12254 results for "fc coins kopen ps4 Besuche die Website Buyfc26coins.com. Coins in Minuten da..Gidj"

in 55.92 milliseconds.

• Optimizing Primary Stroke Prevention in Children with Sickle Cell Anemia (STOP II)

  The STOP II trial evaluated whether prophylactic transfusion in patients with sickle cell disease and high risk of stroke can be safely halted after 30 months of treatment during which patients became low risk for stroke.Stroke causes substantial morbidity in children with sickle cell disease. To prevent first strokes, the Stroke Prevention Trial in Sickle Cell Anemia (STOP) used prophylactic transfusions in children who were identified by transcranial Doppler (TCD) ultrasonography as being at high risk for stroke. This strategy reduced the incidence of stroke among such children from 10% per year to less than 1% per year, leading to recommendations for TCD screening and prophylactic transfusion for children with abnormal velocities on ultrasonography. Despite the reduced risk of stroke, long-term use of transfusions can cause adverse side effects, such as iron overload or alloimmunization. However, cessation of transfusions is associated with recurrence of stroke, and at the time of the STOP II trial, there were no clinical or laboratory indicators to guide the duration of prophylaxis. Therefore the STOP II trial was initiated to determine whether transfusions could be limited by monitoring patients with TCD examinations after transfusions were halted and resuming transfusions if the examination indicated a high risk of stroke.The trial was halted for safety concerns after 79 of a planned 100 children were randomized. Discontinuation of transfusion for the prevention of stroke in children with sickle cell disease resulted in a high rate of reversion to abnormal blood-flow velocities on Doppler studies and stroke incidence.Instructions for requesting individual-level data are available on BioData Catalyst at https://biodatacatalyst.nhlbi.nih.gov/resources/data/. Apply for data access in dbGaP. Upon approval, users may begin accessing requested data in BioData Catalyst. For questions about availability, you may contact the BioData Catalyst team at https://biodatacatalyst.nhlbi.nih.gov/contact.

  Study phs002386

• Cardiovascular Health Study (CHS) Cohort: an NHLBI-funded observational study of risk factors for cardiovascular disease in adults 65 years or older

  The Cardiovascular Health Study (CHS) is a prospective study of risk factors for development and progression of CHD and stroke in people aged 65 years and older. The 5,888 study participants were recruited from four U.S. communities and have undergone extensive clinic examinations for evaluation of markers of subclinical cardiovascular disease. The original cohort, enrolled in 1989-90, totaled 5,201 participants. A supplemental cohort of 687 predominantly African-American participants was enrolled in 1992-93. Clinic examinations were performed at study baseline and at annual visits through 1998-1999, and again in 2005-2006. Examination components included medical and personal history, medication inventory, ECG, blood pressure, anthropometry, assessment of physical and cognitive function, and depression screening. Other components done less frequently included phlebotomy, spirometry, echocardiography, carotid ultrasound, cerebral magnetic resonance imaging, measurement of ankle-brachial index and retinal exam. Participants were contacted by telephone annually between exams to collect information about hospitalizations and potential cardiovascular events. Since 1999, participants have been contacted every six months by phone, primarily to identify cardiovascular events and to assess physical and cognitive health. Standard protocols for the identification and adjudication of events were implemented during follow-up. The adjudicated events are myocardial infarction, angina, heart failure (HF), stroke, transient ischemic attack (TIA), claudication and mortality. The Cardiovascular Health Study Cohort is utilized in the following dbGaP substudies. To view genotypes, analysis, expression data, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" section of this top-level study page phs000287 Cardiovascular Health Study (CHS) Cohort: an NHLBI-funded observational study of risk factors for cardiovascular disease in adults 65 years or older. phs000226 STAMPEED: Cardiovascular Health Study (CHS) phs000301 PAGE: CaLiCo: Cardiovascular Health Study (CHS) phs000377 CARe: Candidate Gene Association Resource (CARe) phs000400 GO-ESP: Heart Cohorts Exome Sequencing Project (CHS) phs000667 CHARGE: Cardiovascular Health Study (CHS)

  Study phs000287

• mRNA capture sequencing and RT-qPCR for the detection of pathognomonic, novel and secondary fusion transcripts in formalin-fixed paraffin-embedded tissue: a sarcoma showcase

  RNA sequencing is widely used to study gene abundance patterns, but less frequently to assess structural alterations such as fusion transcripts. In this study, we assess the performance of messenger RNA (mRNA) capture sequencing to identify fusion transcripts in formalin-fixed paraffin-embedded (FFPE) tissue of different types of sarcoma, followed by orthogonal confirmation using RT-qPCR. To validate our workflow, we used the TruSight RNA Pan-Cancer Panel to analyze a first cohort of 6 positive control tumors for which the diagnostic workup demonstrated the presence of a specific chromosomal rearrangement. Fusion transcript calling by FusionCatcher confirmed all known aberrations and enabled the identification of both fusion gene partners and breakpoints. Next, whole transcriptome TruSeq RNA Exome sequencing was applied to a second cohort of 17 patients, diagnosed with fusion gene-negative alveolar rhabdomyosarcoma (ARMS) or undifferentiated round cell sarcoma (URCS), for whom fluorescence in situ hybridization (FISH) did not identify the classical pathognomonic rearrangements. Remarkably, for 6 out of 17 patients, mRNA capture sequencing readily detected a pathognomonic fusion transcript, i.e. PAX3-FOXO1 in 2 ARMS patients, and EWSR1-FLI1, EWSR1-ERG or EWSR1-NFATC2 in 4 URCS patients. These data show that RNA capture sequencing may enhance the detection rate of pathognomonic fusion genes in sarcoma. For the 11 patients with no known pathognomonic fusion transcript, 11 newly identified fusion transcripts were confirmed by RT-qPCR, including COPS3-TOM1L2, NCOA1-DTNB, WWTR1-LINC01986, PLAA-MOB3B, AP1B1-CHEK2 and BRD4-LEUTX fusion transcripts in ARMS patients. Additionally, recurrently detected secondary fusion transcripts in two patients diagnosed with EWSR1-NFATC2-positive sarcoma were confirmed (COPS4-TBC1D9, PICALM-SYTL2, SMG6-VPS53 and UBE2F-ALS2). Our results provide new insights into the underlying genetic causes of these malignancies.

  Study EGAS00001005202

• Exome Sequencing to Define the Landscape of Plasma Cells in Systemic Light chain Amyloidosis

  Systemic light chain amyloidosis (AL) is characterized by the deposition of immunoglobulin light chains as amyloid fibrils in different organs, where they form toxic protein aggregates. The underlying disease is a plasma cell disorder, but limited whole exome data are available. We report the findings of an exome sequencing study in AL to define a plasma cell signature and compare this to monoclonal gammopathy of undefined significance (MGUS) and myeloma (MM). Twenty-four samples from unselected newly diagnosed untreated AL patients were analysed. CD138+ cells were isolated from bone marrow cells using MACSorting (Miltenyi Biotech, Bisley, UK). Cells were lysed in RLT+ buffer and DNA/RNA extracted using the AllPrep kit (Qiagen, Manchester, UK). Peripheral blood was isolated from patients, white blood cells purified by Ficoll-Pacque and DNA extracted using the QIAamp DNA mini kit (Qiagen). There were a median of 47 acquired nonsynonymous variants (range 4-253) per patient. Thirty percent of patients yielded a mutation in a myeloma driver gene. These mutations were either clonal or sub-clonal. There was evidence of MAPK activation with NRAS mutations, NF-κB activation and DNA repair pathway alterations. Exome data were used to determine the cytogenetic groups of AL samples and identified hyperdiploidy in 33% of cases and t(11;14) in 33% of cases. All translocations were generated via class switch recombination and breakpoints on chromosome 11 fell into the expected regions. A novel translocation, unlikely to be driving disease progression was identified involving RCC1. Finally, further analysis of the APCS gene encoding for the SAP protein did not show any biased genotype in the AL population in comparison to the general population. We conclude that exome sequencing identifies a genetic make-up of AL that is similar to other plasma cell disorders such as MM and MGUS. This not only includes copy number abnormalities and translocations but also nonsynonymous mutations.

  Study EGAS00001001418

• Successful immune checkpoint blockade in a patient with advanced stage microsatellite unstable biliary tract cancer (H021)

  Cancers acquire multiple somatic mutations that can lead to the generation of immunogenic mutation-induced neoantigens. These neoantigens can be recognized by the host’s immune system. However, continuous stimulation of immune cells against tumor antigens can lead to immune cell exhaustion, which allows uncontrolled outgrowth of tumor cells. Recently, immune checkpoint inhibitors have emerged as a novel approach to overcome immune cell exhaustion and re-activate anti-tumor immune responses. In particular, antibodies blocking the exhaustion-mediating programmed death receptor (PD-1)/PD-L1 pathway have shown clinical efficacy. The effects were particularly pronounced in tumors with DNA mismatch repair deficiency and a high mutational load, which typically occur in the colon and endometrium. Here, we report on a 24-year old woman diagnosed with extrahepatic cholangiocarcinoma who showed strong and durable response to the immune checkpoint inhibitor pembrolizumab, although treatment was initiated at an advanced stage of disease. The patient’s tumor displayed DNA mismatch repair deficiency and microsatellite instability (MSI), but lacked other features commonly discussed as predictors of response towards checkpoint blockade, such as PD-L1 expression or dense infiltration with cytotoxic T cells. Notably, high levels of HLA class I and II antigen expression were detected in the tumor, suggesting a potential causal relation between functionality of the tumor’s antigen presentation machinery and the success of immune checkpoint blockade. We suggest determining MSI status in combination with HLA class I and II antigen expression in tumors potentially eligible for immune checkpoint blockade even in the absence of conventional markers predictive for anti-PD-1/PD-L1 therapy and in entities not commonly linked to MSI phenotype. Further studies are required to determine the value of these markers for predicting the success of immune checkpoint blockade. (H021)

  Study EGAS00001002441

• Single Cell Dissection of the Tumour Microenvironment Reveals Dynamic Interplay Shaping the Tumour Immunity Continuum in Ovarian Cancer

  Diverse tumour immune phenotypes with distinct T cell infiltration patterns result in different responses to cancer immunotherapies. However, the key determinants and biology underpinning these phenotypes remain elusive. Here, we provide a high-resolution dissection of the tumour microenvironment representative of different tumour immune phenotypes. By performing single-cell RNA sequencing (scRNAseq) of the tumour, immune, and stromal compartments from 15 ovarian cancer patients, we characterized the diverse cellular and functional phenotypes, as well as dynamic interplay within and between these components. Infiltrated and excluded tumours markedly differed from desert tumours in several tumour cell intrinsic features, including high interferon response, antigen presentation and oxidative phosphorylation. Moreover, these tumours were characterized by tumour associated macrophage (TAM)-like myeloid subsets, while desert tumours were enriched in myeloid derived suppressive cell (MDSC)-like myeloid subsets. Infiltrated and excluded tumours differed in their T cell composition and fibroblast subsets. While dysfunctional CD8+ GZMB T cells and IL1-activated fibroblasts (IL1 CAFs) were associated with infiltrated tumours, pre-dysfunctional CD8+ GZMK T cells and TGFB-activated fibroblasts (TGFB CAFs) were enriched in excluded tumours. These findings validated in bulk transcriptomic profiles of 1071 ovarian tumours and using in situ hybridization. Furthermore, our study revealed chemokine receptor-ligand interactions within and across compartments as potential mechanisms mediating immune cell infiltration, exemplified by the tumour cell-T cell crosstalk via a CXC16-CXCR6 axis, stromal-immune cell crosstalk via CXCL12/14-CXCR4 signalling, and TAM-like macrophage-T cell crosstalk through CXCR3-CXCL9/10/11 signalling. Our in-depth characterization of the tumour environment and intercellular interactions provides novel insights into potential molecular mechanisms that shape the distinct biology of tumour immune phenotypes. Our findings may inform novel therapeutic strategies for potentially shifting tumours along the immunity continuum to improve clinical benefit from cancer immunotherapies.

