shibato

first: Randeep

last: Rakwal

first: Seiji

last: Shioda


title: Development of peptidomimetic inhibitors of the ERG gene fusion product in prostate cancer (expression)

summary: Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a critical role in prostate oncogenesis. Here, we identified a series of peptides that interact specifically with the DNA binding domain of ERG. The most prevalent consensus peptide series matched the tumor suppressor Deleted in Liver Cancer 1 (DLC1).  ERG inhibitory peptides and derived peptidomimetics (EIPs) bound with high affinity and specificity leading to proteolytic degradation of ERG. The EIPs attenuated ERG-mediated transcription, chromatin recruitment, protein-protein interactions, cell invasion, and tumor growth.  Thus, peptidomimetic targeting of transcription factor fusion products may provide a promising therapeutic strategy for prostate cancer as well as other cancers.

overall_design: ERG genes in VCaP cell were knocked down by siERG or siControls for 48 hrs. Biological replicates:  2 control replicates, 2 experimental replicates. ERG proteins were destablized by RI-EIP1 or RI-muEIP1 for 72 hours. Biological replicates:  2 control replicates, 2 experimental replicates.

first: Xiaojun

last: Jing


title: Development of peptidomimetic inhibitors of the ERG transcription factor in prostate cancer (ChIP-seq)

summary: Transcription factors play a key role in the development of a number of cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the ETS transcription factor ERG is recurrently rearranged and likely plays a critical role in prostate oncogenesis. Here we identified a series of peptides from a phage-display library that interact specifically with the DNA binding domain of ERG. The interactive interface was mapped to 9-residues in the 3rd helix of the ETS domain that is critical for ERG transcriptional activity. The peptides were found to efficiently disrupt ERG-mediated protein-protein interactions, transcription, DNA damage, and cell invasion, as well as attenuate ERG recruitment to target gene loci.  Furthermore, a retroinverso peptidomimetic version of the peptide sequence suppressed tumor growth, intravasation, and metastasis in vivo. Taken together, our results demonstrate that transcription factors have specific residues important for protein-protein interactions and disrupting those critical interactions may be an effective therapeutic strategy.

overall_design: Examination of ERG in VCaP cells with respect to peptidomimetics treatment

first: Marcin

last: Cieslik


title: Transcriptional profiling of atmbd4, atmbd6 and atmbd11 mutants of Arabidopsis thaliana

status: Public on Jul 09 2014

city: delhi

first: Adwaita

middle: Prasad

last: Parida

state: Delhi

address: Benito Juarez Road

department: plant molecular biology

country: India

institute: university of delhi, south campus

summary: Methyl CpG Binding (MBD) proteins are a class of protein that binds with methylated DNA. In the model plant Arabidopsis thaliana there are 13 MBD proteins are there. To understand the gene regulation we performed microarray analysis of mutants of three genes (atmbd4, atmbd6 and atmbd11). Ten day old seedlings of these three mutant were compared  with the wild type plants grown in same condition.

overall_design: Surface sterilized Arabidopsis seeds were grown in MS media. Ten days old seedlings were used for isolation of RNA. The wild type plants along with T-DNA mutants of atmbd4, atmbd6 and atmbd11 were used to isolate the RNA. Three biological replicates of each sample were analyzed representing wild type, atmbd4, atmbd6 and atmbd11 of Arabidopsis.

