20311 results for "Fc coins Buyfc26coins.com is EA Sports official for FC 26 coins They are efficient and quick always..Z2Xg"

in 42.03 milliseconds.

• Single cell atlas of human glioma

  We profiled 87 primary-recurrentpatient-matched paired GBM specimens with single-nucleus RNA and bulk-DNA sequencing and single-cell open-chromatin and spatial transcriptomics/proteomics assays. We found that recurrent GBMs are characterized by a shift to a mesenchymal phenotype in response to therapy

  Dataset EGAD00001008811

• lymphoma plasma cfRNA

  Dataset contains total RNA sequencing data from plasma of 65 different human donors: 30 diffuse large B-cell lymphoma (DLBCL) and 13 primary mediastinal large B-cell lymphoma (PMBCL) patients, and 22 cancer-free controls. Samples were sequenced on a NovaSeq 6000 and are provided in FASTQ format.

  Dataset EGAD00001010259

• PacBio Rare Disease Study

  This study leverages PacBio HiFi long-read sequencing technology to comprehensively analyze the genomic architecture of rare diseases. By generating highly accurate, long-read sequences, we aim to resolve complex structural variants, repeat expansions, and other genomic features that are often missed by short-read sequencing. Our approach facilitates improved variant detection and interpretation, advancing the understanding of rare disease etiology and enabling more precise genetic diagnoses.

  Dataset EGAD00001015611

• Evolution of Chronic Lymphocytic Leukemia to Richter's Syndrome (RS)

  Richter's syndrome arising from chronic lymphocytic leukemia is a striking example of an aggressive malignant histology that emerges from indolent cancer. To understand this process, we reconstructed phylogenies based on whole exome sequencing of matched normal, CLL and RS samples. We computationally deconvoluted CLL and RS clones and identified drivers of transformation. We additionally performed whole genome sequencing, whole transcriptome sequencing and single-cell transcriptome sequencing to understand the mutational signatures, genome-wide events and gene expression changes associated with transformation.

  Study phs002458

• Comprehensive molecular profiling of pulmonary pleomorphic carcinoma

  Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. Whole exome sequencing (WES) of fresh-frozen tissue samples and target-capture sequencing of formalin-fixed-paraffin-embedded (FFPE) samples were performed. Fresh-frozen tissue samples and FFPE samples were subjected to WES and target-capture sequencing as normal control, respectively. Fresh-frozen tissue samples and 56 FFPE samples were subjected to RNA-seq.

  Study JGAS000297

• CARE idiopathic subglottic stenosis bulk transcriptomics.

  Idiopathic subglottic stenosis (iSGS) is a severe chronic orphan disease characterised by recurrent scarring of the subglottis, predominantly affecting Caucasian females in their fourth to sixth decade of life. Due to its rarity, understanding the clinical trajectory and molecular factors involved in iSGS disease development and prognosis has been challenging. In this study, we prospectively enrolled patients with iSGS, trauma-induced subglottic stenosis, and controls to investigate the clinical, transcriptional, and genetic features that may be associated with disease pathogenesis and treatment outcomes.

  Study EGAS50000000879

• Genetic ancestry contributes to somatic mutations in lung cancers from admixed Latin American populations

  Inherited lung cancer risk, particularly in non-smokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden (TMB), and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score predicted EGFR and KRAS mutation frequency more strongly than global ancestry, suggesting that germline genetics (rather than environmental exposure) underlie these disparities.

  Study EGAS00001004752

• Single-Cell RNA-Sequencing Analysis of Responses to Pembrolizumab in Sezary Syndrome

  This phase 2 single arm clinical trial assessed the efficacy of pembrolizumab in patients with previously treated mycosis fungoides or Sezary syndrome. Pembrolizumab was found to have a 38% overall response rate, and a 27% overall response rate in subjects with Sezary syndrome. We performed single-cell RNA-sequencing on samples collected before the first treatment and after 3 weeks of pembrolizumab treatment. Sequencing was performed on cryopreserved peripheral blood T-lymphocytes isolated from 6 trial participants, including 3 patients who responded to pembrolizumab treatment and 3 patients who did not respond. A total of 118,961 peripheral blood T-cells are included in this data set.

  Study phs002933

• Whole exome sequencing of familial MDS, Two patients

  Although several causal genes of familial myelodysplastic syndromes (MDS) have been identified, the genetic landscape and the molecular pathogenesis are not totally understood. To explore novel driver genes and their pathogenetic significance, we performed whole exome sequence analysis of two individuals from a familial MDS pedigree and several candidate single-nucleotide variants were identified. Knockdown screening revealed that downregulation of a candidate gene enhanced colony forming capacity of primary murine bone marrow (BM) stem/progenitor cells. Our results indicate that a familial MDS-associated germline mutation in the candidate gene induces accumulation of DNA double-strand breaks, possibly through impaired PCNA polyubiquitination.

  Study JGAS000162

• HSP90 inhibitor resistant cell line

  Genetic analysis of K562 cell which are resistant against HSP90 inhibitors.

  Study EGAS00001006381

• Cell fate mapping of human glioblastoma reveals an invariant stem cell hierarchy pre- and post-treatment

  Human glioblastomas (GBMs) are thought to harbour a subpopulation of glioblastoma stem cells (GSCs) that initiate tumour formation and regrowth following treatment. However, the origin of their proliferative heterogeneity during tumour growth pre- and post-treatment remains poorly understood. Here we study the clonal evolution of DNA barcoded GBMs following their serial propagation in xenograft mouse models to define the fate behaviour of individual GBM cells. Through quantitative analysis of clone sizes scored across multiple passages, we show that the growth of GBM clones in vivo are consistent with a remarkably neutral process resulting from a conserved proliferative hierarchy. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, that in turn generates short-lived cells that lack proliferative ability. We also identify rare "outlier" clones that deviate from these dynamics, and further show that chemotherapy reproducibly facilitates the selective expansion of pre-existing drug-resistant GBM lineages. Finally, we show that coexisting, functionally distinct GSCs may be targeted separately with epigenetic compounds. These findings show that, independent of an evolving mutational signature, the clonal dynamics of human GBM can be surprisingly robust, with intratumoural heterogeneity derived primarily from the defined stochastic fate behaviour of tumour cells within a conserved proliferative hierarchy.

  Study EGAS00001002424

• Immune induction strategies to enhance the sensitivity to PD-1 blockade in metastatic triple negative breast cancer: the TONIC-trial

  The response rate in metastatic triple negative breast cancer (TNBC) to PD-1 blockade is low, highlighting an urgent clinical need for strategies that render the TNBC tumor microenvironment (TME) more sensitive to PD-1 blockade. Immunomodulatory mechanisms have been proposed for both chemotherapy and irradiation, but it has not been established whether these therapies may improve efficacy of PD-1 blockade by favorably changing the TME. In the first stage of this adaptive, non-comparative phase II trial (TONIC-trial; NCT02499367), 67 patients with metastatic TNBC were randomized to nivolumab without induction or to one of four induction treatments, consisting of irradiation of one metastatic lesion (3x8 Gy) or a two- week low-dose regimen of cyclophosphamide, cisplatin or doxorubicin, all followed by nivolumab. In the overall cohort of 66 evaluable patients, the objective response rate (ORR; iRECIST16) was 20% (95% CI: 11%-31%), with two complete responses and 11 partial responses. The majority of clinical responses were observed on nivolumab in the cisplatin (ORR 23%; 3/13) and doxorubicin (ORR 35%; 6/17) cohorts. After doxorubicin and cisplatin induction, we detected an upregulation of immune-related genes, involved in PD-1/PD-L1, and T-cell cytotoxicity pathways. This was further supported by enrichment among upregulated genes related to inflammation, JAK-STAT and TNFα-signaling after doxorubicin. In addition, we observed a trend towards increased T-cell infiltration, measured using T-cell receptor (TCR) sequencing, after doxorubicin. Together, the clinical and translational data of this study testing different immune induction strategies prior to nivolumab suggest that short-term doxorubicin and cisplatin may induce a more favorable TME and increase the likelihood of response to PD-1 blockade in TNBC. These data warrant further confirmation in TNBC and exploration of induction treatments prior to PD-1 blockade in other cancer types.

