title: BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis [scRNA-seq]

city: Chicago

first: Luis

last: Barreiro

state: Illinois

address: 900 E 57th Street

institute: University of Chicago

summary: The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remains unknown. Here we show that access of Bacillus Calmette-Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSC) and multipotent progenitors (MPP) leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically-modified macrophages that provide significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.

overall_design: Single cell gene expressoin profiles of LKS+ Hematopoietic stem cells from BCG-iv vaccinated, and PBS-control mice.

first: Eva

last: Kaufmann

first: Jonathan

middle: L

last: Dunn

first: Joaquin

last: Sanz

first: Nargis

last: Khan

first: Alain

last: Pacis

first: Fanny

last: Tzelepis

first: Erwan

last: Pernet

first: Anne

last: Dumaine

first: Jean-Christophe

last: Grenier

first: Eisha

last: Ahmed

first: Jad

last: Belle

first: Rickvinder

last: Besla

first: Bruce

last: Mazer

first: Irah

last: King

first: Anastasia

last: Nijnik

middle: B

first: Maziar

last: Divangahi


title: Microarray analysis of CD8+ T cell subsets during LCMV infection

status: Public on Dec 15 2017

city: La Jolla

first: John

middle: Justin

last: Milner

state: CA

address: 9500 Gilman Dr. MC0377

country: USA

institute: UCSD

summary: Tissue-resident memory CD8+ T cells (Trm) are positioned at common sites of pathogen exposure where they elicit rapid and robust protective immune responses1,2. However, the molecular signals controlling Trm differentiation and homeostasis are not fully understood. Here we show that mouse Trm precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory populations at the levels of gene expression and chromatin accessibility. Exploiting computational and functional RNAi in vivo screens, we identified the transcription factor (TF) Runx3 as a key regulator of Trm differentiation and homeostasis. Runx3 was required to establish Trm populations in diverse tissue environments and supported expression of critical tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Analysis of the accessibility of Runx3 target genes in Trm-precursor cells revealed a distinct regulatory role for Runx3 in controlling Trm differentiation despite relatively widespread and uniform expression among all CD8+ T cell subsets. Further, we show that human and murine tumor-infiltrating lymphocytes (TIL) share a core tissue-residency gene-expression signature with Trm. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+ TIL failed to accumulate in tumors, resulting in greater rates of tumor growth and mortality. Conversely, overexpression of Runx3 enhanced TIL abundance, delayed tumor growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of Trm differentiation, these results provide novel insight into the signals that promote T cell residency in tissues, which could be leveraged to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer.

overall_design: 20 samples, 2-3 replicates each, P14s sorted on D7 or D35 of LCMV infection

first: J

middle: J

first: A

middle: W

last: Goldrath


title: Gene expression data from fetal human liver cells

status: Public on Dec 14 2017

city: Bronx

first: Sanjeev

last: Gupta

state: NY

address: 1300 Morris Park Ave.

department: Medicine

institute: Albert Einstein College of Medicine

summary:
Understanding the biological potential of fetal stem/progenitor cells will help define mechanisms in liver development and homeostasis. We isolated epithelial fetal human liver cells and established phenotype-specific changes in gene expression during continuous culture conditions. Fetal human liver epithelial cells displayed stem cell properties with multilineage gene expression, extensive proliferation and generation of mesenchymal lineage cells, although the initial epithelial phenotype was rapidly supplanted by meso-endodermal phenotype in culture. This meso-endodermal phenotype was genetically regulated through cytokine signaling, including transforming growth factor-b, bone morphogenetic protein, fibroblast growth factors, and other signaling pathways. Reactivation of HNF-3a (FOXA1) transcription factor, a driver of hepatic specification in the primitive endoderm, indicated that the meso-endodermal phenotype represented an earlier developmental stage of cells. We found that fetal liver epithelial cells formed mature hepatocytes in vivo, including after genetic manipulation using lentiviral vectors, offering convenient assays for analysis of further cell differentiation and fate. Taken together, these studies demonstrated plasticity in fetal liver epithelial stem/progenitor cells, offered paradigms for defining mechanisms regulating lineage switching in stem/progenitor cells, and provided potential avenues for regulating cell phenotypes for applications of stem/progenitor cells, such as for cell therapy.
Gene expression was analyzed

overall_design: We studied EpCAM+ fetal hepatic stem/progenitor cells. Gene expression profiles were obtained in primary cells, designated PP cells, cells in primary culture (P0 cells), or cells cultured for  three (P3) or six passages (P6).


title: Gene expression profiles of CD34+ cells from patients with myelodysplastic syndrome CAA or AML

status: Public on Dec 13 2017

city: Shanghai

first: ai

middle: ping

last: jiang

address: No.151, Libing Rd., Zhangjiang Hi-tech Park, Pudong

country: China

institute: Shanghai Biotechnology Corporation

summary:
To identifying candidate genes which may assist in furthering our knowledge of the mechanisms of the development and progression of MDS AML or CAA. Or finding biomarkers in the future, facilitating the diagnosis of MDS, AML or CAA.
Gene expression profiles in the hematopoietic cells of MDS patients have been studied using microarray

overall_design: CD34+ cell samples isolated for microarray analysis from eight patients [comprising two cases of RA, one RAS, two RAEB, two AML, and one case of chronic aplastic anemia (CAA)] , and one healthy individual, were subjected to microarray hybridization for gene expression profiling.

first: Xiaofei

last: Qi

first: Zixing

last: Chen


title: RNA sequencing of a Spinocerebellar ataxia type 3 (SCA3) mouse model containing the full human ATXN3 gene with a repeat expansion of 75-80 CAGs I

city: Leiden

first: Lodewijk

last: Toonen

address: einthovenweg 20

department: human genetics

country: Netherlands

institute: LUMC

type: Expression profiling by high throughput sequencing

summary: We have performed RNA sequencing analysis of brain tissue and blood from the MJD84.2 mouse model for SCA3 (described by Cemal et al, Human molecular genetics 2002, 11:1075-1094). Mice were 17.5 months of age at sacrifice and brainstem, cerebellum, cortex and striatum were sequenced. Transgenic SCA3 mice showed most transcriptional changes in striatum and brainstem. Axon guidance, synaptic transmission, pi-3k cascade and cholesterol biosynthesis pathways are implicated to be affected based on the transcriptional changes.

overall_design: 8 wildtype vs 6 transgenic SCA3 mice. Brainstem, cerebellum, cortex and striatum at 17.5 months of age.

first: Willeke

middle: M

last: van Roon-Mom


title: Stage-specific metabolic features of differentiating neurons: implications for toxicant sensitivity

city: Cologne

first: Agapios

last: Sachinidis

state: NRW

address: Robert-Kochstr. 39

department: Institute of Neurophysiology

country: Germany

institute: University of Cologne

summary: Developmental neurotoxicity (DNT) may be induced when chemicals disturb a key neurodevelopmental process, and many tests focus on this type of toxicity. Alternatively, DNT may occur when chemicals are cytotoxic only during a specific neurodevelopmental stage. The toxicant sensitivity is affected by the expression of toxicant targets and by resilience factors. Although cellular metabolism plays an important role, little is known how it changes during human neurogenesis, and how potential alterations affect toxicant sensitivity of mature vs. immature neurons. We used immature (d0) and mature (d6) LUHMES cells (dopaminergic human neurons) to provide initial answers to these questions. Transcriptome profiling and characterization of energy metabolism suggested a switch from predominantly glycolytic energy generation to a more pronounced contribution of the tricarboxylic acid cycle (TCA) during neuronal maturation. Therefore, we used pulsed stable isotope-resolved metabolomics (pSIRM) to determine intracellular metabolite pool sizes (concentrations), and isotopically non-stationary 13C-metabolic flux analysis (INST 13C MFA) to calculate metabolic fluxes. We found that d0 cells mainly use glutamine to fuel the TCA. Furthermore, they rely on extracellular pyruvate to allow continuous growth. This metabolic situation does not allow for mitochondrial or glycolytic spare capacity, i.e. the ability to adapt energy generation to altered needs. Accordingly, neuronal precursor cells displayed a higher sensitivity to several mitochondrial toxicants than mature neurons differentiated from them. In summary, this study shows that precursor cells lose their glutamine dependency during differentiation while they gain flexibility of energy generation and thereby increase their resistance to low concentrations of mitochondrial toxicants.

overall_design: Conditionally immortalized humand dopaminergic neurons (=LUHMES) can be either kept as proliferating precursors or differentiated within 6 days into fully mature dopaminergic neurons. We assessed changes in transcriptome, metabolome and proteome through the differentiation of the cells.

first: Marcel

last: Leist


title: Microarray analysis of total naïve and YFV-17D specific CD8 T cells in humans

city: Atlanta

first: Rama

middle: S

last: Akondy

state: GA

address: 1462 CLifton Rd

department: Emory Vaccine Center

institute: Emory University

summary: CD8 T cells play an importart role in adaptive immunity to intracellular pathogens. Naïve CD8 T cells , that have not encountered antigen previously can be identified by virtue of their distinct  phenotype. Upon antigenic encounter, they proliferate rapidly and undergo massive reprograming to differentiate to cytotoxic T lymphocytes. The yellow fever live virus vaccine (YF-17D) provides a model primary acute viral infection that can be used to follow this response.Here we characterize the resting, non-activated naive CD8 T cells in nine healthy adults and YF-specific CD8 T cells elicited in response to YF-17D vaccination from the same donors during the effector (2 weeks after vaccination) and memory (5-8 months later) stages.

overall_design:
The dataset contains 3 sets of samples obtained using an IRB approved protocol and after informed consent of volunteers. Donors in this study were vaccinated with the yellow fever vaccine (subcutaneos, single immunization) and whole blood drawn in CPT tubes,  total peripheral blood mononuclear cells (PBMC) were separated and used as a source  for flow cytometry based isolation of CD8 T cell populations.
The first set of samples is from nine healthy adults were recruited and naïve CD8 T cells (identified by their CD45RA+ CCR7+ CD3+ CD8+ phenotype) before vaccination and effector CD8 T cells (HLA-DR+CD38+ CD3+CD8+ T cells) 2 weeks after vaccination were sorted using a FACS vantage sorter.
In the second set, 4 donors were recruited and naive CD8 T cells were isolated as before while effector CD8 T cells were isolated 2 weeks after vaccination using the HLA-A2 restricted NS4B-214 tetramers. Total RNA was isolated from the sorted cells and used for microarray analysis on Affymetrix Human Genome U133 plus 2.0 arrays.
In the third set, pre vaccination samples  were obtained as before and sorted tetramer-specific samples were acquired during the memory stage, 5 to 80 months after YF-17D vaccination. All tetramer specific sorts were done using the HLA-A2 restricted NS4B214 tetramer (Akondy et al, J. Immunol 2009).

