7188 results for "({!join from=dataset_studies to=id v=$q1}) OR ("transcriptome" OR "RNA-seq" OR "rna sequencing" OR "rna-sequencing")"

in 194.11 milliseconds.

• RNAseq of blood, fat and muscle samples from 45,X, 46,XX, 46,XY and 47,XXY

  Samples of blood, muscle and fat were collected from individuals with TS (n = 33) and KS (n = 22) and from male (n = 16) and female (n = 44) controls. The RNA-seq libraries were multiplexed paired-end sequenced on an Illumina Novaseq 6000 (100 bp) and subjected to initial quality control using FastQC (BAbraham Bioinformatics). In addition to trimming of low-quality ends, adaptor removal was conducted using Trim Galore with default settings (BAbraham Bioinformatics).

  Dataset EGAD00001010052

• G-SAM: Transcriptional Evolution of Glioblastomas Treated With Standard of Care

  Collection of mostly matching primary and recurrent glioblastoma RNA-seq sample pairs, also matching with an earlier DNA sequencing study

  Dataset EGAD00001007860

• Identification of differentially expressed protein-coding genes in HCC and adjacent non-cancerous tissues

  Twenty samples were collected in pairs, i.e., HCC tissue and adjacent non-cancerous tissue. The collected tissue samples were stored in liquid nitrogen. First, 50 mg of tissue was lysed in TRIzol (Invitrogen) to extract RNA following the manufacturer’s instructions. Next, ribosomal RNA was depleted using a RiboZero Gold kit (Epicentre Bio-technologies). RNA integrity was assessed with an Agilent Bioanalyzer 2100. An RNA-Seq library was generated with the rRNA-depleted samples using an Illumina standard RNA Sample Prep kit according to the manufacturer’s instructions. The library was subsequently sequenced on an Illumina HiSeq2500 as 125-bp paired-ends with approximately 300-bp size selection.

  Dataset EGAD00001003397

• Genomic Advances in Sepsis (GAinS): RNA-seq

  Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. This cohort comprises a subset of patients enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 34 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected on the first, third and/or fifth day following ICU admission. RNA was extracted from leukocytes isolated at the bedside using LeukoLOCK kits. We have previously identified sepsis response signatures (SRSs), transcriptomic endotypes that are associated with differential early mortality (Davenport et al, Lancet Respir Med, 2016; Burnham et al, AJRCCM, 2017) and response to treatment in a clinical trial (Antcliffe et al, AJRCCM, 2018). We generated RNA sequencing data on 903 samples, including 134 samples repeated from our previously released microarray data. Libraries were prepared using NEB Ultra II Library Prep kits (Illumina) and sequenced on a NovaSeq 6000. Reads were aligned to the reference genome (GRCh38) using STAR and gene counts quantified using featureCounts (annotation Ensembl v99). Counts were TMM-normalised and log-transformed. Following QC, processed data were available on 864 samples from 667 unique patients.

  Dataset EGAD00001008730

• Single Cell Analysis of Pulmonary Fibrosis

  Pulmonary fibrosis is a heterogenous syndrome in which fibrotic scar replaces normal lung tissue. We performed massively parallel single-cell RNA-Seq on lung tissue from eight lung transplant donors and eight patients with pulmonary fibrosis. Combined with in situ RNA hybridization, with amplification, these data provide a molecular atlas of disease pathobiology. We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to non-overlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. Analysis of a cryobiopsy specimen from a patient with early disease supports the clinical application of single-cell RNA-Seq to develop personalized approaches to therapy.

  Study phs001750

• Defining and Overcoming Intrinsic T Cell Dysfunction to Enable Pediatric Immunotherapy

  T-cells from 71 children and young adults with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy were analyzed. These T-cells represent the pre-manufacture T-cells that were subsequently used for CAR T manufacture. Bulk RNA-Seq was performed on sorted T-cell subsets for all patients, in addition to CITE-Seq and single-cell ATAC-Seq on a subset of 6 patients. The primary clinical outcome was duration of B-cell aplasia, a surrogate measure of functional CAR T-cell persistence. From these data, molecular signatures associated with long and short-term CAR T-cell persistence were identified. This data submission includes bulk RNA-Seq, CITE-Seq, and single-cell ATAC-Seq data from this study.

  Study phs002323

• The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas

  Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the central nervous system TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to the impaired circulation of cerebrospinal fluid resulting in hydrocephalus and raised intracranial pressure in patients with TSC. Currently, surgical resection and mTORC1 inhibitors are the recommended treatment options for patients with SEGA. Here, we performed RNA-Seq and small RNA-Seq on SEGAs (n=19) and periventricular controls (n=8) to gain a better understanding of the underlying molecular basis of SEGAs, so that novel treatment targets could be identified.

  Study EGAS00001003787

• Human transcriptomic (RNA-Seq) and epigenomic (ATAC-Seq) data of early B-cell lineage (bulk and single-cell) DAC

  Dac EGAC00001003265

• 20200417_PNET_methylation_paper

  Illumina platform RNA-seq data from 47 Pancreatic neuroendocrine tumour samples

  Dataset EGAD00001006063

• UTSW KCP DAC

  This DAC manages access to WES and RNA-Seq data from studies approved under the IRBs of KCP principal investigators.

  Dac EGAC50000000203

• UROMOL 2020 - RNA-seq data for validation

  Total RNAseq data from 47 patients with NMIBC.

  Study EGAS00001005050

• IMpower133 subtype assignments

  This dataset contains subtype assignments for 271 tumor samples profiled by RNA-seq.

  Dataset EGAD00001006926

• Urothelial Cancer - Genomic Analysis to Improve Patient Outcomes and Research (UC-GENOME): A Bladder Cancer Advocacy Network (BCAN)-Led Collaborative Research Pilot Study

  UC-GENOME is a real-world cohort of patients with metastatic urothelial carcinoma (UC). The study consisted of two co-equal aims: 1) to provide targeted DNA sequencing for clinical decision making at no cost to patients; and 2) to create a resource for collaborative translational science including a clinically annotated biobank. The submitted data represents the foundational analysis of 218 patients accrued at 7 academic medical centers. The analysis includes 176 patients with both targeted DNA sequencing and RNA sequencing. The genomic data was combined with clinical variables to model response to chemotherapy and immune checkpoint inhibitors (ICI). Due to additional sharing restrictions, data from one site can be found in phs003094.

  Study phs003066

• Inhibition of CDK4/6 Promotes CD8 T Cell Memory

  Inhibitors of Cyclin-Dependent Kinase 4 and 6 (CDK4/6) have been recently deployed for the treatment of advanced breast cancer. Despite their success, the mechanism of action of these drugs is unclear. In mice, treatment with a CDK4/6 inhibitor improve T cell memory responses and protect mice against tumor rechallenge. We aimed to identify the correlates of this finding in human subjects. In this study, blood was collected from 5 breast cancer patients before and during treatment with the CDK4/6 inhibitors abemaciclib or palbociclib. Blood was also collected from 2 breast cancer patients who did not receive a CDK4/6 inhibitor. Recently activated CD8 T cells (CD45RO+ CD45RA+) were sorted and subjected to single-cell RNA sequencing.

  Study phs002448

• Urothelial Cancer - Genomic Analysis to Improve Patient Outcomes and Research (UC-GENOME): a Bladder Cancer Advocacy Network (BCAN)-Led Collaborative Research Pilot Study - for Samples Collected at Johns Hopkins

  UC-GENOME is a real-world cohort of patients with metastatic urothelial carcinoma (UC). The study consisted of two co-equal aims: 1) to provide targeted DNA sequencing for clinical decision making at no cost to patients; and 2) to create a resource for collaborative translational science including a clinically annotated biobank. The submitted data represents the foundational analysis of 218 patients accrued at 7 academic medical centers. The analysis includes 176 patients with both targeted DNA sequencing and RNA sequencing. The genomic data was combined with clinical variables to model response to chemotherapy and immune checkpoint inhibitors (ICI).The larger dataset for this study can be found in dbGaP study phs003066.

  Study phs003094

• Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

  Mechanisms of acquired resistance to immune checkpoint inhibitors (ICIs) are poorly understood. The purpose of this study was to investigate whether alterations in genes encoding components of the HLA Class I antigen processing and presentation machinery or interferon signaling pathways play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Whole exome sequencing was performed on tumor samples collected from patients with advanced non-small cell lung cancer at the time of resistance to PD-1 axis inhibitors and on available matched pre-treatment and normal samples. Patient-derived xenografts successfully established from the ICI-resistant samples were also exome sequenced. Additionally, RNA sequencing was performed on cases with sufficient tissue.

  Study phs001464

• Single Cell Genomic Analysis of Lymphoma

  Our study aimed to define the extent of heterogeneity between anatomically separated tumor manifestations in follicular lymphoma at single-cell resolution. We subjected single-cell suspensions derived from nodal, synchronously-acquired fine needle aspirations from two distinct tumor sites to high-throughput microfluidics-based single-cell RNA sequencing. By comparing the relative composition of the tumor subpopulations between the two tumor sites, we found that some patients can exhibit site-to-site differences. While the overall composition of the tumor microenvironment did not differ significantly between sites, we did detect a specific correlation between site-to-site tumor heterogeneity and T follicular helper cell abundance. Our study demonstrates the significant limitations of a solitary biopsy in defining the full scope of a patient's disease.

  Study phs002188

• 1. Identidication of molecular biological mechanism associated with the development and prognosis of uterine cancer, uterine sarcoma, and endometrial hyperplasia / 2. Identification of molecular biological mechanism associated with the development of endometriosis and malignant transformation, ovarian cancer, fallopian tubal cancer, peritoneal cancer, and other malignant tumors in gynecological organs

  To clarify the biological difference between clear cell carcinoma and other histological subtypes in ovarian carcinomas by comparing copy number variants, and to identify molecular subtypes and carcinogenesis in clear cell ovarian carcinomas by whole-exome sequencing and RNA-sequencing. Then, characterize high-grade serous carcinomas by NGS-based, integrative genomic analyses, with focus on homologous recombination deficiency, molecular subtypes, prognostic factors and effectiveness of PARP inhibitor. Based on the results of whole-exome sequencing, an investigator-initiated, phase 2 clinical trial will be conducted to evaluate the efficacy and safety of the PARP inhibitor olaparib in HRD-positive cases.

