Search Results - EGA European Genome-Phenome Archive

Alternative splicing isoforms in patient-derived hepatocellular carcinoma cells

The aim of this study was to obtain a landscape of alternative splicing (AS) in human hepatocellular carcinoma (HCC). We applied hybrid sequencing by integrating Pacbio long-read and Illumina short-read RNA sequencing data from 8 patient-derived HCC cell lines, and used an immortalized hepatocyte cell line as reference. This study revealed features of annotated and novel splice variants in HCC cells, including transcript length, AS type and protein changes. We also identified novel isoforms and tumor specific isoforms, which may represent potential biomarkers and targets for therapeutic development.

Study EGAS00001002697

Pediatric tumor in a single child of three large nuclear families

We identify three nuclear families in which a pediatric tumor had been diagnosed in a single child and neither parent had been diagnosed with cancer. These families had 4, 5, and 7 children, respectively. Diagnoses included Wilms tumor, low-grade astrocytoma, and Burkitt’s lymphoma, respectively. We used whole-genome sequencing to profile normal cells from each family member and a linked-read technology for genomic phasing, which enabled us to identify compound-heterozygous and de novo variants in addition to simple-heterozygous and homozygous-alternate variants.

Study EGAS00001005321

WES data from 165 tumor/germline samples with muscle invasive bladder cancer.

In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (< pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). WES was performed using DNA from 165 tumors (76x median coverage) and associated germline DNA (46x median coverage). Data provided here consist of 5,828 fastq files for WES.

Study EGAS00001004507

Genomics of pediatric myeloid neoplasms

Genomic profiling of pediatric myeloid tumors (AML, therapy-related myeloid neoplasms, MDS and others) has shown significant differences when compared adult myeloid neoplasms. This includes the recognition of pediatric-enriched entities including UBTF-TD and NUP98 rearranged leukemias. Collectively we have described over 23 unique molecular subtypes of pediatric AML with unique expression signatures, driver mutations, patterns of cooperating mutations and distinct outcomes. Some of the subtypes (KMT2A and NUP98, for example) have remarkable heterogeneity in fusions partners, cellular phenotypes and molecular signatures.

Study EGAS00001005760

Whole genome sequencing based on short and long reads from GM09237 cell line with and without folate depletion

To asess changes in the DNA-sequence occurring as a result of folate deprivation, DNA extracted from the GM09237 cell line grown with and without folate was sequenced using short read and long read sequencing. The DNA was extracted from cells cultured with either normal medium or medium with no folic acid for 5 days, and then sequenced by BGI PE100 platform (100 bp paired-end sequencing 60x coverage; performed by BGI), or PacBio Sequel system (SMARTbell; performed by BGI) respectively.

Study EGAS00001005345

Genetics of non-syndromic idiopathic autism spectrum disorders in India

The study explores the genetic architecture of patients diagnosed with non-syndromic autism spectrum disorders (according to the DSM-V criteria) in India. Patients were previously screened for aneuploidies using chromosomal G-banded karyotyping (at 500 band resolution) and Fragile-X using TP-PCR. Whole exome sequencing was performed on germline DNA from 100 idiopathic patients. Target enrichment was carried out using either Agilent SureSelect V6 or SureSelect Clinical Research Exome V2 kits. Pooled libraries were sequenced on Illumina HiSeq platform at an average coverage of 80-100x in 2x150bp configuration.

Study EGAS00001006060

Cancer and germline exomes, and cancer RNA-seq consisiting of FASTQ paired-end reads from melanoma, lung and colon cancer samples

Discovery of patient-specific tumor antigens usually requires in vitro-expanded autologous tumor infiltrating lymphocytes (TILs), among which tumor antigen-specific T cells are however often rare, thus limiting sensitivity. We designed in vitro culture conditions to improve the identification of rare tumor antigen-specific CD8 TILs. This innovative yet accessible pipeline allows highly-sensitive identification of tumor antigens and cognate T cell receptors (TCRs), greatly improving the selection of candidates for personalized cancer vaccines and TCR-based cellular immunotherapies.

Study EGAS00001005513

Genomic History of the Solomon Islands

The aim of this study was to provide for a better understanding of the genetic relationships among and between populations of Near and Remote Oceania, with a focus on the initial settlement of the Solomon Islands and their role in the first dispersal of people from Near into Remote Oceania. Irina Pugach, Ana T Duggan, D Andrew Merriwether, Françoise R Friedlaender, Jonathan S Friedlaender, Mark Stoneking, "The Gateway from Near into Remote Oceania: New Insights from Genome-Wide Data", Molecular Biology and Evolution, Volume 35, Issue 4, April 2018, Pages 871–886

Study EGAS00001006116

RNAseq data from human colon organoid infected by KP

The aim of this study is to identify the specific bacteria that are responsible for pathological bacterial translocation and subsequent Th17 priming in the liver in primary sclerosing cholangitis (PSC). To clarify the mechanism of how microbiota interacts with the intestinal epithelial barrier, monolayered human intestinal organoids were cultured with the specific bacteria. Gene expression analysis using RNA sequencing in epithelial cells cultured with Klebsiella pneumoniae derived from a PSC patient (KP-P1) or commercially obtained Klebsiella pneumoniae strain (KP JCM1662) was performed in this study.

Study EGAS00001003332

Multi-region whole-exome sequencing of 10 neuroblastoma cases

To investigate intratumour heterogeneity and to better understand tumour evolution in neuroblastoma, we have performed a multi-region whole-exome sequencing on a total of 51 spatially separated tumor samples from 9 primary neuroblastomas (2 low-risk, 1 intermediate-risk and 6 high-risk) and 1 relapsed neuroblastoma. We also assessed the impact of chemotherapy on the clonal expansion by sequencing tumour regions from one medium risk and one high-risk tumour for which we had matched samples obtained at diagnosis and after chemotherapy.