  Study EGAS00001003535

• Genomic Characterization of Metastatic Castration Resistant Prostate Cancer

  Biopsies of castration resistant prostate cancer metastases were subjected to whole genome sequencing (WGS), along with RNA-sequencing (RNA-Seq). The overarching goal of the study is to illuminate molecular mechanisms of acquired resistance to therapeutic agents, and particularly androgen signaling inhibitors, in the treatment of metastatic castration resistant prostate cancer (mCRPC).

  Study phs001648

• Whole Genome Sequencing in Psychotic Major Depression

  The goal of this case-control study, "Whole Genome Sequencing in Psychotic Major Depression", is to identify genes that contribute to the psychotic major depression phenotype. The samples herein were used as controls and were obtained from the NIMH Repository Study #108, "Sustaining Remission of Psychotic Depression".

  Study phs001625

• A distinct monocyte cellular state links systemic immune dysregulation to pulmonary impairment in long COVID

  This is an independent cohort of Long COVID patients recruited from a rehabilitation centre. These patients had Long COVID from 8 months to more than 2 years since their acute COVID-19 disease. PBMC from these patients were collected and single cell transcriptomics dataset was generated.

  Study EGAS50000001216

• Targeted_sequencing_of_candidate_genes_in_calcific_aortic_valve_stenosis

  The objective is to identify new disease genes involved in calcific aortic valve stenosis (CAVS) by screening newly identified candidate genes. The recruitment of patients with CAVS has been achieved by l’institut du thorax (Nantes, France). DNA from the selected patients has been analysed by targeted capture (Agilent SureSelect) and massively parallel sequencing (Illumina).

  Study EGAS00001000308

• Studying the single cell characteristics of pancreatic cancer

  Pancreatic cancer is a dangerous malignancy in the pancreas. In this study we use single-cell RNA sequencing technique to help understand the transcriptome characteristics of pancreatic tumor cells. This study help understands the complex microenvironment of pancreatic tumors and will likely to benefit clinical research of pancreatic cancer treatments.

  Study EGAS00001003889

• Multi-omics of Richter syndrome

  Richter syndrome (RS) is the aggressive transformation of Chronic Lymphocytic Leukemia, mostly with Diffuse Large B-Cell Lymphoma histology. While histologically similar, RS and de novo DLBCLs present with different clinical courses. We characterized the RS epigenome by combining genome-wide DNA methylation with transcriptome-sequencing on a large RS cohort.

  Study EGAS00001005495

• Targeted Sequencing of Human Myeloid Malignancies

  This study involves targeted sequencing of samples from myeloid malignancies at different timepoints to assess clonal evolution of malignancy a. 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 EGAD00001002225

• RNA sequencing, ATACseq, and TCR-seq of Tfh cells and CXCR5- CD4+ T cells in HIV infected lymph nodes

  The high dimensional analyses of CD4+ T cells in human lymph nodes are case-based analyses of the TCR repertoire, transcriptome, and epigenetic signatures of various CD4+ T cells in human lymph nodes. The study aims to determine clonal overlap between phenotypically distinct CD4+ T cells and the similarities between these populations on transcriptional and epigenetic levels. This study performs TCR repertoire sequencing using Molecular Identifier Clustering-based Immune Repertoire Sequencing (MIDCIRS). We found clonal overlap between a population of CXCR5- T cells and follicular helper T (Tfh) cells. We also show epigenetic and transcriptional similarities between CXCR5-PD-1+ T cells and Tfh cells. This study shares an overlapping set of donors with phs001548.

  Study phs001849

• danMAC5

  Three whole genome sequecing of three independent cohorts. The three cohorts derives from projects including samples of inviduals with Danish origin. Data is deviden into males and female and compiled.

  Dataset EGAD00001009756

• Whole transcriptome RNA sequencing on bone marrow and peripheral blood samples from patients with acute myeloid leukemia at diagnosis or relapse.

  One hundred cryopreserved bone marrow and peripheral blood samples from patients with acute myeloid leukemia (AML) with 10-90% blasts were selected from the biobank of the Department of Hematology of Leiden University Medical Center (LUMC). The AML cases cover all subtypes, and specifically include known subtype-defining balanced chromosomal translocations according to the WHO classification. The samples were obtained from 96 patients and include three pairs of de novo and relapsed AML and one pair of de novo and presumed therapy-related AML (tAML). Total RNA was isolated from mononuclear cells without prior enrichment for leukemic blasts. The quality and integrity of total RNA was checked and RNA libraries were prepared using the TruSeq RNA library preparation kit v2 (Illumina, San Diego, CA) in an ISO/IEC 17025-accredited protocol. This workflow started with enrichment of messenger RNA by oligo dT magnetic beads. After fragmentation, cDNA synthesis was performed, followed by adaptor ligation and PCR amplification. Paired-end sequencing with a read length of 126 bp was performed on an Illumina HiSeq 2500 v4 sequencer to at least 12.5 Gbp per sample. Image analysis, base calling, and quality check was performed with Illumina data analysis pipeline RTA v1.18.64 and Bcl2fastq v1.8.4. RNAseq reads are provided in compressed Sanger FASTQ format.

  Dataset EGAD00001004187

• Paired RNA sequencing of Thymic epithelial tumors - Additional Dataset

  Paired RNA sequencing of additional samples of Thymic epithelial tumors. Uploaded are the paired fastq files, sequencers were Illumina HiSeq 2500, HiSeq 4000, NovaSeq 6000 and HiSeq X Ten. The kits used were Illumina Truseq RNA and Illumina Truseq stranded mRNA.

  Dataset EGAD50000000324

• Selected samples from the Boston Children's Hospital Childrens Rare Disease Cohorts initiative

  These are some selected exomes from the first year of the Childrens Rare Disease Cohorts initiative at Boston Children's Hospital. Patients were drawn from the following cohorts: immunodeficiency, epilepsy, IBD, hearing loss, and orphan diseases. Raw sequencing was performed on Illumina NovaSeq 6000 machines, and aligned to hs37d5.

  Dataset EGAD00001006179

• Colon adenomas and adenocarcinomas and matched mucosae

  Whole exome sequencing of neoplastic colorectal lesions, matched normal mucosa and peripheral blood leucocytes from 7 individuals. Data is contained within FASTQ files.

  Dataset EGAD00001010875

• Phase II Study of Cryoablation and Post-Progression Immune Checkpoint Inhibition in Metastatic Melanoma

  Percutaneous cryoablation guided by imaging is a well-established, minimally invasive treatment for oncological conditions. We posited that cryoablation could alter the immune microenvironment by directly influencing the tumor, potentially eliciting an anti-tumor response in cases resistant to immune checkpoint inhibition (ICI). In this non-randomized phase II single-center study (NCT03290677), individuals with unresectable melanoma experiencing progression on ICI underwent cryoablation in a single progressing metastasis, while ICI was continued for at least two additional cycles. The main objectives were to assess safety and feasibility and to evaluate tumor response in non-ablated lesions. Between May 2018 and July 2020, 17 patients participated in the study. The treatment regimen proved safe, revealing an objective response rate of 23.5% and a disease control rate of 41% (comprising 4 partial responses and 3 stable diseases). In our investigation into the factors influencing response to cryoablation therapy in ICI-resistant melanoma, we conducted single-cell RNA sequencing (scRNA-seq) using both 10x Genomics and Smart-seq2 technologies on biopsies from metastatic sites of 15 patients. We collected pre-treatment samples from all patients and post-treatment samples from 5 patients, totaling 20 samples. After quality control, excluding cells specific to anatomical sites or rare cell types (e.g., alveolar type II, neurons), and batch correction, we analyzed 49,071 single cells spanning melanocyte, endothelial, stromal, T, myeloid, and B/plasma cell lineages. Differential gene expression (DGE) analysis between myeloid cells identified the genes MARCKS and IL10, two genes involved in anti-inflammatory responses that can inhibit macrophages activation to be associated with failed response. Moreover, DGE analysis of T cells identified the gene TXK, which acts as a Th1 transcription factor, and the gene CMKLR1 (chemerin-like-receptor-1), which triggers migration of CD8 T-cells to be upregulated in patients who benefited from cryoablation treatment. In contrast, MTHFD2 and GGH, two genes involved in one-carbon metabolism and the folate cycle, were upregulated in T cells from patients who did not respond to therapy. Our analysis revealed a significant increase in B/plasma cells in patients who responded positively to the therapy combination, along with an enrichment of oxidative phosphorylation in T cells among non-responsive patients with progressive disease. These findings advocate for further investigation into this innovative and synergistic therapeutic approach.

