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• Whole genome sequencing data of paediatric KMT2A-rearranged acute lymphoblastic leukemia

  Whole genome sequencing data from infant (<1 y) paediatric (< 18 y) KMT2A-rearranged acute lymphoblastic leukemias. Dataset includes fastq and BAM files from diagnostic and remission (control) samples of 3 patients. Dataset consists of two experiments depending on library preparation method; "Experiment 1" is made using normal WGS library preparation (pcr+), and "Experiment 2" is made using pcr-free library preparation method.

  Dataset EGAD50000001568

• WGS data of paediatric hyperdiploid B cell acute lymphoblastic leukemia (set5)

  The dataset includes FASTQ and CRAM files from diagnostic and matched remission (control) samples of four hyperdiploid ALL patients (ALLT-502, ALLK-130, ALLK-137, ALLK-139). Sequencing libraries were made using PCR free-based WGS library preparation (PCR-), using Novogene NGS DNA Library Prep Set (Cat No. PT004). Both diagnostic (90x) and remission (30x) samples were sequenced using Illumina NovaSeq X Plus.

  Dataset EGAD50000002428

• Next generation sequencing data of circulating tumor DNA and matched tumor tissues

  For each subject, genomic DNA from whole blood, circulating cell free DNA and tumor tissues (whenever possible) were performed targeting next generation sequencing on Illumina Miseq or Hiseq 4000 platforms. The sequencing results of whole blood were used to distinguish germline and somatic mutations. Specimens were collected from patients with different kinds of solid tumors, but most are lung cancer patients.

  Dataset EGAD00001003176

• STAMPEED: Cardiovascular Health Study (CHS) GWAS to identify genetic variants associated with aging and CVD risk factors and events

  The primary aim of the study is to conduct a genome-wide association study to identify genetic variants associated with the incidence of myocardial infarction (MI), stroke, and heart failure (HF) among participants enrolled in the Cardiovascular Health Study (CHS) who were free of clinical cardiovascular disease at baseline. The secondary aim is to conduct genome-wide association study of other phenotypes in CHS. The study is an ancillary study to CHS. CHS is a population-based cohort study of risk factors for heart disease and stroke among older adults recruited at 4 US sites in 1989-1990. Subjects underwent an extensive baseline examination, and annual follow-up examinations through 1988-1999.

  Study phs000226

• Influence of age on molecular changes and treatment stratification in multimodal glioblastoma therapy

  Background: The increasing life expectancy has led to a rise in high-grade gliomas, particularly in patients of older age. The impact of chronological age, associated molecular changes and contributing factors on therapy response, progression-free survival (PFS) and overall survival (OS) remain uncertain. Methods: Between January 1st, 2016, and December 31th, 2021, patients with glioblastoma IDH-wt (CNS WHO grade 4) were included. RNA- and T-cell receptor sequencing was performed in a subset of patients. Primary outcome parameters were extent of resection (EOR), progression free- and overall survival. Multivariate analysis was performed to identify independent predictors of survival. Results: A total of 286 patients were included. The mean age was 66.4 years. Chronological age did not correlate with overall survival (r=0.12). With age, tumor immune composition changed towards macrophages with M2 phenotype and decreased numbers of CD8+ and neutrophiles. Aging related genes were not enriched. Beyond 69.5 years of age, despite similar PFS (p=0.0783), OS (p&lt;0.0001) was significantly shorter, compared to younger patients. Extent of resection and adjuvant radiochemotherapy were significant predictors of OS (p&lt;0.0001). No difference in PFS and OS was found between younger and older patients treated with maximal safe resection, followed by concomitant RT and chemotherapy and adjuvant chemotherapy. Conclusions: This study suggests that age alone should not be the sole determinant in therapeutic decision-making for glioblastoma patients. Gross total resection and adjuvant therapy, tailored to individual clinical status, significantly impact survival outcomes. Patient-specific treatment strategies are important to minimize undertreatment and optimize therapeutic outcomes in older patients.

