21033 results for "fc 26 coins Buyfc26coins.com is EA Sports official for FC 26 coins The service is affordable and quick..JIZq"

in 37.50 milliseconds.

• DNA and RNA sequencing data from Ovarian Carcinosarcoma patients from the Glasgow Cohort.

  In this study, we analysed DNA and RNA sequencing data from Ovarian Carcinosarcoma patients, from isolated carcinoma and sarcoma components and investigated DNA variants as well as gene expression. Genomic analyses from this data and further investigation from preclinical models of ovarian carcinosarcoma support the conversion theory for disease development and indicate that microtubule inhibitors could be used to suppress EMT and stimulate anti-tumour immunity.

  Study EGAS00001006605

• Baseline epigenetic clock measures in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA)

  Epigenetic clock measures for a subset of 1,870 participants within the NICOLA cohort. The following epigenetic clocks were generated: (±PC)PhenoAge, (±PC)GrimAge, (±PC)Horvath1, (±PC)Hannum, PCDNAmTL and DunedinPACE. +PC represents the use of the principal component adjusted version of the clock.

  Dataset EGAD50000002063

• DNA from colon cancer samples and matched normal samples was hybridized on Human 660W-Quad SNP arrays and sequenced in Illumina HiScanSQ.

  DNA from colon cancer samples and matched normal samples was hybridized on Human 660W-Quad SNP arrays and sequenced in Illumina HiScanSQ. The objective of the study was to introduce methodology for the detection of genomic copy number alterations (CNAs) using high-throughput sequencing data. The samples in this study allow the comparison of the results from the seqCNA R package with those from other methods that detect copy number alterations (CNAs) in tumoural samples, either using SNP-array data or high-throughput sequencing data.

  Study EGAS00001000558

• Finding structural variation and functional consequences from the primary leukemia cells (CLL) at the single-cell level

  In this study, we aimed to identify somatic structural variation of chronic lymphocytic leukemia (CLL) at the single-cell level and investigate its direct consequence on the nucleosome occupancy using scNOVA approach. For this purpose, we performed strand-specific single-cell sequencing of primary leukemia samples from 63-year-old female patient.

  Study EGAS00001004925

• Liver Regulatory Genomics Data Access Committee

  Data access committee for genomic datasets generated for human liver tissue and human primary liver cells by the Regulatory Genomics of Metabolic Disease group (Imperial College London, Section of Genetics and Genomics).

  Dac EGAC50000000715

• Whole-Exome Sequencing Study of Diabetic Nephropathy

  To identify rare variants of diabetic kidney disease (DKD), we conducted a whole-exome sequencing (WES) study. This study employed an extreme case–control design, which included a selection of the 593 most rapidly progressing DKD cases from the Chronic Renal Insufficiency Cohort (CRIC) Study (phs000524). In this two-stage WES study of DKD, participants with DKD from the CRIC were compared with control groups of participants without DKD from another cohort in the first stage. Suggestive signals identified in the first stage were confirmed in the second stage analysis among a diverse population with existing whole-genome sequencing (WGS) data. Generalized linear mixed models, which accounted for genetic relatedness and adjusted for age, sex and ancestry, were used to test associations between single variants and DKD. Gene-based aggregate rare variant analyses were conducted using an optimized sequence kernel association test implemented within our mixed model framework. As a result, we identified four novel gene loci, DIS3L2, KRT6B, ERAP2 and NPEPPS, that achieved exome-wide significance and may play an important role in the DKD disease course. This large WES study provides novel insights into DKD's molecular mechanisms.

  Study phs003429

• Genome-wide cell-free DNA fragmentation in patients with cancer

  Cell-free DNA (cfDNA) in the blood provides a noninvasive diagnostic avenue for patients with cancer. However, characteristics of the origins and molecular features of cfDNA are poorly understood. We developed an approach to evaluate fragmentation patterns of cfDNA across the genome and found that cfDNA profiles of healthy individuals reflected nucleosomal patterns of white blood cells, while patients with cancer had altered fragmentation profiles. We applied this method to analyze fragmentation profiles of 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric, or bile duct cancers and 245 healthy individuals. A machine learning model incorporating genome-wide fragmentation features had sensitivities of detection ranging from 57% to >99% among the seven cancer types at 98% specificity, with an overall AUC of 0.94. Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases. Combining our approach with mutation based cfDNA analyses detected 91% of cancer patients. The results of these analyses highlight important properties of cfDNA and provide a proof of principle approach for screening, early detection, and monitoring of human cancer.