first: Rafi

last: Ahmed


title: DNA Methylation profile of twins with pulmonary tuberculosis

status: Public on Dec 12 2017

city: Tongliao

first: Batudeligen

last: Duan

state: Inn Mongolian

address: 1742 Huolinhe Street

department: Affiliated hospital of Inner Mongolian University for the nationalities

institute: Institute of clinical pharmacology of traditional Mongolian Medicine

type: Methylation profiling by genome tiling array

summary: Genome wide DNA methylation profiling in the blood between Pulmonary tuberculosis patient's and normal people's who have genetic relationship wtih each other.

overall_design: Bisulphite converted DNA from the  the blood between Pulmonary tuberculosis patient's and normal people's who have genetic relationship wtih each other were hybridised to the Illumina Infinium HumanMethylation850 BeadChip


title: Epigenome-wide association study of the whole blood DNA in men with congenital hypopituitarism disease

status: Public on Dec 06 2017

first: Peizhan

institute: Ruijin Hospital North

summary: Congenital hypopituitarism (CH) is chracterized with one or more hormones secreted deficiency by the pituitary gland, which leads to metabolic disorders, amenorrhea and infertility of the patients; however, the involved molecular mechanisms has not yet fully elucidated. We examined genome-wide methylation levels of whole blood DNA in 12 CH patients and 12 age-matched controls using Illumina HumanMethylation450 array. Significantly different methylated loci were further validated in another 40 patients and 40 controls with quantitative bisulfite pyrosequencing method.

overall_design: Case-Control

first: Xuqian

last: Fang


title: Metformin Regulates Metabolic and Non-Metabolic Pathways in Skeletal Muscle and Subcutaneous Adipose Tissues of Older Adults

first: Ameya

last: Kulkarni

state: New York

address: 1301 Morris Park Ave, Price 253

department: Institute for Clinical and Translational Research

summary:
Administration of metformin increases healthspan and lifespan in model systems and evidence from clinical trials and observational studies suggests that metformin delays a variety of age-related morbidities. Although metformin has been shown to modulate multiple biological pathways at the cellular level, these pleiotropic effects of metformin on the biology of human aging have not been studied. We studied ~70-year-old participants (n=14), in a randomized, double-blind, placebo-controlled, crossover trial in which they were treated with 6 weeks each of metformin and placebo. Following each treatment period, skeletal muscle and subcutaneous adipose tissue biopsies were obtained, and a mixed-meal challenge test was performed. As expected, metformin therapy lowered 2-hour glucose, insulin AUC, and insulin secretion compared to placebo. Using FDR<0.05, 647 genes were differentially expressed in muscle and 146 genes were differentially expressed in adipose tissue. Both metabolic and non-metabolic pathways were significantly influenced, including pyruvate metabolism and DNA repair in muscle and PPAR & SREBP signaling, mitochondrial fatty acid oxidation and collagen trimerization in adipose. While each tissue had, a signature reflecting its own function, we identified a cascade of predictive upstream transcriptional regulators, including mTORC1, MYC, TNF, TGFß1 and miRNA-29b, that may explain tissue-specific transcriptomic changes in response to metformin treatment. This study provides the first evidence that, in older adults, metformin has metabolic and non-metabolic effects linked to aging. These data can inform the development of biomarkers for the effects of metformin, and potentially other drugs, on key aging pathways.
Key words: Aging, biguanides, gene expression, metabolism, upstream regulators

overall_design: This study ‘MILES: Metformin in Longevity Study' (ClinicalTrials.gov identifier: NCT02432287) is a randomized, double-blind, placebo controlled, crossover study. 14 men and women aged 60 and older, with impaired glucose tolerance based on 75g Oral Glucose Tolerance Test completed the study. Following a screening visit, the study consisted of two randomly assigned 6-week treatment periods (metformin and placebo). Metformin was introduced at 500 mg twice daily, and increased incrementally to 2000 mg daily at the end of 2 weeks to minimize gastrointestinal side effects. At the end of each 6-week treatment period, skeletal muscle and subcutaneous adipose biopsies were obtained. The samples were immediately homogenized in Trizol, frozen in liquid nitrogen and stored at -80°C for subsequent mRNA extraction. Total RNA was extracted using QIAGEN’s RNeasy Mini kit. Samples showing minimal degradation, as measured by RIN > 7 were processed for library preparation and sequenced in two/three technical replicates using multiplexed 100bp paired-end sequencing on Illumina HiSeq2500. Raw sequence reads were preprocessed using WASP 3.0, and FastQC was used for quality control. The raw FASTQ files were trimmed for adapter sequences using Trim Galore! RSEM algorithm (v1.2.25) in conjunction with STAR aligner (v2.4.2a) were used to quantify the raw reads to GRCh38 build of the reference human genome with transcript annotations from GENCODE. The raw counts matrix was exported from RSEM to edgeR, normalized using TMM normalization and used for differential expression analysis.

first: Erika

middle: F

last: Brutsaert

first: Valentin

last: Anghel

first: Kehao

last: Zhang

first: Noah

last: Bloomgarden

first: Michael

last: Pollak

first: Jessica

middle: C

last: Mar

first: Meredith

last: Hawkins

first: Jill

middle: P

last: Crandall

first: Nir

last: Barzilai


title: Single cell sequencing of the hippocampal niche

city: Utrecht

first: Benedetta

last: Artegiani

address: Upsalalaan 8

institute: Hubrecht

summary: Adult neurogenesis in the murine dentate gyrus occurs in a specialized microenvironment that sustains the generation of neurons during life. To fully understand adult neurogenesis, it is essential to determine the neural stem cell (NSC) and progenitor developmental stages, their molecular determinants, and the niche cellular and molecular composition.   We report on a single cell RNA sequencing study of the hippocampal niche, performed by isolating all the non-neuronal cell populations. Our analysis provides a comprehensive description of the dentate gyrus cells and allows the identification of exclusive cell type-specific markers. We define the developmental stages and transcriptional dynamics of NSCs and progenitors, and find that while NSCs represent a heterogeneous cellular continuum, progenitors can be grouped in distinct subtypes. We determine the oligodendrocyte lineage and transcriptional dynamics, and describe microglia transcriptional profile and activation state. The combined data constitutes a valuable resource to understand regulatory mechanisms of adult neurogenesis.

overall_design: We generated transciptome data from cells unbiasely sorted from the hippocampal neurogenic niche after depleting the neuronal population

first: Anna

last: Lyubimova

first: Mauro

last: Muraro

first: Johan

middle: H

last: van Es

first: Alexander

last: van Oudenardeen

first: Hans

last: Clevers


title: Expression data from hair follicles treated with an osteopontin-derived peptide

status: Public on Dec 05 2017

city: Münster

first: Majid

last: Alam

address: Mendelstraße 17

institute: Monasterium Laboratory

summary:
The human hair follicle is not only regulated, but is a source of transcription factors, hormones, neurohormones etc. which are crucial in regulating its growth.
We used microarrays to determine the early response of microdissected human hair follicles to an osteopontin-derived peptide.

overall_design: Human hair follicles were microdissected from scalp skin from two different patients and were treated for 6 and 24hrs with vehicle (control) and two concentrations of an osteopontin-derived peptide (FOL-005). 12 samples were analysed altogether (6 from each patient, 12 HFs per patient)

first: Marta

last: Bertolini

first: Ralf

last: Paus


title: Mutational and neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

status: Public on Dec 04 2017

city: Lund

first: Martin

last: Lauss

address: Barngatan 2B

department: Dept of Oncology

country: Sweden

institute: Lund University

summary:
Purpose: Utility of immunological treatment in cancer has increased; however, many patients do not respond to treatment. Identification of robust predictive biomarkers is required to correctly stratify patients. Although clinical trials based on adoptive T cell therapy (ACT) have yielded high response rates and many durable responses in melanoma, 50-60% of the patients have no clinical benefit. Herein, we searched for predictive biomarkers to ACT in melanoma.
Methods: Whole exome- and transcriptome sequencing, neoantigen prediction and immune cell signature analysis were applied to pre-treatment melanoma samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously been treated with other immunotherapies.
Results: We found that clinical benefit was associated with significantly higher neoantigen load (P=0.025). High mutation and neoantigen load were significantly associated with improved progression-free and overall survival (P=8x10^-4 and P=0.001, respectively). Further, gene-expression analysis of pre-treatment biopsies showed that clinical benefit was associated with strong immune activation signatures including a high MHC-I antigen processing and presentation score.
Conclusions: These results improve our understanding of clinical benefit of ACT in melanoma, which can lead to clinically useful predictive biomarkers to be used for selecting patients that benefit from these highly intensive treatment regimens.

overall_design:
Gene expression profiles of 25 samples before adoptive T-cell therapy, generated by RNAseq using an Illumina HiSeq 2000 instrument.
The authors state "due to Swedish law, the patient consent, and the risk that the sequencing data contains personally-identifiable information and hereditary mutations, we cannot deposit the short sequencing read data in a repository."
Thus, this submission is incomplete.

first: Göran

last: Jönsson


title: TCRα transmembrane domain coordinates antigen triggering by regulating bilayer immersion and CD3 associations

status: Public on Dec 01 2017

city: Boston

first: Kevin

last: Bi

state: MA

address: 450 Brookline Ave.

department: Pediatric Oncology

institute: Dana-Farber Cancer Institute

summary: Initial molecular details of cellular activation following αβT-cell receptor (TCR) ligation by pMHC remain unexplored. We determined the NMR structure of the TCRα subunit transmembrane (TM) segment revealing a bipartite helix whose segmentation fostersdynamic movement. Positively charged TM residues Arg251 and Lys256 project from opposite faces of the helix, with Lys256 controlling immersion depth. Their modification causes step-wise reduction in associations with T-cell surface CD3ζζ and CD3εγ/CD3εδ, respectively, leading to an activated transcriptome. Optical tweezers reveal that Arg251 and Lys256 mutations alter αβTCR-pMHC bond lifetimes, while mutations within interacting TCRα connecting peptide and CD3δ CxxC motif juxtamembrane elements selectively attenuate signal transduction. Our findings suggest that mechanical forces applied during pMHC ligation initiate T-cell activation by altering the disposition of those basic sidechains to rearrange TCR complex membrane topology and weaken TCRαβ and CD3 associations. This αβTCR dissociative mechanism impacts future immunotherapy and synthetic receptor design on CAR-T cells.

overall_design: Transcriptional profiling of wild type, R251L, K256L, and G259L/N261A T-cell lines

first: Kristine

last: Brazin


title: Ivy Glioblastoma Atlas Project (RNA-Seq)

city: Seattle

first: Ralph

middle: B.

