534 results for "fccoins trustpilot Visit Buyfc26coins.com Pomocni i przyjaźni pracownicy obsługi klienta..qNQH"

in 27.87 milliseconds.

• Complex-I stratification of Parkinson's disease - single nucleus RNAseq

  Single nucleus RNA seq dataset for CI stratification of Parkinson's disease Single nucleus RNA seq dataset of prefrontal cortex tissue from a total of N=18 samples. Tissue samples correspond to patients with idiopathic Parkison's disease (PD) with varying levels of Complex-I activity (N=12) and neurologically healthy controls (N=6). Single nucleus RNA seq was carried out using 10X Genomics Chromium. This dataset corresponds to a subset of the samples sequenced using conventional bulk tissue RNA seq and available within this Study as a separate Dataset.

  Dataset EGAD50000000432

• Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation

  Presurgical studies allow study of the relationship between mutations and response of estrogen receptor positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in Phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 Controls). In poor responders (based on Ki67 change) we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores   occur in approximately 30% of tumours. In Phase II we combine targeted sequencing on another 28 treated patients with Phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.

  Study EGAS00001001940

• Colon cancer ctDNA

  Samples prepared using Safe-SeqS technology. All samples ran on an Illumina MiSeq instrument. Fastq files for read 1 and the index read present (R and I respectively).

  Dataset EGAD00001003579

• Women's Interagency HIV Study (WIHS)

  The Women's Interagency HIV Study (WIHS), a multicenter, prospective study, was established in August 1993 to carry out comprehensive investigations of the impact of HIV infection and its clinical, laboratory, and psychosocial effects in women. The purpose of this study is to collect and evaluate these data from HIV infected and at-risk women to better understand and provide support for women whom are currently HIV infected or who are at risk for HIV infection. Participants will have study visits every 6 months. Questionnaires regarding sexual behavior, health care utilization, medical and obstetric/gynecological history, psychosocial factors, and sociodemographics will be completed by participants. Physical, gynecological, and lipodystrophy examinations will also be conducted at each visit, and current medication regimen will be noted. Blood and other bodily fluid samples will be collected and registered in both local and national repositories of the WIHS in conjunction with NIAID.

  Study phs001503

• Longitudinal Study of Vaginal Flora

  This prospective observational study aims to advance our knowledge of the natural history and abnormal alteration in vaginal microbial flora, and to identify risk factors that are associated with these changes. A total of 5500 healthy, non-pregnant women of reproductive age will be enrolled and followed up in Birmingham, Alabama, for one year (baseline visit plus once every three months afterwards, totaling 5 visits). Detailed information on sociodemographic status, medical history, hygiene practice, sexual behavior and psychosocial stress will be collected through in-person interviews. Routine gynecological and dental examinations will be carried out during the study visits. Samples of vaginal secretion and blood will be collected. Laboratory tests to quantify vaginal microbial flora and to identify infection of bacterial vaginosis as well as common sexually transmitted diseases will be conducted. Future submissions may contain metadata or molecular data from additional subjects.

  Study phs002367

• Stress and Treatment Response in Puerto Rican and African American Children with Asthma (STAR)

  The Stress and Treatment Response in Puerto Rican and African American Children with Asthma Study (STAR) was a 6-week study of response to inhaled corticosteroids (ICS) in youth aged 8-20 years recruited at the University of Puerto Rico Medical Center and UPMC Children's Hospital of Pittsburgh from June 5, 2018 to May 16, 2022. At a baseline visit, participants completed questionnaires and underwent collection of nasal specimens. After nasal sampling, participants were treated with daily medium-dose inhaled Mometasone for 6 weeks, with adherence measured using a dose-counter. Spirometry and fractional exhaled nitric oxide (FeNO) measurements were conducted at baseline and after 6 weeks of ICS. STAR was approved by the institutional review boards (IRBs) of the University of Puerto Rico and the University of Pittsburgh. Written parental consent and assent were obtained from participants

  Study phs004052

• Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE)

  The STRRIDE study is the combination of three interventional trials to evaluate dose and intensity of physical activity on cardiometabolic health. The three component studies are Peripheral Effects of Exercise on Cardiovascular Health (STRRIDE I, ClinicalTrials.gov Identifier: NCT00200993), Effects of Resistence and Aerobic Exercise on Cardiovascular Health (STRRIDE II, ClinicalTrials.gov Identifier: NCT00275145) and Exercise Dose-Response Effects in Prediabetes (STRRIDE-PD, ClinicalTrials.gov Identifier: NCT00962962).

  Study phs001855

• ctDNA raw data (BAMs)

  Raw data of ctDNA profiling using the PredicineWES+ or PredicineBEACON assay in patients enrolled in divarasib phase I GO42144 study.

  Dataset EGAD50000000530

• N2M2 methylation array data

  Methylation profiling of 228 samples, using the approach described in "Molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation (N2M2/NOA-20 phase I/IIa umbrella trial)"

  Dataset EGAD00010002747

• irCLIP library generated from HEK293 cells overexpressing 3FLAG-RIG-I gain-of-function variant C268F

  irCLIP library generated from HEK293 cells transfected with either RIG-IWT or RIG-IC268F (n=3).

  Dataset EGAD50000002390

• Integrated Molecular Profilting in Advanced Cancers Trial

  The present protocol seeks to provide molecular profiling data to the treating physician for patients with advanced breast, non-small cell lung, colorectal, genitourinary, pancreatobiliary gastrointestinal, upper aerodigestive tract, gynecological, melanoma, unknown primary, and rare carcinomas, as well as patients who are phase I trial candidates, in order to help identify which standard regimens or clinical trials of molecularly targeted therapies may be most appropriate for the individual patient.

  Study EGAS00001001897

• We evaluate the PGD/PGS including 129 couples with NGS test and 266 couples with SNP-array test for the detection of embryonic chromosomal abnormalities.

  A total of 395 couples were subjected to IVF-PGD treatment, including 129 couples with NGS test and 266 couples with SNP-array test for the detection of embryonic chromosomal abnormalities. The NGS test was performed using low coverage whole genome sequencing with HiSeq 2000 platform. And the SNP array test was using Affymetrix Gene Chip Mapping Nsp I 262K.

  Study EGAS00001000981

• Dac for "Molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation (N2M2/NOA-20 phase I/IIa umbrella trial)" with PD Dr. med. Tobias Kessler, t.kessler@dkfz.de/ Prof. Dr. med. Wolfgang Wick, wolfgang.wick@med.uni-heidelberg.de

  Dac EGAC00001003521

• Heart Failure Network - Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (HFN EXACT-BioLINCC)

  ObjectivesTo determine the effect of allopurinol after 24 weeks on a composite clinical endpoint that classifies subject's clinical status (improved, worsened, unchanged) in patients with heart failure and high uric acid levels.BackgroundMorbidity and mortality rates for patients with heart failure are high, despite guideline-recommended therapy. Heart failure is characterized by an imbalance between left ventricular (LV) performance and myocardial energy consumption. There is a growing body of evidence that suggests oxidative stress contributes to ventricular and vascular remodeling, and disease progression in heart failure. Targeting potential source(s) of oxidative stress, e.g. Xanthine oxidase (XO), was the focus of recent clinical trials and epidemiological studies. Increased XO activity has been shown to lead to production of superoxide and uric acid (UA). Serum uric acid levels are included in heart failure risk scores, and hyperuricemia is present in about 25% of patients with heart failure. Hyperuricemia is associated with exercise intolerance, reduced survival, and worsening symptoms. The EXACT-HF trial tested allopurinol, an inhibitor of XO, as a potential target therapy for hyperuricemic heart failure patients.Subjects253 subjects were enrolled in the EXACT-HF study. 128 participants were randomized to the allopurinol arm, and of those participants, 119 completed the trial and 9 did not. 125 participants were randomized to the placebo arm, and of those participants, 116 completed the trial and 9 did not.DesignEXACT-HF was a multi-center, double-blind, placebo controlled, 24-week trial of allopurinol. Eligible participants had to be receiving a stable regimen for at least two weeks (3 months for beta-blockers) prior to randomization. Participants were randomized by an automated system to either the allopurinol or placebo arm, and started treatment within 12 hours of completing the baseline visit. During the first week, participants in both treatment arms received 300mg daily of the respective medications. For the following 23 weeks, participants in both treatment arms received 600mg daily of the respective medications. Patients unable to tolerate 600 mg were maintained on 300 mg.The primary endpoint was a composite clinical endpoint (CCE) that classified a subject's clinical status as improved, worsened, or unchanged at 24 weeks. The CCE was determined based on the following: death; hospitalization, emergency room visit or emergent clinic visit for worsening HF; medication change for worsening HF; and Patient Global Assessment using a 7-point scale. Secondary endpoints at 12 and 24 weeks included changes in quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire, and submaximal exercise capacity as assessed by a 6-minute walk test.ConclusionsParticipants who received allopurinol had significantly less serum uric acid laboratory levels after 24 weeks; however, no significant difference was observed in the primary and secondary endpoints between the allopurinol and placebo-treated patients. Therefore, in high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or LVEF at 24 weeks (Circulation. 2015 May 19; 131(20):1763-71).