Study EGAS00001004735

Human and rat skeletal muscle multi-omic profiling

Skeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases and mobility. It is composed of several different cell and muscle fiber types. Here, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We additionally perform multi-omics profiling (gene expression and chromatin accessibility) on human and rat muscle samples.

Study EGAS00001005730

Placebo-only arm transcriptomic analysis of the phase 3 PROTECT clinical trial

It is poorly understood how the tumor immune microenvironment influences disease recurrence in localized clear cell renal cell carcinoma (ccRCC). Here we perform whole-transcriptomic profiling of 236 tumors from patients assigned to the placebo-only arm of a randomized, adjuvant clinical trial for high-risk localized ccRCC. Unbiased pathway analysis identifies myeloid-derived interleukin-6 (IL-6) as a key mediator. Furthermore, a novel myeloid gene signature strongly correlates with disease recurrence and overall survival on uni- and multivariate analysis and is linked to TP53 inactivation across multiple datasets.

Study EGAS00001006344

RNA-seq analysis of metastatic prostate cancer solid tumor biopsies

The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era of modern androgen receptor (AR)–targeting therapy. We sought to characterize the clinical and genomic features of t-SCNC in a multi-institutional prospective study. Patients with progressive, metastatic castration-resistant prostate cancer (mCRPC) underwent metastatic tumor biopsy and were followed for survival. t-SCNC is present in nearly one fifth of patients with mCRPC and is associated with shortened survival.

Study EGAS00001006369

Chromatin accessibility changes in hiPSC-derived neurons after BDNF and KCl stimulations

Brain-Derived Neurotrophic Factor (BDNF) is crucial for neuronal survival, differentiation, synaptic plasticity, memory formation, and neurocognitive health. Molecular mechanisms of BDNF promoting cellular survival and synaptic plasticity have been intensely studied, yet its role in genome regulation is obscure. Using human induced pluripotent stem cell (hiPSC)-derived neurons via lentiviral delivery of the neuronal transcription factor Ngn2, we performed a temporal profiling (1h, 6h and 10h) of chromatin accessibility upon BDNF treatment or depolarization (KCl) to identify BDNF-specific chromatin-to-gene expression programs.

Study EGAS00001006394

Multi-institutional collaboration to characterize 5hmC in prostate cancer, both tumor biopsies and cfDNA.

This study used pull-down sequencing to measure 5-hydroxymethylcytosine (5hmC) levels in tissue biopsy specimens from patients with localized and metastatic castration-resistant (mCRPC) prostate cancer. For a subset of the cohort, the same technique was used to sequence cell-free DNA (cfDNA) isolated from patient plasma. To assess 5hmC levels in cfDNA from a larger number of specimens, plasma samples from another mCRPC cohort were also assayed with this method. The larger cohort of cfDNA samples was further anlayzed with a targeted sequencing gene panel.

Study EGAS00001004942

cfDNA in Hereditary And High-Risk Malignancies (CHARM)

Our goal is to improve early cancer detection by developing a blood test to predict cancer development in carriers using circulating DNA. As carriers develop cancer, they may have pre-cancerous cells which release this DNA into the blood (cell-free DNA; cfDNA), which can be detected with novel genetic technologies. We propose to use three complementary cfDNA assays:shallow whole genome sequencing (sWGS), Liquid-Biopsy Sequencing (LB-Seq) and Cell-free Methylated DNA Immunoprecipitation and High-throughput Sequencing (cfMeDip-Seq) for early cancer detection.

Study EGAS00001006539

DRIP-seq data for Molecular Characterization of ETMRs

This dataset contains DRIP-seq data from 2 patients. DNA–RNA hybrids were extracted from tissue derived from ETMR patient-derived xenograft (PDX) models (BT183) that were treated using topotecan or saline as described previously27. Tumours were subsequently frozen and pelleted using ultracentrifugation. DNA–RNA hybrids were extracted as described previously using the same protocol that is applied for cultured cells21. DNA was extracted using proteinase K followed by phenol–chloroform extraction and ethanol precipitation. Subsequently the DNA was fragmented using the restriction enzymes HindIII, EcoRI, BsrGI, XbaI and SspI (New England Biolabs). Digested DNA was subsequently incubated with the anti-DNA–RNA hybrid anti- body S9.6 (Merck, MABE1095) and immunoprecipitated using agarose beads. Bound DNA–RNA hybrids were eluted and incubated with pro- teinase K and cleaned with an additional phenol–chloroform–ethanol extraction. The DNA was subsequently sonicated and sequenced using a Hiseq 2000 machine with a 50-bp single-read protocol. Each treat- ment condition was performed in duplicate and both RNase H and the input was included as negative controls resulting in 10 Fastq files.

Dataset EGAD00001006219

WES, sWGS and RNA-seq of Asian breast cancer

The dataset contains a full genomics characterization of 527 Asian breast tumours. This includes whole-exome sequencing of tumour tissue at 80X, whole-exome sequencing of matched normal (blood) tissue at 40X, shallow-whole genome sequencing at 0.1X for copy number analyses, and RNA-seq of tumour tissue at 40X coverage (>15 million reads). Whole-exome libraries were prepared using the Nextera Rapid Capture Exome Kit; exome capture was performed in pools of 3 and subjected to paired end 75 sequencing on a HiSEQ4000 platform. RNA libraries were prepared using the TruSeq Stranded Total RNA HT kit with Ribo-Zero Gold as per manufacturer’s instructions and also subjected to paired end 75 sequencing on a HiSEQ4000 platform. Uploaded bam files have been mapped to the hs37d5 human genome and processed using the standard GATK pipelines. Paired clinical, demographic, genotyping, and overall survival data for these patients are available from the associated publications or by request.