  Study JGAS000789

• Identification of potential blood biomarkers for early diagnosis of Alzheimer���s disease through immune landscape analysis

  Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer���s disease (AD). Recent genetic studies have reported on associations between AD risk genes and immunity. Here, we obtained samples and data from 317 AD, 432 MCI, and 107 cognitively normal (CN) subjects and investigated immune-cell type composition and immune clonal diversity of T-cell receptor (TRA, TRB, TRG, and TRD) and B-cell receptor (IGH, IGK, and IGL) repertoires through bulk RNA sequencing. Our prognosis prediction model using the potential blood-based biomarkers for early AD diagnosis, which combined two immune repertoires (IGK and TRA), WDR37, and clinical information, successfully classified MCI patients into two groups, low and high, in terms of risk of MCI-to-AD conversion.

  Study JGAS000532

• Clinical validity of post-surgery circulating tumor DNA (ctDNA) in stage III colon cancer patients treated with adjuvant chemotherapy: the PROVENC3 study

  The PROVENC3 study aimed to determine the clinical validity of post-surgery ctDNA testing in patients with stage III colon cancer treated with adjuvant chemotherapy (ACT). Blood was collected pre-surgery, post-surgery and post-adjuvant chemotherapy. Tumor-informed plasma ctDNA detection was performed through integrated whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue DNA (80x), white blood cell germline DNA (40x) and plasma cell-free DNA (30x). These raw WGS data for 209 patients are shared in .cram format in this EGA submission. For 196/209 of these patients there is overlapping FFPE tumor RNA sequencing data available, shared in .fastq format in this EGA submission.

  Study EGAS50000000804

• Single-cell profiling of the leukemic and non-leukemic immune cell compartments in CD8+ T-cell Large Granular Lymphocytic Leukemia

  We performed a detailed and precise characterisation of the clonally expanded leukemic cells in CD8+ T cell Large Granular Lymphocytic Leukemia (T-LGLL). By combining scRNA+TCRαβ-seq with bulk RNA sequencing data we showed evidence of a strong antigen-driven immune response that shapes the entire immune cell repertoire in T-LGLL. Our study highlights how the whole immune cell repertoire including the hyperexpanded CD8+ T-LGLL cells, the non-leukemic CD8+ cells, CD4+ cells, and monocytes contribute to the CD8+ T-LGLL disease phenotype. Please note that this submission contains the fastq files while the processed count matrices can be found in ArrayExpress by the accession E-MTAB-11170.

  Study EGAS00001005297

• Clonal tracing with somatic epimutations reveals dynamics of blood aging

  In this study, we generated comprehensive single-cell multi-omic datasets from bone marrow samples collected from 13 donors spanning a wide age range. We applied the scTAMseq protocol to profile DNA methylation and nuclear mutations obtained from 7 total bone marrow aspirates (donors A.1-A.7) and 6 CD34+-enriched bone marrow samples ((donors B.1-B.5 & X.1). Complementary surface marker expression data were acquired by integrating CITE-seq into the scTAMseq workflow (scTAMseq_prot). Targeted RNA sequencing (scTAMARA_rna) was performed alongside scTAMARA_DNA on one CD34+-enriched sample (X.1). Additionally, a dedicated mitochondrial panel (TAMITO_seq) was employed on a peripheral blood sample from a healthy donor (X.2) to assess mitochondrial heterogeneity and facilitate lineage tracing.

  Study EGAS00001008056

• EGAD00000000049

  RNA-SEQ data from oestrogen-receptor-alpha-positive metastatic lobular breast cancer sample

  Dataset EGAD00000000049

• Baulac Lab - Paris Brain Institute

  Raw 10X single-nucleus RNA-seq data from human postoperative brain samples of patients with epilepsy and cortical malformations.

  Dac EGAC50000000546

• Patient-Derived Follicular Lymphoma Spheroids recapitulate lymph node signaling and immune profile, uncovering galectin-9 as a novel immunotherapeutic target

  RNA-seq data from CD20+ sorted cells obtained from peripheral blood and lymph node Follicular Lymphoma patients. These samples were unstimulated after thawing and additionally, peripheral blood samples were stimulated during 7 days in culture as described in Dobaño-López C et. al.)

  Study EGAS50000000233

• Application of targeted long-read methylation sequencing to dissected breast cancer tissues

  Four regions defined by pathological view were dissected from fresh frozen sections of breast cancer tissue using Millisect system. DNA and RNA extracted from the dissected tissues were applied to short-read WGS, short-read RNA-seq, short-read EM-seq, and targeted long-read methylation analysis t-nanoEM.

  Study JGAS000758

• Research for biological features by gene expression analysis and biomarkers at diagnosis/therapeutics in lung cancer

  WGS, WES, ATAC-seq and methylation analysis with DNA harvested from lung cancer organoids established from surgery, biopsy, pleural effusion, sputum and blood samples of patients. RNA-seq analysis with RNA harvested from lung cancer organoids established from surgery, biopsy, pleural effusion, sputum and blood samples of patients.

  Study JGAS000610

• Research for biological features by gene expression analysis and biomarkers at diagnosis/therapeutics in lung cancer

  WGS, WES, ATAC-seq and methylation analysis with DNA harvested from lung cancer organoids established from surgery, biopsy, pleural effusion, sputum and blood samples of patients. RNA-seq analysis with RNA harvested from lung cancer organoids established from surgery, biopsy, pleural effusion, sputum and blood samples of patients.

  Study JGAS000609

• Research for biological features by gene expression analysis and biomarkers at diagnosis/therapeutics in lung cancer

  WGS, WES, ATAC-seq and methylation analysis with DNA harvested from lung cancer organoids established from surgery, biopsy, pleural effusion, sputum and blood samples of patients. RNA-seq analysis with RNA harvested from lung cancer organoids established from surgery, biopsy, pleural effusion, sputum and blood samples of patients.

  Study JGAS000557

• Gene expression analysis of clear cell renal cell carcinoma

  To identify genes that are differentially expressed across different conditions (cancer vs normal, normoxic vs hypoxic), we performed RNA-seq in 3 ccRCC cell lines (786-O, A498, UMRC-2), and 1 normal kidney epithelium cell line (HK-2), cultured under normoxic (20% O2) and hypoxic (0.05% O2) conditions.

  Study EGAS50000001324

• An epigenomics time course analysis of covid19 patients from Quebec, Canada

  Investigating the cellular and epigenetic changes at play in severely ill hospitalized COVID-19 patients at admission and how it evolves with prognosis. Single-cell RNA-seq analysis done on longitudinal samples highlighted changes in the monocytic compartment, which we explored using whole-genome epigenomics methods (ATACseq abd WGBS).

  Study EGAS00001005468

• MILK-Omics: Systems Biology of Human Milk and Its Links to Maternal and Infant Health

  The primary objective of the project is to generate a systems-level view of human milk in the context of healthy mothers and their term infants. The study uses biospecimens and clinical data from the Mothers and Infants LinKed for Healthy Growth Study (MILk Study), a prospective observational cohort of approximately 500 exclusively breastfeeding women and their infants who are followed to 6 months of age. The project focuses on mature milk samples collected at 1 month postpartum and infant gut microbiome samples collected at 1 and 6 months of age. Specific Aim 1 is to identify maternal genetic and clinical factors that shape human milk gene expression. Using bulk and single-cell RNA sequencing of the milk cell pellet and genotypes from maternal DNA, we will identify novel genetic determinants of the milk transcriptome and assess potential modification of these genetic associations by gestational weight gain, diet, and other clinical factors. Specific Aim 2 is to describe key features of the normative human milk biosystem and their interactions with one another. Specifically, machine learning techniques will be used to characterize interaction networks and correlational structures among the following features of human milk: transcriptomics, microbiomes, oligosaccharides, metabolomics, lipidomics, and milk macronutrient composition. Specific Aim 3 is to establish how the milk biosystem is related to variation in infant gut microbiomes and health. dbGaP will house the maternal genotype and milk transcriptomics data.The infant microbiome sequence data are associated with BioProject PRJNA1019702.

  Study phs003408

• Massively parallel nanowell-based single-cell gene expression profiling

  Technological advances have enabled transcriptome characterization of cell types at the single-cell level providing new biological insights. New methods that enable simple yet high-throughput single-cell expression profiling are highly desirable. Here we report a novel nanowell-based single-cell RNA sequencing system, ICELL8, which enables processing of thousands of cells per sample. The system employs a 5184-nanowell-containing microchip to capture ~1300 single cells and process them. Each nanowell contains preprinted oligonucleotides encoding poly-d(T), a unique well barcode, and a unique molecular identifier. The ICELL8 system uses imaging software to identify nanowells containing viable single cells and only wells with single cells are processed into sequencing libraries. Here, we report the performance and utility of ICELL8 using samples of increasing complexity from cultured cells to mouse solid tissue samples. Our assessment of the system to discriminate between mixed human and mouse cells showed that ICELL8 has a low cell multiplet rate (< 3%) and low cross-cell contamination. We characterized single-cell transcriptomes of more than a thousand cultured human and mouse cells as well as 468 mouse pancreatic islets cells. We were able to identify distinct cell types in pancreatic islets, including alpha, beta, delta and gamma cells. Overall, ICELL8 provides efficient and cost-effective single-cell expression profiling of thousands of cells, allowing researchers to decipher single-cell transcriptomes within complex biological samples.