  Study phs003533

• Idiopathic Pulmonary Fibrosis Network (IPFNet) Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (IPFNet-STEP-IPF-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: The STEP-IPF study sought to evaluate whether treatment with sildenafil would improve walk distance, dyspnea, and quality of life in participants with advanced idiopathic pulmonary fibrosis (IPF).Background: IPF is a chronic, progressive lung disease of unknown cause that is characterized by the histopathologic pattern of usual interstitial pneumonia. Progression to end-stage respiratory insufficiency and death within 5 years after the onset of symptoms is characteristic. To date, no pharmacologic therapies have definitively been shown to improve survival or quality of life in participants with this disease.Participants with severe IPF have abnormalities of the pulmonary vasculature leading to decreased levels of resting and exercise-induced production of nitric oxide. Since nitric oxide is a potent pulmonary vasodilator, reduced levels are associated with pulmonary vasoconstriction and impaired gas exchange. Sildenafil (Revatio, Pfizer) is a phosphodiesterase-5 inhibitor that stabilizes the second messenger of nitric oxide, cyclic guanosine monophosphate, which leads to pulmonary vasodilatation. Such vasodilatation could improve ventilation–perfusion matching and thus gas exchange in with IPF.Design: STEP-IPF was a double-blind, randomized, placebo-controlled trial of oral sildenafil (20 mg three times daily). Participants meeting eligibility criteria were randomly assigned in a 1:1 ratio to receive sildenafil or matched placebo with the use of a permuted-block design, with stratification according to clinical center. The primary outcome was the presence or absence of an improvement of at least 20% in the 6-minute walk distance at 12 weeks, as compared with baseline. Key secondary outcomes included changes in the 6-minute walk distance, degree of dyspnea, and quality of life.Screening procedures included the taking of a detailed history, a physical examination, spirometry, echocardiography, CT imaging, and measurements of lung volume on plethysmography, carbon monoxide diffusion capacity, and arterial blood gases. Eligible participants returned for an enrollment visit within 6 weeks after screening. All participants received an initial dose of a study drug at this visit and were monitored for 60 minutes for adverse effects. Follow-up visits were scheduled at 1, 6, and 12 weeks. After completion of the 12-week visit, all participants were started on treatment with open-label sildenafil. Visits were scheduled at 13, 18, and 24 weeks; at 28 weeks, serious adverse events and vital status were documented. Testing of the 6-minute walk distance was performed with the use of a standardized protocol at the time of screening and enrollment and at study visits at 6, 12, 18, and 24 weeks. Participants with pulse oxygen saturation below 88% received supplemental oxygen. Conclusions: This study did not show a benefit for sildenafil for the primary outcome. The presence of some positive secondary outcomes creates clinical equipoise for further research. There were small but significant differences in arterial oxygenation, carbon monoxide diffusion capacity, degree of dyspnea, and quality of life favoring the sildenafil group.

  Study phs004085

• A Pharmcogenetic Study of Bipolar Disorder in a Taiwanese Han Chinese Population (TWBP)

  Objective: To identify genetic variants associated with response to lithium prophylaxis treatment. Materials: 294 bipolar I (BPI) patients receiving lithium treatment, a subset of 1761 bipolar I (BPI) patients recruited by the Taiwan Bipolar Consortium. Lithium response was assessed based on the Alda Scale. Methods: Responders to lithium treatment were defined if the patients' Alda Scale > 4, 5, 6, and 7. Genome-wide association (GWA) analysis was carried out on the 294 BPI patients for the 4 definitions of responders. The SNPs showing strongest association in the GWAS were then tested for association in a replication sample of 100 patients and further tested in a prospective follow-up series of 24 patients. Results: Two SNPs on GADL1 showed the strongest associations in the four GWA analyses and in the replication set of 100 patients. These two SNPs had a sensitivity of 0.93 for predicting lithium response and differentiated between the good and poor responders in the follow-up cohort. Summary: These genetic variants are associated with response to lithium prophylaxis treatment for BPI.

  Study phs000692

• The Innate Immune Response as a Therapeutic Target for Cutaneous Leishmaniasis

  The overall goal of the proposed project is to identify innate host functions that contribute to cure or failure during antileishmanial drug therapy, and their related biomarkers. Results from this project enabled the identification of host-specific predictive and prognostic signatures of therapeutic responsiveness, and the bases for rational selection of host-targeted therapeutics that redirect inflammation and revert pathogenicity. Through sequential transcriptomic profiling of blood monocytes (Mo), neutrophils (Nφ), and eosinophils (Eφ) over the course of systemic treatment with meglumine antimoniate, we discovered that a heightened and sustained Type I interferon (IFN) response signature is a hallmark of treatment failure (TF) in Cutaneous Leishmaniasis (CL) patients. The transcriptomes of pre-treatment, mid-treatment and end-of-treatment samples were interrogated to identify predictive and prognostic biomarkers of TF. Results from this study instigate the evaluation of Type-I IFN responses as new immunological targets for host-directed therapies for treatment of CL, and highlight the feasibility of using transcriptional signatures as predictive biomarkers of outcome for therapeutic decision making.

  Study phs003545

• Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors

  Large-cell neuroendocrine lung carcinomas (LCNEC) have similarities with other lung cancers, but their precise relationship has remained unclear. We conducted comprehensive genomic (n=60) and transcriptomic (n=69) analyses of 75 LCNECs and identified two molecular subgroups: “type I LCNECs” with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and “type II LCNECs” enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/NOTCHhigh and upregulation of immune-related pathways. In conclusion, LCNECs are comprised of two molecularly defined subgroups, and distinguishing them from SCLC may allow for stratified targeted treatments for high-grade neuroendocrine lung tumors.

  Study EGAS00001000708

• Interferon lambda 4 impairs viral antigen presentation and attenuates T cell responses

  Genetic variants of the interferon lambda (IFNL) gene locus are strongly associated with spontaneous and IFN treatment induced clearance of hepatitis C virus (HCV) infections. Individuals with the ancestral IFNL4-dG allele are not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. Paradoxically, the IFNL4-dG allele encodes a fully functional IFNλ4 protein with antiviral activity against HCV and coronavirus. Here we describe a hitherto unknown effect of IFNλ4 on HCV antigen presentation. Only minor amounts of IFNλ4 are secreted, because the protein is largely retained in the endoplasmic reticulum (ER) where it induces ER stress. Stressed cells were significantly weaker activators of HCV specific CD8+ T cells. This was not due to reduced MHC I surface presentation or extracellular IFNλ4 effects, since T cell responses could be restored by exogenous loading of MHC with HCV antigens. Rather, IFNλ4 induced ER stress impaired HCV antigen processing and/or loading onto the MHC I complex. Our results provide a potential explanation for the IFNλ4 – HCV paradox.

  Study EGAS00001005396

• A Phase I/II Trial of T Cell Receptor Gene Therapy Targeting HPV-16 E7 for HPV-Associated Cancers

  This is a phase I clinical trial testing the safety and efficacy of gene-engineered T cells expressing a T-cell receptor targeting an HLA-A*02:01-restricted epitope of HPV-16 E7 (E7 TCR T cells) in patients with metastatic HPV-16+ epithelial cancers. A total of 12 patients were treated. The maximum tested dose was tolerated. Side effects were most consistent with the expected toxicities of the lymphocyte-depleting conditioning regimen and high-dose aldesleukin. Six of the 12 patients demonstrated objective clinical responses. Translational studies of the infused T cell characteristics did not correlate strongly with clinical response. Genomic defects in the targeted peptide-HLA complex did demonstrate definitive mechanisms of resistance in some patients.

  Study phs002286

• Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

  Mechanisms of acquired resistance to immune checkpoint inhibitors (ICIs) are poorly understood. The purpose of this study was to investigate whether alterations in genes encoding components of the HLA Class I antigen processing and presentation machinery or interferon signaling pathways play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Whole exome sequencing was performed on tumor samples collected from patients with advanced non-small cell lung cancer at the time of resistance to PD-1 axis inhibitors and on available matched pre-treatment and normal samples. Patient-derived xenografts successfully established from the ICI-resistant samples were also exome sequenced. Additionally, RNA sequencing was performed on cases with sufficient tissue.

  Study phs001464

• Very Low Tumor Mutation Burden Identifies Inflamed Recurrent Glioblastomas Responsive to Cancer Immunotherapy

  A subset of available tumors (with matched blood) from patients enrolled in a phase I clinical trial testing a recombinant poliovirus, published by Desjardins et al. NEJM 2018 (PMID:29943666), were analyzed by whole exome sequencing and RNA-seq. It was discovered that low tumor mutation burden correlated with survival outcome, and also discovered that low tumor mutation burden correlated with higher inflammatory gene signatures by RNA-seq.

  Study phs002270

• Myocardial Infarction Genetics Exome Sequencing Consortium: U. of Leicester

  MI cases were ascertained from two studies: (i) the British Heart Foundation Family Heart Study and (ii) the BRICCS Study. Control subjects were ascertained from the control subjects being recruited as part of the UK Aneurysm Growth Study (UKAGS). All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Illumina's ICE Capture reagent and sequencing was performed on an Illumina HiSeq 2000 or 2500.

  Study phs001000

• Genetic Evaluation of Autoinflammatory Diseases

  Many pediatric patients with early-onset autoinflammatory disease (AID) phenotypes are mutation-negative for genetically known AIDs. Recent data suggest a role for Type-I interferon (IFN) dysregulation in causing AID phenotypes with clinical features that are distinct from those found in patients with IL-1 mediated AIDs. We screened patients for the presence of an IFN-response gene signature (IRS) to characterize their clinical phenotypes, IFN-related biomarkers, and genetic causes.