  Study phs003579

• WGS data of pediatric T-ALL acute lymphoblastic leukemia (set1)

  The dataset includes FASTQ and BAM files from diagnostic and matched remission (control) samples of one T-ALL patient (ALLT-317). Relapsed (BM ALLT-317L and Tonsil ALLT-3107L) sample files are in dataset set2 of this submission. Sequencing library was made using PCR free-based WGS library preparation (PCR-), using TruSeq DNA PCRfree library preparation kit v1 (PE150). Both diagnostic (60x) and remission (30x) samples were sequenced using HiSeq X.

  Dataset EGAD50000002013

• scRNA and V(D)J sequencing of WM under ibrutinib

  Single-cell RNA sequencing (5′ gene expression) and single-cell V(D)J sequencing (B-cell receptor and T-cell receptor) were performed on bone marrow mononuclear cells from patients with Waldenström macroglobulinemia treated with ibrutinib monotherapy. Sequential bone marrow aspirate samples were collected at baseline and after treatment. A total of 222 BAM files are included in this dataset.

  Dataset EGAD50000002279

• mRNA profiling of CAFs and cancer cells in response to TGF-β and BMP signaling

  TGF-β and BMP signalings are important signaling pathways in the tumor microenvironment during cancer progression. This RNA-sequencing (62 fastq pairs) analysis explored how cancer-associated fibroblasts (CAFs) from human (19TT) and mice (Balbc A/B) respond to TGF-β, BMP2, or Gremlin antibody, as well as how cancer cells (66cl4) respond to Gremlin antibodies.

  Dataset EGAD50000001351

• Targeted RNA-Seq

  This dataset contains targeted RNA-Seq generated with the Illumina RNA Pan-Cancer panel. It comprises 2200 cancers from children and adults. The cancers represent a wide range of CNS, solid and haematopoietic tumours. Samples are from pathology specimens including FFPE, fresh frozen, bone marrow aspirate and peripheral blood. Samples were tested in a clinical diagnostic lab to identify relevant SNVs, indels and gene fusions.

  Dataset EGAD50000000980

• Genomic Characterization of Pediatric Low-Grade Gliomas

  Pediatric low-grade gliomas (PLGGs) are the most common pediatric brain-tumor, with more than ten histologic subtypes recognized by the World Health Organization. We performed a genomic analysis of 230 PLGGs of which 73 had whole genome/RNA sequencing performed and show that MYB-QKI fusions define the seizure associated tumor, Angiocentric Glioma (AG). MYB-QKI fusions present in AGs contribute to tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression, and hemizygous loss of QKI, a tumor suppressor gene. Such interplay between three oncogenic mechanisms has diagnostic and therapeutic implications in AGs, and illustrates the functional complexity associated with rearrangements in cancer.

  Study phs001054

• Pathologically Expanded Peripheral B Cell-Helper T Cells in Rheumatoid Arthritis

  PROSET-HD aims to identify and study immune cell populations altered in patients with autoimmune and inflammatory diseases. We have identified a population of PD-1hi CXCR5- 'peripheral helper' T (Tph) cells that are expanded in the joints and circulation of patients with seropositive rheumatoid arthritis. This T cell population uniquely combines potent B cell-helper function with a migratory program that directs homing to inflamed tissues. RNA sequencing was performed on sorted memory CD4+ T cell subpopulations to compare the global gene expression profiles of PD-1hi CXCR5- CD4+ T cells, PD-1hi CXCR5+ follicular helper T cells, and other T cell populations obtained from blood of rheumatoid arthritis patients.

  Study phs001262

• Time-dependent characterization of CNS response in COVID-19

  Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 primarily affects the respiratory system, but the observation of diverse neurological symptoms indicates that other organs, including the brain, may be involved. The pathophysiological mechanisms of COVID-19-associated effects on the central nervous system (CNS) have become clearer during the past two years. Nevertheless, the precise CNS-specific molecular mechanisms are still elusive and raise several questions. To further elucidate the host response at brain tissue level, we profiled single-nucleus transcriptomes and performed proteomics from olfactory mucosa, olfactory bulb, medulla oblongata and cerebellum at different timepoints of the disease in individuals who died of COVID-19 and underwent rapid autopsy.

  Study EGAS00001006442

• Exome sequencing of control DNA samples from patients with BPLL

  DNA extracted from sorted CD3+ cells (16 patients) was used for exome capture with the SureSelect V5 Mb All Exon Kit following the standard protocols. Paired-end sequencing (2 x 100 bp) was performed using HiSeq2000 sequencing instruments.The files are in FASTQ format.

  Dataset EGAD00001004411

• Genomic Advances in Sepsis (GAinS) genotyping

  This cohort comprises a subset of patients enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 35 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected over the first five days of ICU admission to investigate how host genetics affects the individual repsonse to sepsis. DNA was extracted from buffy coat or whole blood samples using the Qiagen DNA extraction protocol, the automated Maxwell Blood purification kit (Promega), or the QIAamp Blood Midi kit protocol (Qiagen). Genotyping data were generated using the Illumina HumanOmniExpress BeadChip (295 patients), the Infinium CoreExome BeadChip (655 patients), and the Infinium Global Screening Array BeadChip (307 patients). Genotyping QC and imputation into the Haplotype Reference Consortium was perfomed within each batch. The datasets were combined and following post-imputation filtering data were available on 1168 samples.

  Dataset EGAD00001015369

• germline SNP6.0

  Over 1.87 million SNP and CNV loci are screened by Affymetrix SNP 6.0 array

  Dataset EGAD00010001635

• leukemia omni2.5

  Over 2.5 million SNP and CNV loci are screened by Illumina Infinium Omni2.5Exome-8 Kit

  Dataset EGAD00010001638

• leukemia SNP6.0

  Over 1.87 million SNP and CNV loci are screened by Affymetrix SNP 6.0 array

  Dataset EGAD00010001637

• germline omni2.5

  Over 2.5 million SNP and CNV loci are screened by Illumina Infinium Omni2.5Exome-8 Kit

  Dataset EGAD00010001636

• Rapid multiplex small DNA sequencing on the MinION nanopore sequencing platform

  Ultra low coverage sequencing results from the project 'Rapid multiplex small DNA sequencing on the MinION nanopore sequencing platform'. Sequencing data of sample NA12877 and NA12878 generated from 3 nanopore sequencing runs are included in this dataset.

  Dataset EGAD00001004052

• Noncoding Mutational Analysis of DLBCL Genomes

  146 DNA samples obtained from 73 DLBCL patients (matching tumor and normal) were sequenced with PCR free 1.0 genome shotgun sequencing. All files are in bam format.

  Dataset EGAD00001004142

• Human normal brain single-cell

  We profiled two human fetal brainstem specimens at 17 and 19 post-conception weeks by single-cell RNA-seq using 10X Chromium Single Cell 3'. The BAM files are provided.

  Dataset EGAD00001005128

• Osteosarcoma capture-based RNA sequencing

  This dataset includes 23 specimens from osteosarcoma patients (primary, relapsed, metastatic). It contains bam files from RNA sequencing using a library in which coding regions of cDNA are captured and short-read, paired-end sequencing.

  Dataset EGAD00001008434

• Pilocytic Astrocytoma RNA sequencing

  This dataset contains RNA sequencing samples from the Duesseldorf/LIsbon pilocytic astrocytoma cohort which was profiled using Proteogenomics (RNA Sequencing, proteomics and methylation). There are 48 samples which were sequenced using paired-end sequencing at the University Hopstial Dusseldorf.

  Dataset EGAD00001009053

• Human tumor single-cell RNA-seq

  We profiled 16 patient tumor samples by single-cell or single-nuclei RNA-seq using 10X Chromium 3'. It includes 4 low-grade gliomas and 12 ependymomas. The raw fastqs are provided.

  Dataset EGAD00001011315

• Small Genomic Insertions Form Enhancers that Misregulate Oncogenes

  ChIP-Seq data from 102 cell lines were processed to identify insertions relative to the human reference genome. To confirm the ability of a computational pipeline to identify insertions that are actually present in these genomes, we PCR-amplified and deeply sequenced regions where insertions were predicted to exist in MOLT4 T-cell acute lymphoblastic leukemia cells. The current study release makes available sequences of amplicons from a tumor cell genome (MOLT4) where a computational pipeline predicted small insertions from orthogonal data.