  Study EGAS00001002320

• DNA hypermethylation and differential gene expression associated with Klinefelter syndrome

  The molecular basis for the phenotypic traits and morbidity in Klinefelter syndrome (KS) are not clarified. As DNA methylation affect gene expression and thereby play a role in disease susceptibility, we performed genome-wide DNA methylation profiling of leucocytes from peripheral blood samples from 67 KS patients, 67 male controls and 33 female controls, in addition to genome-wide RNA-sequencing profiling in a subset of 9 KS patients, 9 control males and 13 female controls. Characterization of the methylome as well as the transcriptome of both coding and non-coding genes identified a unique epigenetic and genetic landscape of both autosomal chromosomes as well as the X chromosome in KS. A subset of genes show significant correlation between methylation values and expression values. Gene set enrichment analysis of differentially methylated positions yielded terms associated with well-known comorbidities seen in KS. In addition, differentially expressed genes revealed enrichment for genes involved in the immune system, wnt-signaling pathway and neuron development. Based on our data we point towards many new candidate genes (AKAP17A, AMOT, APOB, DACT1, DDX58, DOCK7, EIF2S3, FIGNL1, G3BP1, HENMT1, HERC5, IFI44, IFI44L, IFIT1, IFIT3, ISG15, KANK1, LGALS1, NSD1, PEX10, PLSCR1, RSAD2, SHROOM2, SLC25A6, SPEG, SPON2, TXLNG), which may be implicated in the phenotype and further point towards non-coding genes (RP13-216E22.4, RP13-36G14.4, G087825, G088512), which may be involved in X chromosome inactivation in KS and in the regulation of escape genes.

  Study EGAS00001002797

• Brain Cell Type-Specific Enhancer-Promoter Connectivity Maps and Disease Risk Association

  These studies map the epigenetic landscape of microglia, neurons, astrocytes and oligodendrocytes. The initial study compared acutely isolated microglia to cultured microglia from the same donors, to identify changes that occur when microglia are removed from the brain microenvironment. In collaboration with the Rady Children's Hospital, we obtained brain tissue samples from pediatric patients representing putative normal tissue resected to gain access to brain tumors as well as tissue resected to remove epileptic foci. We assayed microglia isolated from these samples using RNA-seq, ATAC-seq and ChIP-seq for PU.1, H3K4me2, and H3K27ac. For patients from whom a sufficient cell number was obtained, we additionally cultured their microglia for up to 7 days and subjected these to the same suite of assays. In a follow-up study, we obtained brain tissue from a comparable cohort of pediatric epilepsy patients from Rady Children's Hospital. We isolated nuclei from microglia, neurons, astrocytes and oligodendrocytes, and assayed for ATAC-seq, ChIP-seq for H3K4me3, and H3K27ac, and PLAC-seq (Proximity Ligated ChIP-seq). We isolated microglia from human fetal and postnatal sample and assayed for bulk RNA-seq, bulk ATAC-seq, bulk H3K27ac ChIP-seq, single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq. For these studies, human microglia are defined by signature genes/proteins, such as P2RY12, SALL1, and CX3CR1.

  Study phs001373

• Transcriptome human nasal epithelium

  1. Odors are detected, firstly, by olfactory sensory neurons (OSNs) in the olfactory epithelium of the nose. This neurons then project directly to the olfactory bulb in the brain. Olfaction depends on cellular regeneration of the OE, olfactory bulb and hippocampus, and on their continual re-wiring. The olfactory neural pathway includes regions of the frontal, temporal and limbic brain, which in turn overlap with brain areas involved in brain disorders. OSNs are the only aspect of the human brain exposed to the external environment. This not only makes them vulnerable to environmental changes, but also accessible for biomedical studies. We have already sequenced and developed a protocol for analyzing the transcriptome of mouse main olfactory epithelium and single OSNs. We propose here to perform a similar study for samples from the human olfactory epithelium. We have developed a minimally invasive method for obtaining human OSNs, among other cells from the nasal epithelium. In this experiment, we have obtained cell samples from the olfactory epithelium, including OSN, from healthy volunteers. We would like to further characterize them by RNA sequencing. This will give us valuable insight into human olfaction. It will also provide a first step into a new avenue to study, and find biomarkers for, brain diseases though the analysis of these easily available neurons. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001002226

• Label-free single-cell RNA Multiplexing leveraging Genetic Variability

  SNP-based demultiplexing of single-cell RNA-seq data

  Dataset EGAD50000000928

• DAC_RNA-seq of murine osteosarcoma cell line genetically modified for CYR61

  Data access committee for RNA-seq of murine osteosarcoma cell line genetically modified for CYR61

  Dac EGAC50000000352

• LOGGIC Core BioClinical Data Bank: Added clinical value of RNA-Seq in an international molecular diagnostic registry for pediatric low-grade glioma patients

  Study EGAS00001007072

• Single-cell RNA-seq of murine splenocytes from Bcl6tg/+ and Cd70-/-; Bcl6tg/+ diffuse large B-cell lymphoma mouse models and Cd70-/- and wild-type controls.

  Study EGAS00001007570

• WXS and RNA-seq raw sequence data for TG project

  WXS sequence data from 112 samples, RNA-seq sequence data from 117 samples, all sequence data are raw sequence data in fastq format, sequenced by Illumina platform.

  Dataset EGAD00001007989

• Transcriptional and DNA binding profiling of CEBPE in REH acute lymphoblastic leukaemia cells using shRNA RNA-Seq and ChIP-Seq

  ChIP-Seq - CEBPE - REH. The ETV6/RUNX1 translocated acute lymphoblastic leukaemia cell line. REH was used to perform ChIP-Seq using a CEBPE antibody. Cells were fixed in 1% formaldehyde for 10mins, prior to preparation of chromatin using Active Motif Express ChIP-IT. 2ug of antibody (anti CEBPE Atlas Antibodies HPA002928)was added to 25ug of chromatin O/N at 4C with rotation. Duplicate reactions were pooled and purified. 10ng of ChIP’d and input DNA used for Illumina NGS preparation (NEBNext ChIP-Seq Library kit; New England Biolabs), CEBPE and Input DNA ChIP samples were sequenced on a MiSeq using 150bp Kit v3 paired end and a HiSeq 2500 using 2x101 version 4 paired end (Illumina) respectively. Reactions performed in duplicate. shCEBPE RNA-Seq - REH. REH cells were lentivirally transduced with a pTRIPZ shRNA vector for transcriptional profiling of CEBPE. Two controls (empty and non-targeting) and two CEBPE shRNAs (V3THS_150517(A13), V3THS_404312(G3) Dharmacon, GE) were transduced into REH cells. Cells were treated with 1ug/ml doxycyclin for 144hrs and total RNA purified using Qiagen RNeasy. Knock down of CEBPE was validated by qRT. RNA integrity >7.7 for all samples. Libraries were prepared using NEBNext Ultra II Directional RNA Library Prep Kit and sequenced on an Illuimna HiSeq 2500 using 2x101 version 4 paired end chemistry. 3 biological replicates of each samples were prepared.

  Dataset EGAD00001004084

• GENCORD2_RNAseq

  GENCORD2 RNA-seq BAM files using BWA

  Dataset EGAD00001000425

• Characterizing Advanced Breast Cancer Heterogeneity and Treatment Resistance through Serial Biopsies and Comprehensive Analytics

  This dataset accompanies the manuscript "Characterizing Advanced Breast Cancer Heterogeneity and Treatment Resistance Through Serial Biopsies and Comprehensive Analytics". In this study we discuss the clinical implications and consequences of molecular heterogeneity in a metastatic breast cancer patient identified through serial biopsies, multi-omic analysis, and longitudinal patient monitoring, performed through the precision oncology program, Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART). This case study describes a metastatic breast cancer patient with a highly heterogenous tumor that began as ER positive/HER2 negative on diagnosis, then was found to be ER negative/HER2 positive in a metastatic liver lesion (Study biopsy #1), and finally triple negative (TNBC) in another metastatic liver biopsy (Study biopsy #2). Multi-omic assays included clinical genomic panel sequencing, clinical immunohistochemistry, a clinical protein profiling assay (Intracellular Signaling Protein Profiling), RNA sequencing, and RPPA. Here we provide the expression data from RNAseq and RPPA data on Study biopsy #2 for the patient discussed in this case report. Note: The first liver biopsy did not yield sufficient material for RNAseq or RPPA.Raw RNA FASTQ files from Study biopsy #2 of the liver Gene expression (RNAseq) files from Study biopsy #2Protein expression (RPPA) files (level 2, 3, 4) for Study biopsy #2

  Study phs002321

• RNA-seq analysis of megakaryocytes and granulocytes in Quebec platelet disorder

  Quebec Platelet disorder (QPD) is a unique bleeding disorder that markedly increases urokinase plasminogen activator (uPA) in megakaryocytes and platelets but not in plasma or urine. The cause is tandem duplication of a 77 kb region of chromosome 10 containing PLAU and C10orf55. Blood cells and cultured megakaryocytes from donors (7 QPD, 10 control subjects) were prepared for total and allele-specific, quantitative reverse transcription polymerase chain reaction, immunoassays, Western blots and RNA-seq. Transcriptomes for cultured megakaryocytes and peripheral blood granulocytes from 4 control and 3 QPD individuals were analyzed using mRNA-seq.

  Study EGAS00001001840

• The Institute for Genomic Medicine at Nationwide Children's Hospital Pediatric Cancer and Blood Disorder Project

  The aim of this study is to enable the unification of the clinical and research arms of comprehensive genomic profiling in the setting of cancer and hematologic disease. Increasingly, studies of the genomic etiology of cancer and hematologic diseases are being utilized for patient management, including prognostication, informing diagnosis, and evaluating eligibility for targeted therapeutics and clinical trials. Clinically available testing can be limited in scope and follow-up, and thus assessment of the impact on patient outcomes is difficult to ascertain. N-of-1 studies have the ability to more broadly impact our understanding of the mechanisms of cancer and hematologic disease, and can have benefit for the individual as well as the larger population of patients with these diseases. Thus, we seek to study and characterize the genomic underpinnings of cancer and hematologic disease through genomic profiling studies bridging both clinical and research components. We will rigorously perform and vet research sequencing and genomic studies protocols for the purpose of transitioning these assays to clinically valid testing for use in clinical patient care. We have been enrolling patients onto this comprehensive genomic profiling study since January 2018. As part of the genomic workup for these patients, we have been performing tumor and normal whole genome sequencing, whole exome sequencing and RNA-Seq. The project is largely supported by the Nationwide Children's Foundation, and we anticipate adding another 50-70 cases per year. This protocol is significant in that it expands our understanding of the etiology of cancer and hematologic disease through a comprehensive analysis aimed at detecting a broad scope of genomic aberrations. Additionally, it improves our understanding of the clinical utility of genomic profiling and has the potential to ultimately improve patient management and surveillance at both level of an individual and general populations of patients affected by these diseases. Primary Objectives: Aim 1: Use diagnostic, relapse, and/or germline samples for augmented whole exome sequencing to characterize the spectrum of germline and somatic genomic alterations in pediatric malignancies and hematologic disease. Aim 2: Examine gene expression and fusion events using whole RNA-seq "transcriptome" analysis or targeted RNA-seq analysis such as the Archer FusionPlex technology. Aim 3: Compare the results of our enhanced molecular profiling vs. that which is detectable by traditional methods as related to cytogenetic, molecular, and minimal residual disease analyses performed as part of standard of care. Aim 4: Examine the utility of comprehensive genomic profiling by collection and evaluation of outcomes data as related to enhancement/alteration in diagnosis, prognosis, treatment management, and clinical benefit. Secondary Objective: Aim 1: Use and clinically validate expanded laboratory methodologies and bioinformatic approaches to more broadly assess genomic complexity (e.g. whole genome sequencing, transcriptome sequencing, in vitro analyses, minimal residual disease testing, clonality assays, proteomics) in the setting of hematologic and oncologic disease. In so doing, we aspire to make novel discoveries and associations, as related to disease phenotypes and subtypes, variant causality, therapeutic targeting, and cancer biology.