  Study phs001946

• The cellular state space of AML unveils novel NPM1 subtypes with distinct clinical outcomes and immune evasion properties

  Acute myeloid leukemia (AML) is a genetically and cellularly heterogeneous disease. We characterized 120 AMLs using bulk genomic and transcriptomic analyses (WES, MP-WGS, RNA-seq), and single-cell RNA sequencing (scRNA-seq). Our results reveal an extensive cellular heterogeneity that distorts the bulk transcriptomic profiles. Notably, NPM1 mutated AML could be stratified into two novel, clinically relevant classes (NPM1class I and NPM1class II).

  Study EGAS50000001084

• 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

• WGS FASTQ files studied in Allogeneic induced pluripotent stem (iPS) cell-derived cartilage transplantation for articular cartilage damage in knee joints: a phase I, first-in-human study

  This data set contains 5 paired fastq files (WGS).

  Dataset EGAD50000001666

• Cell-free DNA sequencing data of healthy control, atrophic gastritis, and gastric cancer patients’ blood

  Sample cohort (n=48) is consisted of healthy, atrophic gastritis and gastric cancer patients. Some of the gastric cancer patients samples are collected at the separate time points: -1 before the operation; -2 after the operation; -3 during the control visit. For the hybridisation capture of the genes unique 15 gastric cancer-related gene panel was developed and very deep sequencing using TruSight Oncology Unique Molecular Identifier (UMI) Reagents (Illumina) was used.

  Dataset EGAD00001011153

• Whole genome sequencing of human induced pluripotent stem cells derived from 5 type I cyctic biliary atresia patients

  We have successfully generated a panel of human induced pluripotent stem cells (hiPSCs) from five Japanese patients carrying type I cystic biliary atresia (BA). These hiPSC lines have exhibited characteristics of self-renewal and pluripotency. These cells held normal karyotypes mostly, but one of them carried hemizygous deletions, of which clinical significance is unknown yet. Whole genome sequence analysis indicated that some of the mutations or single nucleotide polymorphisms (SNPs) commonly found in these patients are related to hepatobiliary abnormality. Given the limited understanding of the molecular pathogenesis of cystic BA, attributed to unknown factors of genetic and environmental causes, these cellular resources will be instrumental in replicating disease phenotypes and in the advancement of novel therapies for this condition.

  Study JGAS000765

• Somatic Mutations in 3,929 HPV-Positive Exfoliated Cervical Cell Samples

  We investigated the detection, timing, and HPV type specificity of cervical somatic hotspot mutations (i.e., previously reported cancer driver mutations) in 3,929 HPV-positive exfoliated cervical cell samples from individuals undergoing routine cervical screening in the U.S. using deep-targeted sequencing of 20 candidate genes. Our study included samples from 3,351 women with the following infection outcomes: 1,478 HPV16-, HPV18- and/or HPV45-positive controls (i.e., HPV infections that did not progress to precancer and/or subsequently cleared), 1,712 cervical precancers, and 161 invasive cervical cancers. We utilized residual exfoliated cervical cell samples from women routinely screened for cervical cancer precursors at Kaiser Permanente Northern California (KPNC) as part of the prospective KPNC-NCI HPV Persistence and Progression (PaP) cohort. We included 3,929 samples collected from these 3,351 women, including 974 serial sample from 396 women collected prior to their most recent screening visit to evaluate somatic hotspot mutation detection prior to diagnosis.

  Study phs003691

• The chemotherapeutic CX-5461 is extremely mutagenic and may increase cancer risk

  The chemotherapeutic agent CX-5461 or pidnarulex has been fast-tracked by the US FDA for treatment of BRCA1-, BRCA2-, and PALB2-mutated cancers. It is under investigation in Phase I/II clinical trials. Here we find that although CX-5461 exhibits synthetic lethality in BRCA1-/BRCA2-deficient cells, it also causes extensive, non-selective, collateral mutagenesis in all cells, to magnitudes that exceed known environmental carcinogens, raising public health concerns regarding its potential for promoting secondary cancers.

  Study EGAS50000000023

• Oncogenomics of Malignant Peripheral Nerve Sheath Tumors

  Malignant peripheral nerve sheath tumors (MPNSTs) are a group of highly aggressive soft tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1-associated), or after radiotherapy (RT-associated). We utilized comprehensive genomic approaches and identified recurrent loss-of-function somatic alterations in the Polycomb repressive complex 2 (PRC2) core components EED or SUZ12. Genetic loss of either of these two genes results in complete loss of H3K27me3 and aberrant transcriptional programming in the affected tumors.

  Study phs000792

• Breast Cancer Genome Guided Therapy Study (BEAUTY)

  The Breast Cancer Genome Guided Therapy Study (BEAUTY) is a prospective neoadjuvant clinical study enrolling 140 women with Stage I-III breast cancer. The goals of this study were to 1) perform comprehensive sequencing of germline and tumor tissues (exome and RNA seq), 2) identify genomic alterations and perturbed pathways associated with response/resistance to standard chemotherapy, and 3) develop patient-derived xenograft (PDX) for testing of therapeutic regimens chosen on the basis of alterations identified by genetic sequencing.

  Study phs001050

• High-Throughput and High-Dimensional Single Cell Analysis of Antigen-Specific CD8+ T Cells

  We developed a high-dimensional, tetramer associated T cell receptor sequencing (TetTCR-SeqHD) method to simultaneously profile cognate antigen specificities, TCR sequences, targeted gene-expression, and surface protein expression. Cultured antigen-specific CD8+ T cell clones were studied as a proof-of-concept experiment. In addition, both the antigen specific CD8+ T cells from healthy subjects and Type I diabetic patients were investigated. 18 individually consented subjects pooled into four groups for sample processing

  Study phs002441

• Single cell RNA sequencing of peripheral blood HSPC from patients with sickle cell anemia and healthy donors

  Neutrophils and monocytes are critical contributors to the pathophysiology of sickle cell anemia (SCA) and are persistently elevated in patients' circulation. While chronic hemolysis has been implicated in this leukocytosis, the underlying mechanisms remain incompletely understood. Our data show a myeloid-skewed transcriptional signature in early progenitor populations, including multipotent progenitors (MPPs) and hematopoietic stem cells (HSCs). Notably, we identify upregulation of the type I interferon signaling pathway in HSPCs as a key driver of early myeloid programming in SCA.

  Study EGAS50000001046

• Clonal_expansion_of_mutated_cell_population_in_bladder_urothelium_

  1cm biospies of from patients undergoing bladder cystectomy will be collected. The underlying muscle and stroma will be removed and the remaining epithelia dissected into small sequential areas which will be sent for ultra-deep exome sequencing using a panel of known cancer and viral genes. Sequence analysis using similar methods to Martincorena I et al (Science 2015, 348:880) will provide an idea of the somatic mutational landscape in these patient samples. Individual patient muscle samples will also be sequenced as a reference.

  Study EGAS00001001687

• Illumina RNA sequencing for HLA expression qauntification

  In this study, we quantified mRNA expression levels of HLA class I and II genes from peripheral blood samples of 50 healthy individuals. The gene- and allele-specific mRNA expression was assessed using unique molecular identifiers, which enabled PCR bias removal and calculation of the number of original mRNA transcripts. We identified differences in mRNA expression between different HLA genes and alleles. Our results suggest that HLA alleles are differentially expressed and these differences in expression levels are quantifiable using RNA sequencing technology.

  Study EGAS00001004931

• Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation

  Presurgical studies allow study of the relationship between mutations and response of estrogen receptor positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in Phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 Controls). In poor responders (based on Ki67 change) we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores   occur in approximately 30% of tumours. In Phase II we combine targeted sequencing on another 28 treated patients with Phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.

  Dataset EGAD00001002651

• Single-cell and bulk RNA-sequencing of nivolumab-treated glioblastoma

  Glioblastoma is a highly aggressive type of brain tumour for which there is no curative treatment available. Immunotherapies have shown limited responses in unselected glioblastoma patients, and it is currently not well understood what separates the few responders from the non-responders at the cellular and molecular level. Here we investigate the phenotypic and transcriptional evolutionary dynamics at single-cell resolution during nivolumab immune checkpoint treatment of eight glioblastoma patients enrolled in a translational phase I/II clinical trial.

  Study EGAS00001007110

• Integration of T Cell Repertoire, CyTOF, genotyping and symptomatology data reveals subphenotypic variability in COVID-19 Patients

  A total of 61 patients (33 mild and 28 severe) with a median age of 51 years who recovered from COVID-19 were included in this study (Table 1). All collected samples were confirmed in diagnosis of COVID-19 by RT-PCR and positive IgG serolog. For the 61 patients, TCR-seq, CyTOF, and genotyping data were generated and analyzed in separate studies, as part of larger cohorts. In total, there are 143 variables, with 129 being quantitative (TCRseq and CyTOF metrics) and 13 being qualitative (symptomatology and genotyping). For more information about cohort characteristics, data adquisition an pre-processing, please visit PMID: 39227859, 36969980 and 37287057.

  Dataset EGAD50000000840

• Genomic Characterization CS-MATCH-0007 Arm I

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm I is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with PIK3CA mutations (without KRAS Mutation or PTEN Loss) are treated with Taselisib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002181

• Transcriptomic profiles of tumor samples from patients with stage I-III TNBC treated with anthracycline-taxane chemotherapy plus fasting-mimicking diet plus/minus metformin in the context of the BREAKFAST trial (NCT04248998)

  BREAKFAST is a randomized, non-comparative, phase II trial enrolling stage I-III (cT>1cm) TNBC pts treated with neoadjuvant doxorubicin-cyclophosphamide q3w for 4 cycles, followed by weekly paclitaxel for 12 cycles. Pts were randomized 1:1 to receive: CT + triweekly 5-day FMD cycles (arm A), or CT + FMD + daily metformin (1700 mg) (arm B). The primary study objective was to investigate if one or both experimental treatments were able to increase pCR rates when compared to anthracycline-taxane CT alone according to historical data. Secondary/exploratory endpoints included biomarker analyses based on tumor transcriptomics analyses. Specifically, we collected fresh-frozen tumor samples at baseline and 14-21 days after the first treament cycle and we analyzed the RNA-seq profiles to identify early predictors of treatment activity.