middle: P

first: Sanjay

last: Kapoor

first: Arun

last: Sharma


title: RMECs: hypoxia-induced group vs. paired untreated group

status: Public on Jul 17 2014

city: Guangzhou

first: Liang

last: Zhang

state: Guangdong

address: Xingnan Road 521

department: Translational Medicine Research Center

institute: Guangdong Women and Children Hospital

summary: Objective To explore the molecular mechanisms of retinopathy of prematurity (ROP) at whole genome scale using cultivated human fetal retinal microvascular endothelial cells (RMECs) under hypoxic condition.  Study design Aborted fetuses with mean gestational age of 20-28 weeks at Guangdong Women and Children’ Hospital were enrolled, 3 males and 2 females, with mean weight 610-2205 g. Primary RMECs were isolated by mechanical morcel and trypsin-collagenase digestion of eyeballs. Cultivated cells were treated with or without 150 μM CoCl2 for 72 h. The dual-color microarray approach was adopted to compare gene expression profiling between treated RMECs and the paired untreated control using Agilent SurePrint G3 Human GE 8x60K Microarray Kit. We applied average-linkage unsupervised hierarchical clustering and TreeView to visualize the results. The one class algorithm in the SAM software was used to screen the differentially expressed genes (DEGs) with a threshold set at fold-change >2.0 and q-value <0.05. Gene Ontology was employed for functional enrichment analysis.   Results There were 326 DEGS between the hypoxia-induced group and untreated group. Of these genes, 198 were up-regulated in hypoxic RMECs, while other 128 hits were down-regulated. More importantly, altered expression genes in iron ion homeostasis pathway were highly enriched under hypoxic condition. Quantitative RT-PCR (qRT-PCR) was performed to validate the results obtained from microarray analysis.  Conclusions Dysregulation of genes involved in iron homeostasis mediating oxidative damage may contribute to the ROP pathogenesis.

overall_design: Primary RMECs isolated from five subjects (3 males, 2 females) with mean weight 610-2205 g. CoCl2 induced hypoxia in primary RMECs vs. cultured cells without CoCl2 treatment. Biological replicates: five treated RMECs and paired untreated control. Dye-swap assays were performed for each sample.

first: Xianqiong

last: Luo

first: Yichun

first: Jiawen

first: Jingbo

last: Jiang

first: Aihua

last: Yin

first: Li

last: Guo

first: Chuan

last: Nie

first: Xuzai

last: Lu

first: Hua

last: Deng


title: Pervasive effects of an endophytic fungus on host genetic and phenotypic expression in a tropical tree (part 2)

status: Public on Jun 30 2014

first: Luis

last: Mejia

overall_design: The objective of this experiment was to identify Theobroma cacao genes that are differentially expressed between leaves inoculated with fungal endophyte Colletotrichum tropicale (E+ leaves) and control un-inoculated leaves (E- leaves) 3 days post endophyte inoculation. The experiment was conducted in a Percival growth chamber (model I35LL, 115 volts, 1/4 Hp, series: 8503122.16, Percival Scientific, Inc., Perry IA) with 12/12 h light/dark photoperiod and temperatures of 30ºC and 26ºC respectively. Inoculation was done  by aspersion of endophyte spores (2X10^6 spore/ml)  to a group of T. cacao seedlings and a second group of seedlings were maintained as control un-inoculated (E- leaves).  Then three biological replicates (each one consisting of one leaf from different plants) per treatment E+ and four leaves per treatment E- leaves)  were collected and processed for a two color oligo microarray analysis.

middle: C

first: Edward

last: Herre

first: Jed

last: Sparks

first: Klaus

last: Winter

first: Milton

last: Garcia

first: Sunshine

last: Van Bael

first: Joe

last: Stitt

first: Zi

last: Shi

first: Yufan

first: Mark

last: Guiltinan

first: Siela

last: Maximova


title: A potential relationship among beta-defensins haplotype, SOX7 duplication and cardiac defects

status: Public on Jun 27 2014

city: Beijing

first: wang

last: liang

address: 7A North Yongchang Road BDA

institute: BioChainBJ

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

summary: To determine the pathogenesis of a patient born with congenital heart defects, who had appeared normal in prenatal screening.

overall_design: In routine prenatal screening, G-banding was performed to analyse the karyotypes of the family and fluorescence in situ hybridization was used to investigate the 22q11.2 deletion in the fetus. After birth, the child was found to be suffering from heart defects by transthoracic echocardiography. In the following study, sequencing was used to search for potential mutations in pivotal genes. SNP-array was employed for fine mapping of the aberrant region and quantitative real-time PCR was used to confirm the results. Furthermore, other patients with a similar phenotype were screened for the same genetic variations. To compare with a control, these variations were also assessed in the general population.

