title: Genome-wide linkage analysis in Spanish melanoma-prone families [Round1]

first: joan anton

last: Puig Butille

summary: The main genetic factors for familial melanoma remain unknown in more than 75% of families. CDKN2A is mutated in around 20% of melanoma-prone families. Other high-risk melanoma susceptibility genes explain less than 3% of families studied to date. We performed the first genome-wide linkage analysis in CDKN2A-negative Spanish melanoma-prone families to identify novel melanoma susceptibility loci. We included 68 individuals from 2, 3 and 6 families with 2, 3 and at least 4 melanoma cases. We detected a locus with significant linkage evidence at 11q14.1-q14.3, with a maximum het-TLOD of 3.449 (rs12285365:A>G), using evidence from multiple pedigrees. The genes contained by the subregion with the strongest linkage evidence were: DLG2, PRSS23, FZD4 and TMEM135. We also detected several regions with suggestive linkage evidence (TLOD>1.9) (1q, 6p, 7p, 11q, 12p, 13q) including the region previously detected in melanoma-prone families from Sweden at 3q29. The family specific analysis revealed three loci with suggestive linkage evidence for family #1: 1q31.1-q32.1 (max. TLOD 2.447), 6p24.3-p22.3 (max. TLOD 2.409) and 11q13.3-q21 (max. TLOD 2.654). Future next generation sequencing studies of these regions may allow the identification of new melanoma susceptibility genetic factors.

overall_design: The study included 29 melanoma cases and 39 non-affected individuals belonging to 11 Spanish melanoma prone families. Genome-wide genotyping was performed using the HumanOmni2.5 SNP array platform (Illumina).

first: Miriam

last: Potrony

first: Joan

last: Puig-Butille

first: James

last: Farnham

first: Pol

last: Giménez-Xavier

first: Celia

last: Badenas

first: Gemma

last: Tell-Martí

first: Paula

last: Aguilera

first: Cristina

last: Carrera

first: Josep

last: Malvehy

first: Craig

last: Teerlink

first: Susana

last: Puig


title: Acute activation of ER-RAC1 P29S in melanocytes

status: Public on Aug 10 2018

city: London

first: Philip

last: East

state: London

address: 1 Midland Road, London

department: Bioinformatics

country: United Kingdom

institute: The Francis Crick Institute

type: Expression profiling by high throughput sequencing

summary: We studied the effects of acute activation of the melanoma oncogene RAC1 P29S using a tamoxifen-inducible ER-fusion protein system in mouse melanocytes

overall_design: An ER-RAC1 P29S fusion protein was stably expressed in the spontaneously immortalized mouse melanocyte cell line melan-a. The fusion protein was activated by treatment with 500 nM 4OH-tamoxifen. RNA was isolated and sequenced at 0 h, 4 h and 40 h post-treatment. The gene expression profiles at 4 h and 40 h were compared to the 0 h time-point. To control for effects induced by 4OH-tamoxifen independent from ER-RAC1 P29S, we performed the same experiment in melan-a cells transduced with an empty vector.

first: Daniel

middle: A

last: Lionarons

first: Julian

last: Downward


title: Genome–wide gene expression profile of adipocytes and infiltration macrophages obtained from abdominal (visceral and subcutaneous) and peripheral (thigh) adipose depots from Normal Glucose Tolerant and Type 2 Diabetics Asian Indians

status: Public on Dec 31 2018

city: Jaipur

first: Dr. Sandeep

middle: Kumar

last: Mathur

state: Rajasthan

address: Tonk Road

department: Department of Endocrinology

country: India

institute: SMS Medical College and Hospital

summary:
We have identified molecular-level alternations in different adipose depots (thigh, visceral and subcutaneous) of Asian Indians (both male and female) suffering from type-2 diabetes as compared to age and BMI matched normal glucose tolerant subjects by functional analysis of differentially expressed genes, and correlation of gene expression estimates with measured intermediate traits associated with T2D and its related co-morbidities (Hb1Ac, HOMA-B, HOMA-R, NEFA, Triglyceride, Total Cholesterol, HDL, LDL, VLDL, Leptin, Adiponectin, TNF-α,  Serum- Creatinine,  IL-6, High sensitivity - serum-creatinine (hs-CRP) and also size of adipocytes).

Funding:
Grant Id: 5/4/8/2012-RMC
Grant title: Clinical, Biochemical and Cellular Correlates of Transcriptome of  Adipose Tissue Among Type-2 Diabetics
Name of the funding source: Indian Council for Medical Research

overall_design: We have recruited 30 controls & 30 diabetic subjects undergoing femur bone surgery and 16 controls & 19 diabetic subjects undergoing abdominal surgery (two samples from each subject, one subcutaneous and one visceral fat biopsy were extracted). So total 130 samples were obtained and analyzed for genome –wide gene expression profile of Adipocytes and infiltration macrophages from three different depots of adipose tissue.

first: S

middle: K

first: Aditya

last: Saxena

first: Pradeep

last: Tiwari


title: Genome-wide linkage analysis in Spanish melanoma-prone families [Round2]

status: Public on Jan 01 2019

city: Barcelona

first: joan anton

last: Puig Butille

address: Villarroel 170

country: Spain

institute: Hospital Clínic

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

first: Miriam

last: Potrony

first: Joan

middle: M

middle: C


title: A Comparative Assessment of iPSC Derived Cardiomyocytes with Heart Tissues in Humans and Chimpanzees

status: Public on Aug 08 2018

city: Chicago

first: Bryan

middle: J

last: Pavlovic

state: IL

department: Human Genetics

country: USA

institute: University of Chicago

summary: To study regulatory differences between species, the field of comparative primate genomics has used several approaches, including the use of post mortem frozen tissues, cell lines, and model organisms. However, there are limited quality cell lines from primates and post-mortem tissues cannot be staged, are not amenable to experimental perturbations and are often subject to high environmental variances. Inducible pluripotent stem cells (iPSCs) are an attractive system to study primate biology in a comparative context. However, the fidelity of iPSC derived cell types to primary tissues needs to be assayed in a comparative primate context before the utility of iPSCs can be fully realized for comparative genomics. In order to comprehensively benchmark the performance of iPSC model systems in a comparative framework, we collected RNA-sequencing from primary adult heart tissue and iPSC derived cardiomyocytes from multiple human and chimpanzee individuals.  We identified the optimal parameters of iPSC differentiation into cardiomyocytes that minimized differences between each species and their respective adult tissue counterparts in a balanced manner across species. We found that iPSC derived cardiomyocytes are able to recapitulate 50% of the interspecies gene expression differences identified between human and chimpanzee in primary post mortem heart tissues. Furthermore, we determined that cultured cardiomyocytes appear more similar to adult hearts than any other single tissue in their ability to recapitulate differences in gene regulation between human and chimpanzee.

sample_organism:
Pan troglodytes
Homo sapiens

platform_organism:
Pan troglodytes
Homo sapiens

overall_design: We differentiated multiple human (9) and chimpanzee (10) iPSC lines into cardiomyocytes (iPSC-CMs) for 15 days using a recently developed protocol (Burridge et al. 2014; Burridge et al. 2015). After replating at day 15, iPSC-CMs were cultured for 12 more days, resulting in a total differentiation time of 27 days. On days 20-27, iPSC-CMs were treated with T3 (methods), a subset of 5 human and 6 chimpanzee iPSC-CMs were cultured in parallel without T3 treatment. We harvested RNA from all source iPSC lines, iPSC-CMs (day 15), T3 treated and untreated iPSC-CMs (day 27) sample. We harvested RNA from an additional set of 5 human and 6 chimp T3 treated day 27 samples in a second batch that did not have a matched day 15 and (-) T3 set.  Finally, we collected RNA from flash frozen primary heart tissues (21 chimps and 11 humans).

first: Lauren

middle: E

last: Blake

first: Claudia

last: Chavarria

first: Yoav

last: Gilad


title: Consensus Molecular Subtype predicts differential vulnerability of colorectal cancer to the survivin suppressant YM155 I

status: Public on Jul 03 2018

city: Heidelberg

first: Tianzuo

last: Zhan

address: Im Neuenheimer Feld 580

country: Germany

institute: German Cancer Research Center

summary: Tumor heterogeneity is a major challenge to the treatment of colorectal cancer (CRC). Recently, a transcriptome-based classification was developed, segregating CRC into four consensus molecular subtypes (CMS) with distinct biological and clinical characteristics. Here, we applied the CMS classification on CRC cell lines to identify novel subtype-specific drug vulnerabilities. We combined publicly available transcriptome data from multiple resources to assign 159 CRC cell lines to CMS. By integrating results from large scale drug screens, we discovered that CMS1 cancer is highly vulnerable to the survivin suppressor YM155. We confirmed our results using an independent panel of CRC cell lines and demonstrate a 100-fold higher sensitivity of CMS1 lines. This vulnerability was specific to YM155 and not observed for commonly used chemotherapeutic agents. In CMS1 cancer, low concentrations of YM155 induced apoptosis and expression signatures associated with NFkappaB and ER stress mediated apoptosis signaling. Using a genome-wide CRISPR/Cas9 screen, we discovered a novel role of genes involved in LDL-receptor recycling as modulators of YM155 response in CMS1 CRC. Our work shows that combining drug response data with CMS classification in cell lines can reveal specific vulnerabilities and propose YM155 as novel CMS1 specific drug.

overall_design: Total RNA from human colorectal cancer cells treated with 10 nM YM155 or DMSO (control) for 24 h

first: Benedikt

last: Rauscher

first: Michael

last: Boutros


title: Consensus Molecular Subtype predicts differential vulnerability of colorectal cancer to the survivin suppressant YM155 II

summary:
Tumor heterogeneity is a major challenge to the treatment of colorectal cancer (CRC). Recently, a transcriptome-based classification was developed, segregating CRC into four consensus molecular subtypes (CMS) with distinct biological and clinical characteristics. Here, we applied the CMS classification on CRC cell lines to identify novel subtype-specific drug vulnerabilities. We combined publicly available transcriptome data from multiple resources to assign 159 CRC cell lines to CMS. By integrating results from large scale drug screens, we discovered that CMS1 cancer is highly vulnerable to the survivin suppressor YM155. We confirmed our results using an independent panel of CRC cell lines and demonstrate a 100-fold higher sensitivity of CMS1 lines. This vulnerability was specific to YM155 and not observed for commonly used chemotherapeutic agents. In CMS1 cancer, low concentrations of YM155 induced apoptosis and expression signatures associated with NFkappaB and ER stress mediated apoptosis signaling. Using a genome-wide CRISPR/Cas9 screen, we discovered a novel role of genes involved in LDL-receptor recycling as modulators of YM155 response in CMS1 CRC. Our work shows that combining drug response data with CMS classification in cell lines can reveal specific vulnerabilities and propose YM155 as novel CMS1 specific drug.
We performed expression profiling experiments in order to validate molecular subtypes for selected cell lines

overall_design: Total RNA from human colorectal cancer cells


title: Direct clonal expansion analyses of cardiomyocytes during development and injury using the Rainbow model