  Study EGAS50000000690

• End motifs analysis of circulating DNA from the plasma of patients with stage II-III breast cancer (n=50), stage I-III non-small cell lung cancer (n=56), metastatic colorectal cancer (mCRC) (n=15) and healthy individuals (n=37)..

  We have developed an algorithm designed to discriminate cancer patients and healthy individuals based on cirDNA fragment end motif analysis assisted by machine learning, using data obtained from shallow whole genome sequencing (a method we call EMA). We applied EMA to cirDNA from the plasma of patients with stage II-III breast cancer, stage I-III non-small cell lung cancer, and metastatic colorectal cancer (mCRC). CirDNA from 158 individuals was prepared following the conventional double-stranded DNA library preparation (DSP). We also performed a single-stranded DNA library preparation (SSP) using mCRC patients and healthy control cirDNA, which allowed us to make the first ever end motif analysis in the literature which compares the use of DSP and SSP.

  Study EGAS50000001319

• Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment

  Whole exome sequencing data from a series of 5 patient derived organoids (PDOs) established from metastatic colorectal cancers (CRCs).

  Dataset EGAD00001005357

• CancerSEEK ctDNA FASTQ files

  Sequencing data from 1,005 cancer patients and 812 healthy controls. All samples prepared using Safe-SeqS technology and sequenced on an Illumina MiSeq and/or HiSeq instrument. Paired FASTQ files for correspond to read 1 and the index read present (R and I respectively).

  Dataset EGAD00001003931

• A Phase I/II Trial of Sirolimus (Rapamune®) and Cyclosporine in Patients with Refractory Aplastic Anemia

  The most successful treatment for aplastic anemia is bone marrow transplantation. However, few patients are eligible for this procedure. For others, treatment usually consists of immunosuppressive agents, such as antithymocyte globulin (ATG) and cyclosporine. Unfortunately, even with immunosuppressive therapy, relapse is common. New combinations of medications may offer alternative and more effective treatment options. Sirolimus and cyclosporine are two drugs routinely used to suppress the immune system and prevent rejection in patients who have received organ transplants. While cyclosporine has been proven effective for treating aplastic anemia, sirolimus has not been tested for this disease. This study will evaluate the safety and efficacy of sirolimus in combination with cyclosporine for treating individuals with aplastic anemia that have not responded to other treatments. This study will last at least 6 months. Participants will first be screened to verify diagnosis of aplastic anemia. The screening will include a physical examination, blood test, bone marrow biopsy from the pelvic bone, and review of medications and medical history. Individuals who are eligible will then start the first treatment period. Participants will receive two medications: cyclosporine will be taken twice a day and sirolimus will be taken once a day. Depending on side effects, the dose of either drug may be temporarily stopped or lowered. On Day 1, blood will be drawn and females will undergo a pregnancy test. Subsequent study visits will occur weekly for the first month, every 2 weeks for 2 months, and then once a month for the remainder of the study. Each visit will include a physical examination, vital sign assessment, and review of side effects and medications. Blood tests will be performed weekly for the first 3 weeks, and then every 2 weeks. After 6 months of treatment, if a participant has shown improvements in disease status without major side effects, the treatment will continue. Over time the doses may be lowered. If a participant has not improved while on the study medication, treatment will stop at 6 months. Whenever treatment is discontinued, the participant will again undergo a physical examination, blood tests, and bone marrow biopsy.

  Study phs000695

• Sickle Cell Disease Natural History Data Resource (SCD NHDR)

  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. BackgroundThe NHLBI initiated the Sickle Cell Disease Natural History Data Resource (SCD NHDR) to leverage existing SCD studies to build a data resource to provide phenotypic data on contemporaneous control cohorts for gene therapy trials and other studies. The potential uses of the NHDR are broad, including providing matched controls for clinical trials, observing a cohort of untreated patients as part of a natural history study, or conducting comparative effectiveness research on a subpopulation with selected co-morbidities or drug treatment profiles. The SCD NHDR includes two multi-center SCD longitudinal cohort studies with extensive annual clinical data and patient surveys, the Sickle Cell Disease Implementation Consortium (SCDIC-I and SCDIC-II) and the Globin Research Network for Data and Discovery (GRNDaD). The SCDIC-I, initiated in 2017 and concluded in June 2022, enrolled over 2400 patients with SCD from 8 US treatment centers. The SCDIC-II reconsented 1220 of the SCDIC-I patients as well as enrolling an additional 450 new patients from the same 8 centers between September 2022 and October 2023, for a total of 1670 in SCDIC-II. Only two of the many GRNDaD centers are submitting data to the SCD NHDR for deposit into BDC (approximately 122 patients). Data submissions from the SCD NHDR to BDC will be annually starting in early 2024. Description of the Study Data All data obtained for the SCD NHDR are considered common data elements (CDEs) important for studies of SCD. These CDEs were identified from several workgroups of SCD experts convened under the NHLBI's Cure-SC Initiative (https://curesickle.org/cde-catalog). The following types of data elements were abstracted from the medical record – variables that describe the SCD diagnosis, SCD co-morbidities and other clinical complications, elements from the physical examination, medications and transfusions, insurance type, laboratory measurements, healthcare utilization, history of SCD-related procedures, and measurements from cardiac procedures. The following types of data were self-reported on the patient survey – demographics, diagnosis information, pain experience, social and mental health information, other patient reported outcome domains (e.g., sleep, fatigue), and alcohol and smoking history. Standard PRO measures were used from ASCQ-Me, PROMIS and Neuro-QoL. Patient surveys were completed approximately annually. Under SCDIC-I, two medical record abstractions and labs were reported at enrollment and approximately 3 years later. Under SCDIC-II and GRNDaD, all data are collected annually. Patients may refuse to complete the survey.

  Study phs003529

• Treatment of genetic screening of hypertriglyceridemia type I, III, and V - HTG Amsterdam

  This is a cohort of patients with extreme hypertriglyceridemia. Patients have been screened for loss of function mutations in LPL, GPIHBP1, APOC2, APOA5 and LMF1.

  Study phs000511

• EATL-II whole-exome sequencing profile

  Enteropathy-associated T-cell lymphoma (EATL), a rare and aggressive intestinal malignancy of intraepithelial T lymphocytes, comprises two disease variants (EATL-I and EATL-II) differing in clinical characteristics and pathological features. Here we report findings derived from whole exome sequencing of 15 EATL-II tumor-normal tissue pairs.

  Dataset EGAD00001002220

• clonealign: 10X genomics chromium single-cell RNA-sequencing

  10X genomics chromium single-cell RNA-sequencing of (i) patient derived triple negative breast cancer xenograft (ii) primary tumour and ascites ovarian cancer cell lines at tumour recurrence.

  Dataset EGAD00001004552

• Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA)

  The OPPERA project has two sub-studies investigating effects of genetic, physiological, psychological and clinical factors on the risk of developing painful temporomandibular disorder (TMD). OPPERA I baseline case-control study of chronic TMJD (dbGaP study accession phs000762). This sub-study uses a case-control study design to investigate characteristics associated with chronic TMD. The parent OPPERA phenotype file contains an indicator variable (PHASE1CASECONTROL) identifying participants in this sub-study. Data users should use the relevant case-classification variable (CHRNONICTMDCASE) and apply statistical methods appropriate for case-control studies when analyzing TMJD in this sub-study. OPPERA I prospective cohort for first onset of TMJD (dbGaP study accession phs000850). This sub-study uses a prospective cohort study design to investigate characteristics that predict risk of developing first-onset TMD. The parent OPPERA phenotype file contains an indicator variable (PROSPECTIVECOHORT) identifying participants in this sub-study. Data users should use the relevant case-classification variable (INCIDENTCASE) and the relevant time-in-study variable (FOLLOWUPYEARS) when analyzing TMJD in this sub-study. It is recommended that data users apply statistical methods appropriate for cohort studies of a dynamic population (for example, Cox regression models, where INCIDENTCASE is the censoring variable and FOLLOWUPYEARS is time in study).

  Study phs000761

• Comparison Between qPCR and RNA-Seq Reveals Challenges of Quantifying HLA Expression

  Human leukocyte antigen (HLA) class I and HLA class II loci are essential elements of innate and acquired immunity. Their exceptional influence on disease outcome is well documented by GWAS and candidate gene studies. The impact of HLA allelic variation on human disease through allele-specific presentation of antigenic peptides to T cells has been the main focus to determine HLA effects on disease susceptibility/pathogenesis. However, HLA expression levels have also been implicated in disease, adding another dimension to the extreme diversity of HLA that impacts variability in immune responses across individuals. HLA expression levels routinely rely on quantitative PCR (qPCR). An alternative is adoption of high throughput technologies such as RNA-Seq. This provides the opportunity to quantify HLA expression in large datasets, but also allows comparison between RNA-Seq and qPCR. In this study, we analyze expression data for HLA Class I genes for a matched set of individuals (N = 96) by RNA-Seq, qPCR and cell surface expression. Samples were obtained from the Research Donor Program (NCI-Frederick). We observed a moderate correlation between RNA-Seq and qPCR. We suggest technical and biological factors that might contribute to differences in the techniques.