  Study phs001242

• Genetic Effects on miRNA Expression During Mid-Gestation Neocortical Development

  In this study we aimed to find common genetic variants that influence miRNA expression during mid-gestation neocortical development. Small RNA-sequencing from 212 fetal cortical tissue samples between 14 and 21 weeks gestation were used to profile miRNA expression. Combined with donor genotypes, we were able to find miRNA-eQTLs during neocortical development. The dataset provided here includes 212 Small RNA-sequencing files in FASTQ format from cortical wall samples. Also provided here are 212 donor genotypes in PLINK format (hg19).

  Study phs003106

• The Role of GPD1L in the Pathogenesis of Brugada Syndrome

  This study performed exome sequencing on a proband with Brugada Syndrome, as well as high-density SNP array data from the proband, affected family members, and unaffected family members. The principal findings of this study were the identification of GPD1L-A280V as the only plausible variant present in a linkage region on chromosome 3, which co-segregated with the Brugada Syndrome phenotype in this family. Exome sequencing data of the proband, as well as SNP array data from the family, are available.

  Study phs003468

• Gut microbiota analysis after 3months probiotic-like bacteria or placebo treatment in subjects with metabolic syndrome

  Background: Probiotic-like bacteria treatment has been described to be associated with gut microbiota modifications. Goal: To decipher if the effects of the tested probiotic-like bacteria are due to the bacteria itself or due to the effects of the bacteria on the gut microbiota. Methodology: In this study, gut microbiota has been analyzed from feces samples of subjects with metabolic syndrome and treated with one of the 2 tested probiotic-like bacteria or with the placebo during 3months.

  Study EGAS00001003585

• We performed an integrative analysis to determine genomic aberrations common to sporadic schwannomas.

  Schwannomas are common peripheral nerve sheath tumors that can cause significant debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to sporadic schwannomas. Exome sequence analysis with validation by targeted DNA-sequencing of 125 samples uncovered, in addition to expected NF2 disruption additional recurrent mutations. RNA sequencing identified a recurrent in-frame SH3PXD2A-HTRA1 fusion in 12/125 (10%) cases, and genomic analysis demonstrated the mechanism as resulting from a balanced 19Mb chromosomal inversion on chromosome 10q.

  Study EGAS00001001886

• A_compendium_of_mutational_signatures_due_to_environmental_exposures

  Analysis of mutational signatures caused by exposure to known mutagens in human induced pluripotent stem (iPS) cells. A reference human iPS cell-line will be exposed to 100 chemicals known or proposed to be mutagenic. Following exposure to mutagen, cells will undergo a period of recovery before sub clones are generated and sequenced. The progenitor “parental” IPS cell-line will be used to generate reference sequence data, in order to determine the mutational signatures acquired as a result of exposure to different mutagens.

  Study EGAS00001002060

• Defining structural variation associated with breast cancer susceptibility by long-read genome sequencing

  Germline structural variants (SVs) are challenging to identify by conventional genetic testing assays. Long-read sequencing has improved the global characterization of SVs, but its sensitivity at genetic loci associated with high- and moderate-penetrance cancer susceptibility has not been reported. This study used long-read genome sequencing performed on the Oxford Nanopore Technologies' PromethION to resolve variants underlying breast cancer susceptibility in sixteen individuals with pathogenic germline SVs in BRCA1, BRCA2, CHEK2 or PALB2.

  Study EGAS00001005872

• There are 116 liver cancer cases in this study and belong to LICA-CN project.The NGS test was performed with whole exome sequencing with HiSeq 2000 platform.

  There are 116 liver cancer cases in this study and belong to LICA-CN project

  Dataset EGAD00001003174

• Targeted sequencing of Human esophageal epithelium microbiopsies

  NOTCH1 mutant clones occupy the majority of normal human esophagus by middle age, but are comparatively rare in esophageal cancers, suggesting NOTCH1 mutations may promote clonal expansion but impede carcinogenesis. Here we test this hypothesis. Visualizing and sequencing NOTCH1 mutant clones in aging normal human esophagus, reveals frequent biallelic mutations that block NOTCH1 signaling.  In mouse esophagus, heterozygous Notch1 mutation confers a competitive advantage over wild type cells, an effect enhanced by loss of the second allele.  Notch1 loss alters transcription but has minimal effects on epithelial structure and cell dynamics. In a carcinogenesis model, Notch1 mutations were less prevalent in tumors than normal epithelium. Deletion of Notch1 reduced tumor growth, an effect recapitulated by anti-NOTCH1 antibody treatment.  We conclude that Notch1 mutations in normal epithelium are beneficial as wild type Notch1 promotes tumor expansion. NOTCH1 blockade has therapeutic potential in esophageal squamous tumors.

  Dataset EGAD00001006969

• Genome-wide SNP genotyping and DNA methylation epigenotyping of African rainforest hunter-gatherers and neighbouring agriculturalists

  The epigenomic landscape of the human genome, in particular DNA methylation, is increasingly recognised as an important driver of phenotypic diversity in health and disease. However, the impact that genetic variation and changes in lifestyle and ecological habitat have on this epigenetic mark remains unknown. To address this question, we analysed genome-wide SNP and DNA methylation profiles of 362 individuals from African populations of rainforest hunter-gatherers and sedentary farmers with different past and present lifestyles and ecologies.

  Study EGAS00001001066

• Plasma MicroRNA Signatures of Aging

  Background. MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally and show differential expression in various tissues with aging phenotypes. Detectable in circulation, extracellular microRNAs reflect (patho)physiological processes and hold promise as biomarkers for healthy aging and age-related diseases. This study aimed to explore plasma extracellular microRNAs as biological aging indicator and their associations with health outcomes using population-level data. Methods. We quantified plasma expression levels of 2,083 extracellular microRNAs using targeted RNA-sequencing in 2,684 participants from the population-based Rotterdam Study cohort. The training and test sets included 1,930 participants from the advanced-aged initial and second subcohort (RS-I/RS-II; median age: 70.6), while the validation set comprised 754 participants from the middle-aged fourth subcohort (RS-IV; median age: 53.5). Based on 591 microRNAs well-expressed in plasma, we examined differential expression of microRNAs with chronological age, PhenoAge –a composite score of age and nine multi-system blood biomarkers–, the frailty index, and mortality. Next, elastic net models were employed to construct composite microRNA-based aging biomarkers predicting chronological age (mirAge), PhenoAge (mirPA), frailty index (mirFI), and mortality (mirMort). The association of these aging biomarkers with different age-related health outcomes was assessed using Cox Proportional Hazard, linear regression, and logistic regression models in the test and validation sets. Results. We identified 188 microRNAs differentially expressed with chronological age within the RS-I/RS-II advanced-aged population (ntraining=1158, ntest=772), of which 177 microRNAs (94.1%) were replicated in the middle-aged RS-IV subcohort (nvalidation=754). Moreover, 227 miRNAs showed robust associations with PhenoAge, 61 with FI, and 16 with ten-year mortality independent of chronological age. Subsequently, we constructed four plasma microRNA-based aging biomarkers: mirAge with 108, mirPA with 153, mirFI with 81, and mirMort with 50 miRNAs. Elevated scores on these microRNA-based aging biomarkers were associated with unfavorable health outcomes, including lower subjective physical functioning and self-reported health and increased mortality and frailty risk, but not with first- or multi-morbidity. Overall, larger effect estimates were observed for mirPA, mirFI, and mirMort compared to mirAge. Conclusions. This study describes distinct plasma microRNA-aging signatures and introduces four microRNA-based aging biomarkers with potential to identify accelerated aging and age-related decline, providing insights into the intricate process of human aging.