first: Fei

last: Long

first: Xike

last: Wang

first: Shaohai

last: Fang

first: Yuejuan

last: Xu

first: Kun

last: Sun

first: Sun

last: Chen

first: Rang


title: Profiling of Gene Expression in Idiopathic Pulmonary Fibrosis

city: Reno

first: Tong

last: Zhou

state: NV

address: 1664 N Virginia St

institute: University of Nevada School of Medicine

summary: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial disease of unknown cause. It remains impractical to conduct early diagnosis and predict IPF progression just based on gene expression information. Moreover, the relationship between gene expression and quantitative phenotypic value in IPF keeps controversial. To identify biomarkers to predict survival in IPF, we profiled protein-coding gene expression in peripheral blood mononuclear cells (PBMCs). We linked the gene expression level with the quantitative phenotypic variation in IPF, including diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC) percent predicted. In silico analyses on the expression profiles and quantitative phenotypic data allowed for the generation of a set of IPF molecular signature that predicted survival of IPF effectively.

overall_design: Total RNA was isolated from PBMCs using standard molecular biology protocols without DNA contamination or RNA degradation. Sample processing (e.g., cDNA generation, fragmentation, end labeling, hybridization to Affymetrix GeneChip Human Exon 1.0 ST arrays) was performed per manufacturer’s instructions. A total of 45 healthy controls and 70 IPF patients were included in the microarray analysis.

first: T

first: W

last: Zhang

first: S

last: Ma

first: M

last: Wade

first: I

last: Noth

first: J

middle: G


title: miRNA expression profiling in hereditary breast tumors

status: Public on Jun 21 2014

city: Belgrade

first: Miljana

last: Tanic

address: Pasterova 14

department: Experimental Oncology

country: Serbia

institute: Institute for Oncology and Radiology of Serbia (IORS)

summary: The objective of the study was to characterize hereditary breast tumors based on their miRNA expression profiles. To this end, we performed global miRNA expression analysis of more than 800 human miRNA genes   in a large series of 80 FFPE breast tissue samples. The series included 66 hereditary breast primary tumors from 13 BRCA1 mutation carriers, 10 BRCA2 mutation carriers and 43 non-BRCA12 tumors denominated hereafter as BRCAX tumors. In addition we have analyzed 10 sporadic breast carcinomas and 4 normal breast tissues obtained after breast reduction surgery from healthy donors with no family history of breast cancer. To avoid contamination with normal breast tissue, tumoral area on FFPE blocks was marked by a pathologist and macrodissected for subsequent total RNA extraction.

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

overall_design: Microarray expression profiling was performed using miRCURY LNATM microRNA Array v.11 (Exiqon A/S, Denmark), in a single color experiments in a pairwise comparison experimantal design.

first: Beatriz

last: Martinez-Delgado

first: Javier

last: Benitez

first: Ivan

last: Marquez-Rodas

first: Maria

middle: S

last: Rodriguez-Pinilla

first: Victoria

last: Fernandez

first: Ana

last: Osorio


title: Pervasive effects of an endophytic fungus on host genetic and phenotypic expression in a tropical tree (part 1)

first: Luis

last: Mejia

summary: Inoculation of endophyte-free (E-) Theobroma cacao leaves with Colletotrichum tropicale (E+), the dominant foliar fungal endophyte in healthy T. cacao, induced significant changes in the expression of hundreds of host genes. Further, E+ leaves exhibit enhanced pathogen resistance, increased lignin and cellulose content, reduced maximum rates of photosynthesis (Amax), and enrichment of nitrogen-15 and carbon-13 isotopes that all correspond to the changes in expression of specific functional genes in related pathways. Moreover, a cacao gene highly up-regulated in E+ leaves increases pathogen resistance apart from any direct endophyte effects. Thus, benefits of increased pathogen resistance in E+ plants are partially due to enhanced induction of intrinsic host defense pathways, and potential costs include reduced photosynthetic capacity and endophyte metabolism of host tissues. Similar effects are likely to be properties of most plant-endophyte interactions, suggesting general relevance to the design and interpretation of studies of genetic and phenotypic expression in plants.

overall_design: The objective of this experiment was to identify Theobroma cacao genes that are differentially expressed between leaves inoculated with fungal endophyte Colletotrichum tropicale (E+ leaves) and control un-inoculated leaves (E- leaves) 14 days post last endophyte inoculation. The experiment was conducted in a Percival growth chambers (model I35LL, 115 volts, 1/4 Hp, series: 8503122.16, Percival Scientific, Inc., Perry IA) with 12/12 h light/dark photoperiod and temperatures of 30ºC and 26ºC respectively. A total of four endophyte spore inoculations (1X10^6 spore/ml) were made by aspersion to a group of T. cacao seedlings and a second group of seedlings were maintained as un-inoculated.  Then six biological replicates per treatment (E+ leaves and six E- leaves) each one belonging from a different seedling were collected and processed for a two color oligo microarray analysis. A total of six arrays were processed, each one hybridized to an inoculated and a control un-inoculated sample in a dye swap design.