Dataset EGAD00001006399

Tagged-amplicon deep sequencing

This dataset contains a collection of tumour samples from high grade serous ovarian carcinoma patients with recurrent disease collected near the point of diagnosis as well as tumour samples collected after patient relapse upon or some time after study entry. Whole blood samples were also collected from patients at study entry for the purpose of germline variant detection. The majority of diagnosis samples were preserved in neutral buffered formalin whereas the majority of post-relapse samples were preserved in universal molecular fixative (UMFIX, Sakura Finetek USA, Inc). DNA was extracted and the tagged-amplicon deep sequencing assay was applied (TAm-Seq, Forshew et al. 2002, Sci Transl Med) with the aid of fluidigm access array technology. Targeted loci were sequenced at very high depths (typically >100X) for the detection of both somatic and germline variants. Sequenced reads were aligned to the GRCh37 reference genome (release hs37d5).

Dataset EGAD00001011058

Genomic variants in 121 genes associated with ovarian cancer in cancer tissue and derived organoids

High-grade serous ovarian cancer (HGSOC) likely originates from the fallopian tube (FT) epithelium, but advanced stages are mostly found outside the FT. We used ex-vivo cultures of HGSOC and knock-out of tumor suppressors in FT organoids to study changes in epithelial cells and niche requirements for normal and transformed FT cells. We found that transformed cells require BMP signaling and are growth arrested in Wnt rich medium. A SureSelectXT Automation Custom Capture Library (Agilent) target enrichment panel was designed. The enrichment panel comprised all coding exons of 121 genes associated with ovarian cancer. Capture was performed according to the manufacturer’s instructions using an NGS Workstation Option B (Agilent) for automated library preparation starting with 3 μg DNA per sample. Sequencing was performed on a Illumina Hiseq 2500 system gnerating 2x100bp paired end reads and a target coverage of >200 per sample. Sequence reads were mapped to the haploid human reference genome (hg19) using BWA. Variants where called with FreeBayes v1.1.

Dataset EGAD00001005279

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

This dataset contains bulk transcriptomes from the inoperable cohorts of the LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19). Transcriptomes were prepared from pre-treatment oesophageal tumour biopsies using a ribodepletion approach in order to assess both previously reported (e.g. PD-L1 expression) and novel predictive expression-based biomarkers for immunochemotherapy treatment in this setting. On-treatment and post-treatment biopsies were generated as well to characterize response to therapy, and samples were also prepared from paired normal GI tissues for a subset of patients. scRNA-seq based deconvolution was also applied to bulk transcriptomes in this study to estimate the cell composition of tumour biopsies and assess the link between the presence of specific cell types with immunochemotherapy outcomes.

Dataset EGAD00001009399

Lenalidomide Resistance in del(5q) Myelodysplastic Syndrome Follows Loss of RUNX1/TP53-mediated Megakaryocytic Differentiation

Interstitial deletion of the long arm of chromosome 5 (del(5q)) is the commonest structural genomic variant in myelodysplastic syndromes (MDS). Lenalidomide (LEN) is the treatment of choice for patients with del(5q) MDS, but half of the responding patients become resistant within two years. TP53 mutations are detected in ~20% of patients who become resistant to LEN. Our data show that patients who become resistant to LEN harbor either TP53 or RUNX1 mutations or loss of RUNX1 expression. Here we show that LEN-induced degradation of IKZF1 permits a RUNX1/GATA2 complex to drive megakaryocytic differentiation and consequent del(5q) MDS progenitor cell death via CRBN-mediated CSNK1A1 degradation. Overexpression of GATA2 is able to restore LEN sensitivity in the context of RUNX1 or TP53 mutations by enhancing LEN-induced megakaryocytic differentiation. Screening for TP53 and RUNX1 mutations or downregulation should identify patients resistant to LEN, and strategies to activate GATA2 may resensitize del(5q) MDS cells to LEN.

Dataset EGAD00001005769

Alignment BAM files and gene count files of the Illumina Sequencing Data (10 tumor samples)

Reads were processed with the RNA-seq workflow 1.3.0 developed by the DKFZ Omics IT and Data Management Core Facility (https://github.com/DKFZ-ODCF/RNAseqWorkflow). First, FASTQ reads were aligned via two-pass alignment using STAR 2.5.3a. The STAR index was generated from the 1000 Genomes assembly and GENCODE Version 19 gene models with a sjdbOverhang of 200. Duplicate marking of the resultant main alignment file was done with sambamba 0.6.5. Gene-specific read counting was performed using featureCounts (from Subread 1.5.1) over exon features based on GENCODE Version 19 gene models. Both reads of a paired fragment were used for counting, and the quality threshold was set to 255, indicating that STAR found a unique alignment. Strand-specific counting was also used. For RPKM and TPM calculations, all genes on chromosomes X and Y, the mitochondrial genome, as well as rRNA and tRNA genes were omitted as they are likely to introduce library size estimation biases.

Dataset EGAD00001008969

RNA-sequencing of ex vivo exhausted human antigen-specific T cells

Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. To explore new pathways for reinvigoration of anti-tumor immune functions, we developed a human ex vivo exhaustion model by repetitive antigenic stimulation of primary CD8 T cells. This results in T cells that resemble patient-derived T cells in tumors on a phenotypic and transcriptional level. Four human healhy donor CD8+ T cells were isolated, transduced with an NY-ESO-1 TCR lentivirus construct, stimulated in four different conditions (Trested, Ttumor, Tex, Teff) with T2 tumor cells and specific peptides over 12 days. Cells were then sorted for TCR Vbeta 13.1+ (NY-ESO-1 TCR) CD8+ CD3+ CD56- CD4- DAPI- cells. RNA-seq TruSeq libraries were generated from polyA-enriched mRNA isolated from the samples, and sequenced in paired-end mode (2x51bp) on 2 lanes of an Illumina NovaSeq 6000 flow-cell. FASTQ sequence files were generated with the Illumina RTA version 3.4.4 and Base-calling Version bcl2fastq-2.20.0.422.