  Study phs001820

• Whole blood RNAseq from a large ALS case-control study at Univ of Michigan

  This dataset consists of 694 bulk RNA-seq data (sorted aligned BAM files) from whole blood of ALS participants meeting the Gold Coast definition of ALS during their clinical visit (n=422) and healthy controls (n=272) at the University of Michigan (UM). Samples were collected as part of the UM Pranger ALS Clinic between 2011-2021, and prepared either using poly-A selection of rRNA depletion (see Experiments). RNAseq was performed on the NovSeq 6000 S4 at the UM Advanced Genomics Core, resulting in 150bp paired-end reads. Raw reads were trimmed using Cutadapt (v2.3) and aligned to hg38 using STAR (v2.5.3a). Age provided is the age at blood sample collection date.

  Dataset EGAD50000001488

• Pediatric Papillary Thyroid Carcinoma RNA-Seq

  38 PPTCs were sequenced using RNASeq to identify oncogenic variants in driver-unknown tumors and to explore gene expression patterns. RNA libraries were quantified by qPCR using the Kapa Library Quantification Illumina/ABI Prism Kit protocol (KAPA Biosystems). Libraries were pooled in equimolar quantities and paired-end sequenced on 2 lanes of a High Throughput Run Mode flowcell with the V4 sequencing chemistry on an Illumina HiSeq 2500 platform following Illumina’s recommended protocol to generate paired-end reads of 126-bases in length.

  Dataset EGAD00001007499

• Single-cell RNA-seq of peripheral blood mononuclear cells in classic Hodgkin lymphoma

  Abstract: Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (paired samples from cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors.

  Dataset EGAD00001011360

• UCSF-CASCADE analysis of metastatic prostate cancer

  Targeted cancer therapy inevitably selects for tumor cells that harbor some form of therapy resistance. This phenomenon is a principle reason why advanced prostate cancer, which can be treated with agents targeting androgen signaling dependency and DNA repair failure, is a lethal condition. The influence of a patient's clinical history and disease evolution on how their disseminated tumors develop resistance has been difficulty to study, because few autopsy studies have been performed in heavily treated patients with DNA-repair deficient metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed how resistance to targeted cancer therapies evolved in an autopsy cohort of 54 mCRPC tumors from six men. This dataset includes targeted sequencing, exome sequencing, and RNA-seq conducted on these biopsies.

  Dataset EGAD00001010275

• PDAC organoid genomic heterogeneity

  Two primary tumor-derived PDAC organoids were subjected to SNP array, RNA-seq, and single-cell WGS

  Dataset EGAD00010002408

• Long Read sequencing data from 4 tumor/germline samples with non muscle invasive bladder cancer

  A better understanding of the molecular landscape of non-muscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and identify potential therapeutic targets. Here, we perform a comprehensive genomic analysis of patients diagnosed with NMIBC based on whole-exome- (n=438), shallow whole-genome- (n=362), and total RNA-sequencing (n=414). Additionally, tumor/germline samples from 4 patients were sequenced using Oxford Nanopore technology. This dataset contains 8 BAM files corresponding to the Long read sequencing data.

  Dataset EGAD50000000731

• Bulk RNA sequencing of Singapore colorectal cancer patients (SG-BULK)

  The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.

  Study EGAS00001005978

• Mapping genetic variants underlying gene regulation in healthy intestinal cell types to identify novel IBD drug targets (2020-05-12)

  Biopsies from the terminal ileum and rectum of healthy individuals are digested on ice to single cells and processed for single-cell RNA-sequencing (10X Genomics and Illumina) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ . This dataset contains all the data available for this study on 2020-05-12.

  Dataset EGAD00001006139

• Whole-genome sequencing of rhabdomyosarcoma tumouroids (2025-09-30)

  This study investigates high-risk rhabdomyosarcoma (RMS) using multiple single-cell and spatial genomic technologies. We generated and analysed single-cell and single-nucleus RNA-sequencing, chromatin accessibility, and spatial transcriptomics data from primary tumours and validation samples. These datasets characterise cellular diversity within rhabdomyosarcoma and identify cell states associated with aggressive disease. The data support research into tumour biology, risk stratification, and therapeutic target discovery. This repository houses the whole-genome sequencing of RMS tumoroids data. . This dataset contains all the data available for this study on 2025-09-30.

  Dataset EGAD00001015707

• Single cell study of infant leukemias

  We have performed single cell RNA-sequencing for infant and childhood B-cell acute lymphoblastic leukemias as well as infant acute myeloid leukemias at diagnosis. The sequencing was performed with 10X Chromium single cell 3’ and 5’ chemistry.

  Dataset EGAD00001007854

• Whole Genome-sequencing of rhabdomyosarcoma tumour tissue (2025-09-30)

  This study investigates high-risk rhabdomyosarcoma (RMS) using multiple single-cell and spatial genomic technologies. We generated and analysed single-cell and single-nucleus RNA-sequencing, chromatin accessibility, and spatial transcriptomics data from primary tumours and validation samples. These datasets characterise cellular diversity within rhabdomyosarcoma and identify cell states associated with aggressive disease. The data support research into tumour biology, risk stratification, and therapeutic target discovery. This repository houses the whole-genome sequencing of RMS tumours data. . This dataset contains all the data available for this study on 2025-09-30.

  Dataset EGAD00001015709

• Whole Genome-sequencing of rhabdomyosarcoma tumour tissue (2025-09-30)

  This study investigates high-risk rhabdomyosarcoma (RMS) using multiple single-cell and spatial genomic technologies. We generated and analysed single-cell and single-nucleus RNA-sequencing, chromatin accessibility, and spatial transcriptomics data from primary tumours and validation samples. These datasets characterise cellular diversity within rhabdomyosarcoma and identify cell states associated with aggressive disease. The data support research into tumour biology, risk stratification, and therapeutic target discovery. This repository houses the whole-genome sequencing of RMS tumours data. . This dataset contains all the data available for this study on 2025-09-30.

  Dataset EGAD00001015716

• Peripheral blood DNA transcriptomics of vedolizumab treatment response in patients with Crohn's disease

  Data pertains longitudinal transcriptomic data measured from blood obtained from patients with Crohn's disease that were starting treatment with vedolizumab. Samples were obtained prior to treatment and approximately 26 weeks into treatment during response assessment. At response assessment, patients were classified as responders (R) or non-responders (NR) based on a strict combination of endoscopic, biochemical and clinical criteria: ≥50% reduction in the endoscopic SES-CD score, corticosteroid-free clinical remission (≥3 point drop98 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 mg/L and fecal calprotectin ≤250 µg/g). Modified response was defined as a combination of corticosteroid-free clinical- (HBI ≤4) and biochemical (CRP ≤5 mg/L and/or fecal calprotectin ≤250 µg/g) remission between week 26-52 without treatment change through week 52. Transcriptomic analyses was conducted through RNA sequencing, wherein mRNA was extracted utilizing the QIAsymphony system, converted into cDNA and sequenced in a paired-end format on the Illumina NovaSeq6000 at the Amsterdam UMC Core Facility Genomics, generating a dataset comprising 40 million 150 bp-reads.

  Dataset EGAD50000000385

• Peripheral blood DNA transcriptomics of ustekinumab treatment response in patients with Crohn's disease

  Data pertains longitudinal transcriptomic data measured from blood obtained from patients with Crohn's disease that were starting treatment with ustekinumab. Samples were obtained prior to treatment and approximately 26 weeks into treatment during response assessment. At response assessment, patients were classified as responders (R) or non-responders (NR) based on a strict combination of endoscopic, biochemical and clinical criteria: ≥50% reduction in the endoscopic SES-CD score, corticosteroid-free clinical remission (≥3 point drop98 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 mg/L and fecal calprotectin ≤250 µg/g). Modified response was defined as a combination of corticosteroid-free clinical- (HBI ≤4) and biochemical (CRP ≤5 mg/L and/or fecal calprotectin ≤250 µg/g) remission between week 26-52 without treatment change through week 52. Transcriptomic analyses was conducted through RNA sequencing, wherein mRNA was extracted utilizing the QIAsymphony system, converted into cDNA and sequenced in a paired-end format on the Illumina NovaSeq6000 at the Amsterdam UMC Core Facility Genomics, generating a dataset comprising 40 million 150 bp-reads.