  Study EGAS00001003611

• Adult granulosa cell tumor WGS data cohort with corresponding reference germline WGS data

  Adult granulosa cell tumors (AGCTs) harbor a somatic FOXL2 c.402C>G mutation in ~95% of cases and are mainly surgically removed due to limited systemic treatment effect. In this study, potentially targetable genomic alterations in AGCTs were investigated by whole genome sequencing on 46 tumor samples and matched normal DNA. Copy number variant (CNV) analysis confirmed gain  of chromosome 12 and 14, and loss of 22. Pathogenic TP53 mutations were identified in three patients with highest tumor mutational burden and mitotic activity, defining a high-grade AGCT subgroup. Within-patient tumor comparisons showed 29-80% unique somatic mutations per sample, suggesting tumor heterogeneity. FOXL2-wildtype AGCTs had DICER1, TERT(C228T) and TP53 mutations and similar CNV profiles as FOXL2-mutant tumors. Our study confirms that absence of the FOXL2 c.402C>G mutation does not exclude AGCT diagnosis. The lack of overlapping variants in targetable cancer genes, indicates the need for personalized treatment for AGCT patients 

  Study EGAS00001004249

• DNA Methylation loss coupled with mitotic cell division promotes immune evasion of tumours with high mutation load

  Mitotic cell division increases tumour mutation burden and copy number load with a positive and inverse correlation, respectively, with the clinical benefit of immunotherapy. Markers of cell division correlate also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation as a combination regimens for precision immunotherapy.

  Study EGAS00001003731

• Epithelioid haemangioendothelioma (EHE) case series from the Stafford Fox Rare Cancer Program

  Nine EHE cases with comprehensive histologic and molecular profiling from the Walter and Eliza Hall Institute of Medical Research Stafford Fox Rare Cancer Program were collated via nation-wide referral to the Australian Rare Cancer Portal. Molecular analysis of RNA, DNA or both was possible in seven of nine cases. Survival was highly variable and unrelated to molecular profile. DNA sequences for two cases are deposited here.

  Study EGAS00001007474

• Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma_CM67-RNASeq

  Purpose Exploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma. Patients and Methods Patients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS. Results In the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (> median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature. Conclusions Combined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.

  Dataset EGAD00001006306

• Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma - CM066-WES

  Purpose Exploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma. Patients and Methods Patients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS. Results In the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (> median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature. Conclusions Combined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.

  Dataset EGAD00001006309

• NCT03343197: Clinical Biomarker Data

  Patients with IDH1-mutated low-grade glioma were treated with AG-120 (ivosidenib), AG-881 (vorasidenib), or Placebo for 28 days before surgical resection. A portion of the surgical sample was submitted for exome capture-based transcriptome sequencing (Personalis ACE Whole Transcriptome). Following surgery, subjects had the option to continue (or initiate) treatment with AG-120 or AG-881.This dataset comprises next-generation sequencing data from biopsies obtained in the clinical trial: NCT03343197 (Study of AG-120 and AG-881 in Subjects with Low Grade Glioma).

  Study phs003148

• Metatranscriptomic Sequencing of Pre-Transplant Bronchoalveolar Lavage in Pediatric Stem Cell Transplant Patients

  Children with malignancies, immunodeficiencies, and other life-threatening diseases sometimes receive allogeneic hematopoietic cell transplantation (HCT) as a treatment for their disease. The HCT process can be complicated by the development of lung disease from infection, alloreactivity, or other causes. To identify patients at-risk for post-HCT lung disease, this study uses metatranscriptomic RNA sequencing of bronchoalveolar lavage (BAL) obtained prior to HCT. Sequencing results are associated with the development of post-HCT lung injury. 