Dataset EGAD00001009754

The scRNA dataset for TIGIT in MCL with CART

We collected longitudinal samples from 15 patients with MCL at various clinical time points before and after CAT-T therapy brexucabtagene autoleucel (BA) infusion. The patients were grouped into three categories based on their clinical responses after BA treatment: 1) responsive (n = 9), 2) relapsed (n = 5), and 3) refractory (n = 1). All patients in category #1 and #2 had initially attained a complete response (CR) after BA therapy. The responsive group maintained CR with no relapse at the time of last follow up, while the relapsed group achieved initial CR but eventually relapsed. The 10x Chromium™ Single-Cell 5′ Reagent Kit v2 (PN-1000190, 10x GENOMICS) and Chromium Single-Cell Human TCR amplification Kit (PN-1000252, 10x GENOMICS) were used to perform single-cell separation, cDNA amplification, and library construction for gene expression and TCR repertoire following the manufacturer’s guidelines. Thirty-nine samples passed quality control and underwent single-cell transcriptome profiling with simultaneous single-cell T-cell receptor (TCR) repertoire analysis.

Dataset EGAD00001010180

Selection of somatic escape variants in SERPINA1 in liver tissue of patients with alpha-1 anti-trypsin deficiency - WGS

Somatic variants accumulate in non-malignant tissues with age. Functional variants leading to clonal advantage of hepatocytes accumulate in the liver from patients with acquired chronic liver disease (CLD). Whether somatic variants are common to CLD from differing aetiologies is unknown. We analysed liver somatic variants in patients with genetic CLD from alpha-1 anti-trypsin (A1AT) deficiency or haemochromatosis. We show that somatic variants in SERPINA1, the gene encoding A1AT, are strongly selected for in A1AT deficiency, with evidence of convergent evolution. Acquired SERPINA1 variants are clustered leading to truncation or coding change at the C-terminus of A1AT. In vitro and in vivo, C-terminal truncation variants reduce disease-associated Z-A1AT polymer accumulation and disruption of the endoplasmic reticulum, supporting the C-terminal domain swap mechanism. Therefore, somatic escape variants from a deleterious germline variant are selected for in A1AT deficiency, suggesting functional somatic variants are disease-specific in CLD and point to disease-associated mechanisms.

Dataset EGAD00001015430

Understanding the development of resident memory T cells (Trm) in the human small intestine using integrative multiomic approaches: Adult RNA (2025-10-14)

Animal studies have demonstrated that resident memory T (Trm) cells provide enhanced protective responses to a broad array of tissue-tropic pathogens, thus making Trm cells promising targets for novel vaccination strategies. However, the biological pathways that enable the long-term survival of Trm cells are poorly understood in humans. Here, we will employ a unique human intestinal transplantation setting that allows us to study the retention of persistent T cells in the grafts and the temporal development of resident T-cell populations from recruited recipient T cells. We will integrate high resolution transcriptomics, epigenetics, proteomics and immune repertoire single-cell data from purified intestinal T cells. These single-cell multiomics approaches will uncover the diversity and differentiation of the T cell populations in the human intestine, allowing us to temporally resolve the generation and maintenance of gut resident T cells. . This dataset contains all the data available for this study on 2025-10-14.

Dataset EGAD00001015739

Raw DNA and RNA data from breast cancer organoids, control samples and biopsies

Whole genome sequencing data for primary tumors, matching control material from blood and their corresponding organoid. Whole transcriptome data for organoids.

Dataset EGAD00001003751

The landscape of somatic mutation in normal colorectal epithelial cells

The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic events and consequent clonal expansions leading to cancer. As for most cancer types, however, understanding of the earliest phases of colorectal neoplastic change, which may occur in morphologically normal tissue, is comparatively limited because of the difficulty of detecting somatic mutations in normal cells. Each colorectal crypt is a small clone of cells derived from a single recently-existing stem cell. Here, we sequenced hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed, some ubiquitous and continuous, others only found in some individuals, in some crypts or during some phases of the cell lineage from zygote to adult cell. Likely driver mutations were present in ~1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium.

Dataset EGAD00001004192

A practical guide for mutational signature analysis in hematological malignancies

Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data.

Dataset EGAD00001005028

Selection of somatic escape variants in SERPINA1 in liver tissue of patients with alpha-1 anti-trypsin deficiency - Exome

Somatic variants accumulate in non-malignant tissues with age. Functional variants leading to clonal advantage of hepatocytes accumulate in the liver from patients with acquired chronic liver disease (CLD). Whether somatic variants are common to CLD from differing aetiologies is unknown. We analysed liver somatic variants in patients with genetic CLD from alpha-1 anti-trypsin (A1AT) deficiency or haemochromatosis. We show that somatic variants in SERPINA1, the gene encoding A1AT, are strongly selected for in A1AT deficiency, with evidence of convergent evolution. Acquired SERPINA1 variants are clustered leading to truncation or coding change at the C-terminus of A1AT. In vitro and in vivo, C-terminal truncation variants reduce disease-associated Z-A1AT polymer accumulation and disruption of the endoplasmic reticulum, supporting the C-terminal domain swap mechanism. Therefore, somatic escape variants from a deleterious germline variant are selected for in A1AT deficiency, suggesting functional somatic variants are disease-specific in CLD and point to disease-associated mechanisms.