  Dataset EGAD50000000386

• RNA-sequencing from duodenal bipsies of Celiac disease patients

  Samples, in a form of PAXgene fixed and paraffin-embedded biopsies, were collected from the multi-site, double-blind, randomized, placebo-controlled trial, aimed at dose-finding and assessing the efficacy and tolerability of a 6-week treatment with ZED1227 capsules vs. placebo in subjects with well-controlled celiac disease undergoing gluten challenge. Total RNA was extracted from the PaxFPE biopsy specimens (n = 116) using additional cuttings from the samples on which histomorphometry was previously assessed. For the extraction, an RNeasy Kit (Qiagen, Hilden, Germany) was used according to the manufacturer’s instructions. Library preparation and next-generation sequencing (NGS) were performed by the Qiagen NGS Service. A total of 10 ng of purified RNA was converted into cDNA NGS libraries. Library preparation was quality controlled using capillary electrophoresis. Based on the quality of the inserts and the concentration measurements, the libraries were pooled in equimolar ratios and then sequenced on a NextSeq (Illumina Inc., San Diego, USA) sequencing instrument according to the manufacturer’s instructions, with 100 bp read length for read 1 and 27bp for read 2. The raw data were de-multiplexed, and FASTQ files for each sample were generated using bcl2fastq2 software (Illumina Inc., San Diego, USA).

  Dataset EGAD50000000491

• IκBε deficiency accelerates disease development in chronic lymphocytic leukemia

  The NFKBIE gene, which encodes the NF-κB inhibitor IκBε, is mutated in 3-7% of patients with chronic lymphocytic leukemia (CLL). The most recurrent alteration is a 4-bp frameshift deletion associated with NF-κB activation in leukemic B cells and poor clinical outcome. To study the functional consequences of NFKBIE gene inactivation, both in vitro and in vivo, we engineered CLL B cells and CLL-prone mice to stably down-regulate NFKBIE expression and investigated its role in controlling NF-κB activity and disease expansion. We found that IκBε loss leads to NF-κB pathway activation and promotes both migration and proliferation of CLL cells in a dose-dependent manner. Importantly, NFKBIE inactivation was sufficient to induce a more rapid expansion of the CLL clone in lymphoid organs and contributed to the development of an aggressive disease with a shortened survival in both xenografts and genetically modified mice. IκBε deficiency was associated with an alteration of the MAPK pathway, also confirmed by RNA-sequencing in NFKBIE-mutated patient samples, and resistance to the BTK inhibitor ibrutinib. In summary, our work underscores the multimodal relevance of the NF-κB pathway in CLL and paves the way to translate these findings into novel therapeutic options.

  Dataset EGAD50000000754

• RNA sequencing data of 257 samples from the CORALLEEN trial

  Early-stage Luminal B breast cancer is frequent and is a major cause of breast cancer death due to its poor prognosis. Our proposal aims to study the biology behind the sensitivity and resistance of Luminal B breast cancer to chemotherapy (CHT) or a non-CHT regimen composed of hormone therapy in combination with ribociclib, a CDK4/6 inhibitor. To accomplish this, we first completed the SOLTI-1402 CORALLEEN phase II trial, a study where 106 patients with early-stage Luminal B breast cancer were randomized to standard neoadjuvant CHT for 6 months, or neoadjuvant letrozole and ribociclib for 6 months. After treatment, patients underwent surgery. The primary results of the study, which showed that the response rate to letrozole+ribociclib was similar to CHT, was reported (Prat et al; Lancet Oncol). Tumor biopsies were available at baseline, week 3 and surgery. A total of 257 samples were analyzed using the Illumina TruSeq Stranded Total RNA w/Ribo Zero Gold with MiSeq in TGL (Sequencer NovaSeq S4/PE/100x)

  Dataset EGAD00001010121

• Integrative Single-Cell Analysis of Transcriptome, Epigenome, and Lineage in HIV Latency and Activation

  With the development of triple combination antiretroviral therapy, routine HIV treatment eliminates nearly all actively infected cells. Nevertheless, the small reservoir of latently infected cells, which can remain dormant for long periods of time before becoming active and producing new virus particles, represents a crucial barrier to completely curing the disease. Identifying markers that identify latently infected cells or the biochemical factors that control latency activation could enable the effective use of a “shock and kill” strategy, where specific targeting or activation of latently infected cells eliminates the viral reservoir. Our recent work suggests that the global transcriptomic and epigenomic changes during hematopoietic differentiation affect viral latency and activation. Additionally, we recently found that global inhibition of histone deacetylase activity increases viral activation in these cells, further implicating epigenomic changes during activation. These results raise fundamental questions: What are the markers of latently infected cells? How do the transcriptomic and epigenomic states of a cell affect latency and activation? How does the differentiation state relate to viral latency? Here, we leverage our experimental platform for identifying latently and actively infected cells, single-cell transcriptome and epigenome sequencing, and our recently developed computational integration methods to investigate these questions. Our interdisciplinary team combines expertise in HIV basic science, HIV clinical treatment, and bioinformatics to develop an experimental and computational framework for integrated gene expression, chromatin accessibility, and lineage into a single picture of viral latency and activation. Specifically, this project will (1) use single-cell RNA-seq and single-cell ATAC-seq to map the diversity of infected cells, (2) investigate the relationship between hematopoietic differentiation state and viral activation, (3) determine viral integration sites through single-cell RNA-seq, (4) computationally integrate single-cell transcriptome and epigenome profiles, and (5) computationally infer cell lineage relationships among viral genomes and infected cells. To accomplish these goals, we will carry out the following aims: (1) Characterize lineage, transcriptomic and epigenomic diversity of single latently and actively infected primary cells. (2) Investigate latency and activation during in vitro differentiation. (3) Survey single cell diversity of re-activated and in vitro infected cells from cART-suppressed patients. Together, these aims will produce a comprehensive, integrated transcriptomic and epigenomic atlas of the HIV reservoir, identify DNA and RNA biomarkers of latency, and characterize clonal expansion patterns. Our work also develops a broadly applicable experimental and computational framework, laying a foundation for the discovery of novel insights into HIV latency and activation.

  Study phs002915

• The role of the mammalian SWI/SNF chromatin remodeling complex in neuroendocrine prostate cancer

  We sought to determine the effects of SMARCA4 and SMARCA2 depletion in prostate cancer cell lines. We performed siRNA-mediated knock-down of SMARCA4 and SMARCA2 in an androgen-sensitive (LNCaP) cell line and in a castration-resistant prostate cancer (CRPC)-adenocarcinoma cell line (22Rv1) and compared global transcriptional alterations using RNA-seq.

  Study EGAS00001004177

• In this study, blood-brain barrier (BBB)-forming brain endothelial-like cells were generated from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). Cells were subsequently exposed to focused ultrasound and microbubbles (FUS+MB) to induce BBB opening and their transcriptome analysed. RNA sequencing (RNA-seq) results demonstrated minimal changes in the gene expression following FUS+MB suggesting safety of FUS+MB application in the clinical setting.

  The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer’s disease (AD). Focused ultrasound applied together with microbubbles (FUS+MB) is a novel technique to transiently open the BBB and increase drug delivery. Evidence suggests that FUS+MB is safe, however the effects of FUS+MB on human BBB cells, especially in relation to AD, remain sparsely investigated. Here we developed a human sporadic AD BBB cell platform to investigate the effects of FUS+MB on BBB cells and screen for the delivery of two potentially therapeutic AD antibodies. We generated BBB cells from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). We utilized this robust and reproducible platform to demonstrate increased delivery of potentially therapeutic antibodies across the BBB, including an analogue of Aducanumab (AduhelmTM) following FUS+MB treatment. Our results also demonstrate the safety of FUS+MB indicated by minimal changes in the cell transcriptome as well as little or no changes in cell viability and inflammatory responses within first 24 h post FUS+MB, with potentially important implications in a clinical setting. Finally, we report a more physiologically relevant hydrogel-based 2.5D BBB model as a key development for FUS+MB-mediated drug delivery screening, with potentially higher translational utility. Our results provide an important advancement for identifying FUS+MB-deliverable drugs and screening for cell- and patient-specific effects of FUS+MB, accelerating its use as a therapy in AD.

  Study EGAS00001005944

• High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation and Hematopoiesis

  In this study, we aimed to explore whether hyperglycemia alters inflammatory properties and microRNA levels in immune cells as well as their extracellular vesicles (EVs) as a mode of intercellular communication in cardiovascular disease. To this end, we isolated EVs from the plasma of diabetic mice as well as from human subjects that included 7 healthy individuals (control), 5 individuals with diagnosed peripheral arterial disease but no diabetes, 9 diabetic individuals with no vascular disease and 5 diabetic subjects with established vascular disease. The human plasma EVs were examined for the content of microRNA and their capacity to communicate signaling when incubated with cultured human THP1 macrophages. Subsequently, the plasma EV-exposed macrophages were examined for total RNA sequencing to identify inflammatory and molecular pathways targeted by the human EVs. 

  Study phs002401

• Next Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases

  Putative oncogenic pathways in squamous cell lung cancer have been recently characterized, although their biologic repercussions in patients is largely unknown. This study sought to discover potential clinical manifestations of major pathways in squamous cell lung cancer, particularly the PI3K pathway. Two key findings emerged: patients with stage IV squamous cell lung cancer whose tumors harbored upstream PI3K aberrations had significantly worse survival and a higher burden of metastatic disease. In addition, brain metastases were significantly more common in these patients than in others. Paired lung primary/brain metastasis genotyping, including RNA sequencing and whole exome sequencing, uncovered a high degree of genetic heterogeneity between lung/brain pairs, and identified potential regulators of the metastatic process to brain.

  Study phs000907

• Single Cell Transcriptomic Data from CD4+ T Cells from Children with MIS-C

  Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections in the pediatric population characterized by fever, multi-organ involvement and systemic inflammation. Single-cell RNA sequencing was used to evaluate the transcriptomic signature of CD4+ T cells obtained from the peripheral blood of patients with MIS-C before (n=3) and after (n=5) immunomodulatory treatment, along with pediatric controls (n=4). Compared to controls and treated children with MIS-C, T cells obtained from pre-treatment MIS-C patients upregulated genes associated with activation, such as NF-kB signaling. This single-cell transcriptomic data was used in the context of a larger study entitled, "Notch1-CD22-Dependent Immune Dysregulation in the SARSCoV2-Associated Multisystem Inflammatory Syndrome in Children."