  Study phs002208

• LCM-ATACseq on human lung macrophages

  In this study we employed Laser Capture Microdissection (LCM) for the multimodal profiling of lung macrophages cell populations as a function of location within the healthy tissue. In detail, macrophage mini-bulks (~100 cells) were collected from 4 healthy human donors in 5 different locations of the airways (a total of 20 biopsies), including parenchyma (L1 – lower left lobe (LLL); L6 – 80% distance from LLL tip), trachea (L2), bronchi (L3 – 1st/2nd generation; L5 – 3rd/4th generation), and processed for ATAC-seq.

  Study EGAS00001006167

• Machine learning to detect the SINEs of cancer

  We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA (cfDNA) through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a novel machine-learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to samples from 5108 individuals, 2037 with cancer and the remainder without cancer. Samples from cancer patients and controls were pre-specified into four cohorts used for: 1) model training, 2) analyte integration and threshold determination, 3) validation, and 4) reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the Validation Cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and 8 common protein biomarkers detected 51% of 1167 cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature – the global reduction of AluS sub-family elements in the circulating DNA of cancer patients. We confirmed this reduction through the analysis of another independent dataset obtained with a very different approach (whole genome sequencing). The evaluation of Alu elements therefore has the potential to enhance the performance of several methods designed for the earlier detection of cancer.

  Study EGAS00001007169

• Diverse transcriptomic and mutational patterns but limited functional pathway alterations in patient-derived SS cells

  We profile the whole-transcriptome of 7 patient-derived Sézary Syndrome (SS) cells to identify expression patterns, functional programs and expressed gene mutations that may provide clues on new therapeutic options for SS patients. The libraries were sequenced on NextSeq500 (Illumina) with a paired-end read length of 2x75bp.

  Study EGAS50000001151

• cell-Free DNA Genomic Profiling and its Clinical Implementation in Advanced Prostate Cancer

  Sixty-eight patients with advanced prostate cancer in castration-resistant or castration-sensitive settings undergoing treatment at the University Hospital Basel or the St. Claraspital Basel (Switzerland) were selected for targeted parallel sequencing analysis on liquid biopsy (plasma cfDNA) and matched formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples.

  Study EGAS50000000234

• ATAC-Seq of CD4 T cell subsets

  Blood samples were taken from 4 age-matched healthy volunteers (two males and two females), and naïve CD4 T cells were isolated using the naïve CD4+ T Cell Isolation Kit II, human (Miltenyi Biotec). Two hundred thousand cells were plated in a 96-well plate, activated with Dynabeads Human T-activator CD3/CD28 (bead-to-cell ratio of 1:1, as recommended by the manufacturer) (ThermoFisher Scientific) and polarized towards CD4 T cell subtypes (Teff, Th1, Th2, rTh17, pTh17, and Treg cells) with specific cocktails of recombinant cytokines and neutralizing antibodies (see details in the material and methods) for each subset. At day 4 post-stimulation, forty thousand cells were used to perform ATAC-Seq on CD4 T cell subtypes. Again, crude nuclei of live CD4+ T cell subsets were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry.

  Study EGAS00001007345

• Risk alleles of membranous nephropathy and recurrence of the disease on the grafted kidney

  The goal of the project was to identify risk alleles that are associated with recurrence of membranous nephropathy in the graft after kidney transplantation. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs.

  Study EGAS00001005435

• Single-cell RNA sequencing on 5063 single T cells isolated from peripheral blood, tumour and adjacent normal tissues from six hepatocellular carcinoma patients.

  Single-cell RNA sequencing on 5063 single T cells isolated from peripheral blood, tumour and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional properties of these individual cells, coupled with the assembled T cell receptor (TCR) sequences, were used to delineate the molecular subtypes, lineage, and functional properties of each T cell group. For five HCC patient, the exome-seq data of matched normal/tumor and bulk RNA-seq data of tumor are also available.

  Study EGAS00001002072

• 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

• GenomeDenmark Phase 2 - variants called on chrY for 62 males.

  Variants on the Y chromosome for 62 danish males in VCF format from the GenomeDenmark Phase 2 cohort. Variants were called using reference based approaches such as the haplotype-caller module from GATK and using alignment of denovo assemblies to the reference using ASMvar.