Dataset EGAD00001015431

Methylation Biomarkers can Distinguish Pleural Mesothelioma from Healthy Pleura and other Pleural Pathologies

Pleural mesothelioma (PM) is a rare cancer type. This study developed a methylation-based biomarker assay to distinguish PM from healthy pleura and other pleural conditions. By analyzing methylation data, 744 hypermethylated CpG sites specific to PM were identified and validated with high accuracy. Using the bisulfite-free IMPRESS technique, the assay was further validated in a diverse cohort, showing strong performance in distinguishing tumoral from non-tumoral samples and PM from pleural metastases. These findings support the assay’s potential as a robust diagnostic tool for PM.

Study EGAS00001008153

Exome Sequencing for Diseases of the Immune System: X-linked Immunodeficiency with Magnesium Defect, EBV Infection, and Neoplasia (XMEN)

The etiologies of primary immunodeficiencies often yield novel insights about the immune system. Although a genetic etiology has been suspected for patients with abnormally low CD4+ T cells in the absence of HIV infection or any known causes of lymphopenia, no genetic mutation has been described to date for any case of primary CD4 lymphopenia. In this study, we characterized a non-consanguineous family with two non-HIV infected boys exhibiting an inverted CD4 to CD8 T cell ratio and a history of recurrent chronic viral infections since birth. Consistent with a decreased thymic output of CD4+ T cells, the percentage of CD31+ cells in the CD4+ naive population of these patients was decreased. In addition, the activation of T cells was significantly impaired in the patient upon TCR stimulation. Given the mother's T cells show completely skewed X chromosome inactivation, we suspected that the nature of this disease is X-linked. We performed X-chromosome exon-capture targeted single-end Solexa sequencing on two brothers and the mother and found a 10 base pair deletion at an intron-exon junction of Magnesium Transporter 1 (MAGT1), a Mg2+ specific transporter. We confirmed that this deletion leads to altered splicing, frameshift, early termination of the mRNA, and deficient protein expression in the lymphocytes of the two patients. Moreover, knockdown of this transporter in T cells isolated from healthy donors can recapitulate the observed T cell activation defect while its ectopic expression in the patients' lymphocytes can restore T cell stimulation. Our discovery highlights the significance of this transporter to T cell function.

Study phs000365

Correlative Studies for Protocol #14-C-0059: T Cells Expressing an Anti-GD2 Chimeric Antigen Receptor in Patients with GD2+ Solid Tumors, a Collaboration with CIMAC-CIDC

This study is a retrospective correlative analysis of immune cell phenotypes in samples from a Phase I clinical trial (NCT02107963) of GD2 CAR-T cells (GD2-CAR.OX40.28.z.iC9) in children and young adults with osteosarcoma and neuroblastoma. The study was a 3+3 dose-escalation study with four dose levels (1 x 10(5) transduced T cells/kg; 1 x 106 transduced T cells/kg; 3 x 106 transduced T cells/kg; and 1 x 107 transduced T cells/kg). Apheresis and final manufactured GD2 CAR-T product samples were analyzed by bulk RNA sequencing and ATAC sequencing. The patients were stratified into good CAR-T expanders (peak CAR-T expansion >1000 GD2 CAR copies/100ng DNA) and poor CAR-T expansion (peak CAR-T expansion Increased naïve T cell subsets in baseline apheresis are associated with patients who experienced good CAR T cell expansion A T cell exhaustion signature was observed in the manufactured GD2 CAR-T product and may have contributed to lack of efficacy observed in this trial Increased myeloid-derived suppressor cell (MDSC) signatures were observed in patients with poor CAR-T expansion CAR-T product in good expanders displayed increased AP-1 factor transcription factor motifs, such as BATF, JUN, and FOS Data provided in dbGaP for this study include: Bulk RNA-Seq data for 11 pre-treatment peripheral blood and 11 GD2 CAR-T product from 14 patients. ATAC sequencing of 22 peripheral blood samples and 5 GD2 CAR-T products from 14 patients.

Study phs003455

Bone marrow breakout lesions act as key sites for tumor-immune cell diversification and exhaustion in multiple myeloma

Multiple myeloma is a disease characterized by the expansion of cancerous plasma cells in the bone marrow. The bone marrow microenvironment plays a pivotal role in supporting myeloma growth and modulating tumor immunity. As the disease progresses, myeloma cells may become independent of the bone marrow environment, leading to extramedullary disease associated with poor prognosis. However, the early processes associated with bone marrow independence and its implications for disease and immune control remain poorly understood. Here, we employed comprehensive single-cell and spatial mapping to identify the disruption of the cortical bone and subsequent expansion of myeloma cells in breakout lesions as a key event in multiple myeloma pathogenesis and tumor immunity. Breakout lesions harbor an adapted niche and a unique immune microenvironment conferred by sustained immune-tumor interactions. In particular, tumor-reactive T cells with a highly exhausted phenotype, alongside unique NK cell and macrophage subtypes, specifically expanded in breakout lesions. Spatially-resolved genomic, transcriptomic and cellular analyses uncovered extensive intra-lesion heterogeneity, suggesting a divergent co-evolution of genomic variation and locally confined T cell responses in distinct subregions. Ultra-high plex imaging revealed that tumor-reactive T cells, together with other immune-regulatory cells and dendritic cells, co-expand and exhaust upon sustained tumor interactions in locally confined immune islands. In contrast, immune-regulatory macrophage and NK cell subsets operate spatially separated within myeloma cell deserts. Jointly, our analyses uncover bone marrow breakout lesions as a hotspot for tumor-immune cell interactions, diversification and exhaustion, representing a key event in myeloma pathogenesis with significant therapeutic implications.