last: Puchalski

state: WA

address: 550 17th Ave., Suite 570

institute: Swedish Neuroscience Institute

summary: The Ivy Glioblastoma Atlas Project (Ivy GAP) is a detailed anatomically based transcriptomic atlas of human glioblastoma tumors.  As collaborators, the Ivy Foundation funded the Allen Institute and the Swedish Neuroscience Institute to design and create the atlas.  The Paul G. Allen Family Foundation also supported the project.  This resource consists of a viewer interface that resolves the manually- and machine-annotated histologic images (H&E and RNA in situ hybridization) at 0.5 µm/pixel, a transcriptome browser to view and mine the anatomically-based RNA-Seq samples, an application programming interface, help documentation that describes the methods and how to use the resource, as well as SNP array data and the supporting longitudinal clinical information and MRI time course data.  The resource is made available to the public without charge as part of the Ivy GAP (http://glioblastoma.alleninstitute.org/) via the Allen Institute data portal (http://www.brain-map.org), the Ivy GAP Clinical and Genomic Database (http://ivygap.org/) via the Swedish Neuroscience Institute (http://www.swedish.org/services/neuroscience-institute), and The Cancer Imaging Archive (https://wiki.cancerimagingarchive.net/display/Public/Ivy+GAP).  The Ivy GAP processed data at GEO includes normalized RNA-Seq FPKM files used for analysis in "An anatomic transcriptional atlas of glioblastoma,” which is under review.  Other processed data files as well as sample and donor meta-data and QC metrics are available at http://glioblastoma.alleninstitute.org/static/download.html. The raw RNA-Seq and SNP array data will be submitted to dbGaP.

overall_design:
The Ivy Glioblastoma Atlas is based on the analysis of ~400 tissue blocks from 42 tumors donated by 41 patients.  A machine learning application was developed to label over ~12,000 H&E images of 7 x 9 mm tissue sections cut adjacent to ~24,000 sections for RNA in situ hybridization (ISH) analyzed with over 500 probes.  Accuracy of the machine annotations was assessed with neuropathology concordance analyses.  Transcriptomic profiles were generated from 270 RNA-Seq samples collected by laser microdissection.  The anatomic structures data set consists of 122 RNA samples of 5 anatomic features of the tumors:  leading edge (LE), infiltrating tumor (IT), cellular tumor (CT), pseudopalisading cells around necrosis (PAN), microvascular proliferation (MVP) identified by H&E staining in 10 tumors.  The cancer stem cells data set consists of 148 RNA samples of putative cancer stem cell clusters identified by ISH with 18 probe reference set in 34 tumors.  The sequencing results were aligned and aggregated at the gene level using the RSEM algorithm, and the resulting fpkm values were normalized across all samples based on genes not enriched in particular anatomic structures.  For more details, please see the Downloads tab in the Ivy Glioblastoma Atlas web application.
-------------------------------
Authors state "Raw files will be made available through dbGaP."

first: Nameeta

last: Shah

first: Jeremy

middle: A

last: Miller

first: Michael

last: Hawrylycz


title: Ivy Glioblastoma Atlas Project

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

overall_design: Refer to individual Series


title: Expression data of human epidermal tissue with knockdown of the SMRT-2 lncRNA

city: Stanford

first: Aparna

last: Bhaduri

address: 269 Campus Drive

institute: Stanford University

summary:
The goal of this study was to identify lncRNAs and novel transcripts that are differentially regulated in cutaneous squamous cell carcinoma (SCC) using RNA sequencing
In this dataset, we include expression data from human skin tissue regenerated in the presence or absence of the putative lncRNA SMRT-2, which we have identified as a new regulator of differentiation.

overall_design: 4 samples total were analyzed. CTRL_1 and CTRL_2 are duplicate human epidermal tissues regenerated with a control siRNA. SMRT2i_1 and SMRT2i_2 are human epidermal tissues regenerated with 2 independent siRNA sequences targeting the SMRT-2 lncRNA

first: Carolyn

last: Lee

first: Vanessa

last: Lopez-Pajares


title: Differential gene expression profile in U937 cells transduced with WT/mutant-DNMT3A

city: TauYau

first: Yun-Shien

state: Taiwan

address: TauYau

department: Dept. Biotechnology

country: Taiwan

institute: Ming Chuan Univ

summary:
DNA methyltransferase 3A (DNMT3A) gene is mutated in various myeloid neoplasms including acute myeloid leukemia (AML), especially at the Arg882 and associated with inferior outcomes. Despite the current progress of functional role of DNMT3A mutations, the molecular pathogenesis of myeloid malignancies remains poorly understood. The mechanisms of AML transformation and functional role of DNMT3A mutations through its target genes in the leukemogenesis remain to be explored. Here we wished to perform the differential gene expression profile in U937 cells over-expressed with DNMT3A-Arg882His/Cys (R882H/C) mutations including DNMT3A-WT and vector.
Results:  Gene expression profiling analysis revealed aberrant expression of several cell-cycle and apoptosis-related genes in U937 cells transduced with mutant DNMT3A compared to WT- or vector control.

overall_design: Expression profiling of U937 cells with empty vector, overexpression of wildtype DNMT3a, DNMT3a mutant R882C or DNMT3a mutant R882H.

first: Rabindranath

last: Bera

first: Lee-Yung

last: Shih

first: Ming-Chun

last: Chiu

first: Ying-Jung

last: Huang

first: Der-Cherng

last: Liang


title: Differential gene expression and genomic methylation profile of U937 cells transduced with WT/mutant-DNMT3A

type:
Expression profiling by array
Methylation profiling by array


title: Expression data of neuroblastoma tissues, spheres and NGP cell line overexpressing CFC1

city: Kitaadachi-gun Ina town

first: Takehiko

last: Kamijo

state: Saitama

address: 780, Komuro

country: Japan

institute: Saitama Cancer Center


title: A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia [array]

status: Public on Nov 30 2017

first: Pamela

middle: S.

last: Becker

address: 1959 NE Pacific St

institute: University of Washington

summary:
We demonstrate a promising approach to identify robust molecular markers for targeted treatment of acute myeloid leukemia. We show that our method outperforms several state-of-the-art approaches in identifying molecular markers replicated in validation data and predicting drug sensitivity accurately.
Finally, we identify SMARCA4 as a marker and driver of sensitivity to topoisomerase II inhibitors, mitoxantrone and etoposide, in AML by showing that cell lines transduced to have high SMARCA4 expression reveal dramatically increased sensitivity to these agents.

overall_design: We measured the gene expression of samples from 30 different AML patients with acute myeloid leukemia in order to identify reliable gene expression markers for drug sensitivity.

first: C

last: Blau


title: Primary constitutional MLH1 epimutations: a focal epigenetic event [blood data sets]

status: Public on Nov 28 2017

city: L'Hospitalet de Llobregat

first: Estela

last: Damaso

state: Barcelona

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

department: Hereditary Cancer Program

country: Spain

institute: Catalan Institute of Oncology (ICO)

summary:
Background: Constitutional MLH1 epimutations are characterized by monoallelic methylation of the MLH1 promoter throughout normal tissues, accompanied by allele-specific silencing. The mechanism underlying primary MLH1 epimutations is currently unknown. The aim of this study was to perform an in-depth characterization of constitutional MLH1 epimutations targeting the aberrantly methylated region around MLH1 and other genomic loci.
Methods: Twelve MLH1 epimutation carriers, 61 Lynch syndrome patients and 41 healthy controls, were analyzed by Infinium Human Methylation 450K beadchip, and targeted molecular techniques were used to characterize the MLH1 epimutation in carriers and their inheritance pattern.
Results: No nucleotide or structural variants were identified in-cis on the epimutated allele in ten carriers, in which intergenerational methylation erasure was demonstrated in two, suggesting primary type of epimutation. CNVs outside the MLH1 locus were found in two cases. EPM2AIP1-MLH1 CpG island was identified as the sole differentially methylated region in MLH1 epimutation carriers compared to controls.
Conclusion: Primary constitutional MLH1 epimutations arise as a focal epigenetic event at the EPM2AIP1-MLH1 CpG island in the absence of cis-acting genetic variants. Further molecular characterization is needed to elucidate the mechanistic basis of MLH1 epimutations and their heritability/reversibility.

overall_design: 12 MLH1 epimutation carriers, 61 Lynch syndrome patients and 41 healthy controls were analyzed by Infinium Human Methylation 450k Beadchip. From all included individuals, DNA from blood was collected. FFPE blocks of normal colorectal mucosa and colorectal cancer tissue were also included when available. The current subset includes only blood samples. FFPE samples can be found in the other associated dataset from Damaso et al. (British Journal of Cancer).

last: Dámaso

first: Adela

last: Castillejo

first: María-del-Mar

last: Arias

first: Julia

last: Canet-Hermida

first: Matilde

last: Navarro

first: Jesús

last: del Valle

first: Olga

last: Campos

first: Anna

last: Fernández

first: Fátima

last: Marín

first: Daniela

last: Turchetti

first: Juan-de-Dios

last: García-Díaz

first: Conxi

last: Lázaro

first: Maurizio

last: Genuardi

first: Daniel

last: Rueda

first: Ángel

last: Alonso

first: Jose-Luis

last: Soto

first: Megan

last: Hitchins

first: Marta

last: Pineda

first: Gabriel

last: Capellá


title: The molecular basis of T-PLL is an actionable perturbation of TCL1/ATM- and epigenetically instructed damage responses

first: Giuliano

last: Crispatzu

address: Joseph-Stelzmann-Straße 26

department: CECAD

institute: University of Cologne (UoC), Germany

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: DNA methylation in PREDIMED-Navarra participants

status: Public on Nov 23 2017

city: Pamplona

first: Ana

last: Arpón

address: Irunlarrea 1

institute: University of Navarra

summary: Genome wide DNA methylation from peripheral white blood cells (PWBCs) from individuals enrolled in PREDIMED trial. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet+EVOO) and the other one in nuts (MedDiet+nuts), was influencing the methylation status of PWBC genes. A group with a low-fat diet was considered as control. The Illumina Infinium 420k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in these samples. Samples included 12 MedDiet+EVOO, 12 MedDiet+nuts and 12 low-fat control group, at baseline (n=36) and after five years of intervention (n=36).

overall_design: Bisulphite converted DNA from the 72 samples  (36 at baseline, 36 at 5 years after intervention, same individuals) were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.

first: Fermín

middle: I

last: Milagro

first: Cristina

last: Razquin

first: Amelia

last: Marti

first: Miguel

last: Martínez-González

first: José

last: Riezu-Boj

first: J

last: Martínez


title: Expression data of tumor tissues and tumor sphere from neuroblastoma patients

first: Takehiko

last: Kamijo

summary:
Cancer stem cells (CSCs) are regarded as the starting point for tumors and are considered to play key roles in relapse and metastasis in many cancers include neuroblastoma (NB). CSCs have become promising target cancer cells for preventing cancer relapse and improving the prognosis of tumor patients. The CSCs marker are not established in NB, but CSCs are able to isolated as tumor sphere.
We used a microarray to profile the transcriptomes of NB tumor spheres to select CSCs candidate molecules.

overall_design: Primary NB tumor tissues were isolated from bone marrow aspirates of two patients (NB1 and NB2). These cells were cultured in sphere forming medium to form tumor sphere. Tumor tissues of NB1 and NB2, and tumor sphere of NB1 and NB2 were analyzed.