  Study EGAS00001008246

• Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors

  Cell-free tumour-derived DNA (ctDNA) allows non-invasive monitoring of various cancers but its utility in renal cell cancer (RCC) has not been well established. A combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n=90) with various renal tumour subtypes, were used to determine ctDNA content in plasma and urine. Our data revealed lower plasma ctDNA levels in RCC relative to other cancers, with untargeted detection of ~33% for both cohorts. A highly sensitive personalised approach, applied to plasma and urine from select patients (n=22), improved detection to ~50%, including in patients with early stage and even benign lesions. A machine-learning based model, applied to untargeted data, predicted this detection, potentially offering a means of triaging patient samples for personalised analysis. We observed that plasma, and for the first time, urine ctDNA may better represent tumour heterogeneity than a single tissue biopsy. Longitudinal sampling of &gt;200 plasma samples revealed that ctDNA can track disease course. These data highlight low ctDNA levels in RCC but indicate potential clinical utility provided improvement in isolation and detection approaches.

  Study EGAS00001003530

• Gene Expression Signatures in CATHGEN

  Case control cohort: The details have been previously published: American Heart Journal. 2010;160:371-379 e372. Briefly, a nested case:control cohort of CATHGEN participants who had experienced death or MI (n = 250) after their index catheterization and age-, sex-, and race-matched controls (n = 250) who were free of death/MI &#62; 2 years after cardiac catheterization was identified as part of the MURDOCK Horizon 1 Cardiovascular Disease Study.21 Sufficient RNA for microarray analysis was available in 447 members of this cohort. Observational cohort: 224 sequential CATHGEN samples were selected for whole blood RNA analysis, of which, 191 had sufficient RNA for microarray analysis.

  Study phs000551

• sWGS of non-cancer controls

  Paired end shallow whole genome sequencing (sWGS) data of cell-free DNA from plasma from self-reporting healthy individuals (MonRec Cohort)

  Dataset EGAD00001005805

• Ultra-Low-Pass Whole Genome Sequencing of Cell-Free DNA for Large B-Cell Lymphoma

  While deep targeted DNA sequencing of liquid biopsies has shown prognostic utility in large B-cell lymphoma (LBCL), the routine clinical adoption of these assays remains limited due to their high costs. Here, leveraging a well-annotated cohort of encompassing both frontline and relapsed/refractory (R/R) LBCL, we profiled patient plasma samples with two complementary modalities – ultra-low-pass whole genome sequencing (ulpWGS) and deep targeted DNA sequencing, the former being a cost-effective method to profile large scale chromosomal abnormalities and estimate tumor burden. Our findings revealed a strong association of high cell-free tumor burden by both genomic profiling modalities with established measures of tumor burden and patient survival. Notably, the associations with survival remained statistically significant after accounting for international prognostic index scoring. Furthermore, we showed that del(17p) in circulating tumor DNA as detected by ulpWGS was strongly associated with TP53 mutation status and predicted for significantly inferior patient outcome in frontline but not R/R LBCL patients. Our study demonstrates that ulpWGS can provide robust prognostic biomarkers for both frontline and R/R LBCL, highlighting its broad applicability for risk stratification.

  Study EGAS50000001027

• Whole genome sequencing data of lung adenocarcinomas

  This dataset includes the whole-genome sequencing data from a study entitled "Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma". Whole-genome sequencing libraries were generated by PCR-free methods, and sequencing run was made in HiSeq X Ten machines. PCR duplicates-marked, indel-realigned, and base-recalibrarted BAM files are provided in our dataset.

  Dataset EGAD00001004793

• STARR-seq of ERa binding sites in MCF7 and Ishikawa cell lines

  A oligo-captured STARR-seq library was generated using as targets ERa binding regions indetified by ChIP-seq in Ishikawa (Endometrial cancer) and T47D (breast cancer) cell lines and, breast cancer primary tissues. STARR-seq assays have been performed in MCF-7 and Ishikawa cell lines. Cells have been cultured for 3 days in hormone deprivated (phenol-red free) media and stimulated for 6 hours by 10nM estradiol (E2) or DMSO (negative control).

  Dataset EGAD50000000015

• Circulating tumor DNA, pathological and immunologic responses to neoadjuvant nivolumab or nivolumab plus relatlimab and chemoradiotherapy in resectable esophageal/gastroesophageal junction cancer

  The dataset for the study “Circulating tumor DNA, pathological and immunologic responses to neoadjuvant nivolumab or nivolumab plus relatlimab and chemoradiotherapy in resectable esophageal/gastroesophageal junction cancer” includes 173 bam files from hybrid capture targeted error-correction next-generation sequencing (TEC-Seq) from plasma cell-free DNA and matched white blood cell DNA from 32 individuals with esophageal/gastroesophageal junction cancer, who received immunotherapy-containing regimens.