Study EGAS50000000304

Rapid Early Action for Coronary Treatment (REACT-BioLINCC)

Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Objectives: This multicenter controlled community study developed and evaluated the impact of a community educational intervention program on participant delay time from onset of symptoms of an acute myocardial infarction (AMI) to arrival at a hospital emergency department.Background: Although early reperfusion or thrombolytic therapy can reduce morbidity and mortality following an AMI, delayed access to medical care in participants is relatively common. Mean delay times from symptom onset to hospital arrival range from more than 4 hours to 24 hours, and the largest component of prolonged delay is participant recognition and action.Participants: A total of 20 communities from 5 field centers in the U.S. were pair-matched (10 pairs) according to geographic proximity and demographic characteristics. After initiation of a 4 month baseline surveillance period, one community in each pair was randomly selected to receive the intervention. The baseline surveillance period was followed by an 18 month community intervention and surveillance period. The community surveillance captured a total of 59,944 adults aged 30 years or older presenting to hospital emergency departments with chest pain, of whom 20,364 met study criteria for suspected acute coronary heart disease (CHD) at admission and discharged with a CHD diagnosis.Conclusions: Delay times were decreased in the intervention and reference communities. The results showed that the multicomponent community intervention program did not differentially reduce delay time from onset of AMI symptoms to arrival at a hospital, but did significantly increase the use of Emergency Medical Services by these participants in the intervention communities. (PMID:10872014).

Study phs003885

The EGA at the International Congress of Human Genetics

Today is the start of the International Congress of Human Genetics (ICHG). This event, hosted by the African Society of Human Genetics (AfSHG) and the Southern African Society for Human Genetics (SASHG), will reunite international experts to highlight how genomic technologies are being managed to address challenges generated by the current status of Human Health and Genomics. The European Genome-phenome Archive (EGA) will be at the Congress participating in workshops, meetings and talks where topics such as data access and discovery as well as the Federated EGA will be present. Data access and discovery In the context of the “Federated data analysis workshop“ that will be held the 26ᵗʰ, managed in the context of the CINECA project, a hands-on-session on Beacon v2 Discovery will be led by Mauricio Moldes. Another session on authorisation and data access will be presented by Mallory Freeberg and Coline Thomas, with and introduction by Thomas Keane. During the workshop, an end-to-end federated data analysis use case will be presented. Data access and discovery In the context of the “ Federated data analysis workshop“ that will be held the 26ᵗʰ, managed in the context of the CINECA project, a hands-on-session on Beacon v2 Discovery will be led by Mauricio Moldes. Another session on authorisation and data access will be presented by Mallory Freeberg and Coline Thomas, with and introduction by Thomas Keane. During the workshop, an end-to-end federated data analysis use case will be presented. During the last four years, CINECA has been identifying gaps in data sharing between Africa, Canada and Europe in order to build a federated solution for data access. Thomas Keane will present the project within the sessions happening the 24ᵗʰ. The Federated EGA at the ICHG A Federated EGA poster will be shown during the Poster Session 1 that will take place the 23ʳᵈ. The objective is to bring awareness of the European Genome-phenome Archive as a resource for permanent archive and secure data sharing. In this context, the network generated by the Federated EGA is key for cases where research data cannot be shared outside local jurisdictions. The Federated EGA was officially launched on 2022 with research institutes from five countries becoming the first nodes of this network. Nowadays, with more than 20 nodes preparing to join, it aims to become the largest human omics data sharing initiative towards understanding human health and disease. The H3Africa Initiative and the African research represented in the EGA 1.1% of the EGA studies include samples from African populations. Countries such as South Africa, Kenya, Uganda or Egypt, among others, are present in the 72.577 samples from African individuals archived at the EGA. 23 EGA datasets are managed by the Human Heredity and Health in Africa Initiative (H3Africa). This Initiative will celebrate its Consortium Meeting the 27ᵗʰ and 28ᵗʰ, back-to-back with the ICHG. H3ABioNet, the Pan African Bioinformatics Network for the H3Africa consortium, will also take this context to celebrate its 10-Year Symposium during the Congress. Members of the EGA team will attend both of them, as the H3ABioNet works in conjunction with H3Africa projects, to submit data to the European Genome-Phenome Archive.

Blog the-ega-at-the-international-congress-of-human-genetics

How upcycled prostate cancer sequences enabled key findings on telomeres length

The length of telomeres, the chromosomes’ end tails, as depicted in the figure below, physiologically shorten with aging. This means that younger cells have longer telomeres compared to their aged counterparts; one could say that the length of cells’ telomeres is a measure of their replicative power. Cancer cells are known to be able to turn this into their favour, and expand their replicative immortality through telomere lengthening and maintenance. Despite being a well-studied pan-cancer hallmark, the relation of the telomeres length to specific cancer genomic features is poorly understood. Julia Livingstone and her colleagues from P.C. Boutros' team in Los Angeles focused their work on prostate cancer. To investigate the relations between telomere length and the clinico-genomics of prostate tumours, they used whole genome sequencing (WGS) of 392 published tumour–reference pairs previously deposited at the EGA under accession numbers EGAS00001000400 and EGAS00001000900. Their work was published on Nature Communications in November 2021. They determined the telomere length of the sequencing sample, from both tumour and non-tumour adjacent tissues, and subsequently ran statistical analysis to investigate possible correlation between the telomeres length with several cancer features. The team discovered that telomeres length does not correlate with any specific driver gene mutation, but it does with the overall frequency of single nucleotides variants in a sample. This finding suggests that tumours with shorter telomeres accumulate more mutations without strong selective pressures for specific ones. While proliferation rate did not correlate directly with telomere length, methylation of almost half of all genes strongly did. The team’s results are massive and reveal a complicated and fascinating relation of different clinical and genomic features of prostate cancer with telomere length. In the paper discussion, they smartly consider different possibilities. As noted above, all these amazing results have been obtained analysing previously sequenced samples. Remarkably, the researchers who generated the samples did not focus at all on telomeres length. They indeed studied specific genes mutations and the features of early and late-onset prostate cancer. This proves, once again, the power of sequencing data re-use. This data is tremendously rich in information, and can hardly be exhausted with any number of analyses. Generating sequencing data, especially Whole Genome Sequencing, even better if tumor-reference paired, is like shopping every last article at the grocery store. You can then cook several recipes, or prepare a seven-course dinner, and still have ingredients left for someone else to borrow and cook something you have not thought about, a recipe that is just not in your cookbook. Noteworthy, the data retrieved from the EGA for this paper is associated with rich and complete metadata, meaning pheno-clinical information regarding the sample donors. As Julia Livingstone and her team wrote, using rich clinical annotations enabled them to assess the relationship between telomere length and patients outcome. This highlights once again the importance of reporting and annotating metadata correctly; It might feel like extra work for the researchers depositing their data, but it really has a huge value. Our team at the EGA is currently working to improve the metadata annotation process, with the aim to maximize the benefits for the scientific community.