status: Public on Dec 23 2018

city: Los Angeles

first: Kathrin

last: Plath

state: CA

address: 615 Charles E. Young Drive South

department: Biological Chemistry

institute: UCLA

summary: αMHC marks a heterogenous population of cardiomyotes with varying proliferative potential

overall_design: αMHC+ single cells were isolated from αMHC-GFP mouse hearts at different embryonic and neonatal timepoints (E9.5, E12.5, and P1) for transcriptomic analysis using the Fluidigm C1 Single-Cell Auto Prep System

first: Konstantina-Ioanna

last: Sereti

first: Ngoc

middle: B

last: Nguyen

first: Paniz

last: Kamran

first: Peng

last: Zhao

first: Sara

last: Ranjbarvaziri

first: Shuin

last: Park

first: Shan

last: Sabri

first: James

middle: L

last: Engel

first: Kevin

last: Sung

first: Rajan

last: Kulkami

first: Yichen

last: Ding

first: Tzung

last: Hsiai

first: Jason

last: Ernst

first: Debashis

last: Sahoo

first: Hanna

last: Mikkola

first: M

last: Iruela-Arispe

first: Reza

last: Ardehali


title: Transcriptomic analysis of adult mouse hippocampal tissue in control and MeCP2 knockdown conditions

status: Public on May 15 2018

first: Ana

last: Oliveira

address: Im Neuenheimer Feld 364

department: Biology

institute: Heidelberg University

summary:
The overall goal of this study was to clarify the role of MeCP2 in adult cognition.
As one of the measures we analyzed gene expression changes associated with MeCP2 loss in the adult hippocampus. The analysis was performed in basal conditions and after exposure to a novel environment.
We report gene expression data of mouse adult hippocampal tissue in which MeCP2 has been knockeddown in both conditions.

overall_design:
Hippocampal mRNA profiles of 3 months old mice after delivery of a control shRNA sequence or a MeCP2-specific shRNA sequence by RNA-seq.
Profiles in basal conditions and after (30 minutes) exposure to a novel environment were obtained. Each condition is in quadriplicate.


title: Adipose depot differences in high fat fed mice

status: Public on Feb 28 2018

city: Lubbock

first: Naima

last: Moustaid-Moussa

state: TX

address: 1301 Akron Street

department: Nutritional Sciences & Obesity Research Institute

institute: Texas Tech University

type: Non-coding RNA profiling by high throughput sequencing

summary:
Purpose : To understand differences in microRNA (miRNA) signatures of different adipose tissue depots to gain mechanistic insight regarding their contribution to metabolic disorders in obesity.
Method : We performed small RNA-sequencing of brown, subcutaneous and visceral adipose depots from high fat diet-fed mice (mice were fed a 45% kcal fat diets from 5-6 weeks of age for 11 weeks). The main animal study reference: Kalupahana et al., J. Nutr, 2010
Results:Using the Gunaratne Next Generation pipeline (published in Creighton et al. 2009) miRNA expression profiles were identified. Counts of each unique read were normalized to total usable reads, and had 40 counts added. We mapped about 13.8 million sequence reads per sample to the Mus musculus genome (build mm 10). Altogether 1251 miRNAs were identified in three adipose tissues and out of which 246 showed differential expression with 1.25 or more fold change and  p value <0.05 in one or more of the pairwise comparisons of the 3 adipose depots. Hierarchical clustering, demonstrated that biological replicates behaved appropriately as they were clustered together. BAT exhibited a different gene/ miRNA expression pattern than the 2 other WATs (SAT and VAT).   SAT and VAT showed a closer relationship with each other than with BAT
Conclusion : High fat diet differentially regulate specific miRNAs expression in different adipose tissue depots

overall_design: MicroRNA profiles of brown, subcutaneous and visceral adipose tissues of 16-17 wk old wild type high fat diet induced obese C57L/6 mice were generated by small RNA sequencing, in triplicate, using Illumina Genome Analyzer II.

first: Nadeeja

middle: N

last: Wijayatunga

first: Mandana

last: Pahlavani

first: Kameswara

middle: R

last: Kottapalli

first: Prathibha

first: Latha

last: Ramalingam

first: Preethi

middle: H

last: Gunaratne

first: Cristian

last: Coarfa

first: Nishan

middle: S

last: Kalupahana


title: Transcriptional profile in human S. haematobium infection (II)

status: Public on Apr 30 2018

city: St. Louis

first: Makedonka

last: Mitreva

state: Missouri

address: 4444 Forest Park Ave

institute: McDonnell Genome Institute

summary: Genome-wide transcriptional survey in peripheral blood mononuclear cells (PBMCs) by RNA-Seq in schoolchildren living in an endemic area in Gabon, with and without Schistosoma haematobium infection before and after treatment with the anthelminthic drug praziquantel.

overall_design: 26 samples; paired pre- and post-treatment for S.haemotobium-infected individuals, plus controls

first: Lucja

last: Labuda

first: Ayola

last: Adegnika

first: Bruce

last: Rosa

first: John

last: Martin

first: Maria

last: Yazdanbakhsh


title: Synthetic lethal interactions and convergent biological effects underlie the mutual exclusivity of MDS-associated spliceosomal gene mutations

status: Public on Aug 13 2018

city: Seattle

first: Khrystyna

middle: Dilai

last: North

state: WA

address: 1100 Fairview Ave N

department: Basic Sciences Division

institute: Fred Hutchinson Cancer Research Center

summary: RNA splicing factor mutations constitute the most common class of alterations in myelodysplastic syndromes (MDS). These occur as heterozygous mutations at restricted residues in SF3B1, SRSF2, and U2AF1 in a mutually exclusive manner. The mutual exclusivity of spliceosomal mutations suggests synthetic lethal and/or convergent biological effects of these mutations; however, there is currently no functional evidence supporting either of these possibilities. Here we report that spliceosomal mutations, despite imparting distinct alterations on gene expression and splicing, are negatively selected for when co-expressed in the same cell or in a homozygous state. Co-expression of these mutations results in additive, rather than synergistic, effects on RNA splicing mechanisms. Despite disparate global effects on splicing, aberrant splicing of distinct kinases by mutant SF3B1 and SRSF2 results in hyperactivated NF-κB signaling. These data identify convergent biological consequences of splicing factor mutations and the functional basis for the mutual exclusivity and heterozygous nature of these mutations.

overall_design: To understand the functional basis of this apparent mutual exclusivity of RNA splicing factor mutations, we generated mice to permit inducible heterozygous expression of two of the most common mutations in RNA splicing factors (the SF3B1K700E/+ and SRSF2P95H/+ mutations) simultaneously (Mx1-Cre Sf3b1K700E/+ Srsf2P95H/+)

first: Robert

last: Bradley

first: Omar

last: Abdel-Wahab

first: Stanley

last: Lee


title: Amiloride, an old diuretic drug, is a potential therapeutic agent for multiple myeloma

status: Public on Sep 10 2018

city: Salamanca

first: Norma C.

last: Gutiérrez

state: Salamanca

address: Campus Miguel de Unamuno

department: Hematologia

institute: Centro de Investigación del Cáncer de Salamanca

summary: The introduction of novel therapeutic agents has considerably improved the median survival of patients with multiple myeloma (MM). However, the natural history of the disease is characterized by continuous relapses over time. As a consequence, the development of new drugs is still required to treat MM recurrence. Here, we report for the first time the potent anti-myeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure. Amilorideinduced apoptosis was observed in a broad panel of MM cell lines and in xenograft mouse models. Moreover, amiloride also had a synergistic effect when combined with dexamethasone and melphalan. RNA-seq experiments showed that amiloride not only significantly altered the level of transcript isoforms and alternative splicing events, but also deregulated the spliceosomal machinery. Additionally, disruption of the splicing machinery in immunofluorescence studies was associated with the inhibition of myeloma cell viability after amiloride exposure. Although amiloride was able to induce apoptosis in myeloma cells lacking p53 expression, activation of p53 signaling was observed in wild-type and mutated TP53 cells after amiloride exposure. On the other hand, the manageable toxicity profile of amiloride is well known and we did not find a significant systemic toxicity in mice treated with amiloride. Overall, our results provide a mechanistic rationale for the use of amiloride as an alternative treatment option for relapsed MM patients.

overall_design: Poly A+ RNA from KMS12-BM and JJN3 cells untreated or treated with amiloride or TG003 (0.1 mM, 0.4 mM, and 0.4 mM respectively) for 24 h was isolated and prepared for RNA-seq.

first: Elizabeta

last: Rojas

first: Luis

last: Corchete

first: Laura

last: San-Segundo

first: Juan

middle: F

last: Martínez-Blanch

first: Francisco

last: Codoñer

first: Teresa

last: Paíno

first: Ramón

last: García-Sanz

first: María

middle: V

last: Mateos

first: Enrique

last: Ocio

first: Irena

last: Misiewicz-Krzeminska

first: Norma


title: RNAseq analysis between mouse ESCs cultured in serum or plus the EZH2 inhibitor EPZ.

status: Public on Dec 01 2017

city: Edinburgh

first: J

last: Thomson

address: Crewe Road

department: IGMM

institute: University of Edinburgh

summary: RNAseq analysis between cell types. RNA extracted using Qiagen mini total RNA isolation protocols (Qiagen, Germany). Samples were treated with DNase (Ambion), and sample integrity verified on the Agilent Bioanalyser with the RNA Nano chip.  Illumina Tru-seq paired end strand specific sequencing (Illumina, USA) was carried out by on a NextSeq-550 sequencer (Edinburgh Clinical Research Facility, Western General Hospital, Edinburgh, Scotland, UK). 500ng of Total RNA underwent ribosomal RNA depletion (rRNA) prior to purification, fragmentation, random hexamer cDNA generation and purification with AMPure XP beads (Beckman-Coulter, USA). Multiple indexing adapters were ligated to ds cDNA with subsequent hybridisation onto flow cells, and DNA fragment enrichment by 15 cycle PCR for sequencing.  Completed libraries were quantified by qPCR using the KAPA Illumina Library Quantification Kit (Illumina, USA) before multiplexing in two equimolar pools and running on two flow cells on the Illumina NextSeq 550. The resulting FastQ files were mapped to the reference genome (mm9) using the Tophat alignment tool (V1) on Illumina Basespace software and reads per kilobase per million (RPKM) scores calculated.

overall_design: We carry out paired end, strand specific RNAseq prior to sequencing on NextSeq-550 sequencer to report on the transcriptional landscape of mouse ESC cultured either in serum alone or in serum plus the EZH2 inhibitor EPZ

first: John

middle: P

first: Ruchi

last: Shukla

first: Heidi

last: Mjoseng

first: Angie

last: Fawkes

first: Richard

last: Clark

first: Lee

last: Murphy

last: Meehan


title: Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis.