  Study EGAS00001008117

• CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development

  The placenta serves as the interface between the mother and fetus, facilitating the exchange of gases and nutrients between their separate blood circulation systems. Trophoblasts in the placenta play a central role in this process. Our current understanding of mammalian trophoblast development relies largely on mouse models. However, given the diversification of mammalian placentas, findings from the mouse placenta cannot be readily extrapolated to other mammalian species, including humans. To fill this knowledge gap, we performed CRISPR knockout (KO) screening in human trophoblast stem cells (hTSCs). We targeted genes essential for mouse placental development and identified more than 100 genes as critical regulators in both human hTSCs and mouse placentas. Among them, we further characterized in detail two transcription factors, DLX3 and GCM1, and revealed their essential roles in hTSC differentiation. Moreover, a gene function-based comparison between human and mouse trophoblast subtypes suggests that their relationship may differ significantly from previous assumptions based on tissue localization or cellular function. Notably, our data reveal that hTSCs may not be analogous to mouse TSCs or the extraembryonic ectoderm (ExE) in which in vivo TSCs reside. Instead, hTSCs may be analogous to progenitor cells in the mouse ectoplacental cone and chorion. This finding is consistent with the absence of ExE-like structures during human placental development. Our data not only deepen our understanding of human trophoblast development but also facilitate cross-species comparison of mammalian placentas.

  Study JGAS000659

• An MTOR mutation hitchhikes through renal embryogenesis, driving multifocal, multiphenotypic tumours - WGS

  Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the seeding of cells predisposed to disease within mature organs, creating a field effect. We characterise an embryonic cancer mutation that drives multifocal, multiphenotypic renal tumours in a 14-year-old girl. Their shared MTOR mutation, absent from normal tissues, increases protein flexibility which enables a FAT domain hinge to dramatically increase mTORC1 activity. Developmental mutations, not usually detected in traditional genetic screening, have vital clinical importance in guiding prognosis, targeted treatment, and family screening decisions for paediatric tumours.

  Dataset EGAD00001011645

• An MTOR mutation hitchhikes through renal embryogenesis, driving multifocal, multiphenotypic tumours - RNA

  Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the seeding of cells predisposed to disease within mature organs, creating a field effect. We characterise an embryonic cancer mutation that drives multifocal, multiphenotypic renal tumours in a 14-year-old girl. Their shared MTOR mutation, absent from normal tissues, increases protein flexibility which enables a FAT domain hinge to dramatically increase mTORC1 activity. Developmental mutations, not usually detected in traditional genetic screening, have vital clinical importance in guiding prognosis, targeted treatment, and family screening decisions for paediatric tumours.

  Dataset EGAD00001011646

• An MTOR mutation hitchhikes through renal embryogenesis, driving multifocal, multiphenotypic tumours - scRNA

  Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the seeding of cells predisposed to disease within mature organs, creating a field effect. We characterise an embryonic cancer mutation that drives multifocal, multiphenotypic renal tumours in a 14-year-old girl. Their shared MTOR mutation, absent from normal tissues, increases protein flexibility which enables a FAT domain hinge to dramatically increase mTORC1 activity. Developmental mutations, not usually detected in traditional genetic screening, have vital clinical importance in guiding prognosis, targeted treatment, and family screening decisions for paediatric tumours.

  Dataset EGAD00001011647

• Immunophenotyping in a COVID-19 Cohort (IMPACC) Transcriptomics and Genotyping Assays

  IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) is a prospective longitudinal cohort study (NCT04378777) launched in May 2020 in response to the worldwide pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH). Patient enrollment and sample analysis involved 20 hospitals associated with 15 U.S. biomedical research centers and 11 centralized Core immunoassay laboratories.The study aimed to enable the identification of potential biomarkers and inform future therapeutic interventions using a longitudinal approach encompassing the whole disease course for a comprehensive understanding of the contributions of the pathogen and host immune response in modulating the manifestations, severity, and post-acute sequelae of the infection. IMPACC enrolled close to 1200 adult symptomatic, molecularly confirmed hospitalized COVID-19 patients in the study within 48 hours of their hospital admission. Clinical data and biological samples (blood, mid-turbinate nasal swabs, and esophageal aspirant) were collected according to minimal risk guidelines at enrollment and on days 4, 7, 14, 21, and 28. Biological samples were collected at 3-month intervals up to 12 months after hospital discharge to assess functional and immunologic recovery measures. Sample collection, processing, and storage procedures were standardized across sites, and samples were transported to centralized assay-specific core laboratories (Core Labs) in batches for testing and analysis. The description of outcome severity was not limited to survival versus death but encompassed a clinical trajectory approach using 5 groups leveraging longitudinal data based on time in the hospital, disease severity by ordinal scale based on the degree of respiratory illness, and presence or absence of limitations at discharge. Disease severity was assessed based on the degree of respiratory illness using a 7-point ordinal scale adapted from the World Health Organization COVID-19 and NIAID disease ordinal severity scales. DNA for genetic analyses was collected from whole blood at a single time point. To identify any genomic determinants of severe COVID-19 disease, single-nucleotide polymorphism (SNP) genotyping and exome sequencing were conducted to assess genetic variants associated with individual susceptibility to severe disease. In addition, IMPACC included bulk transcriptomic analysis of upper airway (nasal swaps) samples, lower airway (esophageal aspirant) samples, and peripheral blood mononuclear cells (PBMCs) to evaluate dynamic changes in cellular composition and cellular response during the course of the disease. Reads were aligned to the GRCh38 human reference genome. Additional information for the IMPACC study has been submitted to The Immunology Database and Analysis Portal (ImmPort) under study accession SDY1760. Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Dr. Steven Kleinstein (steven.kleinstein@yale.edu).

  Study phs002686

• Indonesian Single Cell Data Access Committee

  This Data Access Committee manage and oversee the Data Access Policy sets forth the terms, conditions, and limitations governing access to and use of the raw sequencing data of samples in the Indonesian Single Cell dataset by individuals who are not part of the Data Producer. The IndoSC dataset comprises 203 human whole blood and PBMC samples collected in 4 communities in both Bali and Papua Provinces in Indonesia, that was collected to study the immune cell atlas of ancestrally- and environmentally diversed populations in Indonesia.

  Dac EGAC50000000870

• Neoantigen Immunogenicity Landscapes and Evolution of Tumor Ecosystems During Immunotherapy with Nivolumab

  We performed Whole Exome (WXS) and RNASeq sequencing on samples obtained from the same site before and during therapy from our prospective clinical trial (CA209-153, NCT02066636) of nivolumab in advanced Non-small cell lung cancer (NSCLC) patients that progressed on chemotherapy. There are 58 pre and 42 on therapy WXS samples and 24 pre and 12 on therapy RNASeq samples. All WXS tumor samples have matching normal samples.

  Dataset EGAD00001011302

• Malignant pheochromocytomas/paragangliomas harbor mutations in transport and cell adhesion genes

  One out of ten patients with pheochromocytoma (PCC) and paraganglioma (PGL) develop malignant disease. Today there are no reliable pathological methods to predict malignancy at the time of diagnosis. Tumors harboring mutations in the succinate dehydrogenase subunit B (SDHB) gene often metastasize but the sequential genetic events resulting in malignant progression are not fully understood. The aim of this study was to identify somatic mutations that contribute to the malignant transformation of PCC/PGL. We performed pair-wise (tumor-normal) whole-exome sequencing to analyze the somatic mutational landscape in five malignant and four benign primary PCC/sympathetic PGL (sPGL), including two biological replicates from each specimen. In total, 225 unique somatic mutations were identified in 215 genes, with an average mutation rate of 0.54 mutations/megabase. Malignant tumors had a significantly higher number of mutations compared to benign tumors (p<0.001). Three novel genes were identified as recurrently mutated; MYCN, MYO5B and VCL, and mutations in these genes were exclusively found in malignant sPGL tumors. Mutations in the MYO5B gene could be verified in two publicly available data sets. A gene ontology analysis of mutated genes showed enrichment of cellular functions related to cytoskeletal protein binding, myosin complex, and motor activity, many of which had functions in Rab and Rac/Rho GTPase pathways. Conclusively, we have identified recurrent mutations in genes related to intracellular transport and cell adhesion, and we have confirmed recurrent mutations of MYO5B in PCC/PGL cases with malignant potential. Our study suggests that deregulated Rab and Rac/Rho pathways may be important in PCC/PGL tumorigenesis.

  Study EGAS00001001601

• WGS and WES of 78 pairs Chinese gastric cancer

  Gastric Cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with 3 primary tumours and 2 matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC).