Blog prostate-cancer-sequences-enabled-key-findings-on-telomeres-length

Comparison of capture-based method for transcriptome profiling of formalin-fixed paraffin embedded tumor samples

Background: The need for fresh frozen (FF) tissue limits implementing RNA sequencing (RNA-seq) in the clinic. The majority of clinical samples are stored as formalin-fixed, paraffin-embedded (FFPE) tissues. Exome capture platforms have been developed for RNA-seq from FFPE samples. However, these methods have not been systematically compared. Methods: Transcriptomic analysis of 32 FFPE tumor samples from 11 patients was performed using three exome capture-based methods: Agilent SureSelect V6, TWIST NGS Exome, and IDT XGen Exome Research Panel. We compared these methods to TruSeq RNA-seq of fresh frozen (FF-TruSeq) tumor samples from the same patients. We assessed the recovery of clinically relevant biological features. Results: The Spearman's correlation coefficients between the global expression profiles of the three capture-based methods from FFPE and matched FF-TruSeq were high (rho = 0.72-0.9, p < 0.05). A significant correlation between the expression of key immune genes between individual capture-based methods and FF-TruSeq (rho = 0.76-0.88, p < 0.05) was observed. All exome capture-based methods reliably detected outlier expression of actionable genes, including ERBB2, MET, NTRK1, and PPARG. In urothelial cancer samples, the Agilent assay was associated with the highest molecular subtype concordance with FF-TruSeq (Cohen's k = 0.7, p < 0.01). Both Agilent and IDT detected all the clinically relevant fusions that were initially identified in FF-TruSeq. Conclusion: All exome capture-based methods had comparable performance and concordance with FF-TruSeq. By enabling the interrogation of FFPE tumor samples, our findings will enable the implementation of RNA-seq in the clinic to guide precision oncology approaches.

Study EGAS00001005255

Genetic Risk for Subsequent Neoplasms among Long-term Survivors of Childhood Cancer in the St. Jude Lifetime Cohort

While childhood cancer survivors are known to be at increased risk of subsequent neoplasms (SNs), the contribution of germline mutations in cancer predisposition genes to the risk of SN is largely unknown. Whole-genome sequencing (30X) was performed on 3,006 5+ year survivors of childhood cancer (median age, 35.8 [range: 7.1-69.8] years) from the St. Jude Lifetime Cohort. Survivors underwent a comprehensive clinical assessment. Germline mutations in 156 cancer predisposition genes (SJCPG156), including a subset of 60 (SJCPG60) autosomal dominant genes with moderate to high penetrance, were classified for their pathogenicity. Piecewise exponential regression, stratified by radiation exposure, was used to evaluate the relative rate (RR) and 95% confidence interval (95% CI) of SN occurrence by mutation status. Pathogenic or likely pathogenic mutations in SJCPG156 and SJCPG60 were identified in 11.7% and 5.8% of survivors, respectively. The most frequently mutated SJCPG60 genes included RB1 (n=43), NF1 (n=22), BRCA2 (n=14), BRCA1 (n=12) and TP53 (n=10). Mutations in SJCPG60 were associated with the rate of subsequent sarcoma (RR, 10.3; 95% CI, 4.2 to 25.6) and breast cancer (RR, 13.3; 95% CI, 5.8 to 30.5) among irradiated survivors, and the rate of developing any SN (RR, 4.8; 95% CI, 2.4 to 9.4) and breast cancer (RR, 7.8; 95% CI, 2.5 to 24.0) among non-irradiated survivors. The rate of developing ≥2 histologically distinct SNs was increased 17.8-fold (95% CI, 3.5 to 89.8) among SJCPG60 mutation carriers treated without radiotherapy. Similar but attenuated associations were observed for mutations in SJCPG156. Survivors who develop a SN without prior radiotherapy or who are diagnosed with a subsequent sarcoma or breast cancer within a site of prior radiotherapy should be referred to genetic counseling.