  Study phs003177

• Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers

  Ovarian cancer is the leading cause of death from gynecological cancers worldwide. No effective screening methods exist, and tumors are commonly detected at advanced stages where treatment is much less effective. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker (CA-125 and HE4) analyses to evaluate 591 women from the European Union or the United States with ovarian cancer, benign adnexal masses, or without ovarian lesions. Using a machine learning model that incorporated multi-analyte fragmentome data and protein measurements, we detected ovarian cancer with high specificity >99% and sensitivity of 72%, 69%, 87%, and 100% for stages I–IV, respectively (AUC=0.96, 95% CI: 0.94-0.99), including 90% of high grade serous ovarian cancers. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100% of ovarian cancers for stages I–IV (p=0.001, two-sided test of equal proportions). Additionally, our approach distinguished benign masses from ovarian cancers with high accuracy (AUC of 0.88, 95% CI=0.83-0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation.

  Study EGAS50000000484

• Whole blood RNAseq from a large ALS case-control study at Univ of Michigan

  This dataset consists of 694 bulk RNA-seq data (sorted aligned BAM files) from whole blood of ALS participants meeting the Gold Coast definition of ALS during their clinical visit (n=422) and healthy controls (n=272) at the University of Michigan (UM). Samples were collected as part of the UM Pranger ALS Clinic between 2011-2021, and prepared either using poly-A selection of rRNA depletion (see Experiments). RNAseq was performed on the NovSeq 6000 S4 at the UM Advanced Genomics Core, resulting in 150bp paired-end reads. Raw reads were trimmed using Cutadapt (v2.3) and aligned to hg38 using STAR (v2.5.3a). Age provided is the age at blood sample collection date.

  Dataset EGAD50000001488

• Sleep Abnormalities in Rare Genetic Disorders: Angelman Syndrome, Rett Syndrome, and Prader-Willi Syndrome

  This research study will investigate sleep behavior in the rare neurological disorders Angelman Syndrome (AS), Rett Syndrome (RTT), Prader-Willi Syndrome (PWS) and Early-onset Morbid Obesity (EMO). Sleep is very important to proper health and plays a critical role in learning, memory, brain development and brain function. Sleep disturbances can have negative effects on health and the quality of life of children and their families. Sleep disorders are common in individuals with AS, RTT, PWS and EMO. As a result, individuals with AS, RTT, PWS and EMO are at risk for sleep-related health problems that can worsen existing daytime behaviors and lead to additional problems with learning and memory. The principal objectives of the study are to: Characterize sleep behavior in individuals with Angelman Syndrome, Rett Syndrome, Prader-Willi Syndrome and Early-onset Morbid Obesity. Compare sleep behavior in these individuals with sleep behavior in normal controls Assess the natural history of sleep behavior in individuals with Angelman Syndrome, Rett Syndrome, Prader-Willi Syndrome and Early-onset Morbid Obesity About this Study This is a questionnaire study that will evaluate the sleep behavior of individuals with AS, RTT or PWS (participants), or unaffected siblings of individuals with AS, RTT or PWS (controls). Those participating in the study will already be registered with the Rare Disease Clinical Research Network (RDCRN) and have a confirmed diagnosis of AS, RTT or PWS or be an unaffected sibling. We will look at the medical records on file with the RDCRN to confirm diagnosis of AS, RTT or PWS. Study participants will participate in the study at their regularly scheduled RDCRN clinic visits. Participants will be asked to complete questionnaires at the study visits that will document their sleep behaviors. The questionnaires are not difficult and participants should be able to complete them in approximately 15-30 minutes. Parents and legal guardians are allowed to assist participants or answer on their behalf. Questionnaires will be administered at the initial study visit and at a 12 month follow-up visit to document any changes in sleep behavior. We hope to enroll approximately 1400 individuals with either AS, RTT or PWS or their unaffected siblings.

  Study phs001292

• Potential Modulatory Role of Osteoprotegerin in Bone Metabolism of Patients with 21-Hydroxylase Deficiency

  21-hydroxylase deficiency (21-OHD) is an inherited disorder that results from a mutation on the CYP21A2 gene. It affects the adrenal glands and is the most common cause of congenital adrenal hyperplasia (CAH). 21-OHD CAH causes the body to produce an insufficient amount of cortisol and an excess of androgen, the type of hormone that produces male characteristics. The primary treatment for 21-OHD CAH, glucocorticoid replacement therapy, has been shown to cause bone loss. However, the elevated hormone levels caused by 21-OHD CAH may increase production of the protein osteoprotegerin (OPG), which in turn may protect against bone loss. This study will compare bone density and OPG levels in women who have 21-OHD CAH and have undergone a lifetime of glucocorticoid replacement therapy to that in women who have neither of these criteria. In doing so, the study will aim to determine the relationship between OPG and bone loss. Because of the excess of androgen caused by 21-OHD CAH, women with CAH may exhibit some male-like characteristics. Glucocorticoids are a member of a class of drugs called corticosteroids, which are used in hormone replacement therapy. In order to counteract the effects of 21-OHD CAH, women with the disease are given hormone replacement therapy with glucocorticoids beginning at infancy. Glucocorticoids are known to cause bone loss. Despite many years of treatment with glucocorticoids, however, young women with 21-OHD CAH seem to be protected against bone loss. Researchers believe that the increased androgen levels in these women lead to increased estrogen levels, which in turn increase OPG production. The increase in OPG levels may protect women against bone loss. This study will evaluate bone density and OPG levels in women with and without 21-OHD CAH to determine the relationship between OPG and bone loss. Participants in this observational study will attend only one study visit. At this visit, they will undergo a blood draw; a scan of their lower spine, hip, and forearm; height and weight measurements; and a body fat analysis test. This last test will entail a weak and painless electrical signal being sent from foot to foot. Participants will not attend any follow-up visits for this study.

  Study phs001314

• Genomic Characterization of Meningiomas

  Meningiomas are the most common primary brain tumor in the US. Although the tumor suppressor gene NF2 is disrupted in approximately half of meningiomas, the complete spectrum of genetic changes in meningiomas remains poorly understood, particularly in the large subset of tumors without NF2 alterations. Therefore we performed whole-genome sequencing from 11 Grade I meningioma tumor-normal pairs and whole-exome sequencing from an additional 6 tumor-normal pairs to identify somatic mutations, insertions-deletions, copy-number alterations and rearrangements. We validated our results by performing focused sequencing across 48 additional meningiomas.

  Study phs000552

• Acute lymphoblastic leukemia in children produces endogenous T-cells targeting tumor associated antigens and neoantigens in peripheral blood

  In this study we investigated the presence of endogenous T-cells recognizing private tumor-associated antigens and predicted neoantigens. To this end, HLA-I and HLA-II restricted tumor associated antigens (TAAs) and neoantigens were respectively identified and predicted from matched tumor and germline (PBMCs) in three acute lymphoblastic leukemia patients. Circulating T-cells targeting both Mass spectrometry (MS)-identified TAAs and predicted neoantigens were identified in virtually all pediatric BCP-ALL patients, extending up to two years on remission.

  Study EGAS50000000925

• Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia

  We evaluated the efficacy of proteolysis-targeting chimeras (PROTACs) directed against Janus kinases. Solving the structure of FDA-approved type I JAK inhibitors ruxolitinib and baricitinib bound to the JAK2 JH1 tyrosine kinase domain enabled the rational design and optimization of Cereblon (CRBN)-directed JAK PROTACs utilizing multiple derivatives of JAK inhibitors, linkers and CRBN-specific molecular glues. The resulting JAK PROTACs were evaluated for target degradation by proteomic approaches, and activity tested in CRLF2-rearranged cell line and xenograft models of ALL.

  Study EGAS00001005180

• KIR gene content imputation from single-nucleotide polymorphisms in the Finnish population

  The killer cell immunoglobulin-like receptor (KIR) gene cluster on chromosome 19 encodes cell surface glycoproteins that bind class I human leukocyte antigen (HLA) molecules as well as some other ligands. KIR gene gene copy number variation associates with the outcome of transplantations and susceptibility to immune-mediated diseases. Here we describe a stand-alone and freely available gene content imputation for 12 KIR genes. The models were trained using 818 Finnish biobank samples genotyped for 5774 KIR-region SNPs and analysed for KIR gene content with targeted sequencing.

  Study EGAS00001005457

• PAGE: The Charles Bronfman Institute for Personalized Medicine (IPM) BioMe BioBank

  The Institute for Personalized Medicine (IPM) BioMe Biobank is a consented, EMR-linked medical care setting biorepository of the Mount Sinai Medical Center (MSMC) drawing from a population of over 70,000 inpatients and 800,000 outpatient visits annually. MSMC serves diverse local communities of upper Manhattan, including Central Harlem (86% African American), East Harlem (88% Hispanic Latino), and Upper East Side (88% Caucasian/white) with broad health disparities. IPM BioMe Biobank populations include 28% African American, 38% Hispanic Latino predominantly of Caribbean origin, 23% Caucasian/White. IPM BioMe Biobank disease burden is reflective of health disparities with broad public health impact. Biobank operations are fully integrated in clinical care processes, including direct recruitment from clinical sites waiting areas and phlebotomy stations by dedicated Biobank recruiters independent of clinical care providers, prior to or following a clinician standard of care visit. Recruitment currently occurs at a broad spectrum of over 30 clinical care sites. This study is part of the Population Architecture using Genomics and Epidemiology (PAGE) study (phs000356).