  Study EGAS00001004935

• Genetic Analysis of Normal Human Facial Variation

  The purpose of this project is to identify genes associated with normal human quantitative facial variation. The motivation for this project stems from the fact that very little is known about how variation in specific genes relates to the diversity of facial forms commonly observed in humans. Viable candidates for these morphogenes originate from a number of sources: tissue expression studies, animal models with targeted or spontaneous mutations, and genetic syndromes with craniofacial manifestations. Importantly, understanding the genetic basis for normal facial variation also has important implications for health-related research. For example, this work has the potential to shed light on the factors influencing liability to common craniofacial anomalies such as orofacial clefts. There is now ample evidence that certain facial features (e.g., increased midfacial retrusion) characterize individuals genetically at-risk for orofacial clefts (e.g., biological relatives of affected cases). While these predisposing facial features are statistically over-represented in at-risk groups, they are also common in the general population. Since many of the current candidate genes for clefting are thought to play a critical role in facial morphogenesis, variation in these genes may also underlie normal variation in these facial features. These candidate genes, however, probably represent only a small fraction of the total number of loci influencing normal human facial variation. Phenotypes for this project were obtained from over 3000 healthy Caucasian subjects recruited through three separate studies. The majority of the subjects were recruited as part of the 3D Facial Norms Project, which is described in extensive detail here: (https://www.facebase.org/facial_norms/notes). The provided dbGaP phenotypes include a series of anthropometric craniofacial measurements (linear distances) primarily derived from 3D photographic facial surface scans (see previous hyperlink). The specific genotyping requested is described elsewhere in this document. Our analysis team is pursuing a variety of different analytic approaches to derive genetically informative phenotypes, including various shape-based morphometric methods. For those interested in pursuing more advanced phenotypic approaches, the original 3D surface scans and additional phenotypic traits are available to researchers through the FaceBase Consortium. This dataset has the potential to facilitate the discovery of new genetic loci with an important role in both normal and abnormal facial development. It may also serve as a dataset to test hypotheses regarding specific SNP associations (e.g. as a replication dataset) or as part of a larger meta-analysis.

  Study phs000949

• Mucociliary Clearance Consortium (MCC) Rare Genetic Disorders of the Airways: Cross-section Comparison of Clinical Features, and Development of Novel Screening and Genetic Test

  We have established a consortium of 7 geographically-dispersed clinical research sites that are designed to study rare diseases of the airways, which involve defects in clearance of mucus secretions from the airways (defective "mucociliary clearance"). These sites will collaborate in diagnostic, genetic, and other studies in patients with impairments of mucociliary clearance, including primary ciliary dyskinesia (PCD), variant cystic fibrosis (CF), and pseudohypoaldosteronism (PHA). These disorders reflect genetic defects in airway host-defense, and typically result in chronic infection of the airways. Patients with these disorders of the conducting airways and sinuses have delayed (or incorrect) diagnoses, because diagnostic tests are not readily available. These patients may also have sub-optimal management of their clinical disease, because the cause of these disorders is not well-defined, and treatment regimens are usually not driven by evidence-based medicine. This current protocol is designed to employ a systematic approach to the diagnostic evaluation of these patients with chronic airways disease, which will yield precise diagnoses in individual patients, and will be associated with development of better diagnostic techniques, including genetic testing. In addition, we will compare/contrast clinical features (phenotype) across these disorders. A rigorous cross-sectional comparison of the clinical features will provide better understanding of the clinical disease of these disorders; in turn, this will lead not only to a better standard of clinical care, but will also assist in the identification of novel therapeutic approaches. The patient population for these studies includes individuals carrying a tentative diagnosis of the three disorders (PCD, variant CF or PHA), plus individuals suspected to have one of these disorders, but with inadequate or inconclusive diagnostic tests. Individuals in this latter category must have a preliminary clinical evaluation to evaluate for other more common disorders that may have similar manifestations including classical CF, immunodeficiency, asthma, and severe gastroesophageal reflux. We have an informal agreement with a network of pulmonologists across the United States to perform clinically-indicated (not research) preliminary clinical testing, if not directly available to patients who inquire about these studies. Blood will be collected for DNA to test for genetic mutations. The blood samples will be processed to establish a cell line (lymphocyte transformation) for a source of DNA for future genetic studies, in participants with disease. For participants unable to provide a blood sample, a buccal sample will be obtained for DNA.

  Study phs000595

• Heart Failure Network: Functional Impact of GLP-1 for Heart Failure Treatment (HFN FIGHT-BioLINCC)

  Objectives To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure. Background Heart failure was the leading cause of hospitalization in the United States with more than 4 million admissions per year from 2003–2009. Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). As heart failure progresses, these abnormalities become more pronounced and are observed in both patients with and without type 2 diabetes. At this time of this study, there was no heart failure therapy that targeted these metabolic abnormalities; however, in earlier clinical studies, glucagon-like peptide 1 (GLP-1) agonists showed cardioprotective effects in patients with advanced heart failure, irrespective of type 2 diabetes status. Glucagon-like peptide 1 is an endogenous incretin hormone that improves insulin sensitivity with minimal risk of hypoglycemia. This study was created to determine if use of GLP-1 agonists improved clinical stability in recently hospitalized patients with acute heart failure and reduced LVEF. Participants There were 300 participants. Design Participants were identified by hospital admission records and were enrolled during either the last 24 hours of his or her hospitalization for heart failure or the 2-week interval after the hospitalization. Baseline evaluations were conducted, which included echocardiographic measures, the 6-minute walk test, the Kansas City Cardiomyopathy Questionnaire (KCCQ), and blood tests. After the baseline evaluation, patients were randomized in a 1:1 ratio to receive either the GLP-1 agonist liraglutide or placebo as a daily subcutaneous injection. The protocol involved titration of study drug dosage as tolerated every 14 days from 0.6 mg/d to 1.2 mg/d to 1.8 mg/d during the first 30 days of the trial (as tolerated). Follow-up testing was performed at 30-, 90-, and 180-day study visits. The primary end point was a global rank score in which all participants, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level from baseline to 180 days. Conclusions The GLP-1 agonist liraglutide did not improve post-hospitalization clinical stability in patients with advanced heart failure and reduced LVEF. There was no significant between-group difference in the global rank scores and furthermore, there were no significant differences detected in any of the secondary endpoints.

  Study phs003542

• Long-Term Outcome in Offspring and Mothers of Dexamethasone-Treated Pregnancies at Risk for Classical Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency

  Summary The purpose of this study is to perform the first long-term follow up study both of adolescents and young adults with a history of prenatal treatment with dexamethasone and of their mothers and to test for adverse medical or behavioral side effects. The emphasis will be on the outcome of this prenatal treatment in those fetuses who are not affected with steroid 21-hydroxylase deficiency (21OHD) form of congenital adrenal hyperplasia (CAH) and are either heterozygotes or homozygote-unaffected. Prenatal treatment of 46,XX fetuses with 21OHD (via administration of dexamethasone to the pregnant mother) has been shown to reduce the masculinization of the genitalia and, thereby, the later need for 'corrective' feminizing genital surgery and potential impairment of sexual functioning. Along with the suppression of excess prenatal androgen production and reduction of prenatal masculinization of the genitalia in 46,XX fetuses with 21OHD, prenatal dexamethasone treatment may reduce the behavioral masculinization that is well documented in untreated 46, XX patients with 21OHD. Those fetuses who are partially treated until diagnosis of an unaffected status (heterozygous or homozygous-unaffected) will be studied as well. This latter group is of importance because these fetuses are being unnecessarily treated, but we have no way of diagnosing the unaffected status before the 8th week of gestation when treatment must begin for the female fetus who is affected. As treatment is necessary only until term in the female fetus affected with classical CAH, male fetuses and unaffected or heterozygous female fetuses do not require treatment. Thus, only one out of eight fetuses will require prenatal treatment until term. Findings of adverse effects of glucocorticoid treatment in non-human mammals [1, 2] have raised concerns among other clinicians and investigators about potential adverse side effects of such treatment on the developing human. Thus, this study will address this concern and investigate the potential adverse side effects of prenatal treatment. Detailed Description Females with classical CAH owing to 21-hydroxylase deficiency are born with ambiguous genitalia due to the production of excess androgens in utero. Prenatal treatment with dexamethasone was inaugurated in 1978 by Maguelone Forest and has been the standard of practice in the United States since 1986. Dexamethasone, which crosses the placental barrier, suppresses the fetal adrenal gland production of androgens, thus preventing ambiguous genitalia in the affected female. Children of both sexes are prenatally treated as soon as pregnancies at risk are confirmed. Treatment in females with 21OHD continues to term, but is discontinued in males and unaffected females. To date, 685 pregnancies have been diagnosed, of which 366 fetuses were treated. These investigators will study prenatally treated adolescents and adults 12 years and older with respect to medical and behavioral outcomes (see Table 5). In addition, mothers of children prenatally treated for varying periods of time for suspected 21OHD will be studied for long-term side effects of dexamethasone treatment administered during pregnancy. The long-term outcome in these children and their mothers has never before been studied.