  Dataset EGAD00001003186

• Multimodal epigenetic sequencing analysis of cell-free DNA identifies biomarkers for ALS diagnosis and progression

  The role of the epigenome in age-related neurodegenerative disorders remains understudied. Here, we analyzed circulating cell-free DNA (cfDNA) from blood to detect methylation changes as a liquid-biopsy for Amyotrophic Lateral Sclerosis (ALS). Our study included 20 patients with sporadic ALS, 10 patients with C9orf72-associated ALS, 10 asymptomatic carriers of the C9orf72 repeat expansion mutation, and 21 non-disease controls.

  Dac EGAC50000000739

• scRNA-seq raw data

  This dataset contains scRNA-seq fastq files (trimmed for quality and adapters using Trim Galore) for 3739 intestinal plasma cells of known or unknown antigen specificities from in total 12 individuals (4 untreated coeliac disease patients, 3 treated coeliac disease patients, 5 controls). The data was generated using the Smart-seq2 protocol and sequenced on the Illumina NextSeq500 platform with 75 bp paired-end reads.

  Dataset EGAD00001006436

• Autozygosity pilot - Born in Bradford (2017-05-11)

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing cohort samples from the Born In Bradford study will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples. This dataset contains all the data available for this study on 2017-05-11.

  Dataset EGAD00001003329

• Mapping and phasing of structural variation in patient genomes using nanopore sequencing

  We whole genome sequence 2 patients with congenital abnormalities and known complex de novo chromosomal rearrangements using the Nanopore MinION. We show how we can detect most previoulsy detected de novo rearrangements as well as uncover a few new ones. Furthermore, we perform genome-wide analyses showing the accuracy of SV detection and of phasing, using long reads. The files uploaded here are the whole genome Nanopore data for each of the two patients used, as well as the corresponding whole genome illumina data, used in our comparisons.

  Study EGAS00001002333

• Evaluation of commercial Guardant360 ctDNA test in metastatic prostate cancer

  Circulating tumor DNA (ctDNA) sequencing provides a minimally-invasive method for tumor molecular stratification. We compared the commercial Guardant360 ctDNA test to an academic sequencing approach for profiling of metastatic prostate cancer. Plasma cell-free DNA (cfDNA) from 24 patients was sequenced with a validated, prostate cancer specific targeted research panel, and sent for simultaneous Guardant360 analysis.

  Study EGAS00001003352

• Sequencing data for Hepatoblastoma samples

  This dataset contains DNA sequencing data for twelve hepatoblastoma tumor samples, four of which have matched normals. Nine of the samples also have RNA sequencing data from the tumor sample. The dataset comprises six samples from patient tissues and six from cell lines; see metadata for details.

  Dataset EGAD00001006621

• Diagnostic yield and clinical utility of whole-exome sequencing in pediatric patients with rare and undiagnosed diseases in the Czech Republic

  In our single-center study, we have launched a pilot program for pediatric patients with undiagnosed diseases in the second-largest university hospital in the Czech Republic. WES was implemented as a first-line test after inclusion in the study as part of the diagnostic workflow.

  Study EGAS50000000442

• Lessons learned from the exome sequencing of nine cases of infertility and the way forward

  This study investigated the role of exome sequencing in the diagnosis of male and female infertility. Nine unrelated cases referred between 2019 and 2024 were analysed using exome sequencing, with segregation confirmed by Sanger sequencing and functional assays for splicing variants. We identified nine causative variants in genes including TUBB8, PATL2, CCDC39, STAG3, KIAA0319, FBXO43, AGBL5/BBS7, PLCZ1, and HS6ST1, six of which were novel. The findings highlight diverse reproductive phenotypes such as oocyte maturation arrest, early embryonic arrest, spermatogenic failure, and syndromic infertility. This work demonstrates the value of combining genetic, functional, and clinical approaches to improve diagnostic yield and patient care in reproductive failure.