  Study phs000925

• ctDNA diva aggregate data

  ctDNA biomarker and relevant clinical data for divarasib phase I GO42144 study, including tumor type, KRAS G12C mutation detectability in plasma at baseline, baseline SLD, sites of metastasis, lines of therapy, best response, confirmed best response, PFS, ctDNA tumor fraction and KRAS G12C VAF at baseline/C1D15/C3D1.

  Dataset EGAD50000000454

• clonealign: direct library preparation+ single-cell DNA-sequencing

  Direct library preparation+ single-cell DNA-sequencing of (i) patient derived triple negative breast cancer xenograft (ii) primary tumour and ascites ovarian cancer cell lines at tumour recurrence.

  Dataset EGAD00001004553

• Jackson Heart Study (JHS) Cohort

  The Jackson Heart Study (JHS) is a large, community-based, observational study whose participants were recruited from urban and rural areas of the three counties (Hinds, Madison and Rankin) that make up the Jackson, MS metropolitan statistical area (MSA). Participants were enrolled from each of 4 recruitment pools: (1) random, 17%, (2) volunteer, 30%, (3) currently enrolled in the Atherosclerosis Risk in Communities (ARIC) Study, 31%, and (4) secondary family members, 22%. The final cohort of 5,306 participants included 6.59% of all African American Jackson MSA residents, aged 35-84, during the baseline exam (N-76,426, US Census 2000). Among these, approximately 3,600 gave consent that allows genetic research and deposition of data into dbGaP. Major components of three clinic examinations (see study history) include medical history, physical examination, blood/urine analytes, and interview questions on areas such as physical activity, stress, coping and spirituality, racism and discrimination, socioeconomic position, and access to health care. Extensive clinical phenotyping includes anthropometrics, electrocardiography, carotid ultrasound, ankle-brachial blood pressure index, echocardiography, CT chest and abdomen for coronary and aortic calcification, liver fat, and subcutaneous and visceral fat measurements, and cardiac MRI. At 12-month intervals after the baseline clinic visit (Exam 1), participants have been contacted by telephone to update information, confirm vital statistics, document interim medical events, hospitalizations and functional status, and obtain additional sociocultural information. Questions about medical events, symptoms of cardiovascular disease and functional status are repeated annually. Ongoing cohort surveillance includes abstraction of medical records and death certificates for relevant International Classification of Diseases (ICD) codes and adjudication of nonfatal events and deaths. CMS data are currently being incorporated into the dataset. Note: Regarding date variables warehoused in the Jackson Heart Study (JHS) Cohort on dbGaP, the coordinating center has developed an algorithm that will systematically review and de-identify any of the (nearly 100) date-related variable types stored in the data package. To simultaneously minimize (i) de-identifiability of the data and (ii) impact on analyses utilizing sensitive data elements, a participant-level random number was generated to avoid the necessity of sharing any potentially sensitive data. The coordinating center maintains an archived linkage of these data in their raw form and regularly reviews ad hoc requests to utilize the raw data on a project-by-project basis. The JHS Cohort is utilized in the following dbGaP substudies. To view genotypes, 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 phs000286 JHS Cohort. phs000402 ESP Heart GO JHS phs000498 JHS Allelic Spectrum Seq phs000499 JHS CARephs001069 MI Gen JHS phs001098 T2D GENES Exome Seq phs001356 Exome Chip phs002256 Cardiometabolic Renal Proteomics phs002369 Metabolomics Insulin Resistance

  Study phs000286

• Rapid Acceleration of Diagnostics - Underserved Populations (RADx-UP): COVID-19 Testing and Vaccination Social Network Diffusion for Diverse Criminal Legal Involved Communities

  This RADx-UP Phase II proposal, "Social network diffusion of COVID-19 prevention for diverse Criminal Legal Involved Communities", will implement a situation appropriate COVID-19 testing and vaccination social network diffusion intervention - C3 - building upon RADx-UP Phase I lessons and successful social network prevention interventions developed previously by the research team. C3 Criminal Legal Involved (CLI) populations encompass those non-incarcerated who have experienced recent arrest, incarceration, probation, parole or diversion programs such as drug courts. While increases in COVID-19 testing have been observed among this group, there remain members with limited testing history as well as individuals who are vaccine hesitant. COVID-19 prevention messaging can no longer be simplified to "everyone test and/or everyone vaccinate" as testing and vaccination decisions among community members are sensitive to personal histories (i.e., prior infection), local infection rates (i.e., low rates) and testing/vaccination availability. As COVID-19 prevention efforts have become more complicated (i.e., test if exposed), people tend to focus on the messenger, and particularly those that are close to them. Personal connections and communications within existing personal network structures, such as families, friends and other trusted acquaintances represent the cornerstone to increase situation appropriate testing and overcoming COVID-19 vaccine hesitancy. C3 builds upon RADx-UP I, by using a network diffusion approach facilitated through motivational interviewing purposefully geared to mobilize one's own organic social network to increase context appropriate testing and vaccine uptake. Through this process we will maximize the primary benefit and impact of this type of intervention which also has the intended effect of increasing likelihood that the messenger themselves will undergo the same behavior change that they have been trained to promote. We will leverage infrastructure developed in RADx-UP Phase I, which includes 4 high-impact sites across the Central US from Phase I: Baton Rouge LA, Little Rock AR, Indianapolis IN, and Chicago IL. We will utilize established engagement efforts already in place and continue to fully integrate communities in the strategic application of the intervention. We will use the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to guide implementation. C3 aims to: Aim 1a. Test the efficacy (3-month situation appropriate testing or vaccination) of a network diffusion intervention (C3) versus an existing COVID-19 testing and vaccine linkage to care intervention among: 1) primary study participants (primary outcome); and 2) secondary study participants connected to primary participants (secondary outcome) using a RCT design. Aim 1b. Explore the mechanisms for differential intervention effects at the individual and network-level that may increase situation appropriate testing and/or vaccination uptake. Aim 2. Examine key RE-AIM components in real time tied to the implementation of the network diffusion intervention (C3).

  Study phs003234

• EstMB cohort participants sequenced with MGISEQ-2000 platform

  Participants collected a fresh stool sample immediately after defecation using a sterile Pasteur pipette and placed it in a 15 mL conical polypropylene tube. They were instructed to collect the sample as close as possible to their study center visit. Samples were transported and stored at −80 °C until DNA extraction. Microbial DNA was extracted from 200 mg of stool using a QIAamp DNA Stool Mini Kit (Qiagen), following manufacturer's instructions, after all samples were collected. DNA was quantified using a Qubit 2.0 Fluorometer with a dsDNA Assay Kit (Thermo Fisher Scientific). Library preparation and circularization of equimolarly pooled libraries were done with MGIEasy FS DNA Library Prep Set (MGI Tech Co, Ltd, Shenzhen, China) according to the standard protocol. The sequencing was performed with MGISEQ-2000 High-throughput Sequencing Set (FCL PE150) according to the manufacturer’s instructions (MGI Tech, Shenzhen, China)

  Dataset EGAD50000002213

• Cookies

  Cookies https://ega-archive.org does not identify users on this site. It does use cookies, though. What is a cookie? Cookies are text files containing small amounts of information which are downloaded to your device when you visit a website. They allow a website to remember your preferences and are therefore useful to improve your online experience. Find out more information about cookies. Types of cookies we use Functional These cookies record the columns you wish to display or hide in the results page.Performance These cookies are used to analyse trends, administer the website, track visitor movements and gather broad demographic information for aggregate use. We use the information to compile reports and to help us improve our websites. These cookies are not linked to personally identifiable information. Session cookie A session cookie for a website only exists whilst the user is reading or navigating the website. When the user closes their web browser these cookies are usually removed.

  Documentation cookies

• RNA-seq TPM matrices

  Matrices of TPM-normalized counts from RNAseq data for the three phase II clinical trials (IMvigor210, POPLAR, IMmotion150) and the phase I clinical trial PCD4989g.

  Dataset EGAD00001006741

• Assessment of Neurological Deterioration in Subjects with Late Infantile Neuronal Ceroid Lipofuscinosis

  Late infantile ceroid lipofuscinosis (LINCL) is a rare, rapidly progressing lysosomal storage disease resulting from mutations in the CLN2 gene that lead to deficiency in the lysosomal protease tripeptidyl peptidase I (TPP-I). The symptoms are largely neurological with onset at 2-4 years age with progression to death at age 8-12 yrs. The rareness of the disease and the likelihood of non-uniform progression depending on genotype together limit the data available regarding the natural history of disease progression. Current neurological rating scales are used to give an overall quantitative description of the disease but the categories are generally broad and imprecise. With that background, the primary focus of this study is to use clinical rating scales and magnetic resonance imaging methods to define the natural history of LINCL and to provide objective and sensitive surrogates for neurological status and the impact of experimental treatments in children with LINCL. Together these parameters will be applicable to future clinical studies of novel therapies for LINCL and should be transferrable to other neurological lysosomal storage diseases. Subjects will be assessed at 2 visits separated by ≥1 yr. Brain morphometry, water self-diffusion coefficients and spectroscopic data will be obtained via magnetic resonance. Resulting MRI biomarkers will be compared with neurological assessment of disease severity using the Weill-Cornell LINCL rating scale.