  Study phs001317

• Resuscitation Outcomes Consortium Trial of Continuous Compressions Versus Standard CPR in Patients With out-of-Hospital Cardiac Arrest (ROC CCC-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.Objectives: To compare the rate of survival to hospital discharge after continuous chest compressions versus standard American Heart Association recommended cardiopulmonary resuscitation with interrupted chest compressions in patients with out-of-hospital cardiac arrest.Background: Standard cardiopulmonary resuscitation (CPR) consists of manual chest compressions to maintain blood flow and positive-pressure ventilation to maintain oxygenation until spontaneous circulation is restored. Chest compressions during standard CPR are interrupted frequently by ventilations. These interruptions reduce blood flow and potentially reduce the effectiveness of CPR. In animals with cardiac arrest, the interruption of chest compressions has been associated with decreased survival. Observational studies involving humans with out-of-hospital cardiac arrest of presumed cardiac cause have suggested that continuous compressions are associated with higher rates of survival than interrupted compressions.Participants: Of 35,904 patients with out-of-hospital cardiac arrest who were screened, 26,148 were eligible for participation in the trial and were enrolled in the trial during either the run-in phase or the active-enrollment phase. The active-enrollment phase included 23,711 patients, of whom 12,653 were assigned to the intervention group and 11,058 to the control group.Design: There were 114 participating EMS agencies across the eight participating Resuscitation Outcomes Consortium (ROC) sites, which were grouped into 47 clusters. Clusters of agencies were randomly assigned, in a 1:1 ratio, to perform continuous chest compressions or interrupted chest compressions during all the out-of-hospital cardiac arrests to which they responded. Each cluster was required to begin enrolling patients in a run-in phase to demonstrate adherence to the protocol before entering the active-enrollment phase of the trial. Twice per year, each cluster was crossed over to the other resuscitation strategy.Patients assigned to the group that received continuous chest compressions (intervention group) were to receive continuous chest compressions at a rate of 100 compressions per minute, with asynchronous positive-pressure ventilations delivered at a rate of 10 ventilations per minute. Patients assigned to the group that received interrupted chest compressions (control group) were to receive compressions that were interrupted for ventilations at a ratio of 30 compressions to two ventilations; ventilations were to be given with positive pressure during a pause in compressions of less than 5 seconds in duration. The primary outcome was the rate of survival to hospital discharge. Secondary outcomes included neurologic function at discharge, which was measured with the use of the modified Rankin scale, and adverse events. Conclusions: During the active-enrollment phase, 1129 of 12,613 patients in the continuous chest compression group and 1072 of 11,035 patients in the interrupted chest compressions group survived to hospital discharge.In patients with out-of-hospital cardiac arrest, continuous chest compressions during CPR performed by EMS providers did not result in significantly higher rates of survival or favorable neurologic function than did interrupted chest compressions.

  Study phs003901

• Studying Glioblastoma in a Human Organoid Tumor Transplantation Model

  This study comprises two complementary investigations that leverage innovative human model systems and cutting-edge molecular profiling to dissect glioblastoma (GBM) heterogeneity and tumor-microenvironment interactions. The first study uses a novel Human Organoid Tumor Transplantation (HOTT) model, in which freshly dissociated GBM tumor cells from five patients were transplanted into human embryonic stem cell-derived cortical organoids. This system enables the interrogation of tumor and microenvironment interactions in a human-specific, developmentally relevant context. Using single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq), the authors profiled over 216,000 cells, analyzing tumor heterogeneity across multiple media conditions. Ligand-receptor analysis (CellChat), immunofluorescence, and RNAScope were used to validate findings. The study revealed that the HOTT model faithfully recapitulates primary GBM cell types and microenvironmental components, and uncovered a novel bidirectional signaling axis mediated by PTPRZ1 that influences both tumor migration and cell fate in a context-dependent manner. PTPRZ1 is identified to be important for intercellular communication between tumor and microenvironmental cells, while PDGFRB, NOTCH3, HOPX, FAM107A, CLDN5, RGS5, FOXC1, SOX18 are key markers of the neurovascular progenitor that we identify to be a multipotent, restricted progenitor in GBM. Related datasets include the inclusion of immune cells in the HOTT system, termed “iHOTT”. The second study focuses on identifying and characterizing a rare but functionally potent neurovascular progenitor (NVP) population within GBM tumors. By generating a meta-atlas from seven publicly available GBM scRNA-seq datasets, the authors identified a unique tumor-derived cell population co-expressing neural progenitor and vascular markers. This population was validated in situ and in vivo through immunostaining and lineage tracing via DNA barcoding in the HOTT system. Functional knockdown of NVPs in a murine GBM model resulted in reduced cycling cells, altered tumor composition, and increased survival. Clonal analysis showed NVPs have dual potency to give rise to both neuronal and vascular-like tumor cells, contributing significantly to tumor cell diversity. Molecular technologies used across the studies include: Single-cell and single-nucleus RNA sequencing DNA barcoding and clonal lineage tracing (CellTag) Population information: Tumor samples were obtained directly from multiple GBM patients (all IDH1 wild-type, adult), including core and peripheral tumor regions. Human cortical organoids derived from human embryonic stem cells (hESCs) served as the microenvironment in the HOTT model. Principal findings include: HOTT recapitulates the heterogeneity and cell type fidelity of GBM, while enabling the study of tumor–microenvironment signaling. PTPRZ1 has opposing roles in tumor and microenvironment, influencing GBM cell migration and fate via non-catalytic mechanisms. A novel GBM neurovascular progenitor population (NVP) was identified, validated, and shown to contribute clonally to distinct tumor cell types. Elimination of NVPs in vivo reduces tumor aggressiveness and improves survival. Data to be available through dbGaP: Raw and processed single-cell and single-nucleus RNA-seq data (HOTT model and NVP studies) CellTag barcode-labeled scRNA-seq clonal lineage data Associated metadata including patient of origin, experimental condition, and sample annotations.

  Study phs003936

• DMET Genes, Nicotine Metabolism and Prospective Abstinence

  This study (DA033813; PI: Andrew W Bergen; PMID:26132489) includes samples from two laboratory studies of nicotine metabolism. The Pharmacokinetics of Nicotine Metabolism in Twins study (PKTWIN; PI: Gary E Swan; PMID: 15527659) was based on recruitment from a twin registry (PMID: 23084148). The Integrated Research Project on Tobacco Use and Dependence (IRP; PI: Gary E Swan; PMID: 14578134) was based on recruitment from a pedigree-based longitudinal study of risk factors for substance use, the Smoking in Families study (SMOFAM; DA03706; PI: Hy Hops). These two laboratory studies (PKTWIN and IRP/SMOFAM) served as the Stage I dataset to interrogate Drug Metabolizing Enzyme and Transporter genes with a targeted SNP array for association with the Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine), an established biomarker of nicotine metabolism. In addition to the laboratory studies, samples from eight RCTs (PMID: 23249876) with the NMR and smoking-related measures used to test SNPs identified in Stage I (PMID: 26132489). In a third stage, a lung cancer meta-analysis database (PMID: 24880342) was used to assess association of SNPs identified in Stage II with lung cancer. The objectives of the study were to identify novel genes and SNPs contributing to nicotine metabolism (Stage I), and to validate PK SNPs associated with the NMR from individuals participating in a clinical laboratory protocol with the NMR obtained from treatment-seeking smokers, and then to investigate association with prospective smoking cessation (Stage II). This study built upon existing studies of nicotine metabolism and randomized trials of smoking cessation therapies. Enhanced knowledge of the genes influencing nicotine metabolism and prospective abstinence may help personalize smoking cessation treatment and risk assessment for smoking-related diseases. For Stage I, both subject [fixed-dose NMR, covariates (age, BMI, ethnicity, sex, smoking status, and hormone use), and pedigree relationships] and sample (common DMET SNP genotype, genotyping quality control) data are available in this accession. The analysis protocol, quality control summaries, summary genotype, summary phenotype, and analysis results are available for Stage I, II and III samples (PMID: 26132489). Extensive discussion of the prior CYP2A6 association literature with the NMR, abstinence, smoking heaviness and lung cancer risk is available (PMID: 26132489). The NMR has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis.

  Study phs000931

• Functional characterisation of CpG islands in human tissues

  Functional characterisation of CpG islands in human tissues

  Dataset EGAD00001000212

• 1506_Methylation_M.vd.Berge

  DNA methylation in bronchial biopsies of asthmatics, asthma in remission and healthy subjects

  Dataset EGAD00010001731

• Unmatched WGS from bone marrow samples of 5 chr21 amplified blast phase myeloproliferative neoplasm patients

  We describe recurrent chromothripsis of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ~25% of patients (‘chr21amp’). Chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. Here we provide high-depth whole genome sequencing (WGS) in five chr21amp BP-MPN cases, to a median coverage of 81x [range 77-86] and purity 79% [range 58-88%].

  Dataset EGAD00001011280

• Quantitative Exploratory Proteomics Analysis of Glioblastoma in Initial and Recurrent Tumors

  Shotgun Proteomics; Glioblastoma samples from 11 patients were obtained at initial and recurrent tumor stages. Proteins were extracted, identified and quantified via tandem mass spectrometry based on a TMT isobaric labelling approach. Quatitative proteomics reveals 146 differentially abundant proteins using a patient-matched statistical modelling. Analysis of proteolytic processing reveals differential proteolytic patterns in recurrent tumors. Proteogenomics reveals the presense of 30 single-amino acid variants present in glioblastoma tumor and 1 of those as increased in recurrent tumor.

  Dataset EGAD00010002350

• Gastric Cancer Genetic Analysis of Metastasis

  To identify candidate drivers involved in oncogenesis and tumor evolution, we conducted an extensive genome sequencing analysis of metastatic progression in diffuse gastric cancer. This involved a comparison between a primary tumor from a Hereditary Diffuse Gastric Cancer Syndrome proband and its subsequent recurrence as an ovarian metastasis.

  Study phs000795

• Molecular Characterization of Clinical Renal Tumors

  We performed comprehensive molecular profiling of renal tumors, including whole exome sequencing and transcriptome sequencing, derived from patient samples. This project additionally explores mechanisms of response and resistance to existing and emerging therapies in this disease, as well as mechanisms of tumor evolution in the context of treatment.

  Study phs001018

• BELLINI clinical trial bulk RNA-Seq data: cohorts A, B & С

  RNA-Seq data of 78 breast cancer primary tumors obtained from 45 unique patients from BELLINI clinical trial. The data includes pre- and post-treatment samples. Patients in cohort A (15 patients, 25 samples) received nivolumab for 4 weeks, patients in cohort B (15 patients, 28 samples) received nivolumab + ipilimumab for 4 weeks, and patients in cohort C (15 patients, 25 samples) received nivolumab + ipilimumab for 6 weeks. The included raw transcriptome sequencing data in fastq format was generated using Illumina NovaSeq 6000.

  Dataset EGAD50000000808

• Base modification analysis using single molecule real-time sequencing

  This dataset was generated using single-molecule real-time sequencing for both training and testing purposes. The DNA samples isolated from human buffy coats or placenta of healthy individuals (n=4,) were prepared in a way that four types of base modifications were incorporated, including unmodified controls, 5mC, 5hmC, and 6mA. The sequence data for each sample consists of subreads produced by single-molecule real-time sequencing and stored in a bam format. Details of the specific experiments conducted in this study are outlined in our manuscript.

  Dataset EGAD50000000541

• Spatial and temporal transcriptome analysis on human skeletal muscle regeneration

  Skeletal muscle carries a unique ability for adaptation as well as regeneration that highly depends on a supportive cellular microenvironment. Here we show that spatial and single-cell transcriptomic analysis in human skeletal muscle is a unique approach to illuminate cellular interactions in the microenvironment.

  Study EGAS50000000182

• Multi-omic dataset utilized in the analysis of a phase II study of epigenetic priming followed by nivolumab in lung cancer

  This dataset includes sequence files from whole exome sequencing and bulk RNA sequencing of tissue and blood biospecimens from a phase II clinical trial investigating epigenetic priming followed by immune checkpoint blockade in non-small cell lung cancer (NSCLC; NCT01928576). There are 78 whole exome sequencing files and 36 bulk RNA sequencing files included in this dataset.