first: Koji

last: Chikaraishi


title: Fractalkine receptor CX3CR1 and leukocyte Ig-like receptor B2 LILRB2 are prognostic biomarkers in septic shock

status: Public on Nov 27 2017

city: Lyon

first: Julien

last: Textoris

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

department: Medical Diagnostic Discovery Department (MD3)

country: France

institute: bioMérieux

summary:
Sepsis is a major health concern, with high morbidity and mortality workdwide. In order to identify prognostic biomarkers in septic shock patients, we performed a microarray study exploring the early modulation of gene expression according to day 28 mortality.
Several candidate biomarkers including CX3CR1 and LILRB2 were identified as prognostic biomarkers.

overall_design: 51 septic shock patients and 22 healthy volunteers were included in this study. Septic shock patients were sampled twice, at admission, and a second time at D2 or D3. Admission samples from septic shock patients were compared to healthy volunteers, and according to day 28 survival status. Modulation of gene expression between the 2 time points was also analyzed according to day 28 survival.

first: Alexandre

last: Pachot

first: Marie-Angélique

last: Cazalis

first: Fabienne

last: Venet

first: Elisabeth

last: Cerrato

first: Guillaume

last: Monneret

first: Alain

last: Lepape


title: The molecular basis of T-PLL is an actionable perturbation of TCL1/ATM- and epigenetically instructed damage responses [murine gene expression array]

first: Giuliano

last: Crispatzu

summary: T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. To address its incomplete molecular concept, we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identified novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor / cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM towards a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.

overall_design: GEP of TCL1A-induced murine T-cell leukemia (enriched splenic CD8+ T-cells) using Affymetrix GeneChip Mouse Gene 1.0 ST Arrays. Purified splenic CD3+ pan-T-cells isolated from C57BL/6 mice (3 arrays from T-cell pools of 3 mice each (total n=9) were used as matched controls.


title: Cardiomyocytes microarray

city: Silver Spring

first: Wen Jin

last: Wu

state: Maryland

address: 10903 New Hemisphere Ave

department: OBP/OPQ/CDER

institute: FDA

summary: we employed DNA microarray platform to compare the gene expression patterns in primary human cardiomyocytes treated with trastuzumab (50µg/ml), trastuzumab (50µg/ml) plus pertuzumab (50µg/ml), T-DM1 (10 µg/ml), or control (no treatment).

first: Wen


title: Defining the Triple Negative Breast Cancer Kinome Response to GSK1120212 (RNA-Seq)

status: Public on Nov 29 2017

city: Chapel Hill

first: Gary

last: Johnson

state: NC

address: 4009 Genetic Medicine Building, 120 Mason Farm Road

department: Pharmacology

institute: University of North Carolina School of Medicine

summary: LCCC1122 is a window trial in stage I-IV TNBC patients scheduled to undergo definitive surgery (either lumpectomy, mastectomy or surgical resection of oligometastatic disease). Enrolled patients will receive 1.5 -2.0 mg of the MEK1/MEK2 inhibitor GSK1120212 (trametinib; Mekinist®) orally once daily for 7 days (with treatment initiation dependent on surgical schedule) prior to their surgery, with pre- and post- treatment tissue analyzed for kinome response and resistant signatures. A single blood sample will be obtained for determination of plasma GSK1120212 concentration prior to surgery. Of note, the initiation of study treatment is defined by the surgical schedule; there will be no delays in standard treatment for the purposes of this study.

overall_design:
28 samples representing 12 patients including pre-treatment needle core biopsies and post-treatment surgical resections

Raw data submitted to dbGaP (phs001405.v1.p1; https://www.ncbi.nlm.nih.gov/gap) because of patient privacy concerns.

first: Lisa

last: Carey

first: H

last: Earp


title: Expression data from Huh7.5.1 cells transfected with siNDRG1 or siNT

status: Public on Nov 17 2017

city: Bethesda

first: T. Jake

last: Liang

state: MD

address: 9000 Rockville Pike, Bldg 10 Rm. 9B16

department: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

institute: National Institutes of Health

summary:
Host cells harbor various intrinsic mechanisms to restrict viral infections as a first line of antiviral defense. Viruses have evolved various countermeasures against these antiviral mechanisms. Here we show that N-Myc Downstream-Reguated Gene 1 (NDRG1) limits productive HCV infection by inhibiting viral assembly. Interestingly, HCV infection down-regulates NDRG1 protein and mRNA expression. Loss of NDRG1 increases the size and number of lipid droplets, which are the sites of HCV assembly. HCV suppresses NDRG1 expression by up-regulating MYC, which directly inhibits the transcription of NDRG1.
Up-regulation of MYC also leads to reduced expression of NDRG1-specific kinase SGK1, resulting in markedly diminished phosphorylation of NDRG1. Knockdown of MYC during HCV infection rescues NDRG1 expression and phosphorylation, suggesting that MYC regulates NDRG1 at both transcriptional and post-translational levels. Overall, our results suggest that NDRG1 restricts HCV assembly by limiting lipid droplet formation. HCV counteracts this intrinsic antiviral mechanism by down-regulating NDRG1 via a MYC-dependent mechanism.

overall_design: We knocked down NDRG1 by transfecting cells in triplicate with siNDRG1 or siNT as control, we then analyzed the results to determine differential gene expression and differentially regulated pathways.

first: Cameron

last: Schweitzer

first: Fang

last: Zhang

first: Audrey

last: Boyer

first: Kristin

last: Valdez

first: Maggie

last: Cam

first: T


title: Gene expression of human splenic littoral cells compared with splenic vascular endothelial cells

status: Public on Dec 08 2017

city: New York

first: Jiajing

last: Qiu

address: 1468 Madison Ave, ANBG bldg 24-10

department: Hematology/Oncology Department of Medicine

institute: Icahn School of Medicine at Mount Sinai

summary:
Splenic littoral cells (SLCs) are specialized endothelial cells (ECs) lining the sinusoids of the human spleen and function as the filters and scavengers for senescent or altered red blood cells. In this study we isolated SLCs and vascular ECs from normal human spleens using immunostaining and flow cytometric sorting.
We used microarrays to analyze the underling mechanism of SLC’s unique functions that distinguish themm from splenic vascular ECs and identified sets of differentially expressed genes

overall_design: Normal human spleens were obtained from National Disease Research Interchange (NDRI) from healthy donors who required splenectomy for a traumatic injury. CD34- CD8a+ CD31+ CD3- CD45- SLCs and CD34+ CD8a- CD31+ CD3- CD45 splenic vascular ECs were isolated from the spleens and their gene expression profiles were compared.

first: Ronald

last: Hoffman


title: DNA Methylation profiling in luminal breast cancer cells treated with a novel KDM5 inhibitor, 5-aza-2' Deoxycytidine, or both.

city: Baltimore

first: Benjamin

last: Leadem

address: 1650 Orleans St. Suite 541

institute: Johns Hopkins University

summary: Recently, the H3K4 demethylase, KDM5B, was shown to be amplified and overexpressed in luminal breast cancer, suggesting it might constitute a potential cancer therapy target.  Here, we characterize, in breast cancer cells, the molecular effects of a recently developed small-molecule inhibitor of the KDM5 family of proteins, either alone, or in combination with the DNA demethylating agent 5-aza-2’ deoxycytidine (DAC).  Alone, the KDM5 inhibitor (KDM5i) increased expression of a small number of genes, but when combined with DAC, the drug enhanced the effects of the latter for increasing expression of hundreds of DAC responsive genes.  To determine if this combinatorial action was the result of enhanced DNA demethylation, we profiled genome-wide DNA methylation in cells treated with KDM5i, DAC, or both. Methylation levels at approximately 450,000 unique CpG loci were detected using the Infinium Illumina HumanMethylation 450 array.  We found that KDM5i did not significantly affect DNA methylation either alone, or in combination with DAC.

overall_design: Bisulphite converted DNA from cells treated with either no drug (Mock), an active KDM5 inhibitor (CPI-455), an inactive control compound (CPI-203), DAC, or a combination of KDM5i & DAC  were hybridized to the Illumina Infinium HumanMethylation 450 array.  Cells were treated with either DAC or treatment mock for 3 days, followed by 3 days of either KDM5i or treatment mock.  DNA was extracted immediately after completion of this treatment.

first: Stephen

last: Baylin


title: Primary constitutional MLH1 epimutations: a focal epigenetic event

first: Estela

last: Damaso


title: Primary constitutional MLH1 epimutations: a focal epigenetic event [FFPE data sets]

overall_design: 12 MLH1 epimutation carriers, 61 Lynch syndrome patients and 41 healthy controls were analyzed by Infinium Human Methylation 450k Beadchip. From all included individuals, DNA from blood was collected. FFPE blocks of normal colorectal mucosa and colorectal cancer tissue were also included when available.  The current subset includes only FFPE samples. Blood samples can be found in the other associated dataset from Damaso et al. (British Journal of Cancer).

last: Dámaso

first: Adela

last: Castillejo

first: María-del-Mar

last: Arias

first: Julia

last: Canet-Hermida

first: Matilde

last: Navarro

first: Jesús

last: del Valle

first: Olga

last: Campos

first: Anna

last: Fernández

first: Fátima

last: Marín

first: Daniela

last: Turchetti

first: Juan-de-Dios

last: García-Díaz

first: Conxi

last: Lázaro

first: Maurizio

last: Genuardi

first: Daniel

last: Rueda

first: Ángel

last: Alonso

first: Jose-Luis

last: Soto

first: Megan

last: Hitchins

first: Marta

last: Pineda

first: Gabriel

last: Capellá


title: Increased expression of Ankyrin repeat domain 1 (ANKRD1) associates with the resistance mechanism of osimertinib resistant non-small cell lung cancer

status: Public on Nov 11 2017

city: Sendagi, Bunkyou-ku

first: Akiko

last: Takahashi

state: Tokyo

department: Pulmonary medicine

institute: Nippon Medical School Hospital

summary: EGFR tyrosine kinase inhibitors (EGFR-TKIs) induce a dramastic response in non-small cell lung cancer (NSCLC) patients with the EGFR mutation.However, acquired resistance to EGFR-TKIs in lung cancer cells

overall_design: We established EGFR-TKI-resistant cells (PC-9-afatinib;PC-9-AR, PC-9-osimertinib; PC-9-OR, HCC827-afatinib; HCC827-AR, HCC827-osimertinib; HCC827-OR) to discover a novel mechanism of acquired resistance to EGFR-TKIs and a strategy to conquer EGFR mutation-positive lung cancer.