  Dataset EGAD00001011822

• Peripheral blood DNA methylation of Crohn's disease patients starting treatment with adalimumab, vedolizumab or ustekinumab

  In the current study we performed a longitudinal case-control study comparing the peripheral blood DNA methylome of Crohn's disease (CD) patients that were classified as responders and non-responders to adalimumab, vedolizumab, and ustekinumab. Patients with active CD were prospectively recruited and followed up for around 27 weeks into treatment during which response assessment took place. Response was defined as a strict combination of endoscopic- (≥50% reduction in SES-CD score) combined with either corticosteroid-free clinical- (≥3 point drop87 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 g/mL and fecal calprotectin ≤250 µg/g).

  Study EGAS00001007532

• 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 &amp;gt;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

• Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients

  Genome-wide analysis of cell-free DNA (cfDNA) methylation profile has been recognized as a promising approach for sensitive and specific detection of many cancers. However, scaling such genome-wide assays for clinical translation is impractical due to the high cost of whole genome bisulfite sequencing. We have shown that the small fraction of GC-rich genome is highly enriched in CpG sites and disproportionately harbors the majority of cancer-specific methylation signature. Here, we report on the simple but effective Heat enrichment of CpG-rich regions for Bisulfite Sequencing (Heatrich-BS) platform that allows for focused methylation profiling in these highly informative regions. Our novel method and bioinformatics algorithm enable accurate tumor burden estimation with high sensitivity and quantitative tracking of colorectal cancer patient’s response to treatment, at much reduced sequencing cost suitable for frequent monitoring. We also show, for the first time, tumor epigenetic subtyping from cfDNA using Heatrich-BS, which could enable patient stratification from non-invasive liquid biopsy. As such, Heatrich-BS holds great potential for highly scalable screening and regular monitoring of cancer using liquid biopsy.

  Study EGAS00001006198

• Tumor Profiler Melanoma Study

  The Tumor Profiler Study is an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease. Technologies used are digital pathology, targeted NGS, single-cell RNA, single-cell DNA, bulk RNA, bulk proteotyping, single-cell CyTOF, imaging mass cytometry, pharmacoscopy, 4i Drug Response Profiling, and cell-free DNA. These technologies were applied to 240 tumor samples collected over 3 years across three cancer indications: metastatic melanoma, metastatic epithelial ovarian cancer, and acute myeloid leukemia (AML). Here, we publish the scRNA, scDNA, and bkRNA data of the melanoma cohort.

  Study EGAS50000000599

• Tumor Profiler Ovarian Study

  The Tumor Profiler Study is an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease. Technologies used are digital pathology, targeted NGS, single-cell RNA, single-cell DNA, bulk RNA, bulk proteotyping, single-cell CyTOF, imaging mass cytometry, pharmacoscopy, 4i Drug Response Profiling, and cell-free DNA. These technologies were applied to 240 tumor samples collected over 3 years across three cancer indications: metastatic melanoma, metastatic epithelial ovarian cancer, and acute myeloid leukemia (AML). Here, we publish the scRNA and scDNA data of the ovarian cancer cohort.

  Study EGAS50000000885

• hereditary BrEAst Case CONtrol study

  The BEACCON study aimed to address the lack of power of previous studies to identify novel BC predisposition genes by performing extensive sequencing in 12,000 women (11,511 analysed following exclusions) and further enhancing power by using an ‘extreme phenotype’ design with enrichment of familial non-BRCA1 and BRCA2 cases, compared with a control population of older women with ongoing confirmation of cancer-free status at June 2019. Three-quarters of the 1303 candidate genes screened were selected based on empiric evidence from local (69 multi-case BC families) or international whole exome sequencing studies, and the remainder were included to provide detailed coverage of functional pathways with established associations with BC