  Study phs001575

• An Advanced Molecular Medicine Case Report of a Rare Human Tumor Using Genomics, Pathomics, and Radiomics

  The associated data of this study is derived from a single female patient with pulmonary sclerosing pneumocytoma (PSP). The aim of this study is to provide the most comprehensive, multi-modality sequencing study of a single case of PSP to-date. To this end, the following sequencing experiments were performed: i) RNA-Seq of the primary tumor and adjacent normal tissues (6 replicates for each tissue type), which was intended to analyze RNA-Seq fusions, gene expression, expression mutations, ii) low-pass DNA whole genome sequencing (WGS) from primary tumor tissue and germline, which was intended to analyze copy number aberrations, and iii) DNA targeted panel sequencing of lung cancer associated genes, using primary tumor tissue and germline from white blood cells, which was intended to analyze somatic mutations. Principal findings: i) the PSP hallmark mutation AKT1 (p.E17K) was detected within both the DNA and RNA, and ii) the TP53 signaling pathway was found to be statistically significant by three different pathway analysis tools of analyzing gene expression and pathway ramifications. Among proteins within the TP53 signaling pathway, the p53 inhibitor encoded by MDM2 was found to be overexpressed (by differential gene expression analysis). The original sequencing data (i.e., FastQ files) from each of the aforementioned samples will be accessible through dbGaP.

  Study phs003154

• INSPIRE - Investigator-initiated Phase 2 Study of Pembrolizumab Immunological Response in Metastatic Solid Tumors

  Whole exome and RNA sequencing source data for: Clouthier, D.L., Lien, S.C., Yang, S.Y.C. et al. An interim report on the investigator-initiated phase 2 study of pembrolizumab immunological response evaluation (INSPIRE). j. immunotherapy cancer 7, 72 (2019). https://doi.org/10.1186/s40425-019-0541-0 Bratman S*, Yang SYC*, Iafolla MAJ, Liu Z, Hansen AR, Bedard P, Lheureux S, Spreafico A, Razak AA, Shchegrova S, Louie M, Billings P, Zimmerman B, Sethi H, Aleshi A, Torti D, Marsh K, Eagles J, Cirlan I, Hanna Y, Clouthier D, Lien SC, Ohashi PS, Xu W, Siu LL, Pugh TJ. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nature Cancer. 2020:1:873-881. https://doi.org/10.1038/s43018- 020-0096-5. Yang SYC, Lien SC, Wang BX, Clouthier DL, Hanna Y, Cirlan I, Zhu K, Bruce JP, El Ghamrasni S, Iafallo MAJ, Oliva M, Hansen AR, Spreafico A, Bedard PL, Lheureux S, Razak A, Speers V, Berman HK, Aleshin A, Haibe-Kains B, Brooks DG, McGaha TL, Butler MO, Bratman SV, Ohashi PS, Siu LL, and Pugh TJ. Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity. Nature Comm 2021:12, 5137. https://doi.org/10.1038/s41467-021-25432-7

  Study EGAS00001003280

• Cellular and Molecular Characterization of Renal Cell Carcinoma

  We are performing a comprehensive cellular and molecular characterization of renal cell carcinoma. This work includes an initial cohort of patients whose tumors (and adjacent normal tissue) underwent single cell analysis. Single-cell RNA sequencing (scRNA-seq) and TCR sequencing (scTCR-seq) analysis of untreated clear cell renal cell carcinoma tumor and adjacent normal tissue was performed across disease stages. This initial cohort includes 13 patients: 4 with early stage disease (stage I/II), 4 with locally advanced disease (stage III), and 5 with advanced/metastatic disease (stage IV). Whole exome sequencing on tumor and normal tissue was also performed. 

  Study phs002252

• Single-Cell Transcriptomics of Adult Recurrent Respiratory Papillomatosis

  These single-cell sequencing data were generated from diseased respiratory tract papilloma tissue caused by chronic infection with HPV 6 or 11. Patients from which this tissue was derived participated in a phase I clinical trial using a novel therapeutic vaccine, but these samples were acquired before this experimental treatment. The aim of performing this single-cell sequencing study was to characterize the papilloma cells and other cells in the papilloma microenvironment with single-cell analyses using the 10X Genomics platform. The single-cell gene expression raw data files for each sample will be available in this submission.

  Study phs003349

• "BaTwa" populations from Zambia retain ancestry of past hunter-gatherer groups

  We genotyped and analyzed over two million genome-wide SNPs from two BaTwa populations (40 individuals by population), and from three comparative farming populations (10 to 21 individuals by population) in order to: (i) determine if the Zambian BaTwa carry any genetic material linking them to past hunter-gatherer-groups, and (ii) characterize the genetic affinities of past Zambian hunter-gatherer-groups. We found that both BaTwa populations harbor a hunter-gatherer- like genetic component, representing ∼19% (Bangweulu) and ∼31% (Kafue) of their genetic ancestry, while the rest of their ancestry is similar to western Africans.

  Study EGAS50000000378

• Drug Perturbation of Primary Lymphoma Patient Samples and RNA Sequencing

  This submission contains 3'-end-based shallow-depth RNA sequencing data from 108 patients with chronic lymphocytic leukemia and 8 patients with lymphoma. Each primary patient sample was treated in vitro with DMSO as a control and with up to ten small-molecule drugs (ibrutinib, duvelisib, everolimus, trametinib, nutlin-3a, I-BET762, MK2206, selinexor, compound 26, and a combination of ibrutinib and compound 26). The samples were sequenced after 48 hours. The total data set consists of 1476 RNA sequencing samples from 6 batches (pilot, batch 1, batch 1 replicate, batch 2, batch 3, batch 4).

  Study EGAS50000001500

• Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities

  Despite molecular and clinical heterogeneity, small cell lung cancer (SCLC) is treated as a single entity with predictably poor results. Using tumor expression data, we applied non-negative matrix factorization, which identified four SCLC subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed signature (SCLC-A, N, P and I, respectively). The presence of these subtypes were then validated in tumor gene expression data from the IMpower133 clinical trial.

  Study EGAS00001004888

• Single-cell gene expression data from CD8+ T cells from two Austrian COVID19 patients stimulated with wildtype and mutant SARS-Cov-2 peptides

  The data contains single-cell gene sequencing data (10x Genomics) from FACS-purified CD8 T lymphocytes from two Austrian patients. The cells were stimulated with one MHC class I peptides obtained from a common (wild type) variant and an emerging mutant variant of the SARS-Cov-2 virus. Then the samples were multiplexed using hashtag oligos. We provide the raw and aligned sequence data for: i. The single-cell experiments ii. The PCR-amplified samples for enrichment of the hashtag oligo multiplexing barcodes iii. The PCR-amplified samples for enrichment of the T Cell Receptor (TCR) VDJ region for immuno-profiling. The samples and libraries were processed and obtained in collaboration between St. Anna Children's Cancer Research Institute (CCRI), CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, and the Medical University of Vienna. The cell barcodes and processed data has been submitted to the GEO database with GEO accession GSE166651.

  Dataset EGAD00001006995

• RNA sequencing data of 142 samples from 142 patients with HER2+ breast cancer treated with letrozole or tamoxifen (SOLTI PAMELA trial)

  PAMELA (NCT01973660) is a non-randomized, open-label, multicentric, prospective translational research study in stage I-IIIA HER2+ breast cancer designed to evaluate the ability of the PAM50 intrinsic subtypes to predict pCR in the breast (pCRB) following 18 weeks of neoadjuvant lapatinib and trastuzumab (+/- hormonal therapy if hormone receptor [HR] positive). Patients with HR+ disease received letrozole (if postmenopausal) or tamoxifen (if pre-menopausal). The primary objective was to compare the pCRB rates of the HER2-E versus the non-HER2-E subtypes in the intent-to-treat population.

  Study EGAS00001006410

• Lymphoma_primary_patient_drug_perturbed_RNASeq_samples

  3'-end low-depth RNA sequencing data from 108 patients with chronic lymphocytic leukemia and 8 patients with lymphoma. Each primary patient sample was treated in vitro with DMSO as a control and with up to ten small-molecule inhibitors (ibrutinib, duvelisib, everolimus, trametinib, nutlin-3a, I-BET-762, MK2206, selinexor, compound 26, and a combination of ibrutinib and compound 26). Sequencing was performed on the Illumina HiSeq4000. The dataset contains FASTQ files.

  Dac EGAC50000000578

• DAC Wachten Laboratory and Toma Laboratory, University of Bonn/University Hospital Bonn

  DAC for collaborative projects of the Wachten Laboratory (Institute of Innate Immunity, University of Bonn, University Hospital Bonn) and the Toma Laboratory (Institute of Pathology, University Hospital Bonn). Contact: Prof. Dr. Dagmar Wachten dwachten@uni-bonn.de Institute of Innate Immunity, University Hospital Bonn, University of Bonn, Germany Prof. Dr. Marieta I. Toma Marieta.Toma@ukbonn.de Institute of Pathology, University Hospital Bonn, Germany

  Dac EGAC50000000916

• RNAseq FASTqs

  RNAseq FASTq files from 817 bulk pre-treatment tumors from three indications (mUC, NSCLC and RCC) across three phase II (IMvigor210, POPLAR, IMmotion150) and a phase I (PCD4989g) clinical trials.