first: Masahiro

last: Seike

first: Mika

last: Chiba

first: Satoshi

first: Masahito

last: Nakamichi

first: Masaru

last: Matumoto

first: Susumu

last: Takeuchi

first: Yuji

last: Minegishi

first: Rintaro

last: Noro

first: Shinobu

last: Kunugi

first: Kaoru

last: Kubota

first: Akihiko

last: Gemma


title: Expression data from intestinal epithelial cells (IECs) [MoGene-1_0-st array]

city: Beijing

first: Xicheng

last: Liu

address: 7 Science Park Rd., ZGC life science park

institute: National Institute of Biological Sciences, Beijing

summary:
Polycomb group (PcG) proteins are epigenetic silencers whose dysregulation is frequently linked to cancer via mechanisms that remain unclear. Using conditional knock-out mice in a colitis-associated colorectal cancer (CAC) model, we found that Bmi1 and Mel18 are important initiation and maintenance factors during CAC tumorigenesis. Epithelial depletion of both Bmi1 and Mel18, but not either gene alone, significantly reduces tumor growth and multiplicity.
We used microarrays to detail the global program of gene expression In DKO, Bmi1ΔIEC, Mel18ΔIEC and WT mice and identified distinct classes of up-regulated genes during this process.

overall_design: Mouse IECs were selected at early stages of CAC tumorigenesis for RNA extraction and hybridization on Affymetrix microarrays. To that end, we isolated IECs from the freshly dissected colon of DKO (1), Bmi1ΔIEC (2), Mel18ΔIEC (3) and WT (4) mice for Mouse Gene 1.0 ST array.

first: Rongwen

last: Xi


title: Simultaneous enumeration of cancer and immune cell types from tumor gene expression data

status: Public on Nov 15 2017

city: Lausanne

first: David

last: Gfeller

address: Rue du Bugnon 25A

department: Department of Oncology UNIL CHUV; Ludwig Institute for Cancer Research Lausanne

country: Switzerland

institute: University of Lausanne

summary: Cancers are composed of various cell types. We present an efficient algorithm to simultaneously Estimate the Proportion of Immune and Cancer cells (EPIC) from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-seq analyses of human melanoma and colorectal tumor specimens. Altogether, our work not only improves accuracy but also broadens the scope of absolute cell fraction predictions from tumor gene expression data, and provides a unique novel experimental benchmark for immunogenomics analyses in cancer research.

overall_design: RNA-seq from lymph node bulk samples from 4 melanoma patients.

first: Julien

last: Racle

first: Kaat

last: de Jonge

first: Petra

last: Baumgaertner

first: Daniel

middle: E

last: Speiser


title: Hypoxia-inducible factor-1α promotes cell survival during ammonia stress response in ovarian cancer stem-like cells

status: Public on Nov 22 2017

city: Singapore

first: Henry

last: Yang

address: 28 Medical Drive

country: Singapore

institute: Cancer Science Institute of Singapore

summary: Ammonia is a toxic by-product of metabolism that causes cellular stress. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism that facilitate survival against toxicity have yet to be identified. We demonstrated that hypoxia-inducible factor-1α (HIF-1α) is stabilised and activated by ammonia stress. HIF-1α activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation and glutamine-dependent metabolism under ammonia stress in ovarian cancer stem-like cells expressing CD90. Interestingly, activated HIF-1α counteracts glutamine synthetase function in glutamine metabolism by facilitating glycolysis and elevating glucose dependency. Our studies reveal the hitherto unknown functions of HIF-1α in biphasic ammonia stress management in cancer stem-like cells. GS facilitates proliferation and HIF-1α contributes to metabolic remodelling in cellular energy usage resulting in attenuated proliferation but conversely promoting cell survival.

overall_design: 15 samples consisting of 3 sorted fractions from PEO1 human ovarian cancer cells grown with RPMI-1640 + 10% FBS in triplicate.

first: Shojiro

last: Kitajima

first: Kian

middle: L

last: Lee

first: Ruby

middle: Y

last: Huang

first: Marito

last: Araki

first: Hiroyuki

last: Kato

first: Lorenz

last: Poellinger


title: Transcriptome analysis by expression microarrays of pancreas cancer derived from the Cancer Institute Hospital of Japanese Foundation for Cancer Research.

status: Public on Nov 09 2017

city: Koto

first: Akihisa

last: Takahara

institute: Japanese Foundation For Cancer Research

summary: We performed the expression microarray experiments for mRNA of pancreas cancer tissue.

overall_design: Messenger RNA were extracted from primary tumor of 35 pancreas cancer patients, hybridized and scanned with Affymetrix　HG-U133 plus2.0 Array.

first: Yoshio

last: Miki


title: Global DNA methylation pattern of fibroblasts in idiopathic pulmonary fibrosis: relationship to gene expression

city: Seoul

first: Hyun Sub

last: Cheong

address: #1007, Teihard Hall, Sogang Univ. Baekbum-ro 35, Mapo-gu

department: Genetic Epidemiology

country: South Korea

institute: SNP Genetics, Inc.

summary: Analysis of Idiopathic pulmonary fibrosis (IPF) at gene expression level. The hypothesis tested in the present study was that Epigenetic mechanisms are likely to be associated with pathogenesis in IPF. To determine the DNA methylation change, and their effects on gene expression, we compared microarray data of DNA methylation and RNA expression. Results provide that among the genes whose DNA methylation status and RNA expression were both significantly altered between IPF-rapid and normal controls.

overall_design: Genomic DNA obtained from Idiopathic pulmonary fibrosis samples.

first: Jong-Uk

first: Choon-Sik

last: Park


title: Genome-wide methylomic and transcriptomic analyses identify subtype-specific epigenetic signatures commonly dysregulated in GBM and GSCs

city: Chicago

first: Rajendra

middle: Prasad

last: Pangeni

state: IL

department: Neurology

institute: Northwestern University

summary: Genome-wide DNA methylation and trancription profiling of different subtypes in GBM (TCGA) and glioma stem cells (GSCs) were carried out using Illumina BeadChip HumanMethylation 450K array (450K array) to analyse over 485K CpG sites accross each samples. 450K array data for 94 GBM samples comprising 4 different subtypes i.e. Proneural (PN), Mesenchymal (MES), Classical (CL) and Neural (N) were used for GBM analysis. Similarly, 450K array  for 23 GSCs and 1NHA, RNA seq for 29 GSCs and affimetrix microarray gene expression array for 12 GSCs were used for GBM  data analyses.

overall_design: Bisulphite converted DNA from the for 23 GSCs and a NHA used used for Illumina Infinium 450k Human Methylation array.Differential methylation between the subtype(s) were carried out to generate subtype-specific DNA methylation signatues which were then compared to RNA seq and/or gene expression data.

first: Zhou

last: Zhang

first: Angel

last: Alvarez

first: Namratha

last: Sastry

first: Songijan

last: Lu

first: Taiping

last: Shi

first: Tianzhi

first: Charles

middle: X

last: Lie

last: James

first: Maciej

last: Lesniak

first: John

last: Kessler

first: Cameron

last: Brenann

first: Ichiro

last: Nakano

first: Xinghua

first: Bo

last: Hu

first: Wei

first: Shi-Yuan

last: Cheng


title: DNA methylation profiling of genomic DNA isolated from urine in Diabetic Chronic-Kidney Disease: a pilot study

status: Public on Nov 16 2017

city: Parkville

first: Alexandra

last: Sexton-Oates

state: VIC

address: 50 Flemington Rd

country: Australia

institute: Murdoch Children's Research Institute

summary: Genome wide DNA methylation profiling of urine and blood samples from patients with diabetic chronic kidney disease. The Illumina Infinium MethylationEPIC BeadChip kit was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included two urine and four buffy coat samples from adults with diabetic chronic kidney disease.

overall_design: Bisulphite converted DNA from the six samples were hybridised to the Illumina Infinium MethylationEPIC BeadChip


title: Methylation and expression profiles of monocytes in monozygotic twins: role in Myasthenia Gravis [methylation profiling]

city: Paris

first: Sonia

last: Berrih-Aknin

state: State...

address: 105  Boulevard de l’Hôpital

department: Sorbonne Universités

institute: UPMC - Inserm UMRS 974, CNRS FRE3617

summary: Myasthenia gravis (MG) is a relatively rare autoimmune neuromuscular disorder. Monozygotic twin studies indicate that discordance rate in MG is about 70-60%, suggesting that despite identical DNA unknown factors contribute to disease development. The aim of the current study was to identify novel disease-associated genes in purified monocytes, including both genes associated with predisposition or with disease course, using the unique model of MZ twins. Thus the transcriptome and methylome were compared between twins discordant and concordant for the diseases, as well as MG singletons, and healthy controls. Several transcripts associated with immune homeostasis and inflammation resolution were highlighted in the current study.  High similarity between the healthy and the MG discordant twins found, suggest that genetic predisposition may have a stronger contribution then previously assumed. In addition, results suggest that numerous small changes in expression and DNA methylation might contribute to disease onset making it more difficult to pick up

overall_design: The transcriptome and methylome were compared between twins discordant and concordant for Maysthenia Gravis, as well as MG singletons, and healthy controls

first: Shimrat

last: Mamrut

first: Nili

last: Avidan

first: Frederique

last: Truffault

first: Elsebeth

last: Staun-Ram

first: Mélinée

last: Frenkian

first: Ariel

last: Miller


title: Expression and methylation data of human clear cell renal cell carcinoma

status: Public on Nov 04 2017

first: Hailiang

last: Feng

address: dong dan 3 tiao 5 hao

institute: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences

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

overall_design: Refer to individual Series


title: Methylation microarray data of human clear cell renal cell carcinoma

summary:
Human tumor cell lines are important tools in tumor biological studies, here the authors report the establishment and characterization of 7 new ccRCC stable cell lines with complete clinical data. Gene expression and methylation were profiled with microarrays between the new cells and those had a finite in vitro life span, and the results prompt that genes such as SLC34A2 and VHL play key roles in the continuous in vitro growth and development of ccRCC.
In order to find out what genetic features are related to the successful establishment of stable cell lines, early stage cells of 5 stable cell lines (UT14(P2), UT16(P2), UT33a(P3), UT48(P2), UT56(P1) ), named as P group and 5 finite cell lines (UT13a(P3), UT27(P3), UT37(P2), UT41(P2), UT54(P3) ) which could not be cultured more than 10 generations named as N group were chosen to do gene expression chip. Features such as age, gender, tumor size and Fuhrman nuclear grading were matched in these two groups.