city: Adelaide

first: Susan

last: Woods

state: Select State

address: Level 5 South, SAHMRI building, North Terrace

department: School of Medicine

country: Australia

institute: The University of Adelaide

summary:
Objective: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases, and includes tumours that are amongst the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen activated kinase (MAPK) pathway gene, BRAF, and epigenetic modifications termed the CpG Island Methylator Phenotype (CIMP), leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein.
Design: We utilise organoid culture combined with CRISPR/Cas9 genome engineering, to sequentially introduce genetic alterations associated with serrated CRC and which regulate the stem cell niche, senescence and DNA mismatch repair.
Results: Targeted biallelic gene alterations were verified by DNA sequencing. Organoid growth in the absence of niche factors was assessed, as well as analysis of downstream molecular pathway activity. Orthotopic engraftment of complex organoid lines, but not BrafV600E alone, quickly generated adenocarcinoma in vivo with serrated features consistent with human disease. Loss of the essential DNA mismatch repair enzyme, Mlh1, led to microsatellite instability. Sphingolipid metabolism genes are differentially regulated in both our mouse models of serrated CRC and human CRC, with key members of this pathway having prognostic significance in the human setting.
Conclusion: We generate rapid, complex models of serrated CRC to determine the contribution of specific genetic alterations to carcinogenesis. Analysis of our models alongside patient data has led to the identification of a potential susceptibility for this tumour type.

overall_design: mRNA of engrafted tumours with different genetic alterations and adjacent normal colon tissue profiles were obtained with Illumina HiSeqTM 2500 system. Differential gene expression were analysed by pairwise comparison of tumour with different genetic lesions to normal colon.

first: Tamsin

last: Lannagan

first: Young

last: Lee

first: Tongtong

last: Wang

first: Jatin

last: Roper

first: Mark

last: Bettington

first: Lochlan

last: Fennell

last: Vrbanac

first: Lisa

last: Jonavicius

first: Roshini

last: Somachekar

first: Krystyna

last: Gieniec

first: Miao

last: Yang

first: Jia

middle: Q

last: Ng

first: Nobumi

last: Suzuki

first: Mari

last: Ichinose

first: Josephine

middle: A

last: Wright

first: Hiroki

last: Kobayashi

first: Tracey

last: Putoczki

first: Yoku

last: Hayakawa

first: Simon

last: Leedham

first: Helen

last: Abud

first: Ömer

last: Yilmaz

first: Julie

last: Marker

first: Sonja

last: Klebe

first: Pratyaksha

last: Wirapati

first: Siddhartha

last: Mukherjee

first: Sabine

last: Tejpar

first: Barbara

last: Leggett

first: Vicki

last: Whitehall

first: Deniel

last: Worthley


title: miRNA expression profile associated with response to Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis

status: Public on Nov 15 2017

city: Beijing

first: Yanqiong

last: Zhang

address: No 16, Nanxiaojie, Dongzhimennei

country: China

institute: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences

summary:
miRNA expression profile in peripheral blood mononuclear cells obtained from a discovery cohort
The discovery cohort includes12 RA patients (6 responders and 6 non-responders) treated with TwHF was detected by Affymetrix miRNA 4.0 arrays.

overall_design: To identify potential serum microRNA biomarkers, which are predictive of  rheumatoid arthritis patients' response to TwHF.


title: lncRNA and mRNA expression profiles associated with response to Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis

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

summary:
lncRNA and mRNA expression profiles in peripheral blood mononuclear cells obtained from a discovery cohort
The discovery cohort includes12 RA patients (6 responders and 6 non-responders) treated with TwHF were detected by Affymetrix EG1.0 array.

overall_design: To identify potential serum lncRNA and mRNA biomarkers, which are predictive of  rheumatoid arthritis patients' response to TwHF.


title: Pancreatic islets communicate with lymphoid tissues via exocytosis of insulin peptides

status: Public on Jul 18 2018

first: Pavel

last: Zakharov

state: MO

address: 660 S Euclid Ave Box 8118

department: Pathology and Immunology

institute: Wash.Univ in St. Louis

summary: A difference in the transcriptomes of 8F10 T cells sourced from the NOD (8F10-NOD) or B16A (8F10-B16A) hosts was analyzed. As a result we found a number of biological pathways upregulated in the 8F10-NOD T cells including oxidative phosphorylation (OXPHOS), Myc targets, fatty acid metabolism, mTOR complex 1 (mTORC1) signaling.

overall_design: T and B cell-depleted bone marrow stem cells from TCR alpha chain-deficient insulin peptide-specific 8F10 mice (CD45.2) were adoptively transferred into non-lethally irradiated NOD or B16A hosts (CD45.1). After 6 weeks of parking, the 8F10 T cells were FACS-sorted from inguinal lymph nodes of either host and subjected to RNA sequencing.

first: Xiaoxiao

last: Wan

first: Javier

last: Carrero


title: Transcriptional profile in human S. haematobium infection

status: Public on Jan 31 2018

first: Makedonka

last: Mitreva

overall_design: 14 samples; paired pre- and post-treatment for 4 S. haematobium-infected individuals, plus 3 controls

first: Lucja

last: Labuda

first: Ayola

last: Adegnika

first: Bruce

last: Rosa

first: John

last: Martin

first: Maria

last: Yazdanbakhsh


title: SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia [RNA-seq]

status: Public on Feb 22 2018

city: Essen

first: Ludger

last: Klein-Hitpass

address: Virchowstr. 173

department: Universitaetsklinikum

institute: Institut fuer Zellbiologie

summary: We identified novel recurrent genetic lesions in T-PLL affecting genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, HERC2). Mutations of the tumor suppressor gene SAMHD1 causing amino-acid exchanges or protein truncations as well as copy number variations in SAMHD1 were seen in 20% of cases.

overall_design: RNA sequencing (Illumina HiSeq 2500) of 10 index patients compared to 5 healthy donors (controls).

first: Patricia

last: Johansson


title: Gene expression profiling of wild type and BMPR1a-deficient CD4+ T cells

status: Public on Sep 21 2018

city: Columbus

first: Maciej

last: Pietrzak

state: OH

address: 1800 Cannon Drive, 340C Lincoln Tower

department: Department of Biomedical Informatics College of Medicine

institute: Ohio State University

summary: The goal of this study was to compare transcriptome (RNA-seq) of activated Bone Morphogenic Protein Receptor 1a sufficient and deficient CD4+ T cells. Naive wild type CD4+ T cells were also analyzed as reference.

overall_design: Three replicas of naive wild type, activated wild type and activated BMPR1a deficient CD4+ T cells were analyzed.

first: Piotr

last: Kraj


title: Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655 (RNA-seq data set)

city: Ulsan

first: Donghyuk

last: Kim

address: 50 UNIST-gil, Eonyang-eup, Ulju-gun

department: Department of Chemical Engineering

country: South Korea

institute: UNIST

summary: Transcriptional regulation enables cells to respond to environmental changes. Yet, among the estimated 304 candidate transcription factors (TFs) in Escherichia coli K-12 MG1655, only 185 have been experimentally characterized. Here we developed an integrated workflow that contains the prediction of TFs using machine learning and comprehensive experimental validation using a suite of genome-wide experiments. Applying this workflow we: 1) computationally identified 16 candidate genes encoding uncharacterized TFs; 2) confirmed that ten of these 16 are TF candidates that showed 255 DNA binding sites; 3) found high-confidence TF-binding sequence motifs for six of the ten TFs; 4) reconstructed the regulons of the ten TFs by determining gene expression change upon deletion of each TF; and 5) further determined the regulatory roles of three TFs (YdcI, YeiE and YiaJ) to be regulating acetate metabolism, iron homeostasis under iron limited condition, and utilization of L-ascorbate, respectively. Together, these results demonstrate how the integrated workflow can be used to discover, characterize, and elucidate regulatory functions of uncharacterized TFs. This workflow can be applied to less studied bacteria for systematic discovery and characterization of their transcriptional regulatory networks.

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: Expression profiling data for four uncharacterized transcription factor deletion strains were generated by RNA-seq, in duplicate

first: Ye

last: Gao

first: Ilyas

last: Kabimoldayev


title: Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655 (ChIP-exo data set)

type: Genome binding/occupancy profiling by high throughput sequencing

platform_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: Identification of genome-wide bindings for ten uncharacterized transcripton factors, including 20 replicates


title: IRF3 and type I interferons fuel a fatal response to myocardial infarction [single cell RNA-Seq]

status: Public on Nov 06 2017

city: La Jolla

first: Kevin

last: King

address: 9500 Gilman Dr. MC 0412

department: Medicine and Bioengineering

institute: UC San Diego

summary: Interferon regulatory factor 3 (IRF3) and type I interferons (IFNs) protect against infections1 and cancer2, but excessive IRF3 activation and type I IFN production cause autoinflammatory conditions such as Aicardi?Goutières syndrome3,4 and STING-associated vasculopathy of infancy (SAVI)3. Myocardial infarction (MI) elicits inflammation5, but the dominant molecular drivers of MI-associated inflammation remain unclear. Here we show that ischemic cell death and uptake of cell debris by macrophages in the heart fuel a fatal response to MI by activating IRF3 and type I IFN production. In mice, single-cell RNA-seq analysis of 4,215 leukocytes isolated from infarcted and non-infarcted hearts showed that MI provokes activation of an IRF3?interferon axis in a distinct population of interferon-inducible cells (IFNICs) that were classified as cardiac macrophages. Mice genetically deficient in cyclic GMP-AMP synthase (cGAS), its adaptor STING, IRF3, or the type I IFN receptor IFNAR exhibited impaired interferon-stimulated gene (ISG) expression and, in the case of mice deficient in IRF3 or IFNAR, improved survival after MI as compared to controls. Interruption of IRF3-dependent signaling resulted in decreased cardiac expression of inflammatory cytokines and chemokines and decreased inflammatory cell infiltration of the heart, as well as in attenuated ventricular dilation and improved cardiac function. Similarly, treatment of mice with an IFNAR-neutralizing antibody after MI ablated the interferon response and improved left ventricular dysfunction and survival. These results identify IRF3 and the type I IFN response as a potential therapeutic target for post-MI cardioprotection.

overall_design:
We report the application of inDrop single cell RNA-Seq profiling to the analysis of the infarcted mouse heart 4 days after permanent coronary ligation in wild type (Sample 1) and IRf3-/- mice (Sample 2) as well as comparable section of wild type mouse heart with no myocardial infarction (Sample 3)
Wild type mice and IRF3-/- mice underwent left anterior descending coronary artery occlusion by permanent suture ligation. After 4 days, hearts were flushed with cold saline, and infarct tissue was collected, stained with DAPI, flow sorted to isolate single cells, and subjected to inDrop barcoding per published protocol (Zilionis et al, Nature Protocols 2016, doi:10.1038/nprot.2016.154)


title: IRF3 and type I interferons fuel a fatal response to myocardial infarction

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

overall_design: Refer to individual Series


title: THOC2  RNAi microarray in A375 cell line

status: Public on Jul 01 2018

city: Nanjing

first: Yan

last: Wang

state: Jiangsu province

address: 12 Jiangwangmiao Street

institute: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College

summary: Little is known about THOC2 that affect melanoma cell growth,proliferation and invasion siRNAs may be used to address the role of individual gene in these processes. THOC2 RNAi were used  to gain a comprehensive overview of all genes involved in cell growth, proliferation, migration and other cellular processes.