  Study EGAS50000001320

• Epigenome-wide methylation analysis of colorectal carcinoma, adenoma and normal tissue reveals novel biomarkers addressing unmet clinical needs

  Studies about CRC biomarker discovery have focused on methylation patterns in normal and colorectal tumor tissue, leading to a lack of knowledge of methylation in adenomas. Therefore, we performed the first epigenome-wide study to compare the epigenomes of all three tissue types combined, and to identify discriminatory biomarkers. Public Illumina MethylEPIC® data was collected from 552 normal, 118 carcinoma and 116 adenoma samples. Pairwise analyses were performed for discovery of differentially methylated probes (DMPs). We identified 693 813, 620 643 and 558 897 DMPs when comparing normal vs carcinoma, normal vs adenoma and adenoma vs carcinoma respectively. To double evidence (DE) these DMPs, analysis of Illumina 450K data from public datasets was performed. Through this analysis, 13 DE DMPs with │Δβ│≥0.3 were identified for adenoma vs carcinoma. A binary logistic regression model was generated to evaluate the discriminatory potential of these DE DMPS. The model was validated in an in-house experimental methylation dataset of 13 adenoma and 9 carcinoma samples. Our classifier reached a cross-validated AUC of 0.996 and 0.855 in the discovery and validation datasets respectively. A sensitivity and specificity of 96% and 95% were reached, with an overall accuracy of 96%. Our analysis show that methylation biomarkers have the potential to discriminate between normal, precursor and carcinoma tissues of the colorectum. More importantly, we highlight the power of the methylome, showing that DMPs can be used as biomarkers in the clinic to identify colorectal adenoma and carcinoma. 

  Study EGAS00001007017

• scRNAseq analysis of CD8 T cells infiltrating the bladder and tumor of 4 non-muscle-invasive bladder cancer patients, before and after BCG treatment.

  We performed scRNAseq analysis of CD8 T cells infiltrating the bladder and tumor of 4 non-muscle-invasive bladder cancer patients, before and after BCG treatment. In order to identify tumor-specific T cells, we selected CD8 T cells that were enriched in the tumor of the patient. We also selected CD8 T cells appearing in the bladder after BCG treatment, with the hypothesis that BCG treatment stimulates tumor-specific CD8 T cells. Next, we cloned the TCR of these T cells in a Jurkat cell line and tested these TCR for recognition of tumor-specific antigens.

  Study EGAS50000001384

• Extracellular vesicles from TGF-β-activated cancer-associated fibroblasts remodel the tumor microenvironment through EV surface-associated proteins.

  In this study, we explored the function of extracellular vesicles (EVs) derived from non-activated cancer-associated fibroblasts (CAFs) and TGF-β-activated CAFs. We tested these two types of EVs on other cell types in the tumor environment, including cancer cells, CD8+ T cells, and CAFs. We further explored the protein cargo in EVs altered by TGF-β treatment using quantitative proteomics, and selected several highly upregulated proteins for further analysis. We found that the majority of these proteins were presented on the EV surface, and they regulated the target cells in an EV-cell contact dependent manner.

  Study EGAS50000000922

• Raw sequencing files from WGS and RNA-Seq

  Acute leukemias are the most common malignancies in children with an onset of the disease among 0-6 years-old. The early development of theses malignancies has been proposed as an indicator of their prenatal origin, hypothesis that has been confirmed especially in the case of acute lymphoblastic leukemia. For acute myeloid leukemia (AML), comprising an heterogenous group of different cytogenetics subtypes, this prenatal origin has also been confirmed specially for MLL-rearranged and t(8;21) subgroups. AMLs carrying t(7;12) constitute up to 30% of cases under 2-years-old, frequently being associated with a trisomy of chromosome 19 and an overexpression of MNX1 gene. An in utero origin of this specific subgroup has been suggested but not clearly confirmed. Here, we present the case of a 5-months-old AML patient with t(7;12) in which we have fully characterized a novel breakpoint occurring among ETV6 and NOM1 genes. We demonstrate the presence of this specific ETV6-NOM1 fusion in CD34+ hematopoietic stem and progenitor cells isolated from the cord blood unit from the same patient and stored at birth. Moreover, trisomy +19 present at diagnosis was not detected at birth. Together, our results demonstrate the prenatal origin of the t(7;12) in infant AML, and establish trisomy +19 as a secondary event in this leukemia.

  Study EGAS50000000186

• Study assessing the efficacy and safety of durvalumab plus olaparib plus fulvestrant in selected metastatic or locally advanced ER-positive, HER2-negative breast cancer patients.

  This study aims to evaluate the efficacy of the combination of olaparib, durvalumab, and fulvestrant for the treatment of patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer with BRCA gene alterations or alterations of genes involved in HRR or MSI status, in terms of the progression-free survival rate (PFSR) at 24 weeks.

