14662 results for "PLOS+ONE+Pennsylvania+German+ACS+language+code+pdc+open+access+study"

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• Exome sequencing of early and late passage Patient Derived Xenogratf Tumoroids with matched Patient Derived Xenogratfs and matched normal liver

  The breadth and depth at which cancer models are interrogated contribute to successful translation of drug discovery efforts to the clinic. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, the setting where experimental therapies are typically tested. XENTURION is a unique open-science resource that combines a platform of 129 PDX models and a sister platform of 129 matched PDX-derived tumoroids (PDXTs) from patients with metastatic CRC, with accompanying multidimensional molecular and therapeutic characterization. In this specific dataset we focused our attention on early (passage 3) and late (passage 8-12) PDXTs with their matched PDXs and normal liver

  Dataset EGAD50000000266

• Exome sequencing of primary and relapse neuroblastoma

  In this dataset, 16 trios- primary tumor, relapse and corresponding normals- for patients with neuroblastoma are provided. For one patient, more than one relapse was available for the analyses.

  Dataset EGAD00001001607

• NHLBI TOPMed: Women's Health Initiative (WHI)

  This is Whole Genome Sequencing data from the TOPMed participation of the Women's Health Initiative. Approximately 11,100 subjects were involved in this study: approximately 1,100 cases of VTE, 4,000 cases of ischemic stroke, 900 cases of hemorrhagic stroke, and 5,100 controls. Summary level phenotypes for the WHI Cohort study participants can be viewed at the top-level study page phs000200 WHI Cohort. Individual level phenotype data and molecular data for all WHI top-level study and substudies are available by requesting Authorized Access to the WHI Cohort study phs000200.

  Study phs001237

• using-ega-account

  Using your EGA account The purpose of this page is to help you access and download the data you have been granted permission to view through your EGA account. To obtain an EGA account please register here. Once your account is created, you can find details on how to manage your EGA account here. EGA access policy (New account holders please read) Access to EGA services are only provided to EGA account holders. EGA accounts are created, updated and closed upon direct instruction from the relevant DAC contact, using the EGA account management tools or through EGA Helpdesk. As part of the EGA account creation process, the EGA account holder must reset their password when instructed. Password resets are checked and verified usually within 24 business hours, during which time the EGA account is inaccessible. EGA accounts are assigned on an individual basis for the exclusive use of the registered EGA account holder; log-in details must remain private and only be used by the EGA account holder. Controlled access data files are only provided, in accordance to the permissions set by the DAC, to EGA account holders. EGA controlled access data files are encrypted prior to download and must be decrypted on the EGA account holders side. EGA account holders are provided access to the EGA download streamer to download access approved datasets and files therein. The EGA download streamer represents the primary means for the EGA account holder to download access approved datasets and files therein. EGA account holders may be provided with an EGA download account for accessing approved datasets and files therein, using FTP or Aspera in response to clearly defined technical reasons, which may restrict the use of the EGA download streamer. It is the sole responsibility of the EGA account holder to ensure full compliance to all terms and conditions of the Data Access Agreement are met once data is downloaded from the EGA. Should you move institute you must contact all Data Access Committee's contacts to update your details and, if necessary, re-apply for data access. The Data Access Agreement (DAA) is a contract made between the DAC and the EGA account holder; the EGA is not responsible for enforcing the DAA. EGA reserves the right to place EGA accounts 'onhold', pending DAC approval to re-activate, should EGA account 'misuse' be suspected. Further information Introduction to the EGA Frequently Asked Questions Subscribe to the EGA mailing list

  Documentation using-ega-account

• Using your EGA account

  Using your EGA account The purpose of this page is to help you access and download the data you have been granted permission to view through your EGA account. To obtain an EGA account please register here. Once your account is created, you can find details on how to manage your EGA account here. EGA access policy (New account holders please read) Access to EGA services are only provided to EGA account holders. EGA accounts are created, updated and closed upon direct instruction from the relevant DAC contact, using the EGA account management tools or through EGA Helpdesk. As part of the EGA account creation process, the EGA account holder must reset their password when instructed. Password resets are checked and verified usually within 24 business hours, during which time the EGA account is inaccessible. EGA accounts are assigned on an individual basis for the exclusive use of the registered EGA account holder; log-in details must remain private and only be used by the EGA account holder. Controlled access data files are only provided, in accordance to the permissions set by the DAC, to EGA account holders. EGA controlled access data files are encrypted prior to download and must be decrypted on the EGA account holders side. EGA account holders are provided access to the EGA download streamer to download access approved datasets and files therein. The EGA download streamer represents the primary means for the EGA account holder to download access approved datasets and files therein. EGA account holders may be provided with an EGA download account for accessing approved datasets and files therein, using FTP or Aspera in response to clearly defined technical reasons, which may restrict the use of the EGA download streamer. It is the sole responsibility of the EGA account holder to ensure full compliance to all terms and conditions of the Data Access Agreement are met once data is downloaded from the EGA. Should you move institute you must contact all Data Access Committee's contacts to update your details and, if necessary, re-apply for data access. The Data Access Agreement (DAA) is a contract made between the DAC and the EGA account holder; the EGA is not responsible for enforcing the DAA. EGA reserves the right to place EGA accounts 'onhold', pending DAC approval to re-activate, should EGA account 'misuse' be suspected. Further information Introduction to the EGA Frequently Asked Questions Subscribe to the EGA mailing list