overall_design: Well-known melanoma cell lines  A375, M14 were transduced with the siRNA oligos for  48h. Totel RNA was extracted and RNAs were hybridized to Agilent SurePrint G3 Human Gene Expression v3 (8*60K,Design ID:072363)


title: IRF3 and type I interferons fuel a fatal response to myocardial infarction [bulk RNA-Seq]

overall_design:
We report the application of bulk RNA-Seq profiling to the analysis of day 4 myocardial infarction.
Wild type mice and IRF3-/- mice underwent left anterior descending coronary artery occlusion. After 4 days, hearts were perfused and infarct tissue was collected, and it was subjected to bulk RNA-Seq.


title: Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655


title: An Atlas of Chromatin Accessibility in the Adult Human Brain

status: Public on Jun 21 2018

city: New York

first: Panos

last: Roussos

state: NY

address: 1470 Madison Ave

department: Psychiatry

institute: Icahn School of Medicine at Mount Sinai

summary: The majority of common genetic risk variants associated with neuropsychiatric disease are non-coding and are thought to exert their effects by disrupting the function of cis regulatory elements (CREs), including promoters and enhancers. Within each cell, chromatin is arranged in specific patterns to expose the repertoire of CREs required for optimal spatiotemporal regulation of gene expression. To further our understanding of the complex mechanisms that modulate transcription in the brain, we utilized frozen postmortem samples to generate the largest human brain and cell type-specific open chromatin dataset to date. Using the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq), we created maps of chromatin accessibility in 2 cell types (neurons and non-neurons) across 14 distinct brain regions of 5 individuals. Chromatin structure varies markedly by cell type, with neuronal chromatin displaying higher regional variability than that of non-neurons. Among our findings is an open chromatin region (OCR) specific to neurons of the striatum. When placed in the mouse, a human sequence derived from this OCR recapitulates the cell-type and regional expression pattern predicted by our ATAC-seq experiments. Furthermore, differentially accessible chromatin overlaps with the genetic architecture of neuropsychiatric traits and identifies differences in molecular pathways and biological functions. By leveraging transcription factor binding analysis, we identify protein coding and long noncoding RNAs (lncRNAs) with cell-type and brain region specificity. Our data provides a valuable resource to the research community and we provide this human brain chromatin accessibility atlas as an online database “Brain Open Chromatin Atlas (BOCA)” to facilitate interpretation.

overall_design: Open chromatin profiles in neuronal and non-neuronal nuclei from 14 brain regions of 5 control samples

last: Fullard

first: Mads

last: Hauberg

first: Jaroslav

last: Bendl


title: Single-cell RNA-seq reveals differentiation hierarchy of normal human bone marrow and a distinct transcriptome signature of aneuploid cells

status: Public on Oct 13 2017

city: Bethesda

first: Shouguo

state: MD

address: 9000 Rockville Pike

department: NHLBI

institute: National Institutes of Health

summary: In order to get a better understanding of the gene signature of aneuploid cells, we applied single cell RNA sequencing on human bone marrow cells from healthy donors and patients with bone marrow failure and cytogenetic abnormalities. We chacterized normal hemaopoiesis as binary differentiation and identified aneuploid cells from patient samples.

overall_design:
Single Cell RNA-seq
The processed 'normalizedExpression.csv' file includes data for cells which pass the quality controls.

first: Xin

last: Zhao


title: RNA Misplicing in Fuchs Endothelial Corneal Dystrophy II

status: Public on Mar 23 2018

city: Rochester

first: Xiaojia

last: Tang

state: MN

address: 200 1st ST SW

institute: Mayo Clinic

summary: RNA-Seq splicing data from the  corneal endothelia of FECD patients and controls reveal hundreds of differential alternative splicing events. These include events previously characterized in the context of myotonic dystrophy type 1 and epithelial-to-mesenchymal transition, as well  as splicing changes in genes related to proposed mechanisms of FECD pathogenesis.

overall_design: RNA-Seq was used to compare corneal endothelial specimens from subjects with Fuchs endothelial corneal dystrophy. Control samples from normal subjects were also provided.

first: Michael

last: Fautsch

first: Keith

last: Baratz

first: Eric

middle: D

last: Wieben


title: Global gene expression analysis of the response of Salmonella Enteritidis to egg-white exposure

status: Public on Jun 09 2017

city: Rennes

first: Florence

last: Baron

address: 65 rue de Saint Brieuc

country: France

institute: Agrocampus Ouest

summary: Transcriptional profiling of Salmonella Enteritidis to egg-white exposure at 45°C for 7 min, 25 min and 45 min

sample_organism: Salmonella enterica subsp. enterica serovar Enteritidis

overall_design: 3 biological replicates, 2 technical replicates and one or two probes / gene

first: F

first: S

last: Bonnassie

first: M

last: Alabdeh

last: Cochet

last: Nau

first: C

last: Guérin-Dubiard

last: Gautier

last: Jan

last: Andrews


title: Defining the Essential Function of Yeast Hsf1 Reveals a Compact Transcriptional Program for Maintaining Eukaryotic Proteostasis

status: Public on Jan 11 2018

city: Chicago

first: David

last: Pincus

institute: University of Chicago

summary: We used the conditional chemical genetics approach known as “anchor away” (AA) to rapidly inactivate the essential yeast transcription factor Hsf1. We coupled Hsf1-AA to RNA-seq and NET-seq to define the genes whose expression depends on Hsf1 and performed Hsf1-3xFLAG-V5 ChIP-seq to validate direct targets. We also carried out a number of other perturbations to yeast stress pathways to show that most of the gene expression changes during heat shock are Hsf1-independent but depend on PKA signaling and the Msn2/4 general stress transcription factors. Finally, we generated RNA-seq in mouse ES cells and MEFs in wild type and hsf1-/- cells to define HSF1 targets in murine cells.

sample_organism:
Saccharomyces cerevisiae
Mus musculus

platform_organism:
Saccharomyces cerevisiae
Mus musculus

overall_design: yeast RNA-seq samples, 4 yeast NET-seq samples, 8 murine RNA seq samples and 1 yeast ChIP-seq sample

first: Vlad

last: Denic


title: MAPK/ERK activation determines a distinct transcriptional program following neuronal activity in the murine hippocampus

status: Public on Jun 14 2017

city: Berlin

first: Nils

last: Blüthgen

address: Chariteplatz 1

department: Institute of Pathology

institute: Charite Universitätsmedizin Berlin

summary: Kanate was used to induce seizures in mice, and gene expression in the hippocampus was measured Using MEK inhibitors, MEK-dependent gene expression was assessed.

overall_design: Untreated controls were measured in biological quadruplicates, three mice were used for each condition (3 hippocampi for vehicle controls, kinate induced seizures, MEK inhibitor treated, and MEK inhibitor plus kinases induced seizures)

first: Guido

last: Hermey


title: Integrative analysis of RNA Polymerase II and transcriptional dynamics upon Myc activation [RNA-seq]

status: Public on Aug 23 2017

city: Milano

first: Stefano

last: de Pretis

address: Via Olgettina, 58

department: Center for Omics Sciences

country: Italy

institute: IRCCS San Raffaele Institute

summary: Over-expression of the Myc transcription factor causes its widespread interaction with regulatory domains in the genome, but leads to the up- and down-regulation of discrete sets of genes. The molecular determinants of these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis of transcription and mRNA dynamics following Myc activation in proliferating mouse fibroblasts, based on chromatin immunoprecipitation, metabolic labeling of newly synthesized RNA, extensive sequencing and mathematical modeling. Transcriptional activation correlated with the highest increases in Myc binding at promoters. Repression followed a reciprocal scenario, with the lowest gains in Myc binding. Altogether, the relative abundance (henceforth, “share”) of Myc at promoters was the strongest predictor of transcriptional responses in diverse cell types, predominating over Myc’s association with the co-repressor Miz1. Myc activation elicited immediate loading of RNAPII at activated promoters, followed by increases in pause-release5, while repressed promoters showed opposite effects. Gains and losses in RNAPII loading were proportional to the changes in the Myc share, suggesting that repression by Myc may be largely indirect, owing - at least in part - to competition for limiting amounts of RNAPII. Secondary to the changes in RNAPII loading, the dynamics of elongation and pre-mRNA processing were also rapidly altered at Myc regulated genes, leading to the transient accumulation of partially or aberrantly processed mRNAs. Altogether, our results shed light on how over-expressed Myc alters the various phases of the RNAPII cycle and the resulting transcriptional response.

overall_design: Time course profiling of 4sU-labeled and total RNA upon Myc activation in 3T9-MycER mouse fibroblasts

first: Theresia

last: Kress

first: Bruno

last: Amati

first: Mattia

last: Pelizzola


title: Obesity Alters the Composition and the Activity of the Hematopoietic Stem Cell Compartment Through Dysregulation of Gfi1 Expression (Bulk RNA-Seq)

status: Public on Nov 23 2017

city: Cincinnati

first: Nathan

last: Salomonis

address: 3333 Burnet Avenue

department: Biomedical Informatics

institute: Cincinnati Children's Hospital

summary: Obesity is a chronic organismal stress that disrupts multiple systemic and tissue-specific functions. Here, we describe the effects of established obesity on the activity of the hematopoietic stem cell (HSC) compartment. We show that obesity promotes the selection of a quiescent HSC subset primed for activation, leading to aberrant hematopoietic stress responses. We establish that the transcription factor Gfi1 is a key regulator of the HSC fate in obesity as its increased expression in obesity induces their abnormal activity. We demonstrate that these dysregulations are initially triggered by the chronic oxidative stress associated with obesity. Once acquired, we show that the impact of obesity on HSCs is long lasting and cannot be reversed by weight loss or transplantation. These results demonstrated that obesity promotes irreversible changes on the long-term fitness of the HSC compartment, a phenomenon that is likely to contribute to the hematopoietic dysregulations observed in obese patients.

overall_design: RNA seq to identify the gene expression changes associated with obesity in murine CD150+CD48-LSK HSCs.  In 3 independent experiments, 20,000 HSCs were isolated from WT and leptin-receptor mutant mice (db/db) at 4 months of age.