  Study EGAS50000001166

• Clinical and Genetic Evaluation of Individuals with Undiagnosed Disorders through the Undiagnosed Diseases Network (UDN)

  The National Human Genome Research Institute and the NIH Clinical Center established the intramural Undiagnosed Diseases Program (UDP) in 2008 to make progress in uncovering, understanding, and treating rare disorders. Based on the success of the UDP, the NIH Common Fund established the Undiagnosed Diseases Network (UDN) in FY 2013 (Phase I, 9/16/2015-8/31/2018) to achieve this type of cross-disciplinary approach to disease diagnosis in academic medical centers around the United States. The NIH Common Fund expanded the network in 2018 (Phase II, 9/1/2018-6/20/2023) to increase the availability of diagnostic services, foster opportunities for collaboration between laboratory and clinical investigators, provide resulting data and protocols to the broader community, and assess development of a sustainable national resource after Common Fund support ends. The UDN transitioned from Common Fund in 2023. The National Institute of Neurological Disorders and Stroke (NINDS) will oversee the Network in Phase III, which launched in July 2023, with help from 17 different NIH Institutes and Centers along with the NIH Office of the Director. With help from patients, family members, patient advocacy groups, a Data Management and Coordinating Center (DMCC), several Clinical Sites, and other stakeholders, the NIH envisions the UDN evolving into a larger, diverse, and self-sustained network that fosters scientific discovery and provides expert diagnostic services for undiagnosed patients across the nation. The overarching goals of the UDN in Phase III include: Continuing the proven success of the UDN in improving the clinical evaluation of difficult-to-diagnose patients using a collaborative team approach and investigating and validating promising new diagnostic technologies. Facilitating research into the etiology of undiagnosed diseases by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures. Promoting a broader integrated and collaborative community across multiple Clinical Sites and among laboratory and clinical investigators prepared to investigate the genetic, pathophysiologic, cell biologic, and molecular mechanisms underpinning these difficult-to-diagnose conditions.

  Study phs001232

• Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia

  Purpose Genomic alterations of IKZF1 are common and associated with adverse clinical features in B-ALL, but the relationship between the type of IKZF1 alteration, disease subtype and outcome are incompletely understood. Patients and Methods We used transcriptome and genomic sequencing, and SNP microarray data to determine leukemia subtype and genomic alterations for 688 pediatric patients with B-ALL enrolled into St. Jude Total Therapy 15 and 16 studies. Results IKZF1 alterations were identified in 115 (16.7%) patients, commonly in BCR::ABL1 (78%) and CRLF2-rearranged, BCR::ABL1-like B-ALL (70%), and were associated with five-year cumulative incidence of relapse (CIR) of 14.8 ± 3.3% compared to 5.0 ± 0.9% for patients without any IKZF1 alteration (P < 0.0001). IKZF1 deletions of exon 4-7 (P = 0.0002), genomic IKZF1plus with any IKZF1 deletion (P = 0.006) or with focal IKZF1 deletion (P = 0.0007), and unfavorable genomic subtypes (P < 0.005) were independently adversely prognostic. Patients with both IKZF1 exon 4-7 deletion and unfavorable genomic subtype had a significantly increased risk of relapse (HR = 58.3; 95% CI, 11.9 – 285.4, P < 0.0001) whereas IKZF1 sequence mutations were not independently predictive of outcome. Conclusions Genomic IKZF1plus with any IKZF1 deletion, IKZF1 deletion of exon 4-7, and unfavorable subtype confer increased risk of relapse. The combination of unfavorable genomic subtype and IKZF1 deletion of exon 4-7 identified patients at greatest risk of relapse despite MRD-directed therapy. The type of IKZF1 alteration together with subtype are informative for risk stratification and predict response in patients with B-ALL.

