11002 results for "fc points to coins calculator Visit Buyfc26coins.com Bardzo pod wrażeniem jakości usług..UK7B"

in 21.16 milliseconds.

• ICGC Oesophageal adenocarcinoma - pilot samples

  The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett's oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.

  Study EGAS00001000559

• ESGI_Identification_of_novel_genes_and_mechanisms_leading_to_Primary_Ciliary_Dyskinesia

  Approximately 80% of clinically clearly diagnosed patients suffering from primary ciliary dyskinesia (PCD) cannot be assigned to a specific gene defect. Despite extensive research on PCD and despite the increasing number of PCD genes and knowledge about their sites of action as e.g structural component or cytoplasmic pre-assembly factor, the biology of motile cilia and the pathomechanism leading to PCD is largely unknown. The aim of this study is to identify novel PCD related genes and processes relevant for motile cilia function.We will perform exome sequencing, aiming on the analysis of family trios. In these families, the diagnosis of PCD is secured, but the underlying gene defects has so far not been identified.

  Study EGAS00001000523

• Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data

  Genomic translocation events frequently underlie cancer development through generation of gene fusions with oncogenic properties. Identification of such fusion transcripts by transcriptome sequencing might help to discover new potential therapeutic targets. We developed TRUP (Tumor-specimen suited RNA-seq Unified Pipeline (https://github.com/ruping/TRUP), a computational approach that combines split-read and read-pair analysis with de-novo assembly for the identification of chimeric transcripts in cancer specimens. We apply TRUP to RNA-seq data of different tumor types, and find it to be more sensitive than alternative tools in detecting chimeric transcripts, such as secondaryrearrangements in EML4-ALK-positive lung tumors, or recurrent inactivating rearrangements affecting RASSF8.

  Study EGAS00001000659

• ICGC Oesophageal adenocarcinoma - Barrett's samples

  The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.

  Study EGAS00001000726

• TRACERx 100: RRBS data from a subset of the first 100 TRACERx tumours

  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). This study looks at multi-region RRBS data from the TRACERx100 cohort selected for quantity of material available and high tumour purity. RRBS data was collected for 122 tumour regions across 36 patients each with matched normal. A subset of this cohort was used in a sister study looking at tumour neo-antigen promoter methylation status in NSCLC (71 tumour regions across 28 patients for a total of 99 samples).

  Study EGAS00001003484

• Autoimmunity_and_immunodeficiency_COVID19

  Cell Atlas of COVID-19 patients with Pre-existing Autoimmunity and Immunodeficiency conditions COVID-19 disease is characterized by hyperinflammation of the lungs and poor immune response against the virus, leading to acute respiratory distress syndrome. Patients with pre-existing medical conditions strongly correlated with poorer clinical outcomes upon SARS-CoV-2 infection. This study aims to characterize the cellular response to SARS-CoV-2 infection in controls and in patients with primary immunodeficiency and autoimmune disease. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001004489

• Illumina Omni5 SNP chip genotyping of MacTel cases and unaffected controls for a genome-wide association study

  Macular telangiectasia type 2 (MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS). We genotyped 704 samples, of which 678 have consented to be available here. These samples mainly include MacTel cases but also some unaffected controls (often spouses). The samples were collected through the MacTel Project (funded by the Lowy Medical Research Institute), which includes a registry and extensive clinical analysis to confirm the presence of MacTel in affected individuals. Additional controls were obtained from dbGap [phs000429.v1.p1]. After QC steps, the GWAS utilised 476 cases and 1733 controls of European ancestry.

  Study EGAS00001002249

• Understanding_the_multicellular_dynamics_of_clear_cell_renal_cell_carcinoma___visium

  This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to: Generate a focused, comprehensive phylogenetic characterisation of tumour cells Understand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment Quantify the single cellular composition and functional intra- and inter- tumoural heterogeneity Determine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment Investigate the mechanisms by which the tumour-normal interface constrains tumoural growth.