first: Jung-Mi

last: Lee

first: Bryan

last: Goddard

first: Vinothini

last: Janakiram

first: Ashwini

last: Hinge

first: Marie-Dominique

last: Filippi

first: Kakajan

last: Komurov

first: Bruce

last: Aronow

first: Jose

last: Cancelas

first: H

last: Grimes

first: Damien

last: Reynaud


title: H2AZ Orchestrates Neural Progenitor Cell Proliferation and Differentiation via Setd2-mediated H3K36me3 Modification [RNA-seq]

status: Public on May 29 2017

first: Jianwei

last: Jiao

state: Beijing

address: 1 Beichen West Road

department: State Key Laboratory of Reproductive Biology

institute: Institute of Zoology, Chinese Academy of Sciences

summary:
Purpose:To gain a deeper insight into how H2AZ regulates embryonic neurogenesis, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by H2AZ deletion at E12.
Methods: Total RNA was extracted from E12 telencephalic tissue of H2AZcKO and H2AZfl/fl mice. Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina HiSeq 2500 platform in Annoroad Genomics.
Results: Approximately approximately one thousand transcripts showed differential expression between the H2AZfl/fl and H2AZcKO brain, with a fold change ≥1.5 and p value <0.05. Gene ontology (GO) analysis showed that the down-regulated genes were enriched in the terms related to transcription and cortex development, such as regulation of transcription, cerebellar cortex formation, forebrain development, and cerebellum development. Up-regulated genes showed a significant enrichment of terms involved in negative regulation of cell differentiation, neuron migration, and cognition. These results reflected the importance of H2AZ in cortical development.
Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding how a disruption in the H2AZ gene may contribute to cortical development.

overall_design: Total RNA was extracted from E12 telencephalic tissue of H2AZcKO and H2AZfl/fl mice and generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.

first: Tianjin

last: Shen


title: Shifting the optimal stiffness for cell migration

status: Public on May 23 2017

city: Minneapolis

first: David

middle: J.

last: Odde

address: 312 Church St. SE

department: Biomedical Engineering

institute: University of Minnesota

summary: Cell migration is central to many biological processes including embryonic development, wound healing, and cancer progression. Cell migration is sensitive to environmental stiffness, and many cell types exhibit a stiffness optimum at which migration is maximal. Here we present a cell migration simulator that predicts a stiffness optimum that can be shifted by altering the number of active molecular motors and clutches. This prediction is verified experimentally by comparing cell traction and F-actin retrograde flow for two cell types with differing amounts of active motors and clutches: embryonic chick forebrain neurons (ECFNs; optimum ~1 kPa) and U251 glioma cells (optimum ~100 kPa). In addition, the model predicts, and experiments confirm, that the stiffness optimum of U251 glioma cell migration, morphology, and F-actin retrograde flow rate can be shifted to lower stiffness by simultaneous drug inhibition of myosin II motors and integrin-mediated adhesions.

overall_design: To collect enough mRNA for expression analysis on different stiffnesses, U251 cells were cultured on large polyacrylamide gels covering the surface of a one well chamber glass slide (Lab-Tek 154453). After one day of culture on the gels, mRNA was purified from the cells using an RNeasy Mini Kit (Qiagen 74104). mRNA samples were then analyzed at the University of Minnesota Genomics Center using a HumanHT-12 BeadChip microarray (Illumina BD 103-0204). mRNA was collected from three U251 glioma cultures each on 4.6, 20, and 200 kPa PAGs, as well as plastic for a total of 12 mRNA samples. mRNA counts from the BeadChip were compared to a published list8 of cell migration genes to identify the most likely contributors to the motor-clutch model in U251 glioma cells (Extended Data Table 1). The expression levels on the different stiffnesses were compared to each other to identify any significant expression differences among the stiffnesses.


title: S. cerevisiae RNA-seq in wild-type and sir2Δhst1Δ strains

status: Public on Feb 28 2017

city: Houston

first: Lisha

last: Zhu

address: 7000 fannin st

institute: UT Health Science Center at Houston

summary: RNA-seq to identify differentially expressed genes in the sir2Δhst1Δ strain compared to wild-type

overall_design: The sequenced strains are matα with hmr deleted to avoid pseudodiploid conditions. Differential expression in the sir2Δhst1Δ strain was used to avoid any complementation in a single deletion strain. This experiment represents two technical replicates for each strain

first: Kristen

last: Humphrey

first: Tao

last: Liu

first: Laura

last: Rusche


title: Improved LCL to iPSC reprogramming: RNA Analysis of LCLs, reprogrammed iPSCs, and differentiated NSCs reveal potential regulatory and functional processes involved in these cellular transitions.

status: Public on Feb 11 2017

city: McAllen

first: Satish

last: Kumar

state: Texas

address: 5300 North L Street (MBMRF-2.219)

department: Division of Human Genetics & South Texas Diabetes and Obesity Institute, UTRGV School of Medicine

institute: University of Texas Rio Grande Valley

summary:
Purpose: There exists a rich bio-resource of numerous lymphoblastoid cell line (LCL) repositories generated from a wide array of patients, many of them with extensive genotypic and phenotypic data already generated. We have developed a highly efficient LCL to induced pluripotent stem cells (iPSC) reprogramming method and performed whole genome mRNA and miRNA analysis to understand mechanistic changes that take place at the transcriptome and cellular functional level during reprogramming of LCLs into iPSCs and further differentiation.
Methods: Applying our optimized protocol which utilizes episomal plasmids encoding pluripotency transcription factors and mouse p53DD - p53 carboxy-terminal dominant-negative fragment and commercially available reprogramming media, we reprogrammed six LCLs into iPSCs and then differentiated them into neural stem cells (NSC). The LCLs, their reprogrammed iPSCs and differentiated NSC (n=18) were sequenced for mRNA and smallRNA on an illumina HiSeq 2500. Differential gene expression analysis was performed between LCL-iPSC and iPSC-NSC pairs in combination with functional annotations and Ingenuity® Pathway Analysis (IPA).
Results: Our LCL reprogrammed iPSCs express the majority of genes and miRNAs known to contribute to stemness in human ESCs. The functional enrichment analysis of the up-regulated genes and activation of human pluripotency pathways in the reprogrammed iPSCs showed that the generated iPSCs have a transcriptional and functional profile very similar to that of human ESCs. The reprogrammed iPSCs also showed the potential to differentiate into cells of all three germ layers. Significantly, the transcriptomic effect of EBV encoded oncoproteins which were very pronounced in LCLs, were significantly inhibited in reprogrammed iPSCs.  The transcriptomic and functional enrichment analysis of the NSC differentiated from the reprogrammed iPSCs showed that they share a functional profile of self-renewing NSCs.
Conclusions: We have been able to develop a MEF feeder free protocol for efficient and reproducible reprogramming of LCLs into iPSC. In addition our comprehensive analysis of genome wide miRNA and mRNA of LCLs, their reprogrammed iPSC and differentiated NSCs provides important documentation of differentially expressed genes and miRNAs and their functional consequences during LCL to iPSC reprogramming and NSC differentiations that were previously unknown.

overall_design: Whole genome mRNA and miRNA profiles of six LCLs, their reprogrammed iPSCs and differentiated NSCs (n=18) were generated by deep sequencing using the illumina HiSeq 2500.

first: Joanne

last: Curran

middle: C

last: Glahn

first: John

last: Blangero


title: Characterization of murine pulmonary interstitial macrophages at steady state

status: Public on Mar 13 2017

city: Denver

first: Claudia

last: Jakubzick

state: Colorado

address: 1400 Jackson St

department: Pediatrics

institute: National Jewish Health

summary:
In this study we demonstrate that the lung mononuclear phagocyte system comprises three interstitial macrophages (IMs), as well as alveolar macrophages (AMs), dendritic cells and few extravascular monocytes.
Through cell sorting and RNAseq analysis we were able to identify transcriptional similarities and differences between the three pulmonary IM subtypes, with reference to the more well-characterized alveolar macrophage

overall_design:
Pulmonary Interstitial and Alveolar macrophages were FACS sorted from the lungs of steady state 8-10 week old B6 mice, in triplicate. Extracted RNA was examined by RNAsequencing.

The tar archive GSE94135_jakubzick_2019*tar available at the foot of this page contains the supplementary processed data used for comparisons with data in GSE132911. Data were processed as described in GSE132911.

first: Sophie

last: Gibbings

first: Thomas

last: Danhorn

first: Sonia

middle: M

last: Leach


title: Expression of mRNAs and lncRNAs in cancer revealed by microarray

status: Public on Feb 09 2017

city: Beijing

first: Jiao

last: Yuan

address: 15 Datun Road, Chaoyang District

institute: Institute of Biophysics, Chinese Academy of Sciences

summary: Long noncoding RNAs (lncRNAs), which are noncoding RNAs (ncRNAs) with length more than 200 nucleotides (nt), have been demonstrated to be involved in various types of cancer. In this study, a custom designed microarray platform covering both mRNAs and lncRNAs was applied to tumor tissues of gastric, colon, liver and lung. 316 and 157 differential expressed (DE-) protein coding genes and lncRNAs common to these four types of cancer were identified respectively.

overall_design:
The expression profiles of cancer and adjacent normal tissues form 76 patients (20 with gastric cancer, 20 with colon cancer, 16 with liver cancer and 20 with lung cancer) were studied by microarray and a set of lncRNAs as well as PCGs were identified as potential biomarkers general to different types of cancer.

Please note that experiments were performed technically as dual channel (eg, Cy3 and Cy5-labeled samples hybridized to the same array) but the results were processed though they are single channel (total 152 sample records for 76 raw data files; Cy3 and Cy5 signals are calculated). Therefore, raw data file for each sample was duplicated and linked to each paired sample records. For example, the raw data files for the 'Normal_tissue_Colon_cancer_patient_01'(Cy5) sample and 'Cancer_tissue_Colon_cancer_patient_01'(Cy3) sample are identical.

first: Haiyan

last: Yue

first: Jianjun

last: Luo

first: Runsheng

last: Chen


title: Serum microRNA profile of human type 1 diabetes mellitus

city: Wuhan

first: Li

state: Hubei

address: 1095 Jiefang Road

department: Department of Endocrinology

institute: Huazhong University of Science and Technology

summary: To evaluate whether serum micoRNAs can be biomarkers for diagnosis of type 1 diabetes mellitus, we analyzed the serum microRNA expression profiles in 6 patients with new-onset type 1 diabetes mellitus and 6 age- and gender-matched healthy controls. A difference was observed in 31 miRNAs between the patients and controls (fold change ≥ 2, P < 0.05)

overall_design: 6 serum samples from patients with new-onset type 1 diabetes mellitus and 6 serum samples from age- and gender-matched healthy controls

first: Jianping

last: Weng


title: Network analysis identifies temporal regulation of transcriptomic and physiological responses to early drought perception in Brassica rapa.

status: Public on Aug 19 2017

city: Hanover

first: Kathleen

last: Greenham

state: NH

address: 78 College St.

department: Biological Sciences

institute: Dartmouth College

summary: The temporal control of gene expression leads to time of day effects on metabolism and physiology. To identify early transcript level changes occurring in the Brassica rapa oil-type variety R500 during initial drought perception we performed an RNA-seq time course experiment. Leaf tissue was collected from well-watered and drought treated 18 day old plants grown under 14h light at 22°C/10h dark at 18°C every 4h over 2 days with 2 biological replicates at every time point. We collected physiology measurements at every time point and observed dynamic time of day changes in photosynthetic rate, stomatal conductance, non-structural carbohydrates and PSII efficiency. Using a co-expression network approach, phase dependent gene modules were correlated with the physiology data to reveal temporally regulated drought responses. This study provides insight into the transcriptome level responses occurring in the plant in the early stages of drought perception before visible signs of stress occur.