first: Edward

last: Herre

first: Jed

last: Sparks

first: Klaus

last: Winter

first: Milton

last: Garcia

first: Sunshine

last: Van Bael

first: Joe

last: Stitt

first: Zi

last: Shi

first: Yufan

first: Mark

last: Guiltinan

first: Siela

last: Maximova


title: Pervasive effects of an endophytic fungus on host genetic and phenotypic expression in a tropical tree

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

overall_design: Refer to individual Series


title: Somatic point mutation calling in low cellularity tumors

status: Public on Jun 13 2014

city: St Lucia

first: Darrin

last: Taylor

state: Qld

address: Research Rd

department: Genomics and Bioinformatics

institute: Institute for Molecular Bioscience, Uni of Qld

summary:
Illumina 1M Omni Quad arrays were used to test mutation calling accuracy of qSNP tool (a mutation caller)

Ilumina array genotypes with GenCal (GC score)>0.70 were used in the comparison of genotype calls using next generation sequencing data and qSNP (mutation caller)

overall_design:
2 samples (control cell line and Melanoma cell line). This is the data for a validation step.
contributor: Australian Pancreatic Cancer Genome Initiative

first: K

last: Kassahn

first: O

last: Holmes

last: Nones

first: A

middle: M

last: Patch

first: D

last: Miller

first: I

last: Harliwong

first: Q

last: Xu

first: M

last: Anderson

first: S

last: Wood

first: C

last: Leonard

first: F

last: Newell

last: Song

last: Christ

last: Idrisoglu

last: Nourse

first: E

last: Nourbakhsh

last: Manning

last: Wani

first: J

last: Wu

last: Cowley

last: Pajic

last: Pinese

last: Gill

middle: L

last: Johns

first: P

last: Wilson

first: L

last: Finl

middle: V

last: Biankin

first: N

last: Waddeell

last: Grimmond

last: Pearson


title: Chemotherapy induced dynamic gene expression changes in vivo are prognostic in ovarian cancer

status: Public on Jun 16 2014

city: St Andrews

first: Antonis

last: Koussounadis

address: Sir Harold Mitchell Building

department: Biology

institute: University of St Andrews

summary: Carboplatin and paclitaxel are the most widely prescribed chemotherapeutic agents for ovarian cancer. Not all patients respond to treatment, so there is a need for biomarkers that reliably predict resistance in ovarian tumors. Expression of such biomarkers may be dynamically controlled. Gene expression was assessed for a period of 14 days after treatment with carboplatin or combined carboplatin-paclitaxel in xenografts from two ovarian cancer models: chemosensitive serous adenocarcinoma derived OV1002 and slow growing, chemoresistant HOX424 of clear cell origin. Tumour volume reduction was observed in both cell lines post treatment, with a more prominent effect in OV1002, which subsided in late time points. In OV1002, hierarchical clustering classified differentially expressed genes into four time-related patterns, upregulated and downregulated groups for each early and late expressed genes. Upregulated genes were involved in DNA repair, cell cycle and apoptosis, while downregulated groups were involved in oxygen consuming metabolic processes and apoptosis control. Carboplatin-paclitaxel treatment triggered a more comprehensive response. HOX424 responded only to the combined treatment, while the observed reduction in tumour growth was limited. Several apoptosis and cell cycle genes were upregulated, while Wnt signaling was downregulated in the exclusively late expression pattern observed in this cell line. Late downregulated gene groups post carboplatin-taxane treatment were capable of predicting overall survival in two independent clinical datesets. Pathways overrepresented in these clusters were also predictive of outcome. This longitudinal gene expression study may help characterization of chemotherapy response, identification of resistance biomarkers and guiding timing of biopsies.