  Study EGAS00001006045

• Case Report: Precision medicine target revealed by in-vitro modelling of relapsed, refractory ALL from a child with neurofibromatosis

  Children with neurofibromatosis have a higher risk of developing juvenile myelomonocytic leukaemia and acute myeloid leukaemia, but rarely develop B-cell acute lymphoblastic leukaemia (B-ALL). Through in-vitro modelling, a novel NF1 p.L2467 frameshift (fs) mutation identified in a relapsed/refractory Ph-like B-ALL patient with neurofibromatosis demonstrated cytokine independence and increased RAS signalling, indicative of leukaemic transformation. Furthermore, these cells were sensitive to the MEK inhibitors trametinib and mirdametinib. Bi-allelic NF1 loss of function may be a contributing factor to relapse and with sensitivity to MEK inhibitors, suggests a novel precision medicine target in the setting of neurofibromatosis patients with B-ALL.

  Study EGAS00001006187

• Reliable assessment of telomere maintenance mechanisms in neuroblastoma

  Telomere maintenance mechanisms (TMM) are a hallmark of high-risk neuroblastoma, and are conferred by activation of telomerase or alternative lengthening of telomeres (ALT). However, detection of TMM is not yet part of the clinical routine, and consensus on TMM detection, especially on ALT assessment, remains to be achieved. We here propose a workflow to reliably detect TMM in neuroblastoma. We show that unambiguous classification is feasible following a stepwise approach that determines both, activation of telomerase and ALT. The workflow proposed in this study can be used in clinical routine and provides a framework to systematically and reliably determine telomere maintenance mechanisms for risk stratification and treatment allocation of neuroblastoma patients.

  Study EGAS00001006510

• Single-cell RNA-seq of peripheral blood mononuclear cells in classic Hodgkin lymphoma

  Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (paired samples from cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors.

  Study EGAS00001007569

• comparing the snRNA-seq from placentas of mothers with or without obesity

  Obesity poses risks to maternal health and increases the likelihood of short- and long-term adverse pregnancy outcomes in the offspring. The placenta, a key organ at the maternal-fetal interface, responds to maternal obesity and regulates fetal growth. To investigate the molecular features of physiological adaptation, we perform single-nuclei RNA-seq on human placentas and compared the transcriptomic profiles of women with obesity delivering appropriate- or large-for-gestational age (i.e., AGA and LGA) babies with those from normal-weight healthy controls with AGA babies. The snRNA-seq libraries were generated with Chromium Single Cell 3’ kit v3.1 (10X Genomics) and sequenced on Illumina NovaSeq 6000 at Novogene.

  Study EGAS50000000834

• Dual spatially resolved transcriptomics for human host-pathogen colocalization studies in FFPE tissue sections

  Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.

  Study EGAS00001006186

• An exome sequencing study of the HIV elite-long term non progressors and rapid progressors (CASCADE cohorts)

  Background: A rare subgroup of HIV infected individuals naturally controls infection without treatment. These ?elite controllers? constitute an important model for the natural control of HIV infection. Indeed, the study of these individuals may provide insights into strategies for the development of HIV vaccines. Although several HLA and chemokine alleles are known to be over-represented in elite controllers, only a small portion of HIV phenotypic variation is explained by known genetic variants. The elite controller phenotype is rare and distinct, representing the extreme of an infectious disease trait. As such, this phenotype may be partly explained by variation in host immune control, which may be characterized by differences in rare functional genetic variants. Genomic regions underlying elite control can be potentially identified by comparing the presence or frequency of variants in this group to that representing the opposite extreme. In this context, ?rapid progressors? is a group defined by its rapid immunological and clinical disease progression. Aim: To extend an existing study, in order to identify DNA sequence variants involved in the control of HIV infection with greater statistical resolution. Specifically, we aim to sequence up to 200 exomes from multiple cohort studies within the EuroCoord CASCADE collaboration (a collaboration of 25 HIV seroconversion cohort studies across Europe).

  Dataset EGAD00001002179

• Whole genome sequencing of 198 epileptic individuals.