  Study EGAS50000000106

• Enhancer profiling identifies epigenetic markers of endocrine resistance and reveals therapeutic options for metastatic castration-resistant prostate cancer patients (LuCaP cell line data)

  Androgen Receptor (AR) signaling inhibitors, including enzalutamide, are treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), but resistance inevitably develops. Using metastatic samples from a prospective phase II clinical trial, we epigenetically profiled enhancer/promoter activities with H3K27ac chromatin immunoprecipitation followed by sequencing, before and after AR-targeted therapy. We identified a distinct subset of H3K27ac-differentially marked regions that associated with treatment responsiveness. These data were successfully validated in mCRPC patient-derived xenograft models (PDX). In silico analyses revealed HDAC3 as a critical factor that can drive resistance to hormonal interventions, which we validated in vitro. Critically, we identified the pan-HDAC inhibitor, vorinostat to be effective in decreasing tumor cell proliferation both in vitro and in vivo. Moreover, we uncovered evidence for HDAC3 working together with Glucocorticoid Receptor (GR) as a potential mechanism for this therapeutic effect. These findings demonstrate rationale for new therapeutic strategies including HDAC inhibitors to improve patient outcome in advanced stages of mCRPC. Project Goal: We identified H3K27ac regions associated with resistance in patient samples. Extensive analysis of these regions suggested that HDAC3 may play a role in resistance. To test this, we analyzed ChIP-seq and RNA-seq from cell lines generated from PDX LuCaP samples (recapitulating resistant and non-resistant) to validate findings in patient samples. ChIP-seq samples were used to verify the signals identified from specific factors, such as H3K27ac, AR, FOXA1, GR and HDAC3, their association with resistance and possible mechanisms of action. RNA-seq samples were analyzed to determine the effect of AR signaling in these samples in specific genes in the H3K27ac resistance-associated regions.

  Study EGAS50000000917

• RNASeq files for Roussel-MBPRG

  RNASeq files for Roussel-MPBRG paper titled "Combination of ribociclib and gemcitabine for the treatment of medulloblastoma"

  Dataset EGAD00001008824

• Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP

  We conducted GWAS of sporadic CJD, variant CJD, iatrogenic CJD, inherited prion disease, kuru and resistance to kuru despite attendance at mortuary feasts. After quality control we analysed 2000 samples and 6015 control individuals (provided by the Wellcome Trust Case Control Consortium and KORA-gen), for 491032-511862 SNPs in the European study. Association studies were done in each geographical and aetiological group followed by several combined analyses.

  Study EGAS00000000097

• Preservation of stemness in high-grade serous ovarian cancer organoids requires low Wnt environment

  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.

  Study EGAS00001003821

• Genetic regulation of RNA splicing in human pancreatic islets

  Genetic variants that influence transcriptional regulation in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D). For many susceptibility loci, however, the mechanisms are unknown. To this end, we examined splicing and gene expression QTLs (sQTLs and eQTLs) in pancreatic islets from 399 human donors from publicly available cohorts and in-house data. Here we provide newly generated RNA-seq data and genotyping array data from 101 donors.

  Study EGAS00001006440

• Prevalence and Clinical Characteristics of hearing loss caused by MYH14 mutation

  Mutations in MYH14 are reported to cause autosomal dominant nonsyndromic hereditary hearing loss (ADNSHL), and 35 variants have been reported to cause hearing loss in various ethnic groups, but the information on prevalence as well as clinical features are fragmented. In this study, genetic screening for MYH14 variants was carried out using a large series of Japanese hearing loss patients to reveal the information. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 8074 (including 1336 ADNSHL) unrelated Japanese hearing loss patients (probands) to identify genomic variations responsible for hearing loss. We identified 20 patients with 14 mutations from 15 pedigrees. The prevalence was proved to be 0.19% (15/8074) among hearing loss patients, and 1.12% (15/1336) among ADNSHL patients. The 12 mutations out of 14 mutations identified were novel. The patients typically showed late onset, slowly progressive modelate flat-type hearing loss. The clinical information revealed by the present study would contribute to further diagnosis and management of MYH14-associated hearing loss.

  Study JGAS000323

• Chromatin profiling of baseline and Notch inhibitor treated HCC PDX model

  We generated chromatin accessibility profiles for anti-Notch2 (n=3) and anti-gD (n=3) treated LIV78 tumors. Tumors were isolated, snap frozen in liquid nitrogen and stored at -80C. Tumor tissue was pulverized using a Covaris CP02 CryoPrep Pulverizer. Flash frozen pulverized tumor samples were sent to Active Motif to perform the ATAC-seq assay. Resulting material was quantified using the KAPA Library Quantification Kit for Illumina platforms (KAPA Biosystems), and sequenced with PE42 sequencing on the NextSeq 500 sequencer (Illumina) to produce FASTQ sequencing files.