  Dataset EGAD50000001336

• WES data of pediatric cancer patients with P/LP variants in HBOC-related genes

  The current study aimed to identify (likely) pathogenic germline variants(LP/PVs) in 25 adult-onset HBOC-related genes within a cohort of 372 pediatric cancer patients. For this purpose we performed (paired-end) whole exome sequencing (WES) using Ilumina sequencing technology. The files uploaded here belong to the 27 individuals with such a LP/PV. The project provides insight into the prevalence and spectrum of such variants in childhood cancer, contributing to the understanding of genetic predisposition in pediatric oncology.

  Dataset EGAD50000001561

• Epigenome mapping in purified cells of the digestive and urogenital organs: Participation in International Human Epigenome Consortium (IHEC) (RNA-Seq)

  The aim of this study is to participate in International Human Epigenome Consortium (IHEC, http://ihec-epigenomes.org/), through disclosure of quality epigenome profiles of various normal cell lineages and diseased cells purified from surgically resected materials of multiple Japanese people.

  Study JGAS000028

• Mid-frequency hearing loss is a characteristic clinical feature of OTOA-associated hearing loss

  In this study, we performed NGS analysis of a large Japanese hearing loss cohort, and identified 7 patients with OTOA-associated hearing loss. As novel clinical features identified in this study, the audiometric configurations of OTOA-associated hearing loss patients was found to be mid-frequency.

  Study JGAS000200

• Epigenome mapping in purified cells of the digestive and urogenital organs: Participation in International Human Epigenome Consortium (IHEC) (WGBS)

  The aim of this study is to participate in International Human Epigenome Consortium (IHEC, http://ihec-epigenomes.org/), through disclosure of quality epigenome profiles of various normal cell lineages and diseased cells purified from surgically resected materials of multiple Japanese people.

  Study JGAS000026

• Epigenome mapping in purified cells of the digestive and urogenital organs: Participation in International Human Epigenome Consortium (IHEC) (ChIP-seq)

  The aim of this study is to participate in International Human Epigenome Consortium (IHEC, http://ihec-epigenomes.org/), through disclosure of quality epigenome profiles of various normal cell lineages and diseased cells purified from surgically resected materials of multiple Japanese people.

  Study JGAS000027

• RNA sequencing of untreated head and neck cancer patient-derived xenografts (PDXs) and matched patient tumor tissue.

  RNA sequencing was performed on untreated patient tumor tissue and matched patient-derived xenograft (PDX) models of primary head and neck squamous cell carcinoma (HNSCC). The aim of this analysis was to characterize the transcriptional landscape of the tumors in the in vivo setting.

  Study EGAS50000001595

• scRNA-seq of a 3D human cortical tissue model from human iPSCs exploring 2D versus 3D co-culturing

  Single-cell RNA-seq analysis of human iPSC-derived microglia/astrocytes/neurons in a novel, human in vitro 3D cortical tissue model, as well as 2D co-cultures for comparison. Samples include distinct conditions as described in the Study section. The dataset was generated using the BD Rhapsody technology and sequenced paired-end with Illumina NovaSeq2000. Information on the multiplexing of samples is reported in the Analyses section.

  Dataset EGAD50000002021

• Whole-exome sequencing (WES) analysis of untreated head and neck cancer patient-derived xenografts (PDXs) matched patient tumor tissue and normal mucosa tissue.

  WES analysis was performed on untreated patient tumor/normal mucosa tissue and matched patient-derived xenograft (PDX) models of primary head and neck squamous cell carcinoma (HNSCC) to investigate the preservation of tumor-specific genomic alterations in the in vivo context.

  Study EGAS50000001622

• HipSci_RNASEQ_PID

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNAseq on iPS lines from Platelet and bleeding disorders patients

  Study EGAS00001001990

• Clinical and genetic analysis of a rare syndrome associated with neoteny

  We describe a novel syndrome in six patients with extreme developmental delay and the defining characteristic of neoteny. In an effort to discover any genetic causes of this syndrome whole genome sequence (WGS) analysis of the patients and their families was performed on Complete Genomics’ nanoarray platform.

  Study EGAS00001002419

• Predictor_ChemoNEAR_TNBC

  In this study a collection of core biopsies from breast cancer patients receiving neoadjuvant chemotherapy as part of the ChemoNEAR trial will be investigated. The study is intended to detect early acquired resistance in women with diagnosed breast carcinoma. Samples will undergo whole genome sequencing and analysis, including use of HR Predict.

  Study EGAS00001002806

• RNA-sequencing of adult T-cell leukemia/lymphoma samples

  Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive hematological malignancy derived from mature CD4+ T-lymphocytes. In this study, we performed RNA-sequencing (RNA-seq) analysis for ATL samples including 9 primary tumors and 1 ATL cell line to clarify gene expression profiles in this disease.

  Study EGAS00001003575

• Glioblastoma_CRISPR_Screen

  This is an in vitro genome-wide CRISPR/cas9 screen in human glioblastoma stem cells, screening for genes essential for survival of these cells. These cells express cas9 and have been transfected with a guide RNA library causing gene knockouts. We will analyse the sequencing data for depletion of guide RNAs.

  Study EGAS00001001519

• HipSci_RNASEQ_Usher syndrome and congenital eye defects

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNAseq on iPS lines from Usher syndrome and congenital eye defects.

  Study EGAS00001001997

• WES of clonally related neuroblastoma and teratoma

  Mature teratomas are usually benign tumors that rarely undergo malignant transformation. We report an advanced neuroblastoma arising in a mature teratoma of the ovary. Whole-exome sequencing identified extensive copy-neutral LOH in both neuroblastoma and teratoma elements, suggesting that the neuroblastoma evolved from the teratoma.

  Study EGAS00001005116

• Oesophageal_Adenocarcinoma_Organoid_ATAC

  ATAC Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger. This ATAC data will be combined with other sequencing data in order to generate

  Study EGAS00001003890

• Somatic_evolution_in_the_psoriatic_skin

  We will use laser capture microdissection to dissect groups of a few hundred cells, from which we will isolate and sequence nucleic acids. We aim to whole-genome, whole-exome and RNA sequence the samples in effort to understand the accumulation of somatic mutations in psoriasis and their effect on transcription.

  Study EGAS00001004882

• Anthropological dataset 1 for The admixture histories of Cabo Verde

  Datasets used in the article "The genetic and linguistic admixture histories of the islands of Cabo Verde" by Laurent R et al. eLife 2023 (DOI: https://doi.org/10.7554/eLife.79827 - URL: https://elifesciences.org/articles/79827) File name "eGAdeposit_233CaboVerde_SampleInfo_FINAL_01062022.txt" Column 1 corresponds to individual alphanumeric codes as in the "eGAdeposit_233CaboVerde_GenotypeFile_FINAL_01062022.vcf" genotype file Column 2 corresponds to individual's biological sex as per genetic inference Column 3 corresponds to individual's self-reported age in years Column 4 corresponds to individual's self-reported cumulated number of years spent in academic or professional education

  Dataset EGAD00001008976

• The effect of anti-HER2/CD3 TDB on transcription in human CD8 T cells (bulk RNA-seq)

  RNA was isolated from purified human CD8 cells that were incubated with anti-HER2/CD3 TDB in the presence of SK-BR-3 cells. Sequencing libraries were generated and submitted for transcriptome profiling by high-throughput sequencing. Experiments were performed in triplicates for anti-HER2/CD3 TDB treatment and control. This Dataset is associated with the following ArrayExpress Experiment: E-MTAB-8211 - The effect of anti-HER2/CD3 TDB on transcription in human CD8 T cells (bulk)

  Dataset EGAD00001005187

• WGS dataset of Characterization of UV DNA damage in B-cell precursor acute lymphoblastic leukemia

  Extensive characterization of mutational signature SBS7a in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) samples. We aimed to describe the presentation of SBS7a in BCP-ALL, identify other pediatric cancers presenting with SBS7a, look into the link of SBS7a and UV-light in the context of BCP-ALL and cancers with provable UV exposure, and pinpoint when SBS7a was acquired.

  Dataset EGAD00001015599

• Single-cell GoT sequencing from CH, MDS and AML patients with CH mutations

  Single-cell targeted amplicon RNA sequencing from CH (n = 3), MDS (n = 6, MDS02 in 2 replicates) and AML (n =1, in 2 replicates) samples with mutations in splicing factors (SF3B1 - n = 8 [2 -CH, 6 MDS], U2AF1 n = 1) or transcription regulators (DNMT3A - CH04). The transcripts are targeted to detect a particular CH mutation in the listed genes. U2AF1 GoT are full-length cDNA, while the rest follow the 10x 3' V3 protocol.

  Dataset EGAD00001011284

• Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: WES and RNA sequencing of biopsies from a Phase I Trial

  This dataset contains whole-exome and RNA sequencing of biopsies obtained from patients enrolled in a phase I clinical trial investigating the UV1 vaccine in combination with pembrolizumab in patients with advanced melanoma.

  Dataset EGAD00001011074

• Gene expression in CSF and whole blood of adults with proven bacterial meningitis in Malawi

  Dataset of BAM files from patients with proven bacterial meningitis in Malawi. Samples consist of BAM files from PolyA RNA seq runs from patients classifed as admission whole blood or CSF on admission (pre-antibiotics) in the Emergency Department. Subsequent BAM files are identical runs from whole blood from the same patients, taken at either day 10 or day 40 post admission to hospital. All patients have disease, they are divided into survivors and non-survivors at the day 40 time point.

  Dataset EGAD00001004488

• Mutational Signatures of relapse in rectal cancer FFPE samples in the CR07 clinical trial

  The CRO7 clinical trial recruited patients with clinically operable rectal adenocarcinoma. Patients were randomized to either pre-operative short course surgery followed by chemo-radiotherapy only in those patients at high risk of local relapse. Patients in both arms the received standard %-FU based adjuvant chemotherapy as per local policy. We intend to use FFPE derived DNA from the primary tumours to identify patterns of mutations or copy number alterations that are predictive of local or distant relapse.

  Dataset EGAD00001000875

• Ither NB in Organoids WXS dataset - Exploring high-throughput drug sensitivity testing in neuroblastoma cell lines and patient-derived tumor organoids in the era of precision medicine

  Ither NB in Organoids WXS dataset - We aimed to launch an online repository integrating genomics and transcriptomics with high-throughput drug screening (HTS) of nineteen commonly used neuroblastoma cell lines and fourteen generated neuroblastoma patient-derived organoids (NBL-PDOs) to improve identification of molecularly matched therapies and support clinical uptake.

  Dataset EGAD00001010281

• Whole-genome and transcriptome sequencing of NUT midline carcinoma

  In this study, we sequenced three NUT midline carcinoma genomes and their transcriptomes (NMC1, NMC2 and Ty-82), and two paired normal blood samples (for NMC1 and NMC2). Whole-genome sequencing libraries were generated by PCR-free methods, and sequencing run was made in HiSeq X machines. Transcriptome (mRNA) sequencing was performed in HiSeq 2500 machines. PCR duplicates-marked, indel-realigned, and base-recalibrarted BAM files are provided in our dataset.

  Dataset EGAD00001003117

• Detection of ctDNA in Plasma of Patients with Clinically Localised Prostate Cancer is Associated with Rapid Disease Progression

  Whole genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 hours and 6 weeks) surgery. Tagged-amplicon deep sequencing (TAm-Seq) across the TP53 gene in ctDNA in a cohort of 189 individuals.