  Documentation download/using_ega_account

• Single-cell ATAC-seq analysis for COVID19 patients

  While SARS-CoV-2 infection causes mild respiratory disease in most individuals, a small group of patients develops severe COVID-19. Dysfunctional innate immune responses have been identified to contribute to differences in COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell epigenetics, transcriptomic, and genetics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified 41.3% of significantly up-regulated genes in hospitalized COVID-19 patients potentially induced by differential chromatin accessibility. Sub-clustering and motif-enrichment analyses of monocytes reveal disease condition-specific regulation by transcription factors, such as C/EBPs and SPI1, and their targets, including a long-noncoding RNA LUCAT1, which further regulates interferon responses and is associated with the need for oxygen supply of COVID-19 patients. The interaction between C/EBPs and LUCAT1 was validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (ASoC) in promoters/enhancers of COVID-19 patients. Integrating our data with publicly available expression quantitative trait loci and chromosomal interactions indicates that ASoC SNP rs6800484-C is associated with lower expression of CCR2, which may contributeto higher viral loads in lungs and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to the innate immune responses of different COVID-19 patients.

  Study EGAS00001006559

• Single-cell RNA-seq analysis for COVID19 patients

  While SARS-CoV-2 infection causes mild respiratory disease in most individuals, a small group of patients develops severe COVID-19. Dysfunctional innate immune responses have been identified to contribute to differences in COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell epigenetics, transcriptomic, and genetics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified 41.3% of significantly up-regulated genes in hospitalized COVID-19 patients potentially induced by differential chromatin accessibility. Sub-clustering and motif-enrichment analyses of monocytes reveal disease condition-specific regulation by transcription factors, such as C/EBPs and SPI1, and their targets, including a long-noncoding RNA LUCAT1, which further regulates interferon responses and is associated with the need for oxygen supply of COVID-19 patients. The interaction between C/EBPs and LUCAT1 was validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (ASoC) in promoters/enhancers of COVID-19 patients. Integrating our data with publicly available expression quantitative trait loci and chromosomal interactions indicates that ASoC SNP rs6800484-C is associated with lower expression of CCR2, which may contributeto higher viral loads in lungs and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to the innate immune responses of different COVID-19 patients.

  Study EGAS00001006560

• Bruno et al.: Interferon gamma rebalances immunopathological signatures in Chronic Granulomatous Disease through metabolic rewiring

  Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent life-threatening infections and hyperinflammatory complications. It is caused by mutations in the NADPH oxidase complex and the consequent loss of reactive oxygen species (ROS) production. Recombinant human interferon gamma (rIFN-γ) prophylaxis reduces the risk of severe infections, but the mechanisms behind its efficacy in CGD are still an open question, as it does not restore NADPH oxidase-dependent ROS production. Here, we show that myeloid innate immune cells of CGD patients are transcriptionally and functionally reprogrammed to a hyperactive inflammatory status, displaying an impaired in vitro induction of trained immunity. CGD monocytes have reduced intracellular amino acids concentrations and profound functional metabolic defects, both at the level of glycolysis and mitochondrial respiration. Ex vivo and in vivo treatment with IFN-γ restored these metabolic defects and reduced excessive IL-1β and IL-6 production in response to fungal stimuli in CGD monocytes. These data suggest that prophylactic rIFNγ modulates the metabolic status of innate immune cells in CGD. These data shed light on the effects of NADPH-derived ROS deficiency to the metabolic programs of immune cells and pose the basis for targeting this immunometabolic axis, potentially beyond CGD, with IFN-γ immunotherapy.

  Study EGAS00001005463

• Host pathogen interaction long read transcriptome

  Our incomplete knowledge of the human transcriptome impairs the detection of disease-causing variants, in particular in transcripts only expressed under certain conditions. These transcripts are often lacking from reference transcript sets, such as Ensembl/GENCODE and RefSeq, and could be relevant for establishing genetic diagnoses. We present SUsPECT (Solving Unsolved Patient Exomes/gEnomes using Custom Transcriptomes), a pipeline based on the Ensembl Variant Effect Predictor (VEP) to predict variant impact on custom transcript sets, such as those generated by long-read RNA-sequencing, for downstream prioritization. Our pipeline predicts the functional consequence and likely deleteriousness scores for missense variants in the context of novel open reading frames predicted from any transcriptome. We demonstrate the utility of SUsPECT by uncovering potential mutational mechanisms of pathogenic variants in ClinVar that are predicted to be benign using the reference transcript annotation. In further support of SUsPECT’s utility, we identified an enrichment of immune-related variants predicted to have a more severe molecular consequence when annotating with a newly generated transcriptome from stimulated immune cells instead of the reference transcriptome. Our pipeline outputs crucial information for further prioritization of potentially disease-causing variants for any disease and will become increasingly useful as more long-read RNA sequencing datasets become available.

  Study EGAS00001006779

• Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients

  Despite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequencing of viral samples from patients chronically infected with HBV to investigate the association between viral genome variation and patients’ clinical characteristics. We discovered novel viral variants strongly associated with viral load and HBeAg status. Patients with viral variants C1817T and A1838G had viral loads nearly three orders of magnitude lower than patients without those variants. These patients consequently experienced earlier viral suppression while on treatment. Furthermore, we identified novel variants that either independently or in combination with precore mutation G1896A were associated with the transition from HBeAg positive to negative phase of infection. These observations are consistent with the hypothesis that mutation of the HBeAg open reading frame is an important factor driving CHB patient’s HBeAg status. This analysis provides a detailed picture of HBV genetic variation in the largest patient cohort to date and highlights the diversity of plausible molecular mechanisms through which viral variation affects clinical phenotype.

  Study EGAS00001003689