  Study EGAS00001005043

• Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation

  Despite recent advances, the dynamics of genome architecture and chromatin function during human cell differentiation and its potential reorganization upon neoplastic transformation remains poorly characterized. Here, we integrate in situ Hi-C and nine additional omic layers to define and biologically characterize the dynamic changes in three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) patients. Beyond conventional active (A) and inactive (B) compartments, an integrative analysis of Hi-C data uncovers a highly-dynamic intermediate compartment enriched in poised and polycomb-repressed chromatin. During B cell development, we detect that 28% of the compartments change at defined maturation stages and mostly involve the intermediate compartment. The transition from naive to germinal center B cells is associated with widespread chromatin activation, which mostly reverts into the naive state upon further maturation of germinal center cells into memory B cells. The analysis of CLL and MCL neoplastic cells points both to entity and subtype-specific alterations in chromosome organization. Remarkably, we observe that large chromatin blocks containing key disease-specific genes alter their 3D genome organization. These include the inactivation of a 2Mb region containing the EBF1 gene in CLL and the activation of a 6.1Mb region containing the SOX11 gene in clinically aggressive MCL. This study indicates that 3D genome interactions are extensively modulated during normal B cell differentiation and that the genome of B cell neoplasias acquires a tumor-specific 3D genome architecture.

  Study EGAS00001004763

• Clinical data

  Clinical data for KATHERINE: Clinical data include Treatment Arm, Invasive Disease Free Survival (IDFS), Clinical Stage at Presentation, Hormone Receptor Status, Preoperative HER2 Directed Therapy, Pathological Node.

  Dataset EGAD00001008785

• 125 cfDNA samples from healthy patients

  BAM files corresponding to the sequencing of 125 circulating cell-free DNA from 125 healthy patients. Each sample was sequenced twice.

  Dataset EGAD00001005463

• Activating AKT1 and PIK3CA mutations in metastatic castration-resistant prostate cancer

  This dataset contains all available targeted exon sequencing bam files from our study, "Activating AKT1 and PIK3CA mutations in metastatic castration-resistant prostate cancer". Patient identifiers are denoted by the first segment of the sample aliases (e.g. "P1"), and additional information is appended to reflect which serial sample is referenced (1st, 2nd, 3rd, etc.), and whether the sample represents cell-free DNA ("cfdna") or paired white-blood cell control ("WBC"). All samples were sequenced using Illumina technology.

  Dataset EGAD00001006122

• cfDNA dataset with expanded panel for cfDNA cohort

  Cell free DNA sequencing data for 9 samples with expanded panel across multiple cancer types for cfDNA cohort

  Dataset EGAD50000000667

• Long cell-free DNA molecules in maternal plasma (dataset2)

  consists of 14 bam files

  Dataset EGAD00001008732

• DNA Methylomic Profiling of Preeclampsia Across Pregnancy

  Preeclampsia (PE) is a hypertensive, multi-system disorder of pregnancy that significantly impacts maternal and infant morbidity/mortality across the globe, as it increases risk of cardiovascular disease and remains a leading killer of women and babies. Despite PE&#39;s significant impact on morbidity/mortality, there are no clinically reliable biomarkers that predict PE. DNA methylation, a dynamic regulator of gene expression, represents a mechanism that is known to be impacted by the environment. Because PE stems from a dysfunctional placenta that releases debris into the maternal circulation, we hypothesized that the in-vivo environment created by the dysfunctional placenta will impact DNA methylation in the maternal circulation, and that these blood-based methylation profiles would serve as a systemic biomarker of the maternal response to placental dysfunction. Our overall objective of this pilot study was to longitudinally characterize DNA methylation profiles across the three trimesters of pregnancy in the maternal blood at time points before and after clinically overt PE using a targeted (endoglin and endoglin-related genes) and a discovery-based approach. For this pilot study, 28 normotensive control participants and 28 PE case participants enrolled in the NICHD funded pregnancy study entitled Prenatal Exposures and Preeclampsia Prevention: Mechanisms of Preeclampsia and the Impact of Obesity (PEPP3; P01HD30367) were 1:1 frequency matched on self-reported race, pre-pregnancy BMI, smoking history, and gestational age at sample collection. Methylation data were collected with the Infinium&#174; MethylationEPIC Beadchip. Methylation assay data collection were carried out at Johns Hopkins University Genetic Resources Core Facility, The SNP Center, Baltimore, MD, USA.

  Study phs001937