  Study EGAS00001001056

• Genetic Landscape of Esophageal Squamous Cell Carcinoma Defined by Exome Sequencing on Chinese Patient Cohort and Cell Lines

  Esophageal Squamous Cell Carcinoma (ESCC) is one of the deadliest cancers worldwide. To define the genetic landscape of ESCC, whole exome sequencing was performed on 113 pairs of tumor and normal DNA samples collected from Chinese individuals with treatment-naive primary ESCC, along with 8 cell lines, including 7 from KYSE series ESCC cell lines and one immortalized esophageal squamous epithelial cell line Het-1A.

  Study EGAS00001000932

• Much ado about nothing? - Off-target amplification can lead to false positive bacterial brain microbiome detection in healthy and Parkinson's disease individuals

  Recent studies suggested the existence of (poly-)microbial infections in human brains. Using 16S rRNA gene amplicon sequencing, we tested the hypothesis that there is a bacterial brain microbiome. We evaluated brain samples from healthy human subjects and individuals suffering from PD (olfactory bulb and pre-frontal cortex). We identified off-target amplification as a major confounding factor in low-bacterial/high-host-DNA scenarios.

  Study EGAS00001004757

• Dual-mTOR inhibitor Rapalink-1 reduces prostate cancer patient-derived xenograft growth and alters tumor heterogeneity

  Bone metastasis is the leading cause of prostate cancer (PCa) mortality, frequently marking the progression to castration-resistant PCa. In this study, we compared the molecular pathways enriched in a set of bone metastasis from breast and prostate cancer from snap-frozen tissue. To further model PCa drug resistance mechanisms, we used two patient-derived xenografts (PDX) models of bone-metastatic PCa, BM18 and LAPC9.

  Study EGAS00001004431

• WGS of cell-free DNA derived from plasma of CRC patients and healthy controls, and WGS of matched tumor tissue and saliva

  This dataset contains: 1.) Whole-genome sequencing (WGS) data (~6x) of 259 cfDNA samples obtained from 50 colorectal cancer (CRC) patients and 61 healthy controls. Paired-end sequencing was performed with 2x101 bp reads on the NovaSeq 6000 system. Data is provided as mapped .bam files (aligned to GRCh38/hg38). 2.) WGS data (~1x) of 50 tumor biopsy and 45 saliva samples from CRC patients. Paired-end sequencing was performed with 2x101 bp reads on the NovaSeq 6000 system. Data is provided as mapped .bam files (aligned to GRCh38/hg38).

  Dataset EGAD00001009309

• Legal Notice EGA is a joint effort by the EBI and CRG. Please, check their terms of use and legal notice in order to follow them in the usage of the EGA website. EBI terms of use CRG terms of use

  Documentation legal-notice

• Molecular Characterization of Large Cell Neuroendocrine Carcinoma of the Lung by Multilayered Omics Analysis

  Large cell neuroendocrine carcinoma (LCNEC) is a rare lung cancer type with a very poor prognosis. The underlying molecular features remain unclear. Here, we conducted a multi-omics analysis of 27 LCNEC cases along with 7 small cell lung carcinoma and aimed to propose new classification by extracting genomic and transcriptomic features in LCNEC, leading to the elucidation of the therapeutic approaches.

  Study JGAS000832

• A single-cell atlas of the early COPD lung

  Single cell atlas of the human airways from 10 patients suffering of early stage Chronic Obstructive Pulmonary Disease and 12 healthy age matched volunteers. This dataset was sequenced by 10X Genomics 3’ RNA-seq profiling. It is composed of more than 400 000 cells coming from 119 samples total. Sampling was performed by brushings and biopsies from the nose to the 6 th division of the airways.

  Study EGAS50000000720

• GILD_ExomeSeq_PTNHL

  This study is meant to gain further knowledge in haematological cancers. Patients samples (mainly DNAs or PCR products) from haematolocical cancer patients will be sequenced, and the outputs will be correlated to their diagnosis and/or prognosis; the findings may also add more insight into the understanding of biology in this type of tumour. We will be sequencing Primary Testicular Lymphomas (PTL) to identify genetic drivers of this rare cancer

  Study EGAS00001001613

• Strand-seq of hematopoietic stem and progenitor cells along human aging

  Somatic mosaicism (SM), referring to the presence of somatic mutations in sub-populations of cells within healthy individuals, is associated with an increased risk of a variety of diseases, including cancer. Blood is at particularly high risk of SM, given its rapid turnover and functionally- heterogeneous cell-type composition. While the roles of point mutations and large-scale rearrangements in blood SM have been scrutinised in recent years, the functional impact of mosaic structural variants (mSVs) remains poorly understood. Using haplotype-resolved single-cell multi-omics based on Strand-seq technology, we explored the mSV landscape of human hematopoietic stem and progenitor cells (HSPCs).

  Dataset EGAD00001009402

• Exome sequencing demonstrates a dual origin of relapses in retinoic-acid resistant acute promyelocytic leukemia.

  Retinoic acid (RA) and arsenic target the PML/RARA driver of Acute Promyelocytic Leukemia (APL), their combination now curing over 95% patients. Here we report exome sequencing of 64 matched diagnosis/remission/relapses patients treated with historical RA/chemotherapy protocols. A first subgroup presents a high incidence of oncogenic mutations disrupting key epigenetic or transcriptional regulators (primarily WT1) or activating MAPK signaling at diagnosis. Relapses retain these cooperating oncogenes and exhibit additional oncogenic alterations and/or mutations impeding therapy response (RARA, NT5C2). The second group primarily exhibits FLT3 activation at diagnosis, which is lost upon relapse together with most other passenger mutations, implying that relapses derive from pre-leukemic PML/RARA-expressing cells that survived RA/chemotherapy. Accordingly, clonogenic activity of PML/RARA-immortalized progenitors ex vivo is only transiently affected by RA, but selectively abrogated by arsenic. Our studies stress the role of cooperating oncogenes in direct relapses and suggest that targeting pre-leukemic cells by arsenic contributes to its clinical efficacy.

  Study EGAS00001002893

• Amplicon_based_sequencing_of_drug_resistant_organoids

  A BRAF V600E colorectal organoid which is sensitive to MAP kinase inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a combination of Trametinib, Dabrafenib and Cetuximab. Single cell derived organoids were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors from a screen in 2 2D BRAF V600E colorectal cell lines. Pools of resistant clones were also sequenced.

  Study EGAS00001001639

• The application of RNA sequencing for the diagnosis and genomic classification of pediatric acute lymphoblastic leukemia

  Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy, and implementation of risk-adapted therapy has been instrumental in the dramatic improvements in clinical outcomes. A key to risk-adapted therapies includes the identification of genomic features of individual tumors, including chromosome number (for hyper- and hypodiploidy) and gene fusions, notably ETV6-RUNX1, TCF3-PBX1 and BCR-ABL1 in B-cell ALL (B-ALL). RNA-sequencing (RNA-seq) of large ALL cohorts has expanded the number of recurrent gene fusions recognized as drivers in ALL, and identification of these new entities will contribute to refining ALL risk stratification. We used RNA-seq on 126 ALL patients from our clinical service to test the utility of including RNA-seq in standard of care diagnostic pipelines to detect gene rearrangements and IKZF1 deletions. RNA-seq identified 86% of rearrangements detected by standard of care diagnostics. KMT2A-rearrangements (MLL), whilst usually identified, were the most commonly missed by RNA-seq as a result of low expression. RNA-seq identified rearrangements that were not detected by standard of care testing in nine patients. These were found in patients who were not classifiable using standard molecular assessment. We developed an approach to detect the commonest IKZF1 deletion from RNA-seq data and validated this using a RQ-PCR assay. We applied an expression classifier to identify Ph-like B-ALL patients. T-ALL proved a rich source of novel gene fusions which have clinical implications or provide insights into disease biology. Our experience shows that RNA-seq can be implemented within an individual clinical service to enhance the current molecular diagnostic risk classification of ALL.