  Dataset EGAD00001006369

• RNA-seq dataset of Characterization of UV DNA damage in B-cell precursor acute lymphoblastic leukemia

  Extensive characterization of mutational signature SBS7a in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) samples. We aimed to describe the presentation of SBS7a in BCP-ALL, identify other pediatric cancers presenting with SBS7a, look into the link of SBS7a and UV-light in the context of BCP-ALL and cancers with provable UV exposure, and pinpoint when SBS7a was acquired.

  Dataset EGAD00001015598

• RRBS data from TRACERx non-small cell lung cancer (NSCLC) tumours and matched normal adjacent tissue.

  TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).

  Study EGAS00001008071

• Cardiovascular Cell Therapy Research Network (CCTRN): A Phase II, RCT of Mesenchymal Stem Cells & Cardiac Stem Cells in Subjects With Ischemic HF (CONCERT HF-BioLINCC)

  Data Access Note: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. ObjectivesTo assess the feasibility, safety, and efficacy of autologous mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), alone or in combination, in participants with ischemic heart failure.Background The prognosis of heart failure (HF) caused by chronic ischemic cardiomyopathy (coronary artery disease and prior myocardial infarction), hereby referred to as “ischemic HF”, remains poor. Many studies have explored the use of various types of stem or progenitor cells in participants with chronic ischemic HF, with encouraging results. Several clinical trials have suggested that MSCs and CPCs are both safe and beneficial in participants with ischemic HF. At the time of this study, no information was available on the efficacy of MSCs and CPCs in humans, however, both cell types have been shown to attenuate left ventricle (LV) dysfunction in animal models. Preclinical models indicate that combining MSCs and CPCs increases the therapeutic effects, but this had not yet been tested in humans. The CONCERT-HF study was initiated to assess whether autologous MSCs and CPCs, alone or in combination, can be manufactured and delivered to participants with ischemic HF; are well-tolerated; and improve LV function, quality of life, and functional capacity, and/or reduce scar size. Participants A total of 125 participants were randomized with 33 participants randomized to the MSCs and CPCs group, 29 participants to the MSCs alone group, 31 participants to the CPCs alone group, and 32 participants to the placebo group. Design The CONCERT-HF study was a multi-center Phase II, double-blind, randomized, placebo-controlled trial designed to evaluate the feasibility, safety, and efficacy of MSCs alone, CPCs alone, and their combination compared with placebo as well as each other in patients with ischemic HF. In Stage 1 (open label, lead-in study) participants were randomized 1:1 to either a standard-of-care control group (i.e., they did not undergo harvest, mapping, or injection procedures) or combination therapy (MSCs + CPCs, as described for Stage 2) to complete safety assessments. Once approval was granted for Stage 2, participants were randomized (1:1:1:1) to one of four treatments: placebo, autologous MSCs (target dose, 150 × 106 cells), autologous CPCs (target dose, 5 × 106 cells), or a combination of autologous MSCs and CPCs. At the harvest visit, right ventricular endocardial biopsy (EMB) was performed in participants randomized to receive CPCs alone or a combination of MSCs and CPCs. Participants randomized to receive MSCs alone or placebo had a sham procedure (right heart catheterization without EMB). All participants underwent a bone marrow aspiration and approximately 14 weeks later had transendocardial, electromechanically-guided injections of study product. Visits occurred at 1 day, 1 week, and 1, 3, 6, and 12 months after study product injection. A telephone contact took place at 24 months to assess the participant's current medications, as well as morbidity and mortality. Study endpoints included measures of safety, feasibility, and efficacy. Safety outcomes included all adverse events grade 2 and higher, including major adverse cardiac events (MACE) related to HF (death, hospitalization for worsening HF, and HF exacerbation not requiring hospitalization). Efficacy endpoints included quality of life, MRI measures of LV function and structure, functional capacity, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Conclusions In patients with ischemic HF, autologous MSCs and CPCs, alone or in combination, are safe and feasible; CPCs were associated with a reduction in the incidence of MACE related to HF compared to placebo; MSCs, either alone or in combination with CPCs, were associated with improved quality of life; these seemingly beneficial effects of CPCs and MSCs on clinical outcome were not associated with changes in LV function or structure; and combination therapy with MSCs and CPCs was associated with the best clinical outcomes with respect to both MACE related to HF and quality of life.

  Study phs004055

• DNA Methylation Markers and Pancreatic Cancer Risk in 3 Cohort Studies (NHS, PHS, HPFS)

  Pancreatic cancer is the 4th leading cause of cancer deaths in the US. Due to the lack of early symptoms, pancreatic cancer is difficult to identify at early stages and no screening is available for the general population. Identifying pancreatic cancer at earlier stages could significantly improve survival with increased opportunities for surgery. New high-dimensional arrays designed to measure DNA methylation levels at hundreds of thousands of CpG sites throughout the genome have opened opportunities to examine the role of DNA methylation in cancer risk using blood samples. Using this method, archived samples from prospective studies can be used to examine early changes in the DNA methylation levels in individuals who develop cancer months or years later, providing new opportunities to better understand biological mechanisms and, perhaps, identify biomarkers for early detection. Pancreatic cancer cases and matched controls were obtained from 3 large cohort studies, the Nurses' Health Study (NHS), the Physician's Health Study (PHS), and the Health Professionals Follow-up Study (HPFS), to measure DNA methylation in stored buffy coats using a nested case-control study design.

  Study phs001917

• Nivolumab and Tumor Infiltrating Lymphocytes (TIL) in Advanced Non-Small Cell Lung Cancer

  We performed a trial of adoptive cell therapy using tumor infiltrating lymphocytes (TIL) in metastatic non-small cell lung cancer (NSCLC). We conducted a single-arm open- label phase 1 trial (NCT03215810) of TIL administered with nivolumab in 20 patients with advanced NSCLC. Patients had tumor metastases resected for TIL, and the sequencing data from these tumors is included herein. The primary endpoint was safety, and secondary endpoints included objective response rate, duration of response, and T-cell persistence. Autologous TIL was expanded ex vivo from minced tumors cultured with IL-2. Patients received initial nivolumab for 4 cycles. If they had subsequent evidence of progression, then they proceeded to receive cyclophosphamide and fludarabine lymphodepletion, TIL infusion, and interleukin-2, followed by maintenance nivolumab. The endpoint of safety was met according to pre-specified criteria. Of 13 evaluable patients, 3 had confirmed responses and 11 had reduction in tumor burden, with a median best change of 35%. Two patients achieved complete responses ongoing 1.5 years later. In exploratory analyses, we found T cells recognizing multiple types of cancer mutations were detected after TIL treatment, and were enriched in responding patients.

  Study phs002486

• Genetic Underpinnings of Ethnic Disparities in Bone Toxicities Between Hispanic and Non-Hispanic Children Treated for Acute Lymphoblastic Leukemia

  Acute lymphoblastic leukemia (ALL) is the most common malignancy among children and young adolescents. More than 90% of children are cured with a combination of multiple chemotherapeutic drugs. Some may suffer from debilitating toxicities due to the cytotoxic drugs, necessitating pharmacogenetic research to search for genetic markers predictive of treatment toxicities, so that treatment can be better tailored based on patients' genetic makeup. Bone toxicities, including osteonecrosis and fractures, most often due to glucocorticoids, are the most common complications in ALL, which have long-lasting detrimental impact on the still developing skeletons in children. In DFCI ALL Consortium Protocol 05-001, a multi-center clinical trial for childhood ALL conducted in Canada and the US, we found that Hispanic children had less drug toxicities to their bones than non-Hispanic children. Although reasons for the observed ethnic differences are largely unknown, patients' inherited genetic background may be at play. This study seeks to perform a novel pharmacogenomic study based on multi-site clinical trials DFCI ALL Consortium Protocol 05-001 and 11-001 to identify genetic underpinnings of ethnic disparities in bone toxicities.

  Study phs002317

• The Somatic Mutational Landscape of Thyroid Cancer in Patients with Germline PTEN Mutations

  PTEN hamartoma tumor syndrome (PHTS) is associated with a high rate of thyroid cancer and benign thyroid disease, yet nothing is known of the genomic landscape of PHTS-associated thyroid tumors. In this study, exome sequencing was performed on 58 thyroid tumors (28 cancers, 30 benign nodules) from 19 patients with PHTS, sequenced in tumor-normal pairs. Somatic variant calling was utilized to determine the somatic mutational landscape of thyroid tumors in this population. This was then compared to the known mutational landscape of sporadic thyroid cancer in the general population using sequencing data from The Cancer Genome Atlas. The primary finding of the study was that PHTS-associated thyroid tumors had a unique genomic landscape, including a high frequency of second-hit somatic PTEN alterations compared to the sporadic thyroid tumors. Additionally, PHTS-associated thyroid cancers were found to have somatic alterations in BRAF, RAS family members, and genes associated with DNA double stranded break repair. Data available through dbGAP will include tumor BAM files for each tumor, normal BAM files for each patient, and MAF files for PHTS-associated thyroid cancer and PHTS associated benign thyroid nodules.

  Study phs003640

• Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial

  In HER2-positive breast cancer, clinical outcome and sensitivity to HER2-targeted therapies are influenced by both tumor and microenvironment features. However, we are currently unable to depict the molecular heterogeneity of this disease with sufficient granularity. Here, by performing gene expression profiling in HER2-positive breast cancers from patients receiving adjuvant trastuzumab in the ALTTO clinical trial, we identified and characterized five molecular subtypes associated with the risk of distant recurrence: immune-enriched (IM), proliferative/metabolic-enriched (P/Met), mesenchymal/stroma-enriched (Mes/S), luminal (LUM), and ERBB2-enrichedERBB2-dependent (ERBB2-EERBB2-D). We next validated the biological profiles of the subtypes and explored their prognostic/predictive value in external cohorts, namely the NeoALTTO trial, SCAN-B, I-SPY2, METABRIC and TCGA. IM tumors presented better survival outcomes, in contrast to Mes/S and P/Met tumors, while LUM tumors and ERBB2-EERBB2-D were characterized by low and high rates of pathological complete response, respectively. Of note, these molecular subtypes provide the rationale for treatment approaches leveraging the heterogeneous biology of HER2-positive breast cancer.

  Study EGAS50000000525

• Somatic Mutations in Individual Skin Cells

  Ultraviolet (UV) radiation is the primary cause of melanoma through the acquisition of driver mutations in melanocytes. It also plays a significant role in oncogenesis in other skin cells, such as keratinocytes. However, the mutational profiles vary widely among different skin cancers, and the early mutational processes in different cell types from the same skin, is not well understood. Additionally, our preliminary studies also suggest that the mutation burden in different skin cells vary significantly based on risk factors such as the anatomical site and the use of tanning beds. To explore this, we employed innovative Next Generation Sequencing (NGS) tools to perform a site-matched comparison of the genomic landscapes of melanocytes, keratinocytes, and fibroblasts. From 20 biopsies of physiologically normal skin, collected from various anatomical sites across 16 donors, we have performed DNA-sequencing on 106 melanocytes, 78 keratinocytes and 13 fibroblasts. Of these samples, we have also simultaneously performed RNA-sequencing on 78 melanocytes, 46 keratinocytes and 9 fibroblasts. For normal bulk DNA, we also performed targeted (UCSF500; n=9) or exome sequencing (n=8) of skin or saliva samples from the donors.