  This dataset includes whole genome sequencing of 198 epileptic individuals. Libraries preparation and whole-genome sequencing: gDNA was cleaned up using ZR-96 DNA Clean & ConcentratorTM-5 Kit (Zymo) prior to being quantified using the Quant-iTTM PicoGreen dsDNA Assay Kit (Life Technologies) and its integrity assessed on agarose gels. Libraries were generated using the TruSeq DNA PCR-Free Library Preparation Kit (Illumina) according to the manufacturer’s recommendations. Libraries were quantified using the Quant-iTTM PicoGreen dsDNA Assay Kit (Life Technologies) and the Kapa Illumina GA with Revised Primers-SYBR Fast Universal kit (Kapa Biosystems). Average size fragment was determined using a LabChip GX (PerkinElmer) instrument. The libraries were denatured in 0.05N NaOH and diluted to 8pM using HT1 buffer. The clustering was done on a Illumina cBot and the flowcell was ran on a HiSeq 2500 for 2x125 cycles (paired-end mode) using v4 chemistry and following the manufacturer's instructions. A phiX library was used as a control and mixed with libraries at 0.01 level. Bioinformatics: The Illumina control software was HCS 2.2.58, the real-time analysis program was RTA v. 1.18.64. Program bcl2fastq v1.8.4 was used to demultiplex samples and generate fastq reads. The filtered reads were aligned to reference Homo_sapiens assembly b37. Each readset was aligned to creates a Binary Alignment Map file (.bam).

  Dataset EGAD00001004062

• sWGS of HGSOC samples for fixative comparison study

  Shallow whole-genome sequencing of samples from the study "Methanol-based fixation is superior to buffered formalin for next-generation sequencing of DNA from clinical cancer samples". DNA from each sample (100ng) was sheared on Covaris S220 (Covaris): duty cycle - 10%, intensity -5.0, bursts per sec - 200, duration - 300 sec, mode - frequency sweeping, power - 23V, temperature -5:5 C to 6 C, water level - 13. Libraries were prepared with the TruSeq Nano DNA LT Sample Prep Kit (Illumina) using a modi?ed protocol - Sample Puri?cation Beads were replaced by Agencourt AMPure XP beads (Beckman Coultier) and size selection after the End Repair was done to remove only the short fragments. Quality and quantity for contructed libraries were assessed with DNA 7500 kit on Agilent 2100 Bioanalyzer and with Kapa Quanti?cation kit (KAPA Biosystems) on 7900HT Fast Real-Time PCR System (Applied Biosystems) according to the supplier's recommendations, respectively. Libraries from 18 barcoded samples were pooled together in equimolar amounts and each pool was loaded on a single lane of a HiSeq Single End Flowcell (Illumina), followed by cluster generation on a cBot (Illumina) and sequencing on a HiSeq 2500 (Illumina) in a single-read 50bp mode. Reads were aligned using bwa-mem v0.7.12-r1039 to the 1000 genomes version of human genome build GRCh37. Picard (http://picard.sourceforge.net) was used to remove duplicate reads.