  Study EGAS00001004212

• The mutational landscape of skin tumours in CYLD cutaneous syndrome determined

  Patients with germline mutations in CYLD can develop hundreds of benign skin tumours called cylindromas. The development of multiple tumours within a single patient at sun-protected and sun-exposed sites, varying tumour histological patterns and grades of malignancy allow for the testing of several genetic hypothesis in relation to cutaneous carcinogenesis. By adopting the unprecedented approach of whole genome sequencing of multiple benign skin tumours within individuals in multigenerational families, we set out to study the impact of mutational diversity on models such as multistep carcinogenesis as well as non-sequential carcinogenesis. Using non-negative matrix factorisation (NMF) to discover mutational signatures, we found distinct mutational signatures in identical benign tumours (N=2 patients; n=11 tumours) at sun exposed and sun protected skin tumours within a mother and her daughter. We found recurrent mutations in epigenetic modifying genes in CCS tumours which are known to have an oncogenic dependency on Wnt signalling. We also demonstrate that cutaneous tumours that metastasize to the lung carry a a UV signature, supporting the origin from the skin. Distinct malignant tumours, such as BCC and malignant spiradenocarcinoma carried unique driver mutations. These findings add new dimensions to the existing paradigms of UV-induced skin cancer and highlight the utility of studying rare disease to gain novel insights into genetic mechanisms of tumour formation.

  Dataset EGAD00001004573

• Clonal evolution in myeloma: the impact of maintenance lenalidomide and depth of response on the genetics and sub-clonal structure of relapsed disease in uniformly treated newly diagnosed patients

  The emergence of treatment resistant sub-clones is a key feature of relapse in multiple myeloma. Therapeutic attempts to extend remission and prevent relapse include the maximisation of response and use of maintenance therapy. We used whole exome sequencing to study the genetics of paired presentation and relapse samples from 56 newly diagnosed patients, following induction therapy, randomised to receive either lenalidomide maintenance or observation as part of the Myeloma XI trial. Patients included were considered high risk, relapsing within 30 months of maintenance randomisation. Patients achieving a complete response had predominantly branching evolutionary patterns leading to relapse, characterised by a greater mutational burden, an altered mutational profile, bi-allelic inactivation of tumour suppressor genes, and acquired structural aberrations. Conversely, in patients achieving a partial response the evolutionary features were predominantly stable with a similar mutational and structural profile. There were no significant differences between patients relapsing after maintenance lenalidomide vs observation. This study shows that the depth of response is a key determinant of the evolutionary patterns seen at relapse.

  Study EGAS00001003539

• Acute myeloid leukemia whole exome sequencing (Diagnosis, Complete Remission and Relapse)

  To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed whole exome sequencing to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases. All the samples are bone marrow aspirates.

  Dataset EGAD00001008375

• subset of 11 samples RRMM (RNA-Seq and WGS) from study EGAS00001005973 used also in study EGAS00001006538

  subset of 11 samples (RNA-Seq and WGS) from study EGAS00001005973, which was published earlier and are linked here to study EGAS00001006538

  Dataset EGAD00001009679

• Hi-C in endometrial healthy and tumor tissues

  Hi-C libraries have been prepared by enzymatic digestion with MboI restriction enzyme and sonication. Illumina single-indexig primers have been use to amplify ligated fragments. Hi-C experiments have been performed on 10 slices (30um thick) of fresh-frozen tissues derived from 3 healthy and 3 tumor endometrial tissues of post-menopausal patients. Raw paired-end fastq.gz files are provided.

  Dataset EGAD00001010898

• Neuroblastoma tumor heterogeneity and cell plasticity (from patients)

  Two cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific core regulatory circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain to be defined. Here, we document a spontaneous plasticity between the noradrenergic and mesenchymal identities in a subset of cell lines. Strikingly, mesenchymal neuroblastoma cells revert to a noradrenergic phenotype in vivo. Consistently, tumor cells with a mesenchymal identity are detected in single-cell transcriptomic analyses of neuroblastoma tumors and PDX models. Our data also highlight neuroblastoma intra-tumor heterogeneity with the co-existence of distinct tumor populations, including sympathoblast-like and chromaffin-like cells suggesting that neuroblastoma cells arise from a common sympatho-adrenal progenitor.

  Study EGAS00001005322

• Breast Cancer Family Registry

  The Breast Cancer Family Registry (BCFR) is a multi-center prospective cohort, comprised of over 30,000 women and men from nearly 12,000 families from the United States, Canada, and Australia. Our BCFR resource has been used, and continues to be used, by breast cancer researchers around the world in order to find new ways to prevent, diagnose, and treat cancer. The BCFR provides an extensive and diverse range of resources, expertise, and specialized skills, and has several unique strengths: 1) the collection of a large number of individuals and families across a wide spectrum of breast cancer risk, including both affected and unaffected individuals; 2) the large collection of families with early-onset breast cancer; 3) the large collection of racial/ethnic minority families not replicated elsewhere; 4) the extensive molecular characterization performed to date; and 5) active follow-up of both probands and family members. Thus, the BCFR comprises a unique cohort of probands and family members at familial/genetic risk of breast cancer that will continue to facilitate a wide range of research studies, such as gene discovery, examination of cancer-related outcomes and risk factors in high-risk subjects, investigation of novel behavioral interventions, and cancer prevention trials among at-risk family members. Consequently, the BCFR Cohort, as one of the few cohorts available worldwide with biospecimens and extensive molecular and genetic characterization, combined with epidemiologic data and long-term follow up, will be an invaluable resource for translational research in the genetic epidemiology of breast cancer.

  Study phs002835

• PRADO trial - Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab plus nivolumab in stage III melanoma

  The PRADO trial tested a personalized response-directed treatment approach based on the pathologic response after neoadjuvant ipilimumab plus nivolumab in stage III melanoma patients. In patients achieving a major pathologic response, in their index lymph node (the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with partial response underwent TLND only, whereas patients with pathologic non-response underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Biomarker analyses based on baseline RNA sequencing data were performed in order to find features that are associated with major pathologic response.

  Study EGAS00001007601

• Ultra-Fast Patient-Derived Xenografts Identify Functional and Spatial Tumour Heterogeneities that Drive Therapeutic Resistance

  Treatment of patients with advanced cancers increasingly relies on agents targeting specific molecular or cellular aberrations. These expensive therapies often fail because of pre-existing drug resistance. Intra-tumoural molecular and micro-environmental heterogeneity resistance can create resistance in one or more subclones of a tumour, leading to spatio-functional heterogeneity. We created a rapid approach for quantifying tumour functional phenotypes based on tumour-implantation into the chorioallantoic membrane of chick embryos. We apply this technique to 43 separate biopsies from 6 patients with renal cell carcinoma (RCC) with 36 replicates per biopsy, achieving a 93.6% engraftment rate (1449/1548). Challenging these models with sunitinib, an anti-angiogenic therapy frequently used in RCC allowed us to quantify spatio-functional heterogeneity in individual patients. Prediction of de novo drug resistance in advanced cancer patients would facilitate precision medicine by tailoring systemic therapies and improve clinical trial design outcome measures. We describe a patient-derived xenograft platform where fresh patient tumour samples are implanted into the chorioallantoic membrane (CAM) of chick embryos at high engraftment efficiencies, permitting large scale “tumour avatar” studies to guide the selection of drugs and to predict clinical drug resistance outcomes in renal cell carcinoma (RCC) patients. Applying this “tumour avatar” model in a co-clinical trial on RCC patients, we observe intra-tumoural functional heterogeneity with sunitinib treatment, revealing the presence of drug-resistant clones prior to the initiation of therapy. Multi-regional exome Matched DNA sequencing of the primary tumour and metastases revealed DNA mutational signatures associated with sunitinib resistance at baseline and after treatment. These These studies demonstrate a rapid and affordable method of findings confirm the existence of genetic and surveying functional tumour heterogeneities heterogeneity.

  Study EGAS00001002627

• A prognostic human brain network for diffuse midline glioma

  Diffuse midline glioma (DMG) are near-universally lethal tumours of the paediatric central nervous system. In animal models, DMG form brain-wide, integrated networks through neuron-to-glioma synapses and glioma-to-glioma gap junctional coupling. This extensive connectivity robustly promotes the growth and invasion of DMG and other glial malignancies through paracrine mechanisms and direct neuron-to-glioma synapses. The organisation and clinical implications of these connections in the living human brain, however, remain to be elucidated. Here, we develop tumour network mapping to compute the brain-wide connectivity profile of DMG: defining a conserved brain network across pontine and thalamic DMG associated with patient short-term survival (DMG network). Tumour functional connectivity with the DMG network was independently predictive of patient overall survival across two external validation cohorts. Tumour growth mapped to DMG network-specific trajectories and peak, in-network neurometabolic changes across development spatiotemporally aligned with the peak age incidence of DMG. Single-nucleus RNA-sequencing confirmed diverse synaptic gene enrichment in high-connectivity DMG. Strikingly, incidental surgical resection of high-connectivity thalamic DMG tissue conferred a significant survival advantage. Collectively, these data define a conserved and prognostically important brain network in children with DMG, consistent with the hypothesis that DMG exploit otherwise healthy brain circuits to promote tumour growth.