  Study phs003683

• Defining Cutaneous Gene Expression Signatures in Juvenile Dermatomyositis

  Skin inflammation in juvenile dermatomyositis (JDM) can signal disease onset or flare up and prevent complete disease remission. Our objective was to evaluate JDM cutaneous expression signatures through tape stripping in both lesional and non-lesional skin and as compared to paired blood. A total of 28 JDM and 20 control (CTL) patients participated in the study. All patients had tape strip sampling of non-lesional (NL) skin at enrollment visit. Within our JDM cohort, paired lesional (L) skin was additionally sampled if rash was present. 16/28 of JDM patients had at least one additional skin sample associated with a follow-up (FU) visit (total number of follow-up samples included = 26 NL and 4 L). We identified a common innate immune signature in both lesional and non-lesional JDM skin. Using unsupervised hierarchical clustering of skin expression data, we distinguished a JDM molecular subgroup characterized by a mitochondrial dysfunction signature. In comparison to blood expression data, we determined that skin may more effectively highlight the JDM subgroup characterized by a mitochondrial dysfunction expression signature. Data available include bulk RNA-sequencing data from tape strips and blood of the JDM and control patients from this study.

  Study phs003884

• Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.

  Study: Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer. EudraCT Number: 2014-004417-86 Clinicaltrials.gov Number: NCT02324998 Purpose: Investigate combined PARP and androgen inhibition in primary prostate cancer. Aim: To understand the biological mechanism(s) underlying clinical efficacy, especially in the absence of mutations in homologous recombination (HR) repair pathways. Dataset: Single-nuclear RNA sequencing data from post-treatment radical prostatectomy tissue cores for six patients, 3 from each of olaparib and olaparib and degarelix cohorts. Samples were processed for nuclear isolation and extraction, prior to single-nuclear RNA sequencing. 10x libraries were constructed using the 10x supplied protocol, briefly: individual nuclei were trapped into droplets with a single bead, and poly A transcripts were barcoded during reverse transcription. Complementary DNA was amplified, and libraries were prepared for sequencing on NovaSeq 6000 using S4 flow cell (100k reads per cell). FASTQ files were processed using CellRanger pipeline (10X Genomics). Outputs from the CellRanger pipeline were analysed using the Seurat package (v4.9.9.9049) in R (v4.2.0). Processed data is provided as a Seurat object.

  Study EGAS50000000880

• Whole Genome Sequencing for Metastatic Mutational Burden in Extraskeletal Myxoid Chondrosarcoma

  Extraskeletal myxoid chondrosarcoma (EMC) is an ultra-rare cancer. Though it has a favorable prognosis and an indolent course, it has high rates of local recurrence and metastasis to the lungs. EMC is most often characterized by a translocation involving the NR4A3 gene most often fusing with EWSR1, leading to constitutive expression of NR4A3, the biological significance of which is unknown. Our study presents a case of EMC with case-matched lung and advanced pelvic metastases. We conducted Whole Genome Sequencing to examine differences in the mutational landscape at two different stages of metastasis. This is the first study to our knowledge to analyze mega-base scale structural variants (SVs) in EMC. Our data validates copy number variants (CNVs) found in previous studies. While the primary tumor and lung metastasis had similar somatic variations and CNVs, the pelvic metastasis had more SVs with especially increased mutational burden of SVs in chromosome 2. This suggests that different molecular drivers appear in more advanced, relapsing EMC compared with the primary tumor and early lung metastasis. The sequencing data is available through dbGaP.

  Study phs003305

• The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space

  Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples, and we validate bisulfite sequencing as a multipurpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. On the basis of these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data collected as part of routine clinical practice.

  Study EGAS00001002538

• Defective T-cell expansion in RASGRP1 deficiency

  Inherited CTPS1- CD27- and CD70-deficiencies in humans have revealed key factors of T-lymphocyte expansion, that is a prerequisite for an efficient immunity to Epstein-Barr virus (EBV) infection. RASGRP1 is a T-lymphocyte specific nucleotide exchange factor known to activate the MAP kinases pathway. A deleterious homozygous mutation in RASGRP1 leading to the loss RASGRP1 expression was identified in two siblings who both developed a persistent EBV infection leading to Hodgkin lymphoma. RASGRP1-deficient T cells exhibited defective MAPK activation and impaired proliferation that was restored by expression of wild-type RASGRP1. Similar defects were observed in T cells from healthy individuals when RASGRP1 was downregulated. RASGRP1-deficient T cells also exhibited decreased CD27-dependent proliferation toward CD70-expressing EBV-transformed B cells, a crucial pathway required for expansion of antigen-specific T cells in anti-EBV immunity. Furthermore, RASGRP1-deficient T cells failed to upregulate CTPS1, an important enzyme required for DNA synthesis. These results show that RASGRP1 deficiency leads to susceptibility to EBV infection, and demonstrate the key role of RASGRP1 at the crossroad of pathways required for the expansion of activated T lymphocytes.

  Study EGAS00001002753

• BIOKEY: A single-cell catalogue of the dynamic changes underlying Checkpoint Immunotherapy response in Early Breast Cancer

  Checkpoint immunotherapy combined with neoadjuvant chemotherapy improves complete pathologic response in a subset of breast cancer patients. Here, we applied single-cell profiling to tumor biopsies collected before and during anti-PD1 therapy. One-third of tumors exhibited proliferative T-cells expanding along CD8+ or CD4+ lineages, which were either characterized by increased cytotoxicity and exhaustion or improved T-helper function, respectively. Lineage tracing in non-expanding tumors revealed at which point in the lineage T-cells were impaired, while gene expression modeling along these lineages revealed novel genes and underlying transcription factors involved in T-cell expansion. Interestingly, different dendritic and myeloid cell phenotypes could either stimulate or inhibit expanding T-cells, while cell-to-cell communication revealed an integrated immune context highly predictive of T-cell expansion, consisting of immune-stimulatory/-inhibitory interactions between cancer and various immune cell types. Our data yield unprecedented insights into the dynamic changes underlying checkpoint immunotherapy response in breast cancer.

  Study EGAS00001004809

• Androgen deprivation therapy promotes an inflammatory and obesity-like microenvironment in periprostatic fat

  Prostate cancer is a leading cause of cancer-related death and morbidity worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of androgen deprivation therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity. At the same time, obesity has been associated with both prostate cancer development and disease progression, linked to its effects on chronic inflammation at a tissue level. The connection between androgen deprivation therapy, obesity, inflammation, and prostate cancer progression is well-established in clinical settings; however, an understanding of the changes in adipose tissue at the molecular level induced by castrating therapies is missing. Here we investigated the transcriptional changes in periprostatic fat tissue induced by profound androgen deprivation therapy in a group of patients with high-risk tumours compared to a matching untreated cohort. We find that androgen deprivation therapy is associated with a pro-inflammatory and obesity-like adipose tissue microenvironment. This study suggests that the beneficial effect of androgen deprivation therapy may be partially counteracted by metabolic and inflammatory side effects in the adipose tissue surrounding the prostate.

  Study EGAS00001003286

• Identification of rare germline variants in familial multiple myeloma

  The risk of developing multiple myeloma (MM) in first-degree relatives of affected individuals is 2 to 4 fold higher than in the general population, implying the existence of inherited susceptibility. While over 20 common, low-penetrance variants have been associated with MM risk, less is known about rare, high-penetrance germline predisposition. We aimed to identify and characterize high/moderated penetrance germline variants in MM families using whole genome sequencing. For that purpose we identified families with at least two individuals diagnosed with MM or its precursors MGUS and smoldering MM. Also, patients with solitary plasmacytoma and AL amyloidosis were enrolled. We also recruited unaffected family members, and they were screened to exclude undetected MM or its precursor stages. After whole genome sequencing of blood DNA and filtering for rare variants (minor allele frequency <0.1%) and family segregation, variants are prioritized by a range of published in silico tools and literature search. The most promising variants are subjected to experimental validation to evaluate their functional relevance. Our data will provide guidance to worldwide efforts to unravel germline predisposition in MM and validation of the proposed variants and genes.

  Study EGAS00001004734

• Genome Diversity in Africa Project: Benin (2021-02-16)

  Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene-disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region. The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group). Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics 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 2021-02-16.

  Dataset EGAD00001006970

• Whole genome sequencing of retinoblastoma reveals the diversity of rearrangements disrupting RB1 and uncovers a treatment related mutational signature

  Background: The development of retinoblastoma is thought to require pathological genetic changes in both alleles of the RB1 gene. However, cases exist where RB1 mutations are undetectable suggesting alternative pathways to malignancy. Methods: We applied comprehensive whole genome sequencing (WGS) and transcriptomics to sporadic retinoblastomas derived from twenty patients attending our clinic, contrasting these results to that obtained through customary clinical testing. We sought RB1 and other driver mutations, investigated mutation burden, mutational signatures and phylogenetic relatedness in one case of bilateral retinoblastoma. Results: At least one RB1 mutation was identified in all retinoblastomas. We confirmed RB1 mutations previously identified by clinical screening, identified three new RB1 mutations and provided clarity to the mechanism behind a further six mutations. Eight tumours carried structural rearrangements involving RB1 ranging from relatively simple to extremely complex rearrangement patterns, including a chromothripsis-like pattern in one tumour. Potential driver mutations included mutations in BCOR (5/20) and amplification of MYCN (2/20) and MDM4 (1/20). We show that RB1 mutations are not mutually exclusive of MYCN amplifications, and further reveal that all tumours demonstrate increased MYCN expression suggesting a universal role in retinoblastoma tumorigenesis.  Bilateral tumours obtained from one patient harboured conserved germline but divergent somatic RB1 mutations, indicating independent evolution. In-keeping with previous WGS of paediatric cancers, the mutation burden in retinoblastomas was extremely low. Mutational signature analysis showed a predominance of signatures associated with cell division and an absence of ultraviolet-related DNA damage. In a tumour exposed to chemotherapy prior to enucleation, a profound platinum-related mutational signature was observed. Conclusions: WGS provides a complete picture of the genomic landscape of retinoblastomas, allowing the discovery of mutations otherwise undetected by conventional clinical screening approaches. The presence of at least one RB1 mutation in all retinoblastomas and the relative paucity of driver mutations in other genes suggests mutations beyond RB1, MYCN and BCOR are rare. Whilst most RB1 mutations are identifiable by clinical screening, the increased resolution and ability to detect otherwise elusive rearrangements of RB1 by WGS, confirming whether they are somatic or germline, has important repercussions on clinical management and advice on recurrence risks.