  Dataset EGAD00001006631

• Transcriptomic Profile of Whole Blood Cells from Elderly Subjects fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG) in a Phase I Open Label Study

  Open label study to evaluate the safety of Lactobacillus rhamnosus GG ATCC 53103 (LGG) in elderly subjects. Fifteen healthy elderly volunteers, ages 65-80 were enrolled in a study in which they received LGG capsules containing 1 x 1010 CFU, twice daily for 28 days and were followed through day 56. The study subjects completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits at the Massachusetts General Hospital Clinical Research Center at baseline, day 28 and day 56. During each visit, the subject diary, interim history, potential adverse effects and concomitant medications were reviewed and vital signs and a physical examination were performed. Routine blood tests were obtained to monitor for safety during visits and nasopharyngeal and stool samples were collected for microbiome analysis. Volunteers interested in participating in the effect of LGG probiotic on the Human whole Blood Transcriptome substudy also had blood drawn for DNA and RNA extraction, after signing the substudy consent form. The main objective of the study was to assess the safety and tolerability of 2 x 1010 CFU LGG administered orally to elderly subjects for 28 days. Secondary objectives were to evaluate the richness and microbial diversity in nasopharyngeal and stool specimens using pyrosequencing, and to compare cytokine production in response to bacterial stimulation by following the kinetics of mRNA expression of pro and anti-inflammatory genes and different signaling pathways, in relation to changes in stool Bifidobacterium and Lactobacillus spp. The study was reviewed and approved by the Partners Human Research Committee (IRB # 2010P001695) and was registered at ClinicalTrials.gov (NCT01274598). The main results regarding the clinical signs and safety of intervention is published in PLoS One. 2014 Dec 1;9(12):e113456. doi: 10.1371/journal.pone.0113456. eCollection 2014. PMID: 25438151. RNA sequencing for transcriptome analysis was only done in 11 of the 15 subjects as RNA integrity and quantity had to be optimal for the three times where blood was collected in order for a subject to be included in the study. The information regarding the microbiome data associated with this study is presented in a separate paper, which can be found at dbGaP study accession, phs000896, and PMID: 25873374.

  Study phs000928

• Phase I Study and Cell-Free DNA Analysis of T-DM1 and Metronomic Temozolomide for Secondary Prevention of HER2-Positive Breast Cancer Brain Metastases

  This study is a phase I trial combining ado-trastuzumab emtansine (T-DM1) with Temozolomide (TMZ) for the prevention of additional brain metastases after previous occurrence and local treatment in HER2+ breast cancer patients. Twelve patients were enrolled in this study. Data includes whole exome sequencing (WES) from patients' cerebrospinal fluid (CSF) and plasma samples. The CSF was collected from each patient at trial entry and after the initial two treatment cycles of TMZ and T-DM1 treatment. Blood was collected through a standard peripheral venipuncture at the following four time points: 1) upon trial entry, 2) after two treatment cycles, 3) the treatment cycle prior to the last follow-up, and 4) most recent follow-up. Whole exome libraries were captured by the SureSelect Human All Exon V8 Kit (Agilent, Santa Clara, CA, USA) and sequenced by NovaSeq 6000 S2 Sequencer in paired-end sequencing mode (Illumina, San Diego, CA, USA). Gene mutations in DNMT3A, ELP1, NOTCH4, KMT2B, CRLF2, and KCNJ18 were observed in patients' CSF.

  Study phs003165

• Analysis of mechanisms of CD19- relapse following novel low affinity CD19 Chimeric Antigen Receptor (CAR) T-cells (CD19 CAR T-cells) in a Phase I clinical study in paediatric ALL: CARPALL

  Phase I clinical study (CARPALL, NCT02443831) utilizing a novel low affinity CD19CAR CAR in patients age <25 with high risk CD19+ ALL. Seventeen patients were enrolled and 14 received an infusion of CAR T cells. Among those achieving complete remission, 6 subsequently relapsed, 5 with CD19- disease, 1 with CD19+ disease. Whole exome sequencing of bone marrow DNA from patients with CD19- relapse showed mutations in the CD19 gene predicted to result in loss of surface expression in 4/5 patients. These mutations were not detectable prior to CAR T cell therapy. With a median follow-up of 14 months, 5/14 patients (36%) are alive and disease-free. Overall survival was 84% at 6 months and 63% at 12 months and by the criteria used in the ELIANA study, event-free survival was 67% and 46%. Using more stringent criteria where an event is defined as molecular relapse, molecular EFS was 55% and 29 %. The median duration of remission in responding patients was 7.4 months.

  Study EGAS00001003733

• HSC_population_dynamics___KX004_samples___WGS

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001003768

• HSC_population_dynamics___CB002_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001003743

• HSC_population_dynamics___KX007_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001004193

• HSC_population_dynamics___KX008_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001004490

• HSC_population_dynamics_CBD_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001003091

• HSC_population_dynamics___KX003_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001003550

• HSC_population_dynamics___TG001_2_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001003688

• Radiation-Related Genomic Profile of Papillary Thyroid Cancer after the Chernobyl Accident

  The April 26, 1986 accident at the Chernobyl nuclear power plant in northern Ukraine resulted in the release of radioactive contaminants, which were deposited in the surrounding areas in Ukraine, Belarus, and Russia. The main radiation-related health effect resulting from these exposures is the increased occurrence of thyroid cancer among individuals who were children at the time of the accident or born shortly thereafter. The purpose of this study was to conduct a comprehensive genomic landscape analysis of papillary thyroid tumors arising in individuals who were exposed as children to radioactive iodine (I-131) from the Chernobyl nuclear power plant accident.

  Study phs001134

• HSC_population_dynamics___PX001_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001004146

• HSC_population_dynamics___KX009_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001004580

• HSC_population_dynamics___KX010_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001004581

• HSC_population_dynamics_KSP_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001002762

• HSC_population_dynamics___LEUK4_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001004247

• HSC_population_dynamics___CB001_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001003397

• Distribution of data using Live Distribution

  Live Distribution Welcome to the documentation for using the Live Distribution feature for distributing data files securely through the EGA platform. This guide will walk you through the process of downloading encrypted files and decrypting them using Crypt4GH. Please follow the steps below to ensure a smooth experience. Before Downloading Create an EGA user. Make sure that you have the permissions to download the dataset of interest. In case you don’t have access, request access to the dataset. Add your Crypt4GH-compatible public key to your EGA account. Please allow a few hours for your public key to be synced with your profile. Afterwards, you will be able to connect to your EGA outbox using the SFTP protocol. Download Graphical User Interface (GUI) You can use any GUI that supports SFTP connections, such as FileZilla, an open-source FTP client. For Filezilla as your GUI, follow these steps to download files: Open FileZilla and access Site Manager (File > Site Manager). Create a new connection with the following settings (Figure 1): Protocol: SFTP - SSH File Transfer Protocol Host: __EGA_OUTBOX_DOMAIN__ Logon Type: Key file User: your EGA username Key file: path/to/your/private_key Figure 1: Process of establishing a new connection to __EGA_OUTBOX_DOMAIN__ using a key file as the logon method in FileZilla. The figure showcases the FileZilla version 3.52.2 operating on IOS v11.2.3. By following the depicted steps, users can create a secure and efficient connection to the EGA outbox, ensuring seamless data transfers. Click Connect to access your Outbox. This folder serves as your storage space within the EGA cloud, containing files accessible for download in a secure way. Browse the remote directory on the right side of the FileZilla screen. Select the files you wish to download, right-click, and choose Download (Figure 2). Figure 2: Step-by-step process of manually downñoad files from __EGA_OUTBOX_DOMAIN__ using FileZilla, with FileZilla version 3.52.2 operating on IOS v11.2.3. The figure demonstrates how users can downñoad data from the EGA outbox to their local storage by following the depicted steps SFTP command line You can also use the SFTP command line to securely download files from the EGA Outbox. Using SFTP command line client in Linux/Unix Open a terminal window Enter the following command to connect: sftp username@hostname Enter your EGA password To see a list of available sftp commands type help sftp> put – Upload file sftp> get – Download file sftp> cd path – Change remote directory to ‘path’ sftp> pwd – Display remote working directory sftp> lcd path – Change the local directory to ‘path’ sftp> lpwd – Display local working directory sftp> ls – Display the contents of the remote working directory sftp> lls – Display the contents of the local working directory Type get command to download files. For example: get encrypted_file.c4gh Use the bye command to close the connection (SFTP session). Convenient SSH settings Include the following settings in your SSH config file, located in ~/.ssh/config Host __EGA_OUTBOX_DOMAIN__ EGA-outbox hostname __EGA_OUTBOX_DOMAIN__ User username IdentityFile path/to/the/private/key Replace username and path/to/the/private/key with the appropriate settings, and you will be able to connect to the __EGA_OUTBOX_DOMAIN__ simply using sftp EGA-outbox. How to decrypt Files archived at the EGA are encrypted based on Crypt4GH. Hence, to decrypt the files you need to install Crypt4GH. You can install a python implementation of it, with pip install crypt4gh or directly from the Github repository pip install git+https://github.com/EGA-archive/crypt4gh.git After installing Crypt4GH, decrypt files using the following command: crypt4gh decrypt --sk /path/private/key < encrypted_file.c4gh > decrypted_filename The command reads the encrypted file from stdin (with <) and output the decrypted version to stdout (with >). Replace encrypted_file.c4gh and decrypted_filename with the appropriate filenames but make sure to not use the same filename for both reading and writing because your SHELL would then truncate both files before you even read or write. Frequently Asked Questions What username should I use to log in to my outbox? The authentication process for logging in to the EGA website, as well as accessing your inbox and outbox, requires the use of your username, not your email address. Therefore, if you registered a username different from your email address when creating your EGA account, you must use that username to log in. If you have forgotten your registered username, please, contact our Helpdesk team for assistance. I see that some files in my dataset have 'unavailable' as extension. What should I do? Within your Outbox, you'll find a list of all the datasets available for download. Occasionally, certain files may be marked as "unavailable". These unavailable files can be identified by the "unavailable" extension added to their filenames (