  Study EGAS50000001752

• HiDEF-seq single-molecule sequencing of single-strand mismatches and damage

  Our study sought to resolve, with single-molecule fidelity, the mismatches and damage events that precede DNA mutations. Using a novel single-molecule, long-read sequencing method (HiDEF-seq) we detect base substitutions when present in either one or both DNA strands. We also detect cytosine deamination, a common type of DNA damage, with single-molecule fidelity. This study profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes. These samples revealed single-strand mismatch and damage signatures. Since double-strand DNA mutations are only the endpoint of the mutation process, our approach enables new studies of how mutations arise in a variety of contexts, especially in cancer and aging.

  Study EGAS50000000318

• Bottleneck Sequencing Of Human Tissue (Wgs) (2020-10-20)

  Bottleneck sequencing of human tissue including neurons, cord blood, sperm. 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 2020-10-20.

  Dataset EGAD00001006459

• Identification of the Global miR-130a Targetome Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML

  In this study, we identified miR-130a as a regulator of HSC self-renewal and differentiation. To characterize gene expression changes following enforced expression of miR-130a OE, we performed RNA-seq in CD34+ cord blood (CB) cells transduced with control and miR-130a OE lentiviruses. To capture miRNA targets in an unbiased, transcriptome-wide manner, we perfomed enhanced CLIPseq procol in 2 replicates of CD34+ CB cells and Kasumi-1 cell line, which represent a model system for t(8;21) AML. We chose this cell line, as we found miR-130a to be highly expressed in this AML subtype where it is critical for maintaining the oncogenic molecular program mediated by AML1-ETO. Chimeric Ago2 eCLIPseq in CD34+ CB cells combined with Mass Spectrometry data analysis identified TBL1XR1 as a principal target of miR-130a. To elucidate gene expression changes associated with TBL1XR1 loss of function, we performed RNA-seq in CD34+CD38- CB cells transduced with control and shRNA targeted against TBL1XR1. To determine the functional significance of high miR-130a expression levels in Kasumi-1 cells on the molecular network controlled by AML1-ETO, we performed CUT&RUN assay and RNA-seq in Kasumi-1 cells following miR-130a knock-down (KD). Collectively, our findings reveal a unique role of miR-130a in regulating normal hematopoietic stem cell self-renewal and how elevated levels of miR-130a in t(8;21) AML contribute to the leukemogenesis of this AML subtype.

  Dataset EGAD00001008412

• Whole exome sequencing and methylation profiling of uveal melanoma

  Uveal melanoma (UM) is the most common primary cancer of the eye and frequently leads to metastatic death. Metastatic risk can be stratified into low, intermediate and high based on the presence of mutually exclusive mutations in EIF1AX, SF3B1 and BAP1, respectively. The purpose of this study was to comprehensively profile the genetic aberrations in a set of primary uveal melanomas using whole exome sequencing, as well as DNA methylation profiling of selected samples, to improve understanding of its pathogenesis.

  Study phs001421

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): ILI Labels and Longitudinal Novel Engagement with Symptom Surveillance (ILLNESS) Study

  This study is a prospective observational study, approximately seven months in duration. Participants were asked to complete a weekly survey online asking about their ILI (influenza-like illness) experience over the past seven days. The primary objective of this study was to collect a population-wide, longitudinal dataset of ILI events (with onset and recovery dates) and the associated symptoms, behaviors, and medical information associated with each event.DOI: https://rapids.ll.mit.edu/10.57895/4vfb-4z30

  Study phs002538

• Longitudinal Transcriptomic Profiling of Endothelial Progenitor Cells in Post-COVID-19 Patients: Insights at 3 and 6-Months Post-SARS-CoV-2 Infection

  Bulk RNA-sequencing analysis of endothelial cells isolated from post-COVID patients at 3 and 6 months post-infection, alongside healthy controls. This study aims to identify differentially expressed genes in endothelial cells from post-COVID patients—at both 3- and 6-month time points—compared to those from healthy individuals. The objective is to uncover upregulated and downregulated pathways potentially associated with long-term consequences of SARS-CoV-2 infection.

  Study EGAS50000000993

• RNA-Seq data_MM study cohort (n=73) and human myeloma cell lines

  Multiple myeloma (MM) represents approximately 10 % of all hematological malignancies and patients present with a variety of clinical manifestations and diverse cytogenetic backgrounds While MM patient survival has greatly improved due to novel treatments in the last years, the disease is generally considered incurable with a median survival of approximately 6 years. Therapy resistance remains as a major obstacle, causing almost all patients to eventually relapse, underlining the persisting need to identify novel therapeutic targets and biomarkers associated with disease progression.

  Study EGAS50000000392

• Genomic, transcriptomic and epigenomic profiling of GCTB

  Giant cell tumor of bone is a rare bone neoplasm driven by oncogenic hotspot G34W/L/V mutations in the non-canonical histone variant H3.3. This study provides primary data of genomic (WGS), transcriptomic (RNA-seq) and epigenomic (histone mark ChIP-seq, WGBS, ATAC-seq) profiling of primary GCTB samples from several cohorts in Germany and Korea. We confirm the H3.3-G34 mutations as sole genetic drivers of GCTB, and describe the epigenetic alterations in mutant GCTB stromal cells.

  Study EGAS00001003730

• Genetic profiling of mucosal melanoma

  Primary mucosal melanomas (MMs) arise from melanocytes located in mucosal membranes lining the respiratory, gastrointestinal and urogenital tracts. MMs frequently present late and have a poor prognosis; the 5-year survival rate is only 14%. MM makes up only ~1.4% of all melanomas and it is this rarity that makes knowledge of the genetic changes that contribute to its pathogenesis limited to a small number of exome/genome studies and other targeted studies. Thus to investigate the somatic alterations and mutation spectra in MM genomes, we have extracted genomic DNA from formalin-fixed, paraffin-embedded (FFPE) human MMs, and subjected them to whole exome sequencing. Given the propensity of MM to metastasize, we will also be sequencing metastatic MM lesions; primary and metastatic lesions from the same individual represent an excellent opportunity to identify potential drivers of metastasis in MM. Finally we will sequence 'normal' DNA from the same individual, where possible, to exclude germline variations.

  Dataset EGAD00001003237

• Congenital_anosmia_1

  Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). To date, only a single recessive gene underlying complete anosmia has been identified. Here we sequenced the exomes of 10 individuals from a single family, including three with complete anosmia, across three generations to identify the genetic basis of congenital anosmia in this family. 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/

  Study EGAS00001001124

• Hi-C in breast healthy, primary cancer and metastatic tissues

  Hi-C libraries have been prepared by enzymatic digestion with MboI restriction enzyme and sonication (Covaris). Illumina single-indexig primers have been use to amplify ligated fragments. Hi-C experiments have been performed on 10 slices (50um thick) of fresh-frozen tissues or 10x10e6 Pleural Effusion cells. Raw paired-end fastq.gz files are provided.

  Dataset EGAD50000000643

• RNAseq Data Cyr61-MAC and HUVEC

  Gene expression of MAC enriched by adhesion to Cyr61 in comparison to HUVEC. This dataset includes RNAseq Data from myeloid angiogenic cells (MAC) enriched from peripheral blood by adhesion to Cyr61 (4 samples prepared from different donors) and of human umbilical vein endothelial cells (HUVEC) (4 samples). Illumina NextSeq500 technology was used. FASTQ data are provided.

  Dataset EGAD50000000758

• Whole-exome sequencing of rare autoimmune-related phenotypes

  We aim to whole-exome sequence DNA samples from 75 individuals with severe forms of Inflammatory Bowel Disease and related autoimmune diseases to identify the rare, highly penetrant, variants that we believe underlie these phenotypes. Case samples will be obtained from both new and existing (UK IBD Genetics Consortium) collaborators to ensure only the most extreme cases are sequenced.

  Dataset EGAD00001000408