  Dataset EGAD00001006431

• HLA-DR is absent in primitive macrophages through epigenetic silencing of master regulator CIITA

  The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. This process is poorly understood in humans and in the mouse is thought to be spatially restricted to the yolk sac. Human fetal placental macrophages, Hofbauer cells (HBC), arise during the primitive haematopoietic wave at ~18 days post conception. Here we identify a population of placental erythro-myeloid progenitors (PEMPs) in the early human placenta that give rise to HBC. PEMP are fetal CD34+CD43+ progenitors found exclusively at early gestational timepoints. Transcriptomic analyses reveal that PEMP have conserved features of primitive yolk sac EMPs, including the lack of HLF expression. Using in vitro single-cell culture experiments we show that PEMP generate HBC-like cells that completely lack HLA-DR expression  and demonstrate that this is a conserved feature of all macrophages generated by primitive haematopoiesis in humans. Finally, we demonstrate that the class II transactivator, CTIIA, the master regulator HLA-DR expression, is epigenetically silenced during primitive haematopoiesis, leading to HLA-DRneg macrophages. These findings demonstrate that HBC are derived locally from PEMP and establish the human placenta as an additional site of primitive haematopoiesis.

  Study EGAS00001006981

• Exome sequencing in patients with Calcific Aortic Valve Stenosis

  Exome sequencing in patients with Calcific Aortic Valve Stenosis

  Dataset EGAD00001000053

• Multi-omics analysis of pre-invasive lung adenocarcinoma in never-smokers

  Multi-omics analysis of pre-invasive lung adenocarcinoma in never-smokers

  Dac EGAC50000000385

• UMCG Immunogenetics DAC

  DAC for the data generated in the Immunogenetics group in the genetics department of the University Medical Center Groningen

  Dac EGAC50000000785

• Neurodegenerative_TGS

  An investigation of clonal haematopoiesis in patients with neurodegenerative disease.

  Study EGAS00001002431

• genome-wide cfDNA methylation analysis

  To characterise cfDNA methylome in metastatic prostate cancer

  Study EGAS00001003958

• Plasma DNA profile in DNASE1L3 deficiency

  Plasma DNA profile in DNASE1L3 deficiency

  Dataset EGAD00001006216

• H3K4me3, IgG, and Input ChIP-seq in overexpression of pLV Control, CS-FL and CS-ΔEx4 in SW1116 cells.

  none

  Study EGAS00001008121

• Mayo-Perlegen LEAPS (Linked Efforts to Accelerate Parkinson's Solutions) Collaboration

  We performed a two-tiered, whole-genome association study of Parkinson disease (PD). For tier 1, we individually genotyped 198,345 uniformly spaced and informative single-nucleotide polymorphisms (SNPs) in 443 sibling pairs discordant for PD. For tier 2a, we individually genotyped 1,793 PD-associated SNPs (P<.01 in tier 1) and 300 genomic control SNPs in 332 matched case-unrelated control pairs. We identified 11 SNPs that were associated with PD (P<.01) in both tier 1 and tier 2 samples and had the same direction of effect. For these SNPs, we combined data from the case-unaffected sibling pair (tier 1) and case-unrelated control pair (tier 2) samples and employed a liberalization of the sibling transmission/disequilibrium test to calculate odds ratios, 95% confidence intervals, and P values. A SNP within the semaphorin 5A gene (SEMA5A) had the lowest combined P value (P=7.62E-6). The protein encoded by this gene plays an important role in neurogenesis and in neuronal apoptosis, which is consistent with existing hypotheses regarding PD pathogenesis. A second SNP tagged the PARK11 late-onset PD susceptibility locus (P=1.70E-5). In tier 2b, we also selected for genotyping additional SNPs that were borderline significant (P<.05) in tier 1 but that tested a priori biological and genetic hypotheses regarding susceptibility to PD (n=941 SNPs). In analysis of the combined tier 1 and tier 2b data, the two SNPs with the lowest P values (P=9.07E-6; P=2.96E-5) tagged the PARK10 late-onset PD susceptibility locus. Independent replication across populations will clarify the role of the genomic loci tagged by these SNPs in conferring PD susceptibility. Note: The following instruments were used: 1)clinical assessments form and manual; 2) sibling screening form and manual; 3) unrelated control screening and manual; and 4) risk factors questionnaire and manual. All cases underwent #1, as did sibling controls screening positive (see below). Unrelated controls were not examined. All siblings underwent #2. All unrelated controls underwent #3. All subjects (cases, sibling controls, and unrelated controls) underwent #4. Any publications using the data are to cite the original American Journal of Human Genetics article (Maraganore et al., 2005). Investigators using the data collection instruments are to acknowledge Drs. Maraganore and Rocca, and cite grants ES-10751 and NS-33978.

  Study phs000048

• (Epi)genetic Risk Architectures of Opioid-Dependent Brain

  With nearly 20,000 overdose deaths in 2014 alone, opioid addiction (OA) has emerged as one of the most pressing public health crises in recent US history. One-fifth of individuals who try heroin develop an addiction to opioids. Genetics is a major contributor to OA with an estimated 60% heritability, only somewhat less than schizophrenia (80%) which has recently seen substantial gains in identified underlying genetics. Yet, studies to date have failed to uncover most of the genes that predispose individuals to OA, leaving the overwhelming fraction of OA heritability unexplained. The proposed study takes a novel, integrated "omics-based" strategy to investigate the molecular basis of OA and uncover both genetic and epigenetic factors associated with opioid addiction. The premise for our approach is founded on studies from our labs, and others, implicating regulatory variation in common traits and diseases, including those associated with complex brain phenotypes like addiction. We have collected the largest known cohort of postmortem brains from addicts who overdosed on opioids, along with matched control brains from non-users. From both cases and control specimens, we will isolate cells from 2 regions of the brain closely implicated in the addiction phenotype: the Prefrontal Cortex (PFC) and the Nucleus Accumbens (NAc). In Aim 1, we propose ChIP-seq studies to identify regulatory elements that distinguish cases from controls and define the opioid addiction phenotype. The regulatory differences will be connected to their gene targets through high resolution in situ Hi-C. In Aim 2, we propose QTL-based approaches to identify genetic variants that underlie the regulatory differences (hmQTLs). We also propose eQTL analyses to identify genetic variants that underlie differences in transcript levels between cases and controls. Aim 3 leverages the largest heroin addiction GWAS meta-analysis to date to test the hypothesis that SNPs in regions associated with chromatin and expression differences between cases and controls define novel loci for predisposition to OA. Each Aim has the potential for discovery independent of the others (differential HM, RNAexp, QTLs, and variant-phenotype associations) but their synergy is the most powerful component of the proposed study: identifying regulatory pathways that generate, not only phenotype associations, but hypothesized mechanisms for those associations which can be the focus of new opioid addiction prevention and treatment development.

  Study phs002724

• Region-specific Transcriptome Analysis of the Human Retina and Retinal Pigment Epithelium (RPE)/Choroid

  Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. Reprinted from Whitmore, S.S., Wagner, A.H., DeLuca, A.P., Drack, A.V., Stone, E.M., Tucker, B.A., Zeng, S., Braun, T.A., Mullins, R.F., Scheetz, T.E., 2014. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq. Experimental Eye Research. Used under Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license. Additional RNA sequencing was performed on temporal, macular, nasal, inferior, and superior retina from a fifth subject and is included in this dataset. See original publication for details.

  Study phs001151

• CSER: Clinical Implementation of Carrier Testing Using Next Generation Sequencing (NextGen)

  We will investigate the clinical implementation of genome sequencing (GS) for carrier screening to aid reproductive decision-making in adults. The study is organized into three inter-related Projects. The study population will include women and their partners who receive pre-conception testing. In Project 1, we will conduct a Randomized Clinical Trial to test clinical implementation of WGS compared with usual care. We will integrate WGS results with the electronic medical record (EMR), and measure outcomes from patient and physician perspectives. In Project 2, we will perform whole genome sequencing, including validation and interpretation of the identified variants to identify "actionable variants", meaning variants deemed worthy of reporting. This will include a robust approach using a Return of Results Committee (RORC) for determination of reportable results. In Project 3, we will evaluate the ethical and psychosocial implications of expanded carrier screening using WGS for the return of carrier status and secondary findings, and measure the impact on downstream healthcare utilization and cost. Two groups of women are identified through the electronic medical record. The first group has a clinical carrier screening test, usually Cystic Fibrosis (CF), ordered and completed as part of a preconception planning visit. The second group has a carrier screening test, usually CF, performed during pregnancy, they have delivered their baby and are planning a future pregnancy. Eligible women are randomized to either usual care or genome sequencing (GS). Women randomized into the usual care arm have already received their clinical genetic test. These women will not receive genome sequencing. Women in the GS arm will receive their carrier status results for about 700 gene/condition pairs approximately three months after randomization. If there are results to return, women come in for a genetic counseling session. If there are no results, a letter is sent in the mail. Incidental findings (IF) are returned about one month later. As with the carrier status results, all IF are returned in person, and if there are no results a letter is sent in the mail. If a participant is found to be a carrier of an autosomal recessive condition, her male partner is then eligible and invited to participate in the study and receive GS.

  Study phs000927

• Single Cell RNA Sequencing of Tendon Scar Tissue (Tenolysis)

  This human tenolysis sample was collected as a control (non-diabetic sample) as part of larger study described below.The purpose of the larger study is to define the cellular and molecular environment in tendons, pulleys, synovial sheath, tendon scar tissue, and palmar fascia samples. The samples are isolated from discarded tissues from patients who undergo lower limb amputation surgery, dupuytren's disease, trigger finger release, tenolysis surgery, tenosynovitis surgery, distal biceps tendon repair, common extensor debridement and repair, common flexor debridement and repair, or proximal long head of the biceps tenodesis.The dramatic increase in Type 2 Diabetes Mellitus (T2DM) as part of the obesity epidemic is one of the most pressing health challenges facing the U.S. Type II diabetes results in systemic inflammation and is characterized by metabolic dysfunction including elevated plasma glucose levels (hyperglycemia). There is a clear link between T2DM and musculoskeletal pathologies; T2DM accelerates the progression of osteoarthritis, and increases fracture risk. Moreover, T2DM impairs tendon homeostasis and repair, and increases the risk and severity of tenosynovitis (infection of the tendon and sheath), however there remains a paucity of information regarding the molecular mechanisms of diabetes-induced changes in tendon function. Flexor and extensor tendons facilitate digit range of motion (ROM) and movement of the hand. Tendon gliding can be impaired by tendon fibrosis and an inability to fit within the surrounding synovial sheath, or due to the formation of fibrous adhesions between the tendon and synovial sheath during healing. Fibrosis and increased disorganization of the extracellular matrix are hallmarks of the diabetic hand phenotype observed in T2DM patients. T2DM dramatically affects the baseline function of tendons; up to 50% of diabetic patients experience impaired hand function, including increased rates of tenosynovitis, and carpal tunnel syndrome. In addition to decrements in tendon gliding function, deficits in mechanical properties are also observed, rendering diabetic tendons more susceptible to rupture. Considering that the complication rate of primary flexor tendon repairs is as high as 40% in non-diabetic patients, and that T2DM further impairs tendon healing, it is imperative to understand the cellular and molecular components of diabetic tendinopathy. The study will define the overall cellular and molecular environment in tendon pulleys, palmar fascia, synovial sheath tissue, and scar tissue (tenolysis and tenosynovitis samples) as a function of type II diabetes.