  Dataset EGAD00001001938

• Study of Melanoma Risk in Australia and the United Kingdom

  The results from a small number of melanoma GWAS have been published. Initial studies identified several pigmentation- and nevus-associated loci that mediate an effect on melanoma risk, however, these studies were somewhat limited in that sample number (hence power) was low, they used first-generation low density SNP arrays, or used pools of DNA samples. Subsequently, additional melanoma GWAS have been completed, including a "Phase 2" study by the International Melanoma Genetics Consortium (GenoMEL), a full GWAS of the Australian sample resource previously used in a pooled-DNA GWAS, and study conducted through the MD Anderson Cancer Center and the Brigham and Women's Hospital. The groups who performed these studies have recently shared data and replicated a number of new melanoma susceptibility loci. Aside from the identification of novel loci, there are two additional notable outcomes of these studies. Firstly, an examination of the observed versus expected test statistics (Q-Q plot) from the Australian study, even after removing data from SNPs within known replicated susceptibility loci, reveals that there remains an excess of positive results. Similarly, the latest GenoMEL study finds almost three times as many SNPs reaching p-values between 10-4 and 10-5 as would be expected by chance. In the light of other studies of complex traits [1], these data suggest that studies based on additional melanoma samples from the same population are likely to identify an even larger "polygenic tail" and should prove invaluable in identifying and characterizing the underlying loci. A second observation, is that the effect size for replicated associations differs very little between GWAS. Given the strong effect of ultraviolet radiation (UVR) on risk of melanoma this might be expected to affect penetrance, particularly in the Australian and English samples, which are ethnically similar, but have very different sun exposures. We hypothesize that those SNPs whose effects are strongly mediated by UVR exposure may have smaller marginal effects on risk and are therefore harder to detect initially, suggesting a whole category of genetic effects that are unexplored.Indeed, most melanoma GWAS performed to date used samples from both European and Australian populations in discovery and or replication, and thus, existing studies have been poorly powered to detect associations with a wide difference in effect between these low- and high-UVR populations. Here, we wish to pursue this hypothesis further and plan to genotype additional cases drawn from the English and Australian populations. This will serve two complementary objectives: firstly, it will greatly increase our collective power to detect additional new melanoma risk alleles; secondly, it will highlight associations that are stronger specifically within the context of either low-UVR or high-UVR exposure environments. We posit that these data will be invaluable, not just for identifying novel melanoma-associated loci, but also for addressing gene-environment interactions. We have available a collection of valuable resources to help fulfill our aims. These include a considerable number of well-characterized and ungenotyped Australian and UK melanoma cases, as well as existing genotype data from sets of Australian and UK cases and population-based controls. We propose the following Specific Aims: To extend our current collective melanoma GWAS by genotyping a large number of additional UK and Australian cases. To jointly analyze these data and identify new melanoma risk loci. To determine whether pre-existing and new melanoma risk alleles show different degrees of association between the English and Australian populations, and assess whether these differences might be due to differences in sunlight exposure.

  Study phs000519

• Bogalusa Heart Study (BHS-BioLINCC)

  Objectives: To investigate the early natural history of cardiovascular disease in a cohort of children and young adults in a biracial, semirural community.Background: The Bogalusa Heart Study has been a long-term epidemiologic study. The investigators have identified and followed black and white participants for nearly 40 years, and have described the incidence and prevalence of biologic and behavioral cardiovascular disease risk factors from childhood through adulthood. Their participation has enabled the study to not only document differences between males and females, but also between blacks and whites. The results from the Bogalusa Heart Study have clearly documented that the genesis of atherosclerosis has its basis in childhood, and that prevention can and must begin at the early ages.The Bogalusa Heart Study had been funded over the years by the Specialized Centers of Research (SCOR) Program. The SCOR program was initiated by NHLBI in 1970 to expedite the development and application of new knowledge essential for improved diagnosis, treatment, and prevention of arteriosclerosis, hypertension, pulmonary disease, and thrombosis. In 1984 a Demonstration and Education Component was added to the parent SCOR of the Bogalusa Heart Study in order to translate the experience gained in epidemiological studies into an intervention study designed to retard the development of cardiovascular risk factors in children. Beginning in 1997, the study was supported by the cooperative agreement mechanism. Participants: The Bogalusa dataset includes 11,796 participants that attended at least one of seven cross-sectional pediatric exams and/or the 1995-96 adult examination. Subjects ranged in age from 3 to 20 years at the pediatric exams and 20-37 at the time of the adult exam. Approximately 6,000 have more than one examination constituting a dynamic cohort. Design: The initial survey in 1973-1974 was restricted to children ages 2 1/2 to 14. A physical examination was conducted and information was collected on anthropometric data, hemoglobin, blood pressure, serum lipids, and health history. Over 3,500 children participated. The second cross-sectional survey of 1976-1977 and subsequent surveys expanded the eligible population to include all children ages 5-17 years. The second survey of over 4,000 children also included information on salt intake, smoking, health beliefs, and attitudes, and for girls ages 8-17, menstrual history and oral contraceptive use. The third survey of over 3,500 participants in 1978-1979 also collected anthropometric measurements on skinfold thickness and two measurements of heart rate. The fourth survey of over 3,300 participants in 1981-1982 added data on alcohol use, Type A behavior, peer networks and dieting habits.The Bogalusa Heart Study continued to use a cross-sectional and longitudinal design with the general cross-sectional survey of approximately 3,700 Bogalusa children ages five to seventeen in 1988-1989 in the sixth screen and additional longitudinal studies to recall children in defined subgroups for more intensive evaluation. Half of the 12,000 participants screened since 1973 had been studied three or more times. The Post High School Study examined young adults ages 21 through 30 who previously were examined as children ages five through fourteen in the first Bogalusa Heart Study screening in 1973-1974. The population included approximately 4,603 young adults originally screened and any other children or adolescents examined for the first time in any subsequent surveys. The cardiovascular phenotypes include obesity, blood pressure, lipids, lipoproteins, apoproteins, homocysteine, glucose-insulin, fibrinogen, plasminogen activator inhibitor-1 and von Willebrand Factor. Environmental risk factors consist of sociodemographic characteristics, tobacco and alcohol use, oral contraception, physical activity, cognitive and physical function, and quality of sleep and diet. Subclinical morbidity includes echo-Doppler measurements of cardiac-carotid structure and function.