  Study phs003086

• Multimodal Mapping of the Immune Landscape in Human Pancreatic Cancer

  Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that has rendered it largely refractory to immunotherapy. We used single-cell RNA sequencing on patient tumors and matched blood, and we uncovered a previously unappreciated, complex environment of immune-suppressive cellular interactions. These experiments reveal immune checkpoint expression heterogeneity on individual patient T cells, with corresponding ligands on neoplastic and myeloid cells. TIGIT was upregulated on tumor infiltrating CD8+ T cells and was the only checkpoint receptor consistently expressed by exhausted CD8+ T cells. Clinical annotation of the samples revealed that the exhausted signature is most prominent in patients with advanced stages of disease. Our findings suggest individualized combination therapy, involving anti-TIGIT therapies, may be necessary to extend the benefits of immunotherapy to pancreatic cancer patients.

  Study phs002071

• Dysregulation of Naive T Cell Quiescence during Aging

  TEA-seq (novel trimodal single-cell analysis of mRNA transcripts, surface protein epitopes, and chromatin accessibility) was performed on CD3+ T cells isolated from peripheral blood of healthy pediatric (11–13 yrs, n = 8) and older adult (55–65 yrs, n = 8) female donors. Single-cell RNA sequencing (scRNA-seq) was additionally performed on peripheral blood mononuclear cells (PBMCs) from a healthy cohort of 16 pediatric, 16 young adult (25–35 yrs), and 16 older adult donors with equal sex distribution. Using these data, we dissected the compositional and molecular alterations within the T cell compartment across the spectrum of healthy age, showing broad transcriptional and epigenetic alterations within the T cell compartment of older adults compared to children, as well as a novel population of pediatric-specific CD8aa T cells.

  Study phs003400

• Developing Targeted Therapy for Patients with Multiple Myeloma and Gain or Amplification of Chr1q (1q+)

  Multiple myeloma (MM) frequently presents with gain or amplification of chr1q (1q+), which is associated with inferior response to treatment and poor outcomes. To develop targeted therapy for MM with 1q+, we leveraged external and in-house dependency screens and drug screens, along with single-cell sequencing of patient tumors with subclonal 1q+. We demonstrated that MM with 1q+ exhibits higher sensitivity to MCL1 and PI3K inhibitors, which may be synergistic and act through established and novel mechanisms. Two human MM cell lines with 1q+, KMS12BM and KMS11, were profiled with either single-cell RNA-sequencing (scRNA-seq) alone (KMS12BM, KMS11) or both scRNA-seq and whole-genome sequencing (WGS; KMS12BM) to understand the factors that determine response to MCL1 and PI3K inhibitors and how these inhibitors work.

  Study phs003886

• ECM-free patient-derived organoids preserve diverse prostate cancer lineages and uncover in vitro-enriched cell types

  Patient-derived organoids (PDOs) hold promise for modeling various cancers, yet their application in prostate cancer (PCa) has been limited due to low culture success and the predominance of non-tumor-like cells. Using 164 PCa samples and optimizing culture conditions, we demonstrate that an extracellular matrix (ECM)-free culture method improves PDO take-rates, fostering cell populations with luminal and PCa-specific characteristics. Single-cell RNA sequencing (scRNA-seq) reveals that these ECM-free PDOs closely mirror their original tumors at the transcriptomic level and maintain a diverse array of tumor cell types, unlike traditional Matrigel-based cultures which predominantly yield benign-like cells. This study introduces a PCa PDO single-cell atlas, providing a valuable resource for advancing prostate cancer research.

  Study EGAS50000000807

• IMCISION RNAseq

  RNA sequencing could be performed on all 32 baseline and 30 on-treatment primary tumor biopsies. Based on gene-set enrichment analysis, the epithelial to mesenchymal transition signature was enriched in baseline tumors of patients without MPR, though its expression was insufficient to predict ICB response. Baseline and on-treatment IFNγ and T-cell signature expression (Z-score) were not significantly higher in patients with an MPR.­­­ Baseline primary tumor hypoxia-associated gene expression in IMCISION did not predict ICB response. However, on-treatment biopsies of MPR tumor samples showed significantly lower hypoxia gene expression when compared to non-MPR samples. Moreover, in a paired analysis of baseline and corresponding on-treatment samples, a significant decrease of hypoxia-related gene expression was observed in MPR biopsies, while this decrease was absent in non-MPR biopsies.

  Study EGAS00001005454

• Egyptref: An integrated personal and population-based Egyptian genome reference

  North African individuals are not represented in current genetic data sets. To address this issue, we generated an integrated personal and population-based Egyptian genome reference called Egyptref. Towards this end, we performed a human de novo assembly of an Egyptian individual using long PacBio reads (99x genome coverage) and polished it using Illumina short reads (90x). Variants were phased using 10x Genomics linked reads (80x). This personal genome was complemented with whole genome sequencing-based variant data of 109 further Egyptians and mitochondrial haplogroups from mtDNA sequencing of 326 further Egyptians (of which 100 individuals from EGAD00001001372/EGAD00001001380) to obtain a population-based genome. We used Egyptref for assessing the impact of genetic variation, e.g. by integration of blood RNA sequencing data of the assembly individual.

  Study EGAS00001004303

• DAC Ghent University - Department of Movement and Sports Sciences

  DAC of Ghent University for RNA-seq data of human skeletal muscle biopsies collected at the Department of Movement and Sports Sciences

  Dac EGAC50000000263

• RNAseq counts

  RNA-seq data from ILC samples. This dataset includes raw, unnormalized counts per gene, per sample.

  Dataset EGAD50000000826

• DAC - Department of Periodontology, University of Gothenburg, Sweden

  Data Access Committee to manage external requests. Project: RNA-seq data from soft tissue biopsies harvested from dental implant sites with peri-implantitis

  Dac EGAC50000000241

• Human inflammatory cardiomyopathies following SARS-CoV2 infection and COVID-19 vaccination

  Title: The cellular and molecular responses in human inflammatory cardiomyopathies following SARS-CoV2 infection and COVID-19 vaccination. Abstract: Abstract: Myocarditis is a cardiac disorder with multiple etiologies characterised by inflammatory cell infiltration and can occur after SARS-CoV-2 infection or rarely following mRNA-based COVID-19 vaccination. The underlying cellular and molecular mechanisms driving these pathologies remain poorly understood.Here we performed single-nucleus-RNA-sequencing in left ventricular endomyocardial biopsies from patients with Non-COVID-19 myocarditis, following SARS-CoV-2 infection (Post-COVID-19) and COVID-19 vaccination (Post-Vaccination). We detected specific cytokine expression patterns highlighting a particular role of interferon-γ in Post-COVID-19 and upregulated IL16 and IL18 expression as a Post-Vaccination hallmark. While the myeloid response was similar between groups, CD4+T-cell proportions were higher in Post-Vaccination and cytotoxic CD8+T and NK cells expanded in Post-COVID-19. Endothelial cells showed gene expression changes suggestive of vascular barrier function deficiency in Post-COVID-19 and angiogenesis response to cardiac inflammation in all groups. Together, our results illuminate shared and distinct cellular and molecular architectures of Non-COVID-19, Post-COVID-19 and Post-Vaccination associated myocardial inflammation in human hearts.

  Study EGAS50000000769

• Microbiomic and immunogenic biomarkers of adjuvant chemotherapy efficacy in stage III colorectal cancer

  The standard treatment for stage III colorectal cancer (CRC) is surgery, followed by adjuvant chemotherapy (AC). However, the efficacy of AC is limited, and approximately 30% of patients experience recurrence. Therefore, easily assessable molecular biomarkers that can predict response to AC are needed. Here, we aimed to identify predictive biomarkers of response to AC using tumor transcriptomic data. Tumor specimens from 253 patients who underwent surgery for stage III CRC between 1997 and 2019 were analyzed using RNA sequencing. Transcriptional subtyping and analyses of gut microbiome, immune cell fractions, and T-cell receptor (TCR) were performed to identify factors associated with recurrence-free survival (RFS) in patients treated with or without AC. Of 253 patients, 118 (46.6%) received AC. Twenty phyla and 799 species of the microbiomes were identified, among which Fusobacteria were identified in 247 patients (97.6%). Multivariable Cox proportional hazards regression analysis of patients who received AC showed that intratumoral Fusobacterium and M1 macrophage abundance and diversity of TCR alpha and delta (TRAD) were independently associated with RFS. Fusobacterium and M1 macrophage abundance, and TRAD diversity were associated with the response to AC, suggesting that these factors could serve as biomarkers for personalized treatment in stage III CRC.

  Study JGAS000875

• Next-Generation Sequencing of RNA and DNA Isolated from Paired Fresh-Frozen and Formalin-Fixed Paraffin-Embedded Samples of Human Cancer and Normal Tissue

  Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable resource for clinical research. However, nucleic acids extracted from FFPE tissues are fragmented and chemically modified making them challenging to use in molecular studies. We analysed 23 fresh-frozen (FF), 35 FFPE and 38 paired FF/FFPE specimens, representing six different human tissue types (bladder, prostate and colon carcinoma; liver and colon normal tissue; reactive tonsil) in order to examine the potential use of FFPE samples in next-generation sequencing (NGS) based retrospective and prospective clinical studies. Two methods for DNA and three methods for RNA extraction from FFPE tissues were compared and were found to affect nucleic acid quantity and quality. DNA and RNA from selected FFPE and paired FF/FFPE specimens were used for exome and transcriptome analysis. Preparations of DNA Exome-Seq libraries was more challenging (29.5 % success) than that of RNA-Seq libraries, presumably because of modifications to FFPE tissue-derived DNA. Libraries could still be prepared from RNA isolated from two-decade old FFPE tissues. Data were analysed using the CLC Bio Genomics Workbench and revealed systematic differences between FF and FFPE tissue-derived nucleic acid libraries. In spite of this, pairwise analysis of DNA Exome-Seq data showed concordance for 70-80 % of variants in FF and FFPE samples stored for fewer than three years. RNA-Seq data showed high correlation of expression profiles in FF/FFPE pairs (Pearson Correlations of 0.90 +/- 0.05), irrespective of storage time (up to 244 months) and tissue type. A common set of 1,494 genes was identified with expression profiles that were significantly different between paired FF and FFPE samples irrespective of tissue type. Our results are promising and suggest that NGS can be used to study FFPE specimens in both prospective and retrospective archive-based studies in which FF specimens are not available.