overall_design: 101 samples from 2 cell lines, untreated, carboplatin (Carbo) treated, carboplatin-paclitaxel (Carbotax) treated, over 5 time points (days 1,2,4,7,14)

first: Simon

last: Langdon

first: David

last: Harrison

first: V

last: Smith


title: Transcript Level Expression Profiling: anticancer pathways of Smilax Glabra rhizome extract (SW) [HepG2 cells]

status: Public on Jun 08 2014

first: tiantian

last: she

address: 52 Fucheng Road

department: Biochemistry and Molecular Biology

institute: Peking University Cancer Hospital & Institute

summary:
To find the possible signaling pathways which contribute to the anticancer effect of SW-treated HepG2 cells
Global gene expression profiling is an ideal technique to obtain useful clues for exploration of the anticancer mechanism of SW. Through comparing microarray results between solvent- and SW-treated cells, differentially expressed genes were obtained (>1.5 fold). The microarray results were validated using real-time RT-PCR. We used the KEGG database, STRING database and GO database for further ananlysis, and therefore got the possible signaling pathways underlying the anticancer effect of SW.

overall_design: We analyzed total RNA samples of solvent- and SW-treated HepG2 cells using the Affymetrix Human Gene 1.0 ST platform. No techinical replicates were performed.

first: Tiantian

last: She


title: Microarray for Osrdr1 mutant

status: Public on May 28 2014

city: Changchun

first: Ningning

last: Wang

state: Jilin

address: 2888, Xinchen Street

institute: Jilin Agricultural University

summary: Detection of gene expression variation induced by loss-of-function OsRDR1 in rice.

overall_design: Osrdr1 mutant (3 replicates); sibling wild type (3 replicates).

first: Bao

last: Liu


title: Differential miRNA profiles of pregnancy tissue in ectopic pregnancies

status: Public on Jun 02 2014

city: Valencia

first: Juan

last: Moreno-Moya

address: Catedrático Agustín Escardino

country: Spain

institute: FIVI

summary:
Abstract
Objective: To investigate the physiology of ectopic pregnancy by analyzing the miRNA profiles of the pregnancy tissue from both ectopic and control pregnancies (voluntary termination of pregnancy).
Design: Research study.
Setting: Academic research institute in collaboration with a university hospital.
Patients: Patients suffering from tubal EP and patients with a normal ongoing pregnancy scheduled for a voluntary termination of pregnancy (VTOP) were recruited.
Interventions: Pregnancy tissue samples were analyzed by miRNA microarray and further validated by qPCR.
Main Outcome measures: Gene expression profiles and quantitative PCR measurements.
Results: Four miRNAs were found to be downregulated in EP compared to healthy trophoblast tissue, and three miRNAs were upregulated in EP trophoblast compared to control tissue samples. All genes were validated by q-PCR. We found three statistically significant miRNAs, all of which were upregulated in the EP sample group.
Conclusion: We describe the alteration of seven miRNAs in EP samples that could alter pathways which are critical for correct implantation such as extracellular matrix (ECM) remodeling, or mucin biosynthesis, thus resulting in ectopic pregnancies.

overall_design: This study was authorized by the Institutional Review Board/Independent Ethics Committee of the Hospital Universitario La Fe, Valencia, Spain. Eight patients suffering from tubal EP and another eight patients with a normal ongoing pregnancy scheduled for a VTOP were recruited.

first: Francisco

last: Domínguez

first: Teresa

last: Lozoya

first: A

last: Romero

first: Martínez-Escribano

last: Sebastian

first: Mercedes

last: Monterde

first: M

last: Gurrea

first: B

last: Ferri

last: Núñez

first: Carlos

last: Simón

first: Antonio

last: Pellicer


title: Characterization of MicroRNA Expression Profiles and the Discovery of Novel MicroRNAs Involved in Cancer during Human Embryonic Development

status: Public on May 09 2014

city: Wuhan

first: Wenxin

last: Li

address: Luojia Hill, Wuchang

institute: Wuhan University

summary: MicroRNAs (miRNAs), approximately 22-nucleotide non-coding RNA molecules, regulate a variety of pivotal physiological or pathological processes, including embryonic development and tumorigenesis. To obtain comprehensive expression profiles of miRNAs in human embryos, we characterized miRNA expression in weeks 4-6 of human embryonic development using miRNA microarrays and identified 50 human-embryo-specific miRNAs (HES-miRNAs). Furthermore, we selected three non-conserved or primate-specific miRNAs, hsa-miR-638, -720, and -1280, and examined their expression levels in various normal and tumor tissues. The results show that expression of most miRNAs is extremely low during early human embryonic development. In addition, the expression of some non-conserved or primate-specific miRNAs is significantly different between tumor and the corresponding normal tissue samples, suggesting that the miRNAs are closely related to the pathological processes of various tumors. This study presents the first comprehensive overview of miRNA expression during human embryonic development and offers immediate evidence of the relationship between human early embryonic development and tumorigenesis.