overall_design: early stage cells of 5 stable cell lines (>20 generations in vitro)(UT14(P2), UT16(P2), UT33a(P3), UT48(P2), UT56(P1) ), named as P group and 5 finite cell lines (UT13a(P3), UT27(P3), UT37(P2), UT41(P2), UT54(P3) ) which could not be cultured more than 10 generations named as N group were chosen to do gene expression chip. Features such as age, gender, tumor size and Fuhrman nuclear grading were matched in these two groups

first: Yu

last: Zhang


title: Expression data from  human bone marrow derived mesenchymal stem cells (BMSCs) either cultured alone or co-cultured with human colon cancer cells HT29 or HCT116 respectively

status: Public on Oct 31 2017

first: XIN

last: FU

address: 33 Ba-Da-Chu Road

department: Research Center

institute: Plastic Surgery Hospital (Institute), Peking Union Medical College & Chinese Academy of Medical Sciences

summary:
The cross-talk between mesenchymal stem cells (MSCs) and cancer cells remains controversial. It is imperative to understand how MSC and tumor cells communicate with each other and whether the MSC responds to the tumor according to its stage of progression.
We used microarrays to detail the global programme of gene expression in human BMSCs either cultured alone or co-cultured with colon cancer cells HT29 or HCT116 respectively

overall_design: Human bone marrow-derived MSCs (BMSCs) were isolated from the iliac crest bone marrow of the patient following their bone defect reconstruction. BMSCs cultured alone (B-ctrl), BMSCs co-cultured with HT29 (B-co-HT29) and BMSCs co-cultured with HCT116 for 5 days were collected and their gene expression profiles were assessed by human whole-genome microarray assay. Three batches of BMSCs were analyzed. Total RNA was extract from BMSCs using TRI reagent and the microarray study was performed at CapitalBio Corporation (Beijing, China) using Affymetrix GeneChip Human Genome U133 Plus 2.0 Array according to manufacturer's protocol. Microarray images were processed and the image analysis was performed using the Affymetrix GeneChip Command Console Software and digitized with the Affymetrix Expression Console. Data analysis was performed using Significance Analysis of Microarray software (SAM 3.0, Stanford University, USA; http://www-stat.stanford.edu).

first: Ran

last: Xiao

first: Xin

last: Fu


title: DNA methylation profile of model breast cancer cell lines PMC42-ET and PMC42-LA

city: Clayton

first: Nicholas

last: Wong

state: Victoria

address: Wellington Road

department: Monash Bioinformatics Platform, Central Clinical School

institute: Monash University

summary: The epithelial to mesenchymal transition (EMT), and the reverse process mesenchymal to epithelial transition (MET) is a fundamental biological process that governs embryonic development and patterning. This exquisitely-controlled phenotypic switch between two very different cellular phenotypes is commandeered in a wide range of cancers, and is considered by many to be the initiating molecular event that drives carcinoma metastasis. Because the majority of cancer-related deaths are due to metastatic spread and secondary tumour formation, elucidating the molecular mechanisms governing EMT and MET in metastasis may hold great promise for clinical benefits. Research efforts over the last 20 (?) years have focussed predominantly on identifying individual molecules and cellular signalling cascades that drive EMT/MET. Recently developed high-throughput screening approaches have enabled rapid and comprehensive genome-wide interrogation of the genetic and epigenetic changes associated with cancer to be studied. In this study we have employed Infinium 450K methyl-bead arrays to examine the DNA methylation signatures of a unique pair of isogenic human breast cancer cell lines: The mesenchymal PMC42-ET line and an epithelial-like subline PMC42-LA.

overall_design: Two cell lines, PMC42-ET and PMC42-LA analysed in duplicate for DNA methylation with EGF treatment or, without (control).

first: Erik

middle: W

last: Thompson


title: Methylation and expression profiles of monocytes in monozygotic twins: role in Myasthenia Gravis


title: Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma [adrenal]

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

institute: Helmholtz Zentrum Muenchen

summary:
As overwhelming evidence coming from transgenic mouse models but also from MEN4 patients seem to suggest that loss or inactivation of a single p27 allele plays an important role in neuroendocrine tumorigenesis, we decided to perform a detailed analysis of the phenotype of rats heterozygous for the MENX-associated germline Cdkn1b mutation.
We here show that the reduction to a single functional p27 allele predisposes MENX heterozygous rats to the development of neuroendocrine malignancies.

overall_design: We compared 2 different groups: adrenal gland from wild type rats and adrenal lesions from heterozygous p27Kip1/Cdknb1 mutant rats.

first: Sara

last: Molatore

first: Martin

last: Irmler

first: Natalia

last: Pellegata


title: Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma [pituitary]

summary: As overwhelming evidence coming from transgenic mouse models but also from MEN4 patients seem to suggest that loss or inactivation of a single p27 allele plays an important role in neuroendocrine tumorigenesis, we decided to perform a detailed analysis of the phenotype of rats heterozygous for the MENX-associated germline Cdkn1b mutation. We here show that the reduction to a single functional p27 allele predisposes MENX heterozygous rats to the development of neuroendocrine malignancies.

overall_design: We compared  8 heterozygous mutant rats (p27Kip1/Cdknb1) to five control animals from a previously published dataset (GSE23207)

first: Ilaria

last: Marinoni


title: Expression data from intestinal epithelial cells (IECs)

first: Xicheng

last: Liu


title: Epigenome analysis of placenta samples

status: Public on Oct 25 2017

first: Rebecca

middle: Catherine

last: Fry

address: 1213 MHRC

department: Environmental Sciences and Engineering

institute: UNC-Chapel Hill

summary: Genome wide DNA methylation profiling of placental samples from the Extremely Low Gestational Age Newborn (ELGAN) study

overall_design: Bisulphite converted DNA from 84 placenta samples were hybridised to the Illumina Human Methylation450 BeaChip array

first: Martha

last: Tomlinson

first: Paige

last: Bommarito

first: Elizabeth

last: Martin

first: Lisa

last: Smeester

first: Raina

middle: N

last: Fichorova

first: Andrew

middle: B

last: Onderdonk

first: Karl

last: Kuban

first: T

last: O'Shea


title: Transcriptome analysis by expression microarrays of esophagus cancer derived from the Cancer Institute Hospital of Japanese Foundation for Cancer Research.

first: Akihisa

last: Takahara

summary: We performed the expression microarray experiments for mRNA of esophagus cancer tissue.

overall_design: Messenger RNA were extracted from primary tumor of 23 esophagus cancer patients, hybridized and scanned with Affymetrix　HG-U133 plus2.0 Array  .

first: Yoshio

last: Miki


title: IRAK4 kinase activity mediates IRF5 activation via IKKβ and TAK1

status: Public on Oct 12 2017

city: Cambridge

first: Scott

last: Jelinsky

address: 610 Main Street

department: Inflammation and Immunology

institute: Pfizer

summary: IRAK4 kinase plays a critical role in innate immune responses and inflammation by  modulating the TLR/IL-1R signaling pathway, yet the mechanism by which it regulates downstream pathways and transcription factors to induce inflammatory cytokines is unclear.  IRAK4 can mediate signaling events by mechanisms both dependent and independent of its kinase activity. Understanding this regulation is important for deciphering the role of IRAK4 and for the development of treatments for inflammatory diseases and cancer.  Through transcriptomic and biochemical analyses of primary human monocytes treated with a highly potent and selective inhibitor of IRAK4, we show that IRAK4 kinase activity controls the transcription factor IRF5 which in turn induces inflammatory cytokine and type I interferon transcription in myeloid cells.  We also show that IRAK4 kinase activity does not control activation of NF-κB.  Following TLR stimulation, translocation of IRF5, but not NF-κB, to the nucleus in human monocytes is abolished by IRAK4 kinase inhibition.  In addition, binding of IRF5, but not NF-κB p65, to promoters of inflammatory target genes (TNF-α and IP10) is blocked with an IRAK4 kinase inhibitor.  IKKβ, a known activator of IRF5, is phosphorylated in response to TLR mediated signaling, and inhibition of IRAK4 kinase blocks IKKβ phosphorylation.  Pharmacological inhibition of IKKβ and TAK1, the upstream kinase of IKKβ, in human monocytes blocks IL-1, IL-6 and TNF-α cytokine production, as well as IRF5 translocation to the nucleus.  Taken together, our data suggest a novel mechanism by which IRAK4 kinase activity regulates TAK1 and IKKβ activation, leading to the translocation of IRF5 and induction of inflammatory cytokines in human monocytes.

overall_design: Primary human monocytes from healthy donors were incubated with RosetteSep Monocyte Enrichment Cocktail (Stem Cell Technologies) and purified a.  The isolated monocytes were then re-suspended for culture in RPMI + 0.5% FBS , pretreated with 1 µM IRAK4 inhibitor compound or DMSO  for 30 minutes and then stimulated with 0.5 ug/ml R848 for 1 hour.


title: Gene expression analysis of human dermal fibroblasts (HDF) and human iPSC

city: Kyoto

first: Takuya

last: Yamamoto

address: 53 Kawahara-cho, Shogoin, Sakyo-ku

department: CiRA

institute: Kyoto University

summary: To identify the genes whose expression levels are changed before and after somatic cell reprogramming, we performed global gene expression analysis of iPS cells and their original fibrobrasts.

overall_design: RNAs were extracted from an iPS cell line (201B7) and its original human dermal fibroblast cell line (1388), and analyzed on Affymetrix microarrays.

first: H

last: Ikeda


title: Subtracting the sequence bias from partially digested MNase-seq data reveals a general contribution of TFIIS to nucleosome dynamics

city: Sevilla

first: Gabriel

last: Gutierrez

address: PO BOX 1095

department: Genetics

institute: University of Seville

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Understanding chromatin dynamics is a key to other related processes, including DNA replication, transcription and recombination. As a first step, recently, an increasing amount of effort has been devoted to precisely define nucleosome positioning in different organisms. The most popular method to do so is digestion by Micrococcal nuclease (MNase), nowadays followed by ultrasequencing of the generated fragments. Although the sequence bias of MNase has been known for a long time, a data-based way of correcting this bias for sequencing experiments is still missing. Here we provide such a method, based on the digestion of naked DNA and the use of the bioinformatic tool DANPOS. Using Saccharomyces cerevisiae as a model, we demonstrate that the overall quality of the data is better after the correction proposed here. The characteristics of the method make it perfectly applicable to any other organism. Moreover, we find that the correction affects more to TATA containing genes than to TATA-like genes. Importantly, the correction uncovers a new role for TFIIS in chromatin dynamics. The absence of TFIIS caused a general increase in nucleosome fuzziness, and a higher peak of the -1 nucleosome at some promoters

overall_design: Mnase-Seq experiments in both strains WT and dst1∆ mutant

last: Gutiérrez


title: Lung transcriptome analysis of mice with lung mesechyme specific deletion of Pbx transcription factors

status: Public on Nov 02 2017

city: San Diego

first: David

middle: James

last: McCulley

state: CA

address: 9500 Gilman Drive, MC 0735, Leichtag Building, Room 132

department: Pediatrics

institute: University of California, San Diego

summary:
Two critical events that are required for normal transition from fetal to extrauterine life are development of the alveoli that allow for efficient gas exchange in the lung and relaxation of the pulmonary vascular smooth muscle. Patients with congenital diaphragmatic hernia (CDH) have abnormal lung and pulmonary vascular development that results in a lethal combination of lung hypoplasia and pulmonary hypertension. To better understand the mechanisms responsible for abnormal lung and pulmonary vascular development and function we generated Pbx1/2 conditional knockout mice that lack Pbx1 and Pbx2 expression in the lung mesenchyme. Pbx1 has previously been shown to be required for normal diaphragm development, however its role in alveologenesis, and the mechanisms responsible for pulmonary hypertension, has not been studied. We found that Pbx1/2 CKO mice have failure of alveologenesis and die of severe pulmonary hypertension by 2 to 3 weeks of age. In order to better understand the downstream genetic mis-regulation caused by deletion of Pbx1/2, and identify their potential transcriptional targets, we carried out transcriptional profiling of Pbx1/2 CKO and control mice starting at postnatal day 3 (P3), when a histological phenotype first becomes apparent, and then working back to the time of birth (P0), and embryonic day 14 (E14) when the pulmonary vascular smooth muscle is developing.
In this dataset are the expression data obtained from dissected embryonic and early postnatal lungs of Pbx1/2 CKO and control mice. Pbx1/2 CKO mice are homozygous null for Pbx2 with conditional deletion of Pbx1 in the lung mesenchyme directed by Tbx4 Cre (Tbx4 Cre/wild-type; Pbx1 flox/flox; Pbx2 delta/delta). Control mice are homozygous null for Pbx2 and are heterozygous for Pbx1 in the lung mesenchyme (Tbx4 Cre/wild-type; Pbx1 flox/wild-type; Pbx2 delta/delta). These data are used to identify the transcriptional targets and down-stream effectors of PBX transciptional regulation in the lung.