overall_design: Brassica rapa subsp. trilocularis (R500) plants were grown under 14h light at  22°C and 10h dark at 18°C for 16 days after sowing (DAS) before water was withheld from half the plants. Starting at 18 DAS leaf tissue was collected from well-watered and droughted plants every 4 h for 2 days starting 1h after dawn. We collected 2 replicates for every time point.

first: Carmela

last: Guadagno

first: Malia

last: Gehan

first: Todd

last: Mockler

first: Cynthia

last: Weinig

first: Brent

middle: E

last: Ewers

first: C

last: Robertson McClung


title: Comparison of plant responses upon P. palmivora infection in wild type (A17) line and in the api mutant

status: Public on Dec 01 2016

city: Cambridge

middle: Robert

last: Rey

address: Bateman street

institute: Sainsbury Laboratory Cambridge University

summary: api mutant has been shown to be more resistant to P. palmivora than the A17 wild type (WT) line. In this study we want to compare both WT and mutant plant responses to the pathogen as well as their respective control transciptomes in order to identify api-dependent gene networks. Following germination, A17 or api plants grown in vitro on Agar medium were inoculated (or not = controls) with a P. palmivora zoospores (10^5/ml) and harvested 16 hours after inoculation. Three independent repeats were performed.

platform_organism:
Sinorhizobium meliloti
Medicago sativa
Medicago truncatula

overall_design: 12 arrays - Medicago; normal vs disease comparison,normal vs ems mutant comparison,time course

first: T

first: S

last: Schornack


title: Expression profiles of genes central to tumour metastasis in human triple-negative breast cancer cells

status: Public on Dec 28 2016

city: Oxford

first: Zhichao

last: Ai

address: Roosevelt Drive

department: Kennedy Institute of Rheumatology

institute: University of Oxford

summary: Immortalized human breast cancer cell lines, MDA-MB-231(ATCC® HTB-26™) and MDA-MB-468(ATCC® HTB-132™), were analyzed via RT-qPCR for transcript expression of several classes of protein factors including cell adhesion, ECM components, cell cycle, cell growth and proliferation, apoptosis, transcription factors and regulators and other genes related to tumor metastasis.

overall_design: Human donor monocyte-derived macrophages(MDMs), MDA-MB-231(ATCC® HTB-26™) and MDA-MB-468(ATCC® HTB-132™) were maintained in the respective medium, and MDA-MB-231 and MDA-MB-468 were stimulated with the conditioned mediums generated from MDMs polarised by MDA-MB-231 or MDA-MB-468 cell conditioned medium for 24 hours. Toal RNAs were extracted and expression profiles were generated for each sample by RT² Profiler™ PCR Arrays(Qiagen/SA Biosciences).

first: Luca

last: Cassetta


title: An ancient symbiotic fungal gene network revealed by comparative transcriptomics [Rirregularis_symbiotic_tissues]

status: Public on Sep 29 2017

city: Castanet-Tolosan

first: Christophe

last: Roux

address: Chemin de Borde Rouge

institute: University of Toulouse/CNRS

summary:
Purpose: The recent publication of the fungal mutualist R. irregularis genome facilitated transcriptomic studies. We here wanted to understand the large host range of this fungus, throught its gene regulation in divergent plants
Methods: mRNA from Medicago truncatula (legume), Brachypodium distachyon (grass) and Lunularia cruciata (liverwort) in association with R. irregularis were sequenced. Reads were mapped on the genome assembly with the software CLC workbench. Fungal gene expression in the different plants was compared to extra radical hyphae as a control.
Results: 529, 486 and 523 R. irregularis gene were highly overexpressed (fold change >5 ; FDR <0,05 and experimental value > l10l) in M. truncatula, B. distachyon and L. cruciata, respectively. Among those genes, 262 were induced in all hosts. qPCR validation on 32 genes supported these results in an extended set of hosts (Zea mays spp parviglumis, Pisum sativum, Marchantia paleacea).

sample_organism:
Medicago truncatula
Brachypodium distachyon
Lunularia cruciata
Rhizophagus irregularis

overall_design: Extra radical and intra radical hyphae in association with 3 phylogenetically divergent plants were produced and gene expression in the different plants were compared to gene expression in extra radical hyphae.

first: Mathilde

last: Malbreil


title: Human naive pluripotent stem cells exhibit X chromosome dampening and X-inactivation

status: Public on Oct 21 2016

city: Los Angeles

first: Kathrin

last: Plath

state: CA

address: 615 Charles E. Young Drive South

department: Biological Chemistry

institute: UCLA

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Expression data from mouse liver

status: Public on Aug 25 2016

city: Sydney

first: Samantha

last: Solon-Biet

state: NSW

address: The University of Sydney

department: Charles Perkins Centre

institute: University of Sydney

summary:
Livers from 15 month old mice mainatined on one of 25 different diets varying in protein, carbohydrate, fat (P,C,F) and energy content were analysed. Energy content was categorised as low (8kJ/g), medium (13kJ/g) or high (17kJ/g) Mice were placed on diet from 3 weeks of age and a subset culled for various analyses. The rest of the cohort was allowed to live out their natural life to assess lifespan.
We used microarrays to details the global programme of gene expression as a result of changes in dietary macronutrient composition and intake.

overall_design: 30 cages of male and female mice per diet were used in this experiment. One mouse from each cage was randomly selected for harvest at 15 months old, while the others were left to age naturally. RNA from mouse livers were extracted and hybridized on Affymetrix microarrays

first: Victoria

last: Cogger

first: R

last: Gokam

first: D

middle: G

last: Le Couteur

middle: J

last: Simpson


title: Comparison of the wild-type strain H99W with the hva1∆, hva1∆+HVA1 and a Galleria-passaged strain

status: Public on Aug 11 2016

city: Murfreesboro

first: Erin

last: McClelland

state: TN

address: 1301 East Main Street, P.O. Box 60

department: Biology

institute: Middle Tennessee State University

summary: Changes in gene expression of the serotype A wild-type strain H99W with the hva1∆ (8), hva1∆+HVA1 (8-15) or a Galleria-passaged (P15) strain were examined during log-phase growth at 37 ºC.

overall_design: Analysis included two replicates of each comparison with a Cy3-Cy5 dye swap


title: Transcriptional profiling of Myotonic dystrophy muscle and heart

status: Public on Sep 29 2016

city: Gainesville

first: Eric

middle: T

last: Wang

state: FL

address: 2033 Mowry Rd

institute: University of Florida

summary: Autopsy and biopsy muscle and heart tissue was collected from consented human subjects with and without confirmed myotonic dystrophy type 1, myotonic dystrophy type 2, or Duchenne muscular dystrophy. RNA was isolated for preparation of RNAseq libraries and sequenced on the Illumina platform.

overall_design: 126 samples, comprising 103 distinct individuals, were sequenced. In some cases, several tissues from the same individual were obtained (the anonymized patient identifier can be used to link these). Samples were obtained from 4 different centers around the world (anonymized center identifiers can be used to track these).

first: Daniel

last: Treacy

first: Thomas

first: Joseph

last: Estabrook

first: John

last: Day

first: David

last: Brook

first: Charles

last: Thornton

last: Cooper

last: Housman

first: Chris

middle: B

last: Burge


title: Human naïve pluripotent stem cells exhibit X chromosome dampening and X-inactivation (RRBS)

summary: Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. We found that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Similar to cells of the blastocyst, resulting naive cells exhibited two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment and exit from the naïve state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X-chromosome dosage compensation processes in early human development: X-dampening and X-inactivation. Furthermore, the naïve state reset Xi abnormalities of primed hESCs, providing cells better suited for downstream applications. However, naïve hESCs displayed differences to the embryo because XIST expression was predominantly mono-allelic instead of bi-allelic, and X-inactivation was non-random, indicating the need for further culture improvement.

overall_design: Eight total independent samples were analyzed. All are from UCLA1 hESC line. Independently processed samples from same culture condition are called replicates and labedled as rep1/rep2. All clones are from 5iLAF culture condition.

first: Anna

last: Sahakyan

first: Rachel

last: Kim

first: Constantinos

last: Chronis

first: Shan

last: Sabri

first: Giancarlo

last: Bonora

first: Thorold

middle: W

last: Theunissen

first: Edward

last: Kuoy

first: Justin

last: Langerman

first: Amander

last: Clark

first: Rudolf

last: Jaenisch


title: UTX controls lineage-specific epigenetic program of iNKT cells

status: Public on Jul 12 2016

city: boston

first: Luca

last: Pinello

state: MA

address: 450 brookline avenue

institute: Dana-Farber Cancer Institute

summary: NKT cells are innate-like lymphocytes that protect against infection, autoimmune disease, and cancer. However, little is known about epigenetic regulation of iNKT cell development. Here, we show that the H3K27me3 histone demethylase UTX is an essential cell-intrinsic factor that controls an iNKT lineage specific gene expression program and epigenetic landscape in a demethylase activity dependent manner. UTX-deficient iNKT cells exhibit impaired expression of iNKT signature genes due to a decrease in activation-associated H3K4me3 and an increase in repressive H3K27me3 marks within the promoters that UTX occupies. Notably, we identified JunB as a novel regulator of iNKT development that partners with UTX to establish an iNKT lineage specific gene expression program. Moreover, we demonstrate that UTX-mediated regulation of super-enhancer accessibility is a key mechanism for iNKT lineage commitment. These findings uncover how UTX regulates iNKT cell development through multiple epigenetic mechanisms.

overall_design: Chromatin profiles of Wild type and UTX-KO iNKT cells were generated by ChIP-seq and ATAC-seq using Illumina platform.

first: Semir

last: Beyaz


title: Human naïve pluripotent stem cells exhibit X chromosome dampening and X-inactivation (RNA-Seq)

first: Kathrin

last: Plath

overall_design: Fourteen total independent samples were analyzed. Ten are from UCLA1 hESC line and four are from UCLA4 hESC line. Independently processed samples from same culture condition are called replicates and labedled as rep1/rep2, where available. All UCLA1 clones are from 5iLAF culture condition, and all UCLA4 samples are from 5iLAF culture condition.