Study EGAS00001002499

European BestAgeing Study on microRNA candidates for cardiovascular disease

Background: Circulating miRNAs have emerged as promising biomarker candidates due to their stability and their role in regulating key pathological pathways in cardiovascular disease (CVD). Yet, large-scale, multicenter studies examining their diagnostic and prognostic potential are scarce. This study evaluates the potential of miRNA expression profiles to inform disease classification and risk stratification across major CVD phenotypes, including acute coronary syndrome (ACS), chronic coronary artery disease (CAD), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM), in a large, multicenter European cohort. Methods: We assessed genome-wide miRNA expression profiles in a total of 1,209 cardiovascular patients and 848 controls in a uniform, standardized fashion, which renders this study one of the largest prospective miRNA studies. To focus on only the most biologically plausible miRNAs for clinical translation, we mined all original studies of miRNA candidates in CVD and performed differential miRNA expression and enrichment analysis. We then trained disease-specific binary classification models to evaluate the diagnostic potential of miRNA signatures. Finally, we evaluated prognosis and disease severity based on distinct miRNA levels. Results: 634 original abstracts were identified, detailing 166 ACS, 181 CAD, 56 DCM, and 182 ICM miRNAs. Without further optimization, the signatures of a priori miRNAs already yielded very good diagnostic performance with ROC AUC of 0.83 – 0.95. There was an improvement when considering additional miRNAs in a discovery setting. Interestingly, in ACS, CAD and DCM we observed a significantly worse prognosis in probands with higher scores in the miRNA signatures, indicating additional prognostic information. Conclusions: The European BestAgeing miRNA study reveals emerging associations of several miRNA signatures with cardiovascular disease discrimination and prognostication, providing a foundation for future external validation and potential clinical translation of this class of markers.

Study EGAS00001008346

Tubulointerstitial fibrosis is the histological hallmark of chronic kidney disease (CKD). Hypoxia and inflammation (i.e., interleukin (IL)-1β signalling) are independent mediators of tubulointerstitial fibrosis. However, the physiological response of human kidney tubular cells to IL-1β/IL-1RI signalling under the hypoxic conditions of CKD is poorly understood and remains a clinical imperative for therapeutic targeting. This study reports that hypoxia and IL-1β act in synergy to trigger cell cycle arrest/cellular senescence of ex vivo patient-derived primary proximal tubular epithelial cells (PTECs).

Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patient-derived PTECs were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions in the absence or presence of IL-1β and examined for maladaptive repair signatures. Hypoxic PTECs incubated with IL-1β displayed a discrete transcriptomic profile distinct from PTECs cultured under hypoxia alone, IL-1β alone or under normoxia. Hypoxia+IL-1β-treated PTECs had 692 ‘unique’ differentially expressed genes (DEGs) compared to normoxic PTECs, with ‘cell cycle’ the most significantly enriched KEGG pathway based on ‘unique’ down-regulated DEGs (including CCNA2, CCNB1 and CCNB2). Hypoxia+IL-1β-treated PTECs displayed signatures of cellular senescence, with reduced proliferation, G2/M cell cycle arrest, elevated senescence-associated β-galactosidase (SA-β-gal) activity and increased production of pro-inflammatory/fibrotic senescence-associated secretory phenotype (SASP) factors compared to normoxic conditions. Treatment of Hypoxia+IL-1β-treated PTECs with either a senolytic drug combination, quercetin+dasatinib, or a type I IL-1 receptor (IL-1RI) neutralizing antibody attenuated senescent cell burden. Our data identify a mechanism whereby hypoxia in combination with IL-1β/IL-1RI signalling trigger PTEC senescence, providing novel therapeutic and diagnostic check-points for restoring tubular regeneration in human CKD.

Study EGAS00001007904

Evaluation of size selection on cancer specific sequencing libraries

A couple of previously characterized and sequenced libraries will be repeated using a couple of differing size selection criteria and skim sequenced using an Illumina HiSeq. The resulting sequence will be analyzed to determine the optimal DNA library size for our specific downstream analysis.

Dataset EGAD00001000301

Piloting exome resequencing in consanguineous families with homozygosity mapping intervals

This pilot study aims to generate pilot data to inform future study designs in consanguineous families or inbred populations by resequencing the exome of six individuals from five families with neurodevelopmental diseases. For all of these families a single mapping interval containing the causal variant has previously been identified.

Dataset EGAD00001000341

Tcells_CD_scRNAseq

This set features unfiltered, aligned, UMI-based single cell RNA sequencing count data for 5290 Blood, intraepithelial ileum (IEL) and lamina propria ileum (LPL) T cells from Crohn's disease patients as published in Uniken Venema et al, Gastroenterology 2019

Dataset EGAD00010001649

ChIP-seq ERa in primary breast cancer tissues

ChIP-seq has been perfomed on 5 tumor fresh-frozen primary breast cancer tissues from female patients. Immunoprecipitation has been performed for ERa (SC-543, Santa Cruz). Raw single-end fastq data have been aligned using bwa-mem using Hg19 genome assebly as reference. Unfiltered aligment bam files are provided.

Dataset EGAD50000000014

University of Bergen Rare Monogenic Autoimmune Syndrome (APS-1) Data Access Committee

This is the DAC appointed by the University of Bergen for the datasets related to the study of APS-1 in the Department of Clinical Sciences . These data are from single cell transcriptomic analysis of expanded Tregs from patients with the rare monogenic autoimmune syndrome “APS-1” compared to healthy donors.

Dac EGAC50000000081

Exome sequencing for heterogeneity and evolution of DNA mutation rates

Dataset comprising 27 pairs of high-depth (300x) WES results obtained from 54 PDXs derived from primary CRCs resected synchronously with their corresponding metastases. These exoms sequences are part of a larger study on the heterogeneity and evolution of DNA mutation rates in microsatellite-stable colorectal cancer.

Dataset EGAD50000000208

Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

Targeted cfDNA and WBC sequencing data from patients profiled in the study "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer". Note that 'Exome sequencing' is listed under Dataset Type since there is no option for targeted panel sequencing.

Dataset EGAD50000000303

RNA sequencing

For RNA sequencing: All sample numbers starting with 6717 are tumor samples which has been sequenced using transcriptomics (see BAM files). It concerns biopsies of metastatic lesions from patients with BRAFV600 mutated melanoma, obtained before, during and after the study treatment (see samples metadata). RNA sequencing is performed using the Illumina Novaseq 6000 system.

Dataset EGAD50000000383

11955 results for "safefccoins Visit Buyfc26coins.com for latest FC 26 coins news..zl62"

in 26.81 milliseconds.