  Study phs004173

• Identification of 22 Novel Loci Associated with Susceptibility to Testicular Germ Cell Tumors

  Testicular germ cell tumors (TGCT) are the most common cancers in young men of European ancestry aged 20 to 39 years. The Testicular Cancer Consortium (TECAC) has brought together the largest genome-wise association study (GWAS) study of TGCT to date. We conducted a GWAS of 5,602 cases and 5,006 controls aggregated from 12 locations in the US and Europe. Logistic regression models adjusted for study center and genomic ancestry. Genotypes were imputed against the Human Haplotype Reference Consortium. Meta-analysis was performed to combine GWAS results with summary statistics from five previously published TGCT studies, UK Biobank, deCODE Genetics, and an independent set of cases and controls, for a total of 10,156 cases and 179,683 controls. 22 novel and 45 previously reported loci associated with TGCT surpassed genome-wide significance (p < 5e-08).

  Study phs001349

• Validation of Gene Array to Predict Bacterial Co-infection In Adults Hospitalized with Viral Lower Respiratory Tract Infections (LRTI)

  Accurate tests for microbiologic diagnosis of lower respiratory tract infections (LRTI) are needed. Gene expression profiling of whole blood represents a powerful new approach for analysis of the host response during respiratory infection that can be used to supplement pathogen detection testing. Using qPCR, we prospectively validated the differential expression of 10 genes previously shown to discriminate bacterial and non-bacterial LRTI confirming the utility of this approach. In addition, a novel approach using RNAseq analysis identified 141 genes differentially expressed in LRTI subjects with bacterial infection. Using "pathway-informed" dimension reduction, we identified a novel 11 gene set (selected from lymphocyte, α-linoleic acid metabolism, and IGF regulation pathways) and demonstrated a predictive accuracy for bacterial LRTI (nested CV-AUC=0.87). RNAseq represents a new and an unbiased tool to evaluate host gene expression for the diagnosis of LRTI.

  Study phs001248

• Infant Immune Responses to Early Life Vaccinations

  Infants are vulnerable to life-threatening infections due to an immature immune system. For this reason, vaccinations are provided early in life to increase protection against infectious agents. However, there is a limited understanding on how routine vaccinations alter the different immune cell populations in infants. Here, we profiled peripheral blood mononuclear cells (PBMCs) from six 2-month-old infants at the time of their routine vaccinations. Infants received the standard vaccinations including DTaP (diphtheria, tetanus and acellular pertussis), IPV (inactivated polio vaccine), Hep B (hepatitis B), Hib (Haemophilus influenzae type B), Rotavirus, and PCV13 (pneumococcus conjugate vaccine). Samples were obtained before vaccination, and subsequently around one week, and two-month post-vaccination (n=18 samples). This study sheds light on the dynamic nature of the infant peripheral immune cell transcriptome upon initial routine vaccine exposure. The processed data is available on GEO under GSE204716.