title: Identification and characterization of HVA1 (CNAG_02591) in Cryptococcus neoformans

first: Erin

last: McClelland

platform_organism:
Cryptococcus neoformans
Cryptococcus deneoformans


title: Modeling the Neuropathology of Tuberous Sclerosis with Human Stem Cells Reveals a Role for Inflammation and Angiogenic Growth Factors

status: Public on Jul 25 2016

city: Basel

first: Jitao David

last: Zhang

address: Grenzacherstrasse 124

department: Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel

country: Switzerland

institute: F. Hoffmann-La Roche


title: Modeling the Neuropathology of Tuberous Sclerosis with Human Stem Cells Reveals a Role for Inflammation and Angiogenic Growth Factors [Treatment]

summary: Tuberous sclerosis complex (TSC) is a rare genetic disease characterized by mTOR hyperfunction induced benign tumor growths in multiple organs and neurological symptoms. Because the molecular pathology is highly complex and the etiology poorly understood we employed a defined human neuronal model with a single mTOR activating mutation to dissect the disease-relevant molecular responses driving the neuropathology. TSC2 deficient neural stem cells showed severely reduced neuronal functional maturation and characteristics of astrogliosis instead. Accordingly, transcriptome analysis uncovered an inflammatory response and increased metabolic activity, while ribosome profiling revealed excessive translation of ribosomal transcripts and higher synthesis rates of angiogenic growth factors. Treatment with mTOR inhibitors corrected translational alterations but not transcriptional dysfunction. These results extend our understanding of the molecular pathophysiology of TSC brain lesions, and suggest phenotype-tailored pharmacological treatment strategies.

overall_design: Rapamycin, AZD-8055, and DMSO were given to two TSC+/+ cell lines and two TSC-/- cell lines after six weeks of differentiation. Cells are harvested after 3 hours treatment and are subject to ribosome profiling and RNA-seq analysis.

first: Nils

last: Grabole

first: Jitao

first: Stefan

last: Aigner

first: Nadine

last: Ruderisch

first: Veronica

last: Costa

first: Felix

last: Weber

first: Michel

last: Theron

first: Nikolaos

last: Berntenis

first: Olivia

last: Spleiss

first: Martin

last: Ebeling

first: Gene

last: Yeo

first: Ravi

last: Jagasia

last: Kiialainen


title: Microarray gene expression profiles of peripheral blood mononuclear cells (PBMC) in patients with  obstructive sleep apnea and primary snoring

status: Public on Dec 31 2015

city: Kaohsiung

first: yungche

last: chen

address: 123, Ta-Pei Rd. Niao-Sung Dist.

country: Taiwan

institute: Kaohsiung Chang Gung Memorial Hospital

summary: Therefore, we extended our investigation into OSA patients with long-term continuous positive airway pressure (CPAP) treatment, hypertension, or excessive daytime sleepiness (EDS) by analyzing whole-genome gene expression profiles of PBMC in three comparisons: (1) treatment-naïve moderate to very severe OSA patients versus subjects with primary snoring; (2) moderate to very severe OSA patients with hypertension or EDS versus those without hypertension or EDS, respectively; (3) treatment-naïve very severe OSA patients versus those receiving at least one year of adequate CPAP treatment.

overall_design: We analyzed whole-genome gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients with long-term continuous positive airway pressure (CPAP) treatment (VSOC).

first: Yung-Che

last: Chen

first: Kuang-Den


title: The diatom Thalassiosira pseudonana grown at [normal and elevated CO2] x [normal and elevated light]

status: Public on Nov 06 2015

city: Seattle

first: Justin

last: Ashworth

address: 401 Terry Ave N

institute: Institute for Systems Biology

summary: Transcriptomic profiling of the diatom Thalassiosira pseudonana at normal and elevated CO2 levels and at normal and elevated light levels. Common reference total RNA (Agilent Quick-Amp Cy3-labeled) was used in all arrays as an internal standard.

overall_design: Triplicate batch cultures grown at normal (~400ppm) and elevated (~800ppm) CO2 levels, both at i) normal or ii) elevated light levels. Samples were taken during a) exponential and b) stationary growth during all growth experiments. Result: 72 total transcriptomic measurements.

first: Monica

last: Orellana

first: Nitin

middle: S

last: Baliga


title: Genome-Wide Transcriptome and Chromatin Analysis of Aspergillus nidulans Primary and Secondary Metabolism Reveals Crucial Function for a Kdm5-Family Histone Demethylase.

status: Public on Apr 01 2016

city: Tulln

first: Harald

last: Berger

state: NOE

address: Konrad-Lorenzstraße 43

department: DAGZ

country: Austria

institute: Universität f. Bodenkultur Wien

summary: Histone posttranslational modifications (HPTMs) are involved in regulating the synthesis of fungal bioactive compounds. The exact molecular mechanisms of the silencing/activation of secondary metabolism (SM) clusters by these epigenetic events however are not yet fully understood. This work applies a combined approach of quantitative mass spectrometry (LC-MS/MS) and chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) to identify the chromatin landscape in two metabolic states: primary and secondary metabolism. Furthermore, to link the particular chromatin states to the expression of condition specific genes, genome wide transcriptome (RNA-seq) was performed. Strikingly, we found that silent A. nidulans SM clusters are free of repressive H3K9me3 though this heterochromatic mark forms distinguished peaks flanking the many SM clusters. In addition, silent SM clusters do not contain detectable levels of activating histone marks such as H3K4me3, H3K36me3 or H3Ac, which, to some extent, are established upon activation of the clusters. In order to investigate the function of dynamic H3K4 methylation/demethylation in transcription, we characterized the KdmB- Jarid1 family histone demethylase. The in vitro assay using heterologously expressed KdmB showed that it is an active demethylase; moreover, MS/MS as well ChIP-seq approaches revealed that it targets H3K4me3 in vivo mediating transcriptional repression. KdmB positively regulates the expression of 40% of A. nidulans SM genes and this function appears to be independent of its demethylase activity. Our bioinformatics approach revealed two states of H3K4me3 in A. nidulans genome: loci with low levels of this mark are more disposed to differential expression in response to environmental clues, while the genes marked by high H3K4me3 levels are constitutively transcribed in our experimental conditions. Taken together our data reveal important role of H3K4 methylation/demethylation in transcription regulation. Furthermore, this study presents the first genome-wide map of H3K4me3, H3K9me3, H3K36me3 and H3Ac in A. nidulans in different metabolic conditions.

overall_design: Two strains, wild type and kdmB deletion, at two conditions, growth at primary (17h) and secondary (48h), were analysed. Each sample was replicated.Wild type samples can be found in GSE63672.

first: Agnieszka

last: Gacek

first: Takahiko

last: Sasaki

first: Kathrin

last: Wittstein

first: Clemens

last: Gruber

first: Zachary

last: Lewis

first: Joseph

last: Strauss


title: Olfactomedin 4 serves as a marker for disease severity in pediatric Respiratory Syncytial Virus (RSV) infection

status: Public on Jun 06 2015

city: Wageningen

first: Dick

middle: de

last: de Ridder

address: Droevendaalsesteeg 1

department: Plant Sciences

country: Netherlands

institute: Wageningen University

summary: Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. In conclusion, by combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.

overall_design: Samples were taken of 26 patients with acute RSV infections, divided into mild (n=9), moderate (n=9) and severe (n=8) disease. From moderate and severe diseased patients recovery samples were obtained as well.

first: Kim

middle: H

last: Brand

first: Ingle

last: Ahout

first: Angela

last: van Diepen

first: Yunlei

last: Li

first: Marike

last: Zaalberg

first: Arno

last: Andeweg

first: Nel

last: Roeleveld

first: Ronald

last: de Groot

first: Adilia

last: Warris

first: Peter

last: Hermans

first: Gerben

last: Ferwerda

first: Frank

last: Staal


title: Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans

status: Public on Feb 22 2017

city: Durham

first: Sunil

last: Suchindran

state: NC

address: 101 Science Drive

department: Center for Applied Genomics and Precision Medicine

institute: Duke University

summary: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. We report the first gene expression analysis of the human host response to experimental challenge with ETEC.

overall_design: Gene expression analysis performed on whole peripheral blood RNA samples from subjects in whom severe symptoms developed and a subset of those who remained asymptomatic.

first: William

last: Yang

first: Bradley

middle: P

last: Nicholson

first: Micah

last: McClain

first: Thomas

last: Burke

first: Geoffrey

last: Ginsburg

first: Clayton

last: Harro

first: Subhra

last: Chakraborty

first: David

last: Sack

first: Christopher

last: Woods

first: Ephraim

middle: L

last: Tsalik


title: Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome

status: Public on May 03 2016

city: Salamanca

first: Jesús

middle: Maria

last: Hernández-Rivas

state: Salamanca

address: Paseo San Vicente, 88-182

department: Hematology

institute: Hospital Universitario de Salamanca, Universidad de Salamanca-CSIC

type: Genome variation profiling by genome tiling array

overall_design: aCGH Nimblegen array performed on 265 samples of ALL at diagnosis

first: Maribel

last: Forero-Castro

first: Cristina

last: Robledo

first: Rocio

last: Benito

first: María

last: Abaigar

first: Ana

last: Africa-Martín

first: Maryam

last: Arefi

first: José

last: Fuster

first: Natalia

last: De las Heras

first: Juan

middle: N

last: Rodríguez

first: Jonathan

last: Quintero

first: Susana

last: Riesco

first: Lourdes

last: Hermosín

first: Ignacio

last: De la Fuente-Graciani

first: Isabel

last: Recio

first: Jordi

last: Ribera

first: Jorge

last: Labrador

last: Alonso

first: Carmen

last: Olivier

first: Magdalena

last: Sierra

first: Martha

last: Megido

first: Luis

middle: A

last: Corchete-Sánchez

first: Juana

last: Ciudad-Pizarro

last: García


title: Expression data from WT and transgenic plants overexpressing cold-induced transcription factors

status: Public on Feb 28 2015

city: Beltsville

first: Sunchung

last: Park

address: 10300 Baltimore ave, Bldg001

department: ARS-NEA

institute: USDA -ARS

summary: Our goal in this study is to understand the regulation mechanism of genes including CBF regulon in low temperature. We addressed these issues by overexpressing the transcription factors encoded by genes that are rapidly induced in parallel with the CBF genes.  The results show that the low temperature regulatory network is highly interconneted.

overall_design: Global gene expression profile of the transgenic plants overexpressing TFs was compared with that of WT plants

first: Chinmei

last: Lee

first: Michael

last: Thomashow


title: Single-Cell RNA-seq Defines the Three Cell Lineages of the Human Blastocyst

status: Public on Aug 26 2015

city: London

first: paul

last: blakeley

address: 215 Euston Road

institute: Crick Institute

summary: Here we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human-specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. For example, we identify several genes exclusively expressed in the human pluripotent epiblast including the transcription factor KLF17. Key components of the TGF-β signaling pathway including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1 are also enriched in the human epiblast. Intriguingly, inhibition of TGF-β signaling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although key trophectoderm factors Id2, Elf5, and Eomes are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we also identify genes with conserved expression dynamics including Foxa2/FOXA2, which we show is restricted to the primitive endoderm in both human and mouse embryos. Comparisons of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. Our analysis highlights significant differences in human preimplantation development compared to mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells.

overall_design: Single-Cell RNA-seq

first: Paul

last: Blakeley

first: Kathy

last: Niakan


title: Biphasic GISTs reveal the early mechanisms in GIST high-grade transformation

status: Public on Dec 01 2015

city: Taipei

first: Cher-wei

last: Liang

address: 7 Chung-Shan S. Rd.