  Study phs004076

• Clinical and Molecular Investigation of Familial CEBPA-mutated Acute Myeloid Leukaemia

  Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) are clonal diseases arising from the sequential acquisition of genetic aberrations in haematopoietic stem cells. Whilst the aetiology is predominantly sporadic, rare reports describe the autosomal dominant inheritance of MDS and AML (familial MDS/AML), often presenting in younger patients (<40 years of age) with a germline mutation in one of three haematopoietic transcription factors: RUNX1, CEBPA and GATA2. The clinical recognition of familial disease can be challenging due to wide variations in phenotype, latency and transmission, complicated further by the patients’ awareness and reporting of affected relatives. Distinct clinical manifestations have however been reported for each genetic subtype and whilst RUNX1 and GATA2 mutations can harbour prolonged dysplastic or cytopenic phases, germline CEBPA mutations universally present with AML de novo. Our group were the first to describe germline CEBPA mutations in 3 related individuals, all of whom developed AML between 10-30 years of age. The initial pedigree together with those described in the intervening period, were predominantly isolated case reports with limited follow up, hence long term outcomes for this group of patients remain poorly defined. This contrasts with CEBPA mutations occurring in 10-15% of sporadic AML with normal karytoype (NK-AML), where double mutations (CEBPAdm, found in approximately 50% of all CEBPA-AML) are considered a unique molecular entity, associated with favourable clinical outcomes. In sporadic and familial CEBPAdm AML, N’ terminal mutations enforce translation of the shorter P30-kDa isoform and are typically accompanied by C’ terminal insertions or deletions (disrupting the DNA-binding and/or Leucine zipper domains). Definition of the full molecular landscape awaits extensive whole exome sequencing, although GATA2 mutations (targeting the Zinc Finger 1, ZF1, domain) have been reported in 20-40% of sporadic CEBPAdm AML and recent targeted resequencing analysis revealed a further association with WT1 mutations. With minimal clinical and molecular information available for familial CEBPA-AML, we are often consulted regarding the management of this unique patient population. To address this need, we have investigated a multi-centre cohort of families with germline CEBPA mutations, providing extended clinical follow up, whole exome profiling of secondary mutations and molecular analysis of relapsed disease.

  Study EGAS00001000949

• Genome_Diversity_in_Africa_Project__Benin

  Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformaticsThis 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 EGAS00001001688

• UK10K RARE COLOBOMA

  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. Ocular coloboma is the most common significant developmental eye defect with an incidence of ~1 in 5,000 live births. It results from failure of optic fissure closure during embryogenesis. The position and extent of the fusion failure dictates the clinical appearance and functional effect. ~30% of coloboma cases are associated with other systemic malformations. These UK10K samples will mostly comprise isolated coloboma cases without systemic involvement (aka non-syndromal coloboma). There is strong evidence from family studies that coloboma has a major genetic component with autosomal dominance being the most common pattern of inheritance. However, many cases are isolated or show complex patterns of familial clustering. The genes responsible for isolated coloboma are largely unknown, but in a small number of families mutations in SHH, CHX10, and PAX6 have been identified indicating marked genetic heterogeneity. Thus in addition to the clinical benefits of achieving a molecular diagnosis there are also major scientific advantages to identifying coloboma genes, as these are likely to provide insights into the complex process of optic fissure closure, that is critical to normal eye development. In the longer term, understanding the molecular basis of the disease may provide clues to therapeutic strategies.For further information with regard to this cohort please contact David Fitzpatrick (david.fitzpatrick@ed.ac.uk).

  Study EGAS00001000127

• HLA-A*3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans

  Based on the prior knowledge of involvement of the human leukocyte antigen locus in Han Chinese patients with carbamazepine-induced Stevens-Johnson syndrome, we imputed the HLA types for each case and control subject from the array of SNPs in the Human610-Quad GWAS platform (NCBI Build 36.1). We then performed a genome-wide association test which included the imputed HLA alleles as markers.

  Study EGAS00000000036

• Identification of Recurrent SMO and BRAF Mutations in Ameloblastomas

  RNA-seq data from two cases of ameloblastoma was analyzed for candidate gene fusions and point mutations. Recurrent point mutations identified in the RNA-seq data, as well as mutations identified with limited panel targeted deep sequencing, were validated as somatic. Expanding to a larger cohort of 28, one of two activating mutations was found in 80% of cases. No recurrent gene fusions events were identified.

  Study phs000739

• RNASeq from PPGL-derived PC12 cell lines cultivated in normoxia and hypoxia conditions.

  PC12 cells derived from rat PPGL were then either continued cultivated in the same normoxia condition (37˚C, 5% CO2 and 21% O2 balanced with N2) or were placed in a hypoxic incubator, that maintained a constant hypoxic environment (37˚C, 5% CO2 and 1% O2 balanced with N2), for different short (12h, 24h, and 48h) or prolonged time (36 days, approximately 860h).

  Study EGAS50000000814

• Identification Of Pathogenic Mutations And Application Of Polygenic Risk Scores In Early-Onset Diabetes Patients

  Maturity-onset Diabetes of the Young (MODY) presents a diagnostic challenge. In this study we investigate the genetic background of Latvian early-onset diabetes patients, using whole-genome sequencing data. Additionally, we investigate the utility of previously published and available type 1 diabetes (T1D) and type 2 diabetes (T2D) polygenic risk scores in differentiating monogenic diabetes (MODY) from T1D and T2D cases.

  Study EGAS50000000991

• SCANDARE ovarian WES data

  SCANDARE (NCT03017573) is a multicentric biobanking study, enrolling adult patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), ovarian and cervical cancer. Tumor tissue and blood samples are collected at several time points during patient's journey, including at diagnosis, post-neoadjuvant chemotherapy in case of neoadjuvant treatment, at surgery, at recurrence and at disease progression following treatment initiated at recurrence. Since its launch in 2017 at Institut Curie, SCANDARE has enabled the longitudinal collection and preservation of samples for in-depth analyses. Here, we describe molecular alterations in 91 frozen samples (n = 53 at baseline, n = 31 Post-NAC, n= 7 Recurrence, and n = 62 germline DNA) from 64 ovarian cancer patients using WES technology, with FASTQ files deposited in the dataset.

  Dataset EGAD50000001658

• 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

• ChIP-seq data in MSC_Pat and EWIma1 (FLI1 & H3K27ac)

  Ewing sarcoma is characterized by pathognomonic translocations fusing most frequently EWSR1 with FLI1 (EF1). In addition, Ewing sarcoma can also display alterations in STAG2, TP53 and CDKN2A (SPC). Starting from Ewing sarcoma derived human mesenchymal stem cells (MSCpat), we recapitulated this translocation and SPC alterations using a CRISPR/cas9 approach and generated a bona fide Ewing sarcoma model (EWIma1) displaying transcriptomic and epigenetic hallmarks of EwS.

  Study EGAS50000001172

• RNA-seq data in hMPC, MSC_Pat and EWIma

  Ewing sarcoma is characterized by pathognomonic translocations fusing most frequently EWSR1 with FLI1 (EF1). In addition, Ewing sarcoma can also display alterations in STAG2, TP53 and CDKN2A (SPC). Starting from Ewing sarcoma derived human mesenchymal stem cells (MSCpat), we recapitulated this translocation and SPC alterations using a CRISPR/cas9 approach and generated a bona fide Ewing sarcoma model (EWIma1) displaying transcriptomic and epigenetic hallmarks of EwS.

  Study EGAS50000001173

• SCANDARE TNBC transcriptomics data

  SCANDARE (NCT03017573) is a multicentric biobanking study, enrolling adult patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), ovarian and cervical cancer. Tumor tissue and blood samples are collected at several time points during patient's journey, including at diagnosis, post-neoadjuvant chemotherapy in case of neoadjuvant treatment, at surgery, at recurrence and at disease progression following treatment initiated at recurrence. Since its launch in 2017 at Institut Curie, SCANDARE has enabled the longitudinal collection and preservation of samples for in-depth analyses. Here, we describe molecular alterations in 124 frozen samples (n=84 at baseline and n=40 paired at post-NAC surgery) from 91 TNBC patients using total RNAseq technology, with FASTQ files deposited in the dataset.

  Dataset EGAD50000001416

• Demographic History and Local Adaptation in Asian Population

  Due to harboring high genetic and cultural diversity of populations, Central Asia is one key area for understanding the recent evolutionary history of humans. In this project, our aims include: (1) to resequence genome sequences with high sequencing depth for Central Asian populations Balti; (2) to discern the genomic diversity, populations structure and demographic history of Balti; (3) to investigate the genetic mechanisms for local adaptations in Balti.

  Study JGAS000238

• Study of the role of aneuploidy in cB-ALL

  We modeled two proposed routes to hyperdiploidy, chromosome missegregation and cytokinesis failure, by transiently exposing human fetal liver–derived HSPCs to reversine or cytochalasin-D. Induced hyperdiploidy impaired fitness and delayed differentiation in vitro, causing hyperdiploid cells to be rapidly outcompeted by euploid counterparts. Nonetheless, hyperdiploid cells engrafted immunodeficient mice, where rare clones persisted long-term and acquired non-random chromosomal gains frequently observed in cB-ALL.

  Study EGAS50000001613

• Genomic characterization of germ-cell tumors in childhood

  Germ cell tumors (GCTs) are rare neoplasms affecting approximately 3.5% of pediatric patients, with diverse histological subtypes. Despite their low mutational burden, prevalent alterations in KIT, KRAS, and NRAS genes are observed, but molecular understanding of pediatric GCTs lags behind adult counterparts. We aimed to elucidate the genomic landscape of 16 pediatric GCT patients via whole exome sequencing (WES), which revealed somatic alterations resembling those in adult GCTs.

  Study EGAS50000000619

• HG Transcriptome sequencing in the INTERVAL cohort

  We performed bulk RNA-sequencing on peripheral blood collected from 4,732 blood donors recruited as part of the INTERVAL study. Using these data, we mapped gene expression and splicing quantitative trait loci (QTLs). Then, we integrated these data with protein, metabolite and lipid QTLs in the same individuals. The study aimed to identify the shared genetic etiology across transcriptional phenotypes, molecular traits and health outcomes in humans.

  Study EGAS00001003346

• Analysis of tumor periphery and center-specific mutations in renal cell carcinoma

  Renal cell carcinoma (RCC) is a genomically heterogeneous tumor. In the present project, the question whether intratumoral heterogeneity follows a zonal pattern indicating spatial niches was addressed. Whole exome sequencing of 16 paired samples from tumor periphery and center revealed a number of region-specific functional SNVs and Indels. Therefore, RCCs are not composed of evenly admixed tumor cells but show topological differences in their clonal composition.

  Study EGAS00001001784

• Summary statistics of meta-analysis using two genome-wide association study of inflammatory bowel disease in Koreans.

  Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gastrointestinal tract, is thought to develop due to dysregulated mucosal immune responses to gut flora in genetically susceptible individuals. Crohn’s disease (CD) and ulcerative colitis (UC) are the two major subtypes of IBD. To identify additional susceptibility loci for IBD in Asians, we performed meta-analyses using two genome-wide association studies.

  Study EGAS00001005026