  Study EGAS00001000737

• RNAseq RPKM

  RNA-seq data from ILC samples. This dataset includes counts normalized for sequencing depth and gene length.

  Dataset EGAD50000000828

• Covacta RNAseq merged EGA metadata

  Sample metadata for the RNA-seq dataset. This dataset includes subject-level data and longitudinal visit day information for the corresponding samples.

  Dataset EGAD00001011162

• RNA-Seq Pair End

  RNA analysis of two patients 11 and 15 with WGS done on Illumina HiSeq2000. For research purpose and authorised user only.

  Dataset EGAD00001003429

• The Environmental Determinants of Diabetes in the Young Study (TEDDY)

  Study Overview The Environmental Determinants of Diabetes in the Young (TEDDY) Study is a longitudinal study that investigates genetic and genetic-environmental interactions, including gestational events, childhood infections, dietary exposures, and other environmental factors after birth, in relation to the development of islet autoimmunity and type 1 diabetes (T1D). A consortium of six clinical centers assembled to participate in the development and implementation of the study to identify environmental triggers for the development of islet autoimmunity and T1D in genetically susceptible individuals. Beginning in 2004, the TEDDY study screened over 400,000 newborns for high-risk HLA-DR, DQ genotypes from both the general population and families already affected by T1D. The TEDDY study enrolled around 8,676 participants across six clinical centers worldwide (Finland, Germany, Sweden and three in the United States) in the 15-year prospective follow-up. Participants are followed every three months for islet autoantibody (IA) measurements with blood sampling until four years of age and then at least every six months until the age of 15. After the age of four, autoantibody positive participants continue to be followed at three month intervals and autoantibody negative participants are followed at six-month intervals. In addition to the analysis of autoantibodies, additional data and sample collection are performed at each visit. Parents collect monthly stool samples in early childhood. The parents also fill out questionnaires at regular intervals in connection with study visits and record information about diet and health status in the child's TEDDY Book between visits. Continued long-term follow-up of the currently active TEDDY participants will provide important scientific information on early childhood diet, reported and measured infections, vaccinations, and psychosocial stressors that may contribute to the development of type 1 diabetes and islet autoimmunity. Additional information on the TEDDY study is available in the following articles: Rewers et al., 2008, PMID: 19120261 and Hagopian et al., 2006, PMID: 17130573. Details of the TEDDY protocol can be found in Hagopian et al., 2011, PMID: 21564455. TEDDY data currently available in dbGaP include: gene expression, SNPs, exome, microbiome (gut, nasal, and plasma), RNA sequencing, and whole genome sequencing. For more information on TEDDY Study version history please refer to TEDDY Study dbGaP README File. ImmunoChip SNP DNA from whole blood samples on study participants and their family members (mothers, fathers, and siblings) was obtained and used for SNP genotyping. Genotyping was performed by the Center for Public Health Genomics at the University of Virginia using the Illumina ImmunoChip SNP array, which contains around 196,000 SNPs from 186 regions associated with 12 autoimmune diseases (Hadley et al., 2015, PMID: 26010309). Data cleaning and validation included the removal of subjects with a low call rate (< 5% SNPs missing) and differences in reported sex and prior genotyping at the TEDDY HLA laboratory. Additionally, SNPs with a low call rate or Hardy-Weinberg equilibrium P value < 10-6, except for chromosome 6 due to HLA eligibility requirements, were removed from the final dataset (Törn et al., 2015, PMID: 25422107).TEDDY-T1DExome ArrayDNA from whole blood samples on study participants and their family members (mothers, fathers, and siblings) was obtained and used for genotyping. Genotyping was performed by the University of Virginia using the Illumina TEDDY-T1DExome array. The TEDDY-T1DExome array is a custom chip that contains 550,601 markers from the Infinium CoreExome-24 v1.1 BeadChip and an additional 90,214 tagSNPs specifically selected by the TEDDY investigators based on their associations with nutrients, vitamins, type 2 diabetes, autoimmune diseases, body-mass index, or other exposures and phenotypes measured by TEDDY study.The Illumina GenTrain2 algorithm was used for genotype calling. Sample quality control metrics included sample call rate, heterozygosity rate and concordance of gender between the information reported and genotyped. Gene Expression The TEDDY study collected peripheral blood for the extraction of total RNA from enrolled children starting at 3 months of age, and then at 3 month intervals up to 48 months and then biannually. Total RNA was extracted using a high throughput (96-well format) extraction protocol using magnetic (MagMax) beads technology at the TEDDY RNA Laboratory, Jinfiniti Biosciences in Augusta, GA. Purified RNA (200 ng) was further used for cRNA amplification and labeling with biotin using Target Amp cDNA synthesis kit (Epicenter catalog no. TAB1R6924). Labeled cRNA was hybridized to the Illumina HumanHT-12 Expression BeadChips based on the manufacturer's instructions. The HumanHT-12 Expression BeadChip provides coverage for more than 47,000 transcripts and known splice variants across the human transcriptome. Microbiome The TEDDY microbiome study aimed to characterize the longitudinal development of the microbiome, including bacteria, viruses and other microorganisms in the gut, plasma, and nasal cavity of prediabetic and diabetic subjects compared to autoantibody negative non-diabetic subjects. Stool samples used were collected monthly from 3 to 48 months, after which stool samples were collected every 3 months. Nasal swab samples were collected every 3 months starting at 9 months of age until 48 months, after which nasal swabs were collected every 6 months. Plasma samples were collected every 3 months starting at 3 months of age until 48 months, after which plasma samples were collected every 6 months. If the subject was autoantibody positive at 48 months then they remained on the 3 month collection interval for nasal swab and plasma samples. Samples underwent 16s rRNA gene sequencing, DNA and viral RNA metagenomics shotgun sequencing, and sequencing of the internal transcribed spacer (ITS) regions. Additional information on the TEDDY microbiome data is available in the following articles: Vatanen et al., 2018, PMID: 30356183, Stewart et al., 2018, PMID: 30356187, and Vehik et al., 2020, PMID: 31792456. RNA Sequencing The TEDDY study aimed to characterize the transcriptome in subjects with islet autoimmunity and type 1 diabetes compared to matched control subjects. Peripheral blood was collected to extract total RNA from enrolled children starting at 3 months of age, and then at 3 month intervals up to 48 months and then biannually. Total RNA was extracted using a high throughput (96-well format) extraction protocol using magnetic (MagMax) beads technology at the TEDDY RNA Laboratory, Jinfiniti Biosciences in Augusta, GA. Purified RNA was then sent to the Broad Institute for the generation of the TEDDY RNA sequencing (RNA-Seq) data. The RNA samples were prepped using Superscript III reverse transcriptase and Illumina's TruSeq Stranded mRNA Sample Prep Kit. The TruSeq libraries were run on the Illumina HiSeq2500 platform. Whole Genome Sequencing The TEDDY study aimed to conduct deep whole genome sequencing and examine the genomic variations in subjects with islet autoimmunity and type 1 diabetes compared to matched autoantibody negative and non-diabetic children. DNA from whole blood was obtained from TEDDY children for whole genome sequencing. The WGS data were generated on the Illumina HiSeq X Ten system.

  Study phs001442

• RNA-seq of human embryonic heart, lung, and cerebellum

  Characterization of cell types in the human embronic heart, lung, and cerebellum.

  Study EGAS00001004375

• CGP CORE CELL LINES - RNA-seq

  Genomic characterisation of a large series of cancer cell lines.

  Dataset EGAD00001001357

• Gene Expression Study of Individuals with Sex Chromosome Aneuploidies

  Males and females show dramatic differences in their vulnerability to the same diseases. For example, compared to men, lupus is six times more prevalent, thyroid cancer is three times more prevalent, and unipolar depression is twice as prevalent in women. Diseases with a strong male bias include autism (5:1), dilated cardiomyopathy (3:1), and ankylosing spondylitis (5:1). Historically, such differences have been attributed solely to extrinsic factors such as circulating sex hormones or environmental influences. We hypothesized that intrinsic factors - genetic differences between XX and XY cells - have unappreciated biological consequences throughout the body and contribute to sex differences in disease incidence and severity. This hypothesis stems from our long-term effort to sequence the sex chromosomes of diverse mammalian species, which has identified a set of homologous genes on the X and Y chromosomes that are dosage-sensitive, expressed throughout the body, and encode regulators of chromatin modification, transcription, translation, and protein stability. These X- and Y-encoded genes differ in sequence and expression pattern, which likely manifests in genome-wide differences in gene regulation between XX and XY cells and influences all aspects of human biology, including sex differences in disease susceptibility. These hard-wired molecular sex differences have been largely overlooked and understudied, representing a significant gap in our knowledge of human biology.The gene expression study of individuals with sex chromosome aneuploidies takes advantage of natural human variation in sex chromosome number, i.e. sex chromosome aneuploidy, to investigate alterations in genome-wide gene expression that correlate with changes in X- and Y-chromosome dosage. We analyzed samples from 114 individuals with a variety of sex chromosome aneuploidies, including 45,X; 47,XXY; 47,XYY; 47,XXX; 48,XXYY; and 49,XXXXY. We generated lymphoblastoid cell lines (LCLs) from blood samples and, in some cases, fibroblast cultures from skin biopsies. We supplemented our collection with previously-derived cell lines. To evaluate gene expression, we performed deep profiling of the transcriptome (RNA-seq) from these LCLs and fibroblasts. We performed parallel analyses on samples collected from 62 control 46,XX and 46,XY individuals, 6 individuals with trisomy 21, and 14 individuals with structural variations of the X and Y chromosomes. In addition, we performed CRISPRi knockdowns on 3 of the 46,XX and 3 of the 46,XY fibroblast samples for the homologous transcription factors ZFX and ZFY, encoded on the X and Y chromosomes, respectively.In the April 2024 update, we added RNA-seq datasets derived from isolated CD4+ T cells and monocytes from 76 and 72 adults, respectively, with the following sex chromosome constitutions: 45,X; 46,XX; 46,XY; 47,XXX; 47,XXY; 47,XYY. These individuals are largely a subset of the same cohort described above. In addition, we performed RNA-seq on in-vitro stimulated CD4+ T cells with the following sex chromosome constitutions: 45,X; 46,XX; 46,XY; 47,XXY.In the August 2024 update, we added RNA-seq datasets generated from the following: 1) LCLs derived from individuals with AZFa deletions of the Y chromosome, 2) DDX3X and DDX3Y knockdown (via CRISPRi) in XY fibroblasts, and 3) 5-ethyl uridine (5-EU) treatment in XY and XYYYY LCLs.