department: Pathology

institute: National Taiwan University Hospital

summary: To study the very early changes in high-grade transformation of gastrointestinal stromal tumors (GISTs), 17 biphasic GISTs, with a transitional status in which low-grade and high-grade parts coexist, were collected from 263 continuous cases (6.5%). Nucleic acids of each part were retrieved for gene expression profiling.

overall_design: By definition, biphasic GISTs contained two populations of neoplastic cells that were (1) morphologically different, either in abrupt or gradual transition to the other, and (2) showed a dramatic change in mitotic activity, which was defined as either (a) one population had ≤ 5 mitoses per 5 mm2 (AJCC G1) and the other had > 5 mitoses per 5 mm2 (AJCC G2), or (b) both populations were AJCC G1, but the difference in mitotic activity was equal to or more than 3 per 5 mm2, or (c) both populations were AJCC G2, but the low-grade part was in the range of > 5 and ≤ 10 mitoses per 5 mm2 and the high-grade part exceeded it by equal to or more than 5 mitoses per 5 mm2. In each case, selected low-grade area, high-grade area and normal smooth muscle area (as control) were manually microdissected. RNA was extracted with the RecoverAll™ Total Nucleic Acid Isolation Kit FFPE (Life Technologies, Taipei, Taiwan).

first: Jen-Chieh


title: Next Generation Sequencing Facilitates Quantitative Analysis of Vitis flower Wild Type and the domesticated Vitis Transcriptomes

status: Public on Jan 26 2015

city: Lisboa

first: Margarida

last: Rocheta

address: Tapada da ajuda

country: Portugal

institute: Instituto Superior de Agronomia

summary:
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived flower development transcriptome profiling (RNA-seq) of two subspecies
Methods: Flower mRNA profiles of wild-type (WT) four developmental stages and the same stages of Vitis vinifera subp vinifera  were generated by deep sequencing using Illumina. Initial quality assessment was based on data passing the Illumina Chastity filtering. Subsequently, reads containing adapters and/or PhiX control signal were removed using an in-house filtering protocol. The second quality assessment was based on the remaining reads using the FASTQC quality control tool version 0.10.0. qRT–PCR validation was performed using EvaGreen assays.
Results: Using an optimized data analysis workflow, we mapped about 13 to 19 million sequence reads per Vitis sample, 50 bp in length equivalent to 1.5 Gb of total sequence data by each sample. The exception was male stage G (M_G) were only 7 to 8 million sequence reads were obtained. Five genes (VvTFL1, VvLFY, VvAP1, Vv AP3, VvPI), related to flowering development, were used to validate RNA-Seq data and to test for data reproducibility through qRT–PCR. The coefficient of correlation (r) obtained between the log2 of RPKM (RNA-Seq) versus log2 of mRNA average number (RT-qPCR), varied from ≈ 0.97 (VvTLF) to ≈ 0.73 (VvPI) indicating a good correlation between both techniques and thus validating our RNA-Seq results.
Conclusions: Our study represents the first detailed transcriptome analysis of four Vitis flower developmental stages, with the same individual, in three genders, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and accurate quantitative and qualitative evaluation of mRNA contentper developmental stage. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.

sample_organism:
Vitis vinifera
Vitis vinifera subsp. sylvestris

overall_design: Flowering mRNA profiles of four developmental stages of Vitis wild type (WT) and the domesticated Vitis were generated by deep sequencing using Illumina HiSeq 2500.

first: Miguel

last: Ramos

first: João

last: Coito

first: Helena

last: Silva

last: Cunha

first: Manuela

last: Costa


title: Expression data from WT (Ws-2), CBF1,2,3, and CBF2Δc (a truncated CBF2) overexpression

summary:
CBF1, CBF2 and CBF3 regulons comprise nearly identical gene sets
The vast majority of CBF2 regulon genes were down-regulated less that 50% by overexpression of CBF2Δc, a truncated version of CBF2

overall_design: We used Affymetrix GeneChips to examine the CBF regulons of plants overexpressing CBF1, CBF2, CBF3 and a truncated version of CBF2, CBF2Δc.

first: Sarah

last: Gilmour


title: Comparative transcriptome profiling of human epidermis keratinocyte stem cells (KSC) versus keratinocyte progenitors (KP)

status: Public on May 06 2015

city: Evry

first: Nicolas

middle: O

last: FORTUNEL

address: 2 Rue Gaston Crémieux

department: Institute of Cellular and Molecular Radiobiology (iRCM)

institute: CEA - INSERM U967

summary: To characterize the global transcriptome of human keratinocyte stem cells (KSC) and keratinocyte progenitors (KP), primary basal keratinocyte subpopulations enriched in quiescent stem cells [Itg-α6bright / Trf-Rdim] or in cycling progenitors [Itg-α6bright / Trf-Rbright] were purified by flow cytometry from human skin samples. Sorted keratinocytes were then seeded in culture plates and maintained in culture medium overnight (15 hours), and genome-wide transcriptome analysis of these two subpopulations was directly performed, in order to globally maintain the initial phenotypes. After RNA preparation, gene profiling was performed using oligonucleotide microarrays (26068 probes). LOWESS normalisation was applied.  Keywords: epidermis, keratinocyte stem cells, progenitors, transcriptome, stemness

overall_design: Dye-swap hybridization were performed. Slides were scanned with a Genepix 4000 microarray scanner (Axon Instruments, Molecular devices, Sunnyvale, CA). For each hybridized spot, the Cy3 and Cy5 fluorescence values were obtained by using Genepix Pro 4.0 software (Axon Instruments) and were saved as a result file

first: Walid

last: Rachidi

first: Gilles

last: Lemaitre

first: Pierre

last: Vaigot

first: Franck

last: Amiot

first: Michèle

last: Martin


title: Unique Patients from the Genomics of Pediatric SIRS and Septic Shock Investigators (GPSSSI)

status: Public on May 12 2015

city: Stanford

first: Timothy

last: Sweeney

state: California

address: 1265 Welch Road, MSOB

department: Biomedical Informatics

institute: Stanford University

type:
Expression profiling by array
Third-party reanalysis

summary: This dataset is composed of the unique patients (276; at the Day 1 timepoint) that are present in the six other GEO datasets published by Hector Wong and the Genomics of Pediatric SIRS and Septic Shock Investigators. This dataset thus includes all unique patients from GSE4607, GSE8121, GSE9692, GSE13904, GSE26378, and GSE26440. These are only from the Day 1 timepoint.

overall_design: The original studies examined pediatric patients admitted to the ICU, who were later classified as either SIRS (non-infectious) or Sepsis or Septic Shock (infectious). There is also a group of healthy controls. Although the original studies examine patients at both ICU day 1 and ICU day 3, here we have only aggregated ICU day 1 patients. All samples here were downloaded as .CEL files and re-normalized together using gcRMA using R package 'affy'.  The normalized data can be found on the series record and contains the gcRMA normalized expression values.

first: Hector

middle: R

last: Wong


title: Human naïve pluripotent stem cells exhibit X chromosome dampening and X-inactivation (single cell RNA-Seq)

status: Public on Oct 21 2016

city: Los Angeles

first: Kathrin

last: Plath

address: 615 Charles E. Young Drive South

institute: UCLA

overall_design: Differentiated naïve human embryonic stem cells and naïve human embryonic stem cells at different passages (Exp1 for late passage, Exp2 for early passage) were subjected to single cell RNA sequencing by the Fluidigm C1 Single-Cell Auto Prep System.

first: Anna

last: Sahakyan

first: Rachel

last: Kim

first: Constantinos

last: Chronis

first: Shan

last: Sabri

first: Giancarlo

last: Bonora

first: Thorold

last: Theunissen

first: Edward

last: Kuoy

first: Justin

last: Langerman

first: Amander

last: Clark

first: Rudolf

last: Jaenisch


title: Gene Expression Comparing Col to WS to Identify conserved cold-responsive Affymetrix signatures

status: Public on Dec 31 2014

city: Raleigh

first: Colleen

last: Doherty

address: 128 Polk Hall CB7622

department: Biochemistry

institute: North Carolina State University

summary:
Gene expression Arabidopsis 24h cold-treated, 4c, seedlings to identify a *gold-standard* set of cold-responsive transcripts. Most of the CBF overexpression lines are in WS, therefore, it is necessary to identify a consistent set of transcripts that are detectible as cold-induced on the ATH1 platform for both WS and Columbia, so that appropriate comparisons can be made to determine the effects of low temperature in CBF overexpressing or loss of function plants in a WS background and an attempt can be made to compare the results of altered CBF function to published microarray studies.  We aimed to identify a set of *gold-standard* cold responsive transcripts that were induced in multiple different experiments performed by different researchers and were detectible in both the WS and Col-0 ecotypes.  This series contributes the 24h cold-treated WS ecotypes, along with additional Col-0 cold-treated and control samples for normalization purposes.

Keywords: Expression profiling by array

overall_design: Col-0 and WS seedlings were sown on Gamborg's media with 0.7% agar, stratified for 3d, and grown in continuous low light (60-80 microE) at 22C, for 10 days and either moved to a new 22C chamber or transferred to a 4C chamber. After 24h tissue was harvested and frozen in liquid nitrogen.  Whole seedlings (including root tissue) were taken from the plate).

first: Michael

last: Thomashow


title: Yeast X-Chromosome Associated Protein 5 (Xap5) Functions with H2A.Z to Suppress Aberrant Transcripts

status: Public on Jul 01 2014

city: Davis

first: Shajahan

last: Anver

address: 1002 LSA, One Shields Av

department: Plant Biology

institute: University of California Davis

type: Genome binding/occupancy profiling by array

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

overall_design: Refer to individual Series

first: Assen

last: Roguev

first: Martin

last: Zofall

first: Nevan

last: Krogan

first: Shiv

middle: I

last: Grewal

first: Stacey

last: Harmer


title: Yeast X-Chromosome Associated Protein 5 (Xap5) Functions with H2A.Z to Suppress Aberrant Transcripts [RNA-seq]

summary: Functional characterization of the Xap5 protein using epistatic genetic interaction analysis (E-MAP), RNA-seq and ChIP-chip along with other growth experiments.

overall_design: wild type and mutant cells were grown at 37C in EMM50 and RNA was extracted from exponentially growing cells. Strand specific libraries were constructed with random primers. Ribo zero was used to remove r-RNA. For ChIP-chip Agilent 60mer array was used to analyze DNA recovered by chromatin immunoprecipitation of Xap5 from fission yeast culture.


title: Gene expression profiling of non-invasion and invasion NFPAs

status: Public on Dec 01 2013

city: BEI JING

first: JIE

last: FENG

address: TIANTAN XILI 6, CHONGWEN DISTRICT

institute: BEIJING NEUROSURGICAL INSTITUTE

summary:
The application of gene expression profiling is to investigate the pathogenesis of aggressive NFPAs.
And to identify biomarkers that could play a key role in aggressive behavior of NFPAs

overall_design: Gene expression was measured among pituitary glands,  non-invasion NFPAs and invasion NFPAs

first: Jie

last: Feng

first: Li

middle: Q

last: Hong

first: Ya

middle: Z

last: Zhang