  Dataset EGAD50000000735

• UK10K NEURO EDINBURGH

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set consists of subjects with schizophrenia recruited from psychiatric in-patient and out-patient facilities in Scotland. All diagnoses are based on standard research procedures and family histories are available. Patients have IQ&gt;70 and the cohort includes the following groups: 100 cases with detailed clinical, cognitive and structural and functional neuroimaging phenotypes; 138 familial cases who are the probands of families where DNA has been collected from other affected members; 162 unrelated individuals. In most cases patients and their families may be re contacted to take part in further studies.For further information on this cohort please contact Andrew McIntosh (andrew.mcintosh@ed.ac.uk).

  Study EGAS00001000117

• Single cell transcriptional evolution of myeloid leukaemia of Down syndrome – scRNA

  Abstract: Children with Down syndrome have a 150-fold increased risk of developing myeloid leukaemia (ML-DS). Unusually for a childhood leukaemia, ML-DS arises from a preleukaemic state, termed transient abnormal myelopoiesis (TAM), and via a conserved sequence of mutations. Here, we examined the relationship between the genetic and transcriptional evolution of ML-DS from a rich collection of primary patient samples through single cell mRNA sequencing, complemented by phylogenetic analyses in progressive disease. We distilled the transcriptional consequence of each genetic step in the evolution of ML-DS, showing that TAM-defining GATA1 mutations account for most of the ML-DS transcriptome, including those of progressive disease. This transcriptional backbone may thus represent a common vulnerability in ML-DS. We extracted the transcriptional difference between TAM and ML-DS which, unexpectedly, reflected features shared across childhood leukaemia. Our approach delineates the transcriptional evolution of ML-DS and provides an analytical blueprint for distilling consequences of mutations directly from patient samples.

  Dataset EGAD00001015452

• Evaluation of the Efficacy and Safety of a Clinical Grade Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Patch: A Pre-Clinical Study

  Cardiomyocyte-derived induced pluripotent stem cells (iPSCs) may represent a promising therapeutic strategy for severely damaged myocardium. This study aimed to assess the efficacy and safety of clinical grade human iPSC-derived cardiomyocyte (hiPSC-CM) patches and conduct a pre-clinical proof-of-concept analysis.

  Study EGAS50000000188

• RNA-Sequencing of B-Lymphoblastic Leukemia with Glucocorticoids and PI3K Delta Inhibition

  Mononuclear cells were isolated from bone marrow or peripheral blood of 7 pediatric subjects with B-lymphoblastic leukemia at the time of diagnosis. To determine the effect of PI3K delta inhibition on glucocorticoid-induced gene regulation, B-lymphoblastic leukemia cells were treated with glucocorticoids +/- the PI3K delta inhibitor, idelalisib, for 24 hours prior to RNA extraction and sequencing. Biological replicates were performed for 4 of the 7 subjects; 2 of these subjects had specimens demonstrating an additive response to the combination of glucocorticoids and idelalisib in viability testing in vitro, and 2 subjects' specimens demonstrated a synergistic response. All 7 subjects were analyzed together and the 4 specimens with biological replicates were also evaluated in an additional analysis. An average of 40 million reads per specimen and treatment condition were obtained. We compared gene expression in each treatment condition to vehicle-treated cells and expression in glucocorticoid or idelalisib only treated cells to combination treated cells. Using a high dose of dexamethasone (25 or 50 nM) and an equivalent dose of prednisolone, we found that the addition of idelalisib (500 nM) enhanced prednisolone-induced gene regulation but not dexamethasone-induced gene regulation. Surprisingly, the specimens with additive response to combination therapy demonstrated enhancement of prednisolone-induced gene regulation with the addition of idelalisib, while the specimens with synergistic responses did not. Raw sequencing data (FASTQ) and count tables will be available through dbGaP.

  Study phs003085

• Comprehensive molecular profiling with whole-exome sequencing (WES) of PDX tumors

  To identify biomarkers for the antitumor effects of molecularly targeted therapy, we performed whole-exome sequencing on 795 patient-derived xenograft (PDX) samples established from 269 patients with solid tumors and 125 frozen tissue samples obtained at the time of surgery.

  Study JGAS000853