  Study phs002926

• Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin +/- Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-Poor/HER2-Negative Resectable Breast Cancer: DNA Sequencing

  This randomized phase II trial studies how well paclitaxel with or without carboplatin and/or bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. All participants in this study were female. RNA sequencing data from the same patients were published under phs001863. Subject aliases are the same in the two datasets.

  Study phs003801

• Beacon v2 and Federated EGA, part of the GDI project Starter Kit to enable access to genomic and phenotypic data across borders

  The European Genomic Data Infrastructure project has released a ‘Starter Kit’ based on the rare disease and cancer proof-of-concepts from the Beyond 1 Million Genomes (B1MG) project. The Starter Kit, freely available to any interested parties, contains a set of software applications and components co-developed by the 20 GDI nodes and based on open community standards from the Global Alliance for Genomics and Health (GA4GH). Products in the Starter Kit give all countries the technical capability to access synthetic genomic and phenotypic data across borders. The image above shows the full workflow of the GDI Starter Kit user journey. The dotted circles are not included in the Starter Kit yet The EGA’s work is represented in the Starter Kit with Beacon v2 and Federated EGA among the software applications and components. About Beacon v2 Beacon is a protocol for data discovery. This API allows the search of genomic variants and associated information without breaching the datasets privacy. The European Genome-phenome Archive (EGA) is a key contributor to the Beacon v2 Protocol, the Beacon v2 Reference Implementation (B2RI) and the EGA Beacon(s). About Federated EGA The Federated EGA network offers a tool for data storage and sharing. Officially launched in 2022, this network of connected resources enables transnational discovery of and access to human omics data for research, while also respecting jurisdictional data protection regulations. The Federated EGA Onboarding Website contains all the information related to the establishment of a Federated Node.

  Blog beacon-v2-and-federated-ega-part-of-the-gdi-project-starter-kit

• Germline MBD4 Mutations and Predisposition to Uveal Melanoma

  Uveal melanoma (UM) arises from malignant transformation of melanocytes from the uveal tract. This rare tumor has a poor outcome with frequent liver metastases and primary resistance to treatment1. The only strong predisposing condition for UM is the BAP1 tumor predisposition syndrome due to germline BAP1 deleterious mutations. UMs are generally characterized by a very low tumor mutation burden (TMB). However, some UMs display a high level of CpG to TpG mutations associated with MBD4 inactivation. Here, we explored the incidence of germline MBD4 variants in a consecutive series of 1, 099 primary UMs, and identified 8 deleterious MBD4 mutations, an aprox 10-fold increased incidence compared with the general population. These mutations were associated with a high TMB in tested UMs. We thus demonstrated that MBD4 is the second major predisposing gene for UM.

  Study EGAS00001003941

• Network-based systems pharmacology identifies heterogeneity in LCK and BCL2 signaling and differential vulnerability of T-cell acute lymphoblastic leukemia to targeted therapy

  T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy, and novel therapeutics are much needed. Profiling patient leukemia’ drug sensitivities ex vivo, we discovered striking inter-patient variability in T-ALL response to a panel of targeted agents. Applying network-based systems pharmacology analyses, by integrating ex vivo pharmacotyping, bulk and single-cell RNA-seq, genomics, phospho-proteomics, and genome-wide CRISPR screening data, to examine signal circuitry, we identified the pharmacogenomic basis of T-ALL drug response and revealed a therapeutic vulnerability that is directly related to the developmental stage of leukemia cells. In conclusion, our results indicate that heterogeneity in the differentiation of T-ALL drives activation of key signaling pathways in this leukemia, providing unique opportunities for targeted therapy.

  Study EGAS00001004700