overall_design: Total 10 samples were used microRNAs microarrays hybridization, then the original data from 8 of 10 samples was used final data analysis. The samples ZN18, ZN46/47 and ZN75 were designated as Week 4 of human embryonic development; the samples ZN38, ZN43 and ZN63-1 were designated as Week 5 of human embryonic development; the samples ZN61 and ZN70 were designated as Week 6 of human embryonic development.

first: Mingxiong

last: Guo

first: Yi

last: Lin


title: Expression data from transfected C2C12 cell lines

status: Public on May 01 2014

city: Pieve Emanuele

first: Charlotte

middle: K Y

last: Ng

address: Via Rita Montalcini 4

department: Biomedical Sciences

institute: Humanitas University

summary:
Skeletal muscle differentiation is a highly coordinated multistep process in which proliferating mononucleated myoblasts ﬁrst withdraw from the cell cycle, then differentiate into postmitotic mononucleated myocytes, and subsequently fuse into multinucleated myotubes which ﬁnally bundle to form mature muscle ﬁbers. All these processes are controlled by the sequential activation of myogenic regulatory factors, and especially MYOD1 is activated in the early phase to promote the transcription of muscle-specific genes coding for muscle proteins such as alpha-actin, myosin heavy chain and muscle creatine kinase.
We used microarrays to detail the global gene expression changes associated with MYOD1 L122R mutation and identified MYOD1 L122R blocked myogenic differentiation and had a MYC-like transcriptional potential.

overall_design: C2C12 mouse myoblast cells were introduced wild type MYOD1, MYOD1 L122R, MYC, and GFP by retroviral infection. For retrovirus production, the pcx4 and pBabe vectors system were used.  Retroviruses were obtained by using 293T cells as packaging cells, and were infected into C2C12 cell line and selected with 500 μg/ml Zeocin (Invitrogen, Carlsbad, CA, USA). After selection, RNAs were extracted and processed at MSKCC according to procedures recommended by Affymetrix (Santa Clara, CA, USA).

first: Shinji

last: Kohsaka

first: Marc

last: Ladanyi


title: Comparision of gene expression in miR-17-92 cluster overexpression stable CCLP-1 cells with scrambled control CCLP-1 cells

status: Public on May 31 2014

city: New Orleans

first: Tong

last: Wu

state: Louisiana

address: 1430 TULANE AVE SL-79

department: Pathology and Laboratory Medicine

country: USA

institute: TULANE UNIVERSITY

summary: To further development of our gene expression approach, we have employed whole genome microarray expression profiling as a discovery platform to identify genes which may be regulated by miR-17-92 cluster.   Two stable cell lines were used, one is scrambled control and another is miR-17-92 cluster overexpresion cell lines. The differential gene expression was identified.

overall_design: Total RNA were extracted from two samples from the cell lines.

first: Hanqing

last: Zhu


title: Transcriptome of Dinoroseobacter shibae in co-culture with the dinoflagellate Prorocentrum minimum at different growth stages

city: Třeboň

first: Jürgen

last: Tomasch

address: Novohradská 237

country: Czech Republic

institute: Center Algatech, Institute of Microbiology of the Czech Academy of Science

summary: Transcriptome of D. shibae 5 h in the light after 18,24 and 30 days in coculture with the dinoflagellate P. minimum

sample_organism: Dinoroseobacter shibae DFL 12 = DSM 16493

overall_design: two biological replicates

first: Hui

last: Wang

first: Michael

last: Jarek

first: Sabin

last: Bhuju

first: Irene

last: Wagner-Döbler


title: Cardiogenic genes expressed in cardiac fibroblasts contribute to heart development and repair