overall_design: 3 samples were pooled from Pbx1/2 CKO and control mice at each stage (E14, P0, and P3). We generated pair-wise comparisons between Pbx1/2 CKO and control samples at each stage.

middle: J

first: Xin

last: Sun


title: Expression data of iPSCs, CTraS-iPSCs, embryoid bodies, and their derived neurospheres

city: Sinjuku-ku, Tokyo

first: Koki

last: Fujimori

address: 35 Shinanomachi

department: Physiology

institute: Keio University

summary:
Recent studies indicated that the differentiation tendency of pluripotent stem cells (PSCs) was affected by a certain small molecule treatment. We found the combination of small molecules that bringed out the differentiation potentials of PSCs, and defined such state of PSC as CTraS.
Then, we used microarrays to detail the global programme of gene expression reflecting the effect of CTraS, and carefully compared the characteristics of iPSCs, CTraS-iPSCs, embryoid bodies (EBs), and their derived neurospheres (NSs) based on their expression profiles .

overall_design: We isolated RNA from iPSCs, CTraS-iPSCs, EBs, and NSs derived from them (total 10 samples) for the gene expression microarray analysis. All of the iPSC lines we used were low passage number (less than 15).

last: Matsumoto

first: Hideyuki

last: Okano

first: Wado

last: Akamatsu


title: An analysis of the effect of indacaterol and GSK 256066 alone and in combination on gene expression changes in the BEAS-2B human airway epithelial cell line.

city: Calgary

first: Mark

last: Giembycz

state: Alberta

address: 3280 Hospital Drive NW

department: Physiology & Pharmacology

country: Canada

institute: University of Calgary

summary: Microarray analysis was performed on RNA extracted from BEAS-2B cells treated with indacaterol, GSK 256066 and indacaterol and GSK 256066 in combination to identify differentially expressed genes that may contribute to the beneficial and deleterious effects of β2-adrenoceptor agonists and phosphodiesterase 4 inhibitors in obstructive lung diseases.

overall_design:
Confluent BEAS-2B cells were treated with vehicle, indacaterol (Ind; 10nM), GSK 256066 (GSK; 10nM) or Ind and GSK in combination for 1h, 2h, 6h and 18h. Total RNA was extracted, quantified (NanoDrop 2000) and the quality of each sample was determined by using the Agilent 2100 Lab-on-a-Chip system before being processed for gene expression chnages by Expression Analysis Inc (Dunham, NC, USA).

Please note that the sample records have been updated with additional samples and re-accessioned with the re-processed data on March 14, 2018.


title: Progressive modulation of the human olfactory bulb transcriptome during Alzheimer's disease evolution: novel insights into the olfactory signaling across proteinopathies

status: Public on Nov 01 2017

city: Pamplona

first: Enrique

last: Santamaría

state: Navarra

address: Irunlarrea, 3

institute: Navarrabiomed

summary: Alzheimer's disease (AD) is characterized by progressive dementia, initially presenting olfactory dysfunction. Despite the olfactory bulb (OB) is the first central structure of the olfactory pathway, we lack a complete molecular characterization of the transcriptional events that occurs in this olfactory area during AD progression. To address this gap in knowledge, we have assessed the genome-wide expression in postmortem OBs from subjects with varying degree of AD pathology. A stage-dependent deregulation of specific pathways was observed, revealing transmembrane transport, and neuroinflammation as part of the functional modules that are disrupted across AD grading. Potential drivers of neurodegeneration predicted by network-driven transcriptomics were monitored across different types of dementia, including progressive supranuclear palsy (PSP), mixed dementia, and frontotemporal lobar degeneration (FTLD). Epidermal growth factor receptor (EGFR) expression was significantly increased in the OB of AD and mixed dementia subjects. Moreover, a significant increment in the activation of signal transducer and activator of transcription 3 (STAT3) was exclusively detected in advanced AD stages, whereas total OB STAT3 levels were specifically overexpressed in mixed dementia. Furthermore, transcription factors deregulated in the OB of mixed dementia subjects such as cAMP Responsive Element Binding Protein 1 (CREB1) and AP-1 Transcription Factor Subunit (c-Jun) were not differentially modulated at olfactory level across AD grading. On the other hand, olfactory expression of this signal transducer panel were unchanged in PSP and FTLD subjects. Taken together, this study unveils cross-disease similarities and differences for specific signal transducers, providing new avenues of research into the role of olfactory signaling across proteinopathies.

overall_design: 4 controls, 5 Alzheimer's disease (initial stage), 4 Alzheimer's disease (intermediate stage), 5 Alzheimer's disease (advanced stages).

first: Joaquín

last: Fernández-Irigoyen

first: Victor

last: Segura


title: Gene expression data of human keratinocytes knocked down for SMC1A, SMC3, or control shRNA.

city: La Jolla

first: George

last: Sen

address: 9500 GIlman Drive

department: Dermatology/CMM

institute: UCSD

summary:
The purpose of the study is to understand the impacts of cohesin knockdown on epidermal gene expression. Primary human keratinocytes were knocked down for SMC1A, SMC3, or control to determine its genome-wide gene expression profile.
Global gene expression profiling using U133 plus 2.0 arrays were used to deteremine the genes perturbed by knockdown of SMC1A or SMC3.

overall_design: For gene expression profiling, cultured primary human keratinocytes were transduced with a retrovirus expressing SMC1, SMC3, or control shRNAs.RNA was harvested from these genetically modified cells 10 days post-transduction. Microarray analysis using Affymetrix HG-U133 2.0 plus arrays was performed on duplicate samples.

first: Maria

last: Noutsou


title: 450k methylation array of H9-hESC derived human neural stem cells with combinations of mutant IDH1-R132H overexpression, P53 shRNA knockdown and/or ATRX shRNA knockdown

city: New York

first: Aram

middle: S

last: Modrek

state: NY

address: 460 E 26th Street

department: Radiation Oncology

institute: New York University School of Medicine

summary: Methylation profiling was performed to assess methylation alterations by the addition of serial oncogenic hits (mutant-IDH1, P53 knockdown and ATRX knockdown) in human neural stem cells.

overall_design: Illumina 450k array methylation profiling was performed in duplicates, there are four conditions total. Vector NSCs are the control line and have an empty mCherry vector and a scramble shRNA vector. One hit NSCs express mutant-IDH1 and have a scamble shRNA vector. Two-hit NSCs express mutant IDH1 and have p53 knockdown. Three-hit NSCs express mutant-IDH1, P53 knockdown and ATRX knockdown.

first: Dimitris

middle: G

last: Placantonakis


title: Stable 5-Hydroxymethylcytosine (5hmC) Acquisition Marks Gene Activation During Chondrogenic Differentiation [array]

city: Stanford

first: Nidhi

last: Bhutani

state: California

address: 300 Pasteur Drive, R164 Edwards Bldg

department: Orthopaedic Surgery

institute: Stanford University

summary: Regulation of chondrogenic differentiation by DNA demethylation is little understood. The ten-eleven-translocation (TET) proteins oxidize methylated cytosines (5mC) to 5hmC, 5fC and 5caC eventually leading to DNA demethylation. However, 5hmC is stable and can potentially act as an epigenetic mark as well. In this study, we report that global changes in 5hmC mark chondrogenic differentiation.

overall_design: Progenitor and differentiated chondrocyte gene expression patterns were examined to assess the changing expression profiles over the course of chondrogenesis.

first: Sarah

last: Taylor

first: Ye

middle: H

last: Li

first: Piera

last: Smeriglio


title: Memory CD4+ T cells from Vaccinia vaccinated subjects.

status: Public on Oct 01 2017

city: Bruce

first: Kristine

last: Hardy

state: ACT

address: University of Canberra

institute: University of Canberra

summary: Comparsion of the transcriptomes of naive, resting memory and activated memory CD4+ T lymphocytes.  Peripheral blood lymphocytes were collected at baseline and day 13 post-inoculation of a healthy subject administered with vaccinia virus. Cells were isolated by FACs using antibodies against CD4, CD45RO and CD38.

overall_design: 3 separate biological samples analysed

first: MeeLing

last: Munier

first: Jasmine

first: Sudha

last: Rao

first: Chansavath

last: Phetsouphanh


title: A paradoxical tumor suppressor role for the Rac1 exchange factor Vav1 in early cortical T cell acute lymphoblastic leukemia

status: Public on Sep 30 2017

city: Salamanca

first: L. Francisco

last: Lorenzo-Martín

state: Castilla y León

address: Campus Miguel de Unamuno

institute: University of Salamanca (USAL) – Centro de Investigación del Cáncer (CIC)

summary:
Robles-Valero et al. report a tumor suppression role for the otherwise oncogenic Vav1 Rho GEF. This paradoxical action is mediated by the catalysis-independent buffering of Notch1 signaling in immature T cells.
These data reverse the long-held paradigm that Rho GEFs always favor tumor growth and unveil a new signaling crosstalk likely involved in human T-ALL etiology.