  Study phs002481

• Ribosomal Depleted Total RNA-Seq of PBMCs and Skin from Controls and Systemic Sclerosis Patients

  This study involved prospective collection of skin biopsies and peripheral blood mononuclear cell (PBMC) samples from controls with no self-reported history of autoimmune or inflammatory disease and cases with Rheumatologist-confirmed systemic sclerosis: limited cutaneous systemic sclerosis (lcSSc), diffuse cutaneous systemic sclerosis (dcSSc), very early diagnosis of systemic sclerosis (VEDOSS), and systemic sclerosis sine scleroderma (SSS). Some SSc cases were sampled at a 6 month routine follow-up visit. PBMCs were collected and lysed immediately. Skin punches were stabilized in RNAlater until extraction. All RNA-Seq libraries were created using Takara/Clontech ribosomal depletion kits, and sequenced on either a HiSeq2500 or HiSeq3000.

  Study phs002902

• Counts: Brain transcriptome of hereditary cerebral haemorrhage with amyloidosis–Dutch type (HCHWA-D)

  These are the log2CPM (log2 counts per million) fragments per gene counts associated with the BAM files in EGAD00001003806, in tab separated format. Counts for 36 postmortem brain samples from 9 non-demented control subjects and 9 Hereditary cerebral hemorrhage with amyloidosis-Dutch type subjects are included (1 Frontal cortex sample and 1 Occipital cortex sample per subject). RNA samples were depleted for ribosomal RNA with the Ribo Zero Gold Human kit (Illumina) and strand specific RNA-Seq libraries were generated. Paired-end sequencing was performed on a HiSeq2500 Illumina system (2x50bp reads). Alignments were performed using GSNAP v2014-12-23 with setting "--npaths 1" on GRCh38 reference genome without the alternative contigs. Fragment per gene counting was performed using HTSeq-count v0.6.1p1 with setting "--stranded reverse". The gene annotation used for quantification were UCSC RefSeq genes for GRCh38 downloaded on 2015-07-13.

  Dataset EGAD00010001457

• RNA-Seq of human longitudinal whole blood samples from PCR-positive and PCR-negative recent household contacts of COVID-19 index cases.

  Little is known about the transcriptomic profile of individuals who are exposed to SARS-CoV-2 yet resist becoming PCR positive. To investigate this, longitudinal whole-blood samples were taken (0, 7, 14, and 28 days after enrolment) from PCR positive and PCR negative SARS-CoV-2-naïve household contacts who were recently exposed to a COVID-19 index. Samples were also taken from pre- and post-pandemic unexposed controls. Total RNA was extracted from PAXgene tubes before undergoing poly(A) selection followed by globin and rRNA depletion. DNA libraries were constructed using the NEBNext® Ultra™ II Directional RNA Library Prep Kit for Illumina. All samples were then sequenced across 2 flowcells of an Illumina HiSeq 4000.

  Dataset EGAD50000000684

• Oesophageal adenocarcinoma scRNAseq from LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19)

  This dataset contains single-cell RNA-seq generated from the LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19) and additional donors with Barrett's oesophagus using the 5' Single Cell Gene Expression assay from 10x Genomics. Samples were generated from oesophageal tumours, Barrett's oesophagus, and normal oesophagus and gastric tissues, with the aim of generating a reference atlas for cell types found in normal and disease-associated tissue states in the upper GI tract. This reference atlas was used as the basis for a deconvolution workflow to estimate the cell composition of bulk transcriptomes from these tissues, and to assess cell type-specific expression patterns of potential predictive biomarkers for immunochemotherapy regimens in this setting.

  Dataset EGAD00001009401

• ProstOmics - Spatial Transcriptomics

  Spatial transcriptomics data (ST) from 32 human prostate tissue samples originating from 8 prostate cancer patients (5 patients with post-surgery relapse). The ST data was acquired using the Visium Spatial Gene Expression kit which resulted in over 20 000 spatially defined spots for the 32 tissue samples. The raw transcriptomics data is RNA-seq. The individual samples have information on patient origin and sample type (cancer, cancer-adjacent field-effect normal or normal sample far from cancer). Each ST spot has metadata such as sample origin, histology class (stroma, normal epithelium, cancer of various grading etc), number of cells and estimated cell type fractions. Patient metadata include information of age at surgery, time (months) until reported relapse, total follow-up time, pre-surgery PSA, post-surgery T-stage and metastasis status.

  Dataset EGAD50000000603

• NGS data of human NES cells and tumors

  Raw RNA-seq data for WT and 2 Gorlin NES cells, tumors derived from MYCN mis-expressed WT NES cells, tumors derived from Gorlin NES cells, and tumors derived from Gorlin NES cells transduced with mutant DDX3X (R351W and R534S) and CRISPR/Cas9 targeting GSE1 (each sample has 3 replicates/tumors except Gorlin NES cell tumors have 4). Raw whole exome sequencing data for WT and Gorlin 1 NES cells, tumors derived from MYCN mis-expressed WT NES cells, and tumors derived from Gorlin NES cells (each sample has 3 replicates/tumors except Gorlin NES cell tumors have 4). Raw data for amplicon sequencing of GSE1 and KDM3B at regions targeted by CRISPR/Cas9 in Gorlin NES cells.

  Dataset EGAD00001004990

• RNA-seq study of longitudinal blood cell samples drawn from children at risk of type 1 diabetes

  The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding auto-antibody positivity or reflect progressive b-cell destruction. Here we report the mRNA sequencing-based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4, CD8 cell fractions and unfractionated PBMC samples longitudinally collected from seven children who developed beta-cell autoimmunity (case subjects) at a young age and matched control subjects.

  Dataset EGAD00001005767

• RNA-seq data for study 'Smoking-dependent expression alterations in nasal epithelium reveal immune impairment linked to germline variation and lung cancer risk.'

  RNA-seq data from nasal and bronchial tissues in 649 subjects, many with lung cancer. Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to lifestyle risk in the form of cigarette smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, often many years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk are unclear. CT screening of current and former smokers has been shown to reduce lung cancer mortality by up to 26%. To examine whether clinical risk stratification can be improved upon by the addition of genetic data, and to explore the mechanisms of the persisting risk in former smokers, we have analyzed transcriptomic data from accessible airway tissues of 487 subjects. We developed a model to assess smoking associated gene expression changes and their reversibility after smoking is stopped, in both healthy subjects and clinic patients. We find persistent smoking associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune and interferon related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. Our results provide initial evidence for germline-mediated personalised smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.

  Dataset EGAD50000000333

• Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions

  In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has killed hundreds of thousands of people, including >23,000 in New York City (NYC) alone. The pandemic's sudden emergence highlights the clinical need to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we provide large-scale shotgun metatranscriptomics (total-RNA-seq) for host, viral, and microbial profiling. In version 1, we sequenced a total of 732 clinical specimens (nasopharyngeal (NP) swabs) gathered from 669 unique patients in New York City during the first two months of the outbreak. In version 2, we sequenced an additional 168 clinical specimens from autopsy tissues (lung, heart, kidney, liver, and lymph node) from 60 patients, yielding a broad molecular portrait of the emerging COVID-19 disease across 900 clinical specimens and 729 patients.

  Study phs002258

• Reference Epigenomes and Regulatory Landscape of CLL

  Analysis of the reference epigenomes and regulatory landscape of CLL as a whole and its major clinico-biological subtypes (with mutated and unmutated IGHV) in the light of the normal B-cell differentiation. We have extensively characterized the reference epigenomes of seven primary chronic lymphocytic leukemia samples (CLLs) with mutated (n=5) and unmutated IGHV (n=2) as well as several mature B-cell subpopulations (naive B cells from blood and tonsil, germinal center B cells, memory B cells and plasma cells from tonsil) using genome-wide maps of six histone marks (H3K4me3, H3K4me1, H3K27ac, H3K36me3, H3K9me3 and H3K27me3), DNA accessibility (ATAC-seq), DNA methylation (whole-genome bisulfite sequencing) and gene expression (RNA-seq). Furthermore, we have mapped the regulatory chromatin landscape of 100 additional CLL cases using chIP-seq of H3K27ac and ATAC-seq and linked these data to additional layers of information (whole-genome and/or whole-exome sequencing (WGS/WES), RNA-seq and DNA methylation microarrays) studied in the context of the International Cancer Genome Consortium (ICGC).

  Dataset EGAD00001004046

• RNA-seq data of proliferative vitreoretinal diseases and healthy human retinal pigment epithelium

  This Data Access Committee (DAC) evaluates access requests for RNA-seq data generated from: - Membranes from proliferative vitreoretinal diseases, including proliferative vitreoretinopathy and epiretinal membranes. - Retinal pigment epithelial cells isolated from healthy ocular globes obtained from deceased donors. Collection and analysis of these residual human materials were conducted with the approval of the ULB-Erasme Ethical Committee (P2019/066 A2022/136) and of the Eye Bank (CHU Liège), with no need for informed consent in compliance with Belgian law. All data are pseudonymised, and access is restricted to qualified researchers whose proposed use of the data is consistent with the applicable ethical approval and legal requirements, including the General Data Protection Regulation (GDPR).

  Dac EGAC50000000721

• RNAseq on 20 samples of multiple myeloma patients and 3 normal plasma cells.

  RNAseq was performed using 200 ng of total RNA by GATC Biotech. Directional libraries were performed after mRNA selection by polyA selection using UTP method. RNA-seq libraries were sequenced on HiSeq2500 Illumina machine using 100bp paired-end reads. Reads alignment was performed using the STAR aligner (version 2.4.0f1) and human genome hg19 as reference.

  Study EGAS00001004347