status: Public on May 20 2014

city: Melbourne

first: Milena

middle: B

last: Furtado

state: VIC

address: Wellington Road, Building 75, Level 1

institute: Monash University-Australian Regenerative Medicine Institute

summary:
Cardiac fibroblasts are critical to proper heart function through multiple interactions with the myocardial compartment. Loosely defined based on their mesenchymal origin, capacity to adhere to plastic and to secrete extracellular matrix, cardiac fibroblasts have been largely neglected due to heterogeneity and lack of proper markers.
Objective: To identify genes uniquely expressed in the cardiac fibroblast pool, we performed an unbiased comparative analysis between cardiac and tail fibroblasts, and tracked cardiac fibroblasts after injury to determine their contribution to myocardial regeneration.
Methods and Results: High-throughput cell surface and intracellular profiling identified homogeneously expressed MSC markers in cardiac fibroblasts, as well as a surprising number of cardiogenic markers, some expressed at higher levels than in cardiomyocytes. Genetically marked fibroblasts contributed to interstitial but not cardiomyocyte compartments in infarcted hearts.
Conclusions: The core transcriptional identity of cardiac fibroblasts reflects their embryological origin, provoking novel interpretations for studies on more specialized cardiac progenitors, and offering a novel perspective for reinterpreting cardiac regenerative therapies

overall_design: 3 biological replicates  plated over 5 days after isolation pooled out of 2 animals were used for both tail and heart fibroblasts (6 total samples analysed)

first: Mauro

last: Costa

first: Nadia

last: Rosenthal


title: Immune Variation Project (ImmVar) [CD4]

status: Public on May 02 2014

city: Boston

first: Liang

last: Yang

state: MA

address: 77 Avenue Louis Pasteur

department: Pathology

institute: Harvard Medical School

summary: Gene expression profiling of CD4 T-Cells (CD4+CD62L+) from human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy individuals from the Boston area.

overall_design:
Over the course of 18 months, fresh blood samples from healthy participants were collected following a rigorous, standardized set of procedures (SOP). 15ml of blood was collected and used to isolate peripheral blood mononuclear cells (PBMCs). From the PBMCS, cell population of interest, CD4+CD62L+, underwent a two-step sorting strategy in order to achieve cell purity >99%. mRNAs from these cells were profiled on Affymetrix GeneChip Human Gene ST 1.0 microarrays. Raw data CEL files were processed using the Robust Multichip Average (RMA) algorithm in Affymetrix PowerTools. To account for non-genetic factors such as batch effects, age, gender, and technical artifacts in gene expression data, we used Principal Component Analysis (PCA). PCs were estimated separately from the gene expression matrix for each population and cell type. The optimal numbers of PCs for association analysis were determined based on the PC that resulted in maximum number of cis-eQTLs. This procedure identified 20, 12 and 12 PCs in EU, EA and AA CD4+ T-cells, respectively.

GSE56033_GSM.ImmVarCD4.*.PC*.txt supplementary files: For each population EU, AA, and EA, individual PC-corrected matrices for samples that have passed both Expression QC and Genotyping QC. These are the same expression matrices that were used for the eQTL association analysis.

first: Katie

last: Rothamel

first: Raj

last: Towfique

first: Diane

last: Mathis

first: Christophe

last: Benoist


title: Immune Variation Project (ImmVar)


title: The spatio-temporal program of DNA replication is driven by specific epigenetic signatures in human cells

city: Paris

first: Jean-Charles

last: Cadoret

address: 15 rue hélène Brion

country: France

institute: CNRS/ Université de Paris

summary: We report the application of single-molecule-based sequencing technology for high-throughput profiling of DNA replication origins in K562 mammalian cells. We have optimized a specific method of peak detection adapted to the signal produced by the sequencing of short nascent strands (SNS) that are specific of replication initiation, with the aim to have both a good sensitivity and specificity. We demonstrated the existence of the spatiao-temporal program of DNA replication driven by a specific epigenetic signature.

overall_design: K562 human cells; five samples subjected to SNS-Seq.

first: F

last: Picard

first: J-C

first: B

last: Audit

first: A

last: Arneodo

first: J

last: Poulain

first: L

last: Duret

first: M-N

last: Prioleau