overall_design: DMBA was administered (0.1 ml - 10 mg/m) weekly via intragastric intubation to female mice of indicated genotypes for a total of six weeks. The first administration started when animals were 8-week-old. Mice were then examined weekly until showing obvious physical signs of sickness and thymi were collected

first: Javier

last: Robles-Valero

first: L

middle: F

first: Mauricio

last: Menacho-Márquez

first: Antonio

last: Abad

first: Lluis

last: Espinosa

first: Anna

last: Bigas

first: Xosé

middle: R

last: Bustelo


title: A Multicenter, First-in-Pediatrics, Randomized Study to Evaluate the Safety and Efficacy of Decitabine as Epigenetic Priming with Induction Chemotherapy in Children with Acute Myelogenous Leukemia

city: Phoenix

first: Bodour

last: Salhia

state: AZ

address: 445 N Fifth Street

department: Integrated Cancer Genomics Division

institute: Translational Genomics Research Institute

summary:
Purpose:  Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases indicated for treatment of myelodysplastic syndrome (MDS).   Laboratory evidence shows that pretreatment of AML cell lines can sensitize leukemia cells to chemotherapy and inhibit clonogenic potential. We conducted a randomized study of decitabine when used as priming before standard induction therapy in children with newly diagnosed acute myelogenous leukemia (AML) to evaluate the safety, pharmacokinetics, and any potential early efficacy signal.  Exploratory analyses of genomic methylation and RNA expression patterns and minimal residual disease (MRD) were included to elucidate possible biological mechanisms.
Methods:   This multicenter, randomized, two-arm, open-label study enrolled children ages 1-16 with newly diagnosed de novo AML to either Arm A: daunorubicin, cytarabine, etoposide preceded by a 5-day course of decitabine (experimental arm) or Arm B: daunorubicin, cytarabine, etoposide (control). Following completion of induction therapy, subsequent post-induction treatment was given at the treating physician’s discretion. Patients were monitored for adverse events and samples were collected for PK/PD and biologic analyses.
Results: Twenty patients, ages 1-16 years (median 9.4 yrs in both Arms) were treated (10 per Arm). Eighteen of 20 enrolled subjects completed the prescribed treatment. All subjects experienced neutropenia and thrombocytopenia as is expected during AML induction chemotherapy. The most common grade 3 and 4 non-hematologic adverse events observed were caecitis, 2 (20%) subjects in Arm A and 0 (0%) subjects in Arm B; decreased appetite, 3 (30%) subjects in Arm A and 0 (0%) subjects in Arm B; and hypophosphatemia, 2 (20%) subjects in Arm A and 0 (0%) subjects in arm B.  One subject in Arm A had appendicitis and colon perforation on Day 6 that led to study discontinuation; the cause was later determined to have been leukemic infiltrate of the bowel wall.  Two subjects died (both in Arm A), one of necrotic bowel, pseudomonas sepsis and multisystem organ failure 6 months after study participation and one patient 5 months following study treatment from multisystem organ failure as a complication of stem cell transplant.  Plasma concentrations of decitabine showed PK values (mean+SD) of Cmax, 281+113 ng/mL, AUC0-∞, 198+65.3 ng*h/mL, CL, 156+94.6 L/h, Vdss 109+70 L, t1/2 0.48+0.060 h, and median tmax 0.93 h.  Overall CR/CRi by morphology was similar between the two treatment arms (92% for the control arm and 100% for the experimental arm).  MRD at Day 30 post induction therapy was lower in the control group compared to the decitabine group (67% vs 85% MRD-negative).  Changes in DNA epigenetic and RNA expression patterns demonstrated distinct differences involving selective cellular pathways between the two groups of patients comparing diagnostic to day 30 bone marrow samples.
Conclusions:  This first-in-pediatric trial of epigenetic priming in patients with newly diagnosed AML demonstrates that decitabine pre-treatment followed by standard combination chemotherapy is well tolerated in children with newly diagnosed AML. Morphologic complete responses were similar in both treatment arms.  MRD at Day 30 following induction therapy suggests a deeper remission in patients receiving decitabine.  No differences were observed between treatment arms in hematologic toxicities although decitabine-treated patients were noted to have more gastrointestinal toxicities, anorexia and hypophosphatemia.  Decitabine PK parameters in children were consistent with known adult PK profiles. Molecular changes associated with decitabine pretreatment may be important in the sensitization of clonogenic AML cells.  Pre-treatment with decitabine may represent a therapeutic option for use in pediatric AML, when epigenetic modification is a desired focus for treatment.

overall_design: Bisulphite converted DNA from 36 samples were hybridised to the HumanMethylation450 BeadChip.

first: Lia

last: Gore

first: Robert

last: Arceci


title: Predicting Acute Cardiac Allograft Rejection Using Donor and Recipient Gene Expression

status: Public on Sep 29 2017

city: Vancouver

first: Bruce

middle: Maxwell

last: McManus

state: BC

address: 1081 Burrard Street

department: UBC James Hogg Research Centre

institute: PROOF Centre of Excellence

summary: Acute rejection in cardiac transplant patients is still a contributing factor to limited survival of the implanted heart.  Currently there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplantation acute rejection, which would be of great importance for personalizing immunosuppressive treatment.  Within the Biomarkers in Transplantation initiative, the predictive biomarker discovery focused on data and samples collected before or during transplantation such as: clinical variables, genes and proteins from the recipient, and genes from the donor.  Based on this study, the best predictive biomarker panel contains genes from the recipient whole blood and from donor endomyocardial tissue and has an estimated area under the curve of 0.90.  This biomarker panel provides clinically relevant prediction power and may help personalize immunosuppressive treatment and frequency of rejection monitoring.

overall_design: This study, approved by the Providence Health Care Research Ethics Board and related Ethics Boards, was carried out under the Biomarkers in Transplantation (BiT) initiative on subjects who received a cardiac transplant at St. Paul’s Hospital, Vancouver, British Columbia, and signed consent forms.   A total of 18 subjects, for whom recipient whole blood (collected in average within two week before transplant) and donor heart tissue (collected at time of transplant) was available, were selected for blood and tissue-based biomarker discovery.  Seven of the 18 patients developed acute rejection [AR; ISHLT grade ≥2R] within the first six months post-transplant while 11 did not [non-AR].


title: Malignant rhabdoid tumors originating within and outside the central nervous system are clinically and molecularly heterogeneous

status: Public on Dec 12 2017

city: Memphis

first: Tong

last: Lin

state: TN

address: 262 Danny Thomas Place

department: Biostatistics

institute: St. Jude Children's Research Hospital

type:
Methylation profiling by array
Third-party reanalysis

summary: Multifocal synchronous or metachronous central nervous system (CNS) and extra-CNS malignant rhabdoid tumors (MRTs) are rare and deadly cancers. To further understand these cancers, we performed genome-wide DNA methylation and CNA analysis in 27 tumors (16 of which were paired samples). 26 samples were newly generated and one sample was from a previously published cohort of MRTs. We compared our results with the previously published reference group of 150 atypical teratoid rhabdoid tumors. We showed that that CNS and extra-CNS MRTs for the most part clustered in distinct methylation groups and had heterogeneous molecular characteristics.

overall_design: Twenty-seven human MRTs (CNS [n=13] and extra-CNS [n=13]) were profiled using Illumina Infinium Human 450K (n=1, GSM1755246 [GSE70460] or 850k Bead Array (n=26). This series includes the re-analyzed data of 150 samples from GSE70460.  The entire data matrix with the average beta values for all 176 analyzed samples is available at the foot of this page.

first: Amar

last: Gajjar


title: IRF4 haploinsufficiency in a family with Whipple’s disease

status: Public on Oct 30 2017

city: Doha

first: Nico

last: Marr

address: OPC Al-Luqta Street

department: Systems Biology

country: Qatar

institute: Sidra Medical and Research Center

summary:
Whipple's disease (WD) affects only a very small minority of individuals infected by Tropheryma whipplei (Tw). Asymptomatic and chronic carriage of the causative organism is less rare and therefore, the pathogenesis of WD is poorly understood.
Here we studied transcriptome responses in peripheral blood mononuclear cells (PBMCs) that were obtained from members of a large multiplex French kindred including otherwise healthy WD patients, healthy chronic carriers of Tw and other unrealted control subjects.

overall_design: PBMCs from six IRF4-heterozygous individuals (three patients, P1-P3; and three healthy relatives, HET1-HET3) and six IRF4 WT-homozygous individuals (four healthy relatives, WT1-WT4; and two unrelated controls, C1-C2) were dispensed into a 96-well plate and were either infected in vitro with live Tw at a multiplicity of infection (MOI) of 1, with live BCG (M. bovis-BCG, Pasteur substrain) at a MOI of 20, or were left uninfected (mock). Two wells per condition were combined 24 h post-infection for total RNA isolation followed by microarray analysis.

first: Antoine

last: Guérin

first: Sabri

last: Boughorbel

first: Salim

last: Bougarn

first: Damien

last: Chaussabel

first: Laurent

last: Abel

first: Jean

last: Casanova


title: Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [methylation II]

status: Public on Sep 24 2017

city: Rehovot

first: Yehoshua

last: Enuka

address: Herzl 234

department: Biological Regulation

country: Israel

institute: Weizmann Institute of Science

summary: Growth factors (GFs) suppression by steroid hormones  recurs in embryology and is co-opted in pathology. While studying mammary cell migration, which is stimulated by GFs and antagonized by glucocorticoids (GCs), we found that GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal negative loops. Although no alterations in DNA methylation accompany the transcriptional events instigated by either stimulus, forced demethylation of distal regions broadened the repertoire of inducible genes. Our data indicate that the crosstalk involve transcription factors like p53 and NF-kB, along with reduced pausing (and traveling) of RNA polymerase II (RNAPII) at the promoters (and bodies) of GF-inducible genes. In addition, while GFs hyper-acetylated chromatin at unmethylated promoters and enhancers of genes involved in motility, GCs hypo-acetylated the corresponding regions. In conclusion, stably unmethylated genomic regions that encode feedback regulatory modules and differentially recruit RNAPII and acetylases/deacetylases underlie suppression of growth factor signaling by glucocorticoids.

overall_design: DNA methylation – treatment of mammry cells with different agents for 1 hour: Dexamethasone (DEX), Doxorubicin (DOX), Phorbol Ester (PMA), DMSO, EGF. cells were treated with EGF for additional timepoint of 4 hours. DMSO treatment was used as the control.


title: Global gene expression analysis in PBMCs of individuals from normal and high level natural radiation areas of Kerala Coast, India

status: Public on Oct 26 2017

city: Mumbai

first: Birajalaxmi

last: Das

state: Maharashtra

address: Trombay

department: LLRRS, RB&HSD

country: India

institute: Bhabha Atomic Research Centre

summary:
Gene expression changes in human populations exposed to chronic low level radiation have important implications. There are few areas around the world where human population is exposed to elevated levels of natural background radiation. The high level natural radiation areas (HLNRAs) of Kerala coast in south west India is unique for its wide variation in the background radiation dose (<1.0mGy to 45mGy/year). The areas with a background radiation dose of ≤ 1.5mGy/year are considered as normal level natural radiation areas (NLNRA), whereas areas with > 1.5mGy/year are considered as HLNRA.
We used microarray analysis to find out global changes in gene expression in peripheral blood mononuclear cells (PBMCs) of individuals belonging to different HLNRA groups as compared to individuals from normal level natural radiation areas (NLNRA).

overall_design: Blood samples were collected from individuals of four different background dose groups (Normal level natural radiation areas (Group I, ≤1.5mGy/year, N=9) and three dose groups of high level natural radiation areas (Group II, 1.51-5.0mGy/year, N=9; Group III, 5.01-15.0mGy/year, N=11; and Group IV, >15.0mGy/year, N=7)). Peripheral blood mono-nuclear cells were isolated from each blood sample and used for RNA extraction and hybridization to Affymetrix Chip.

first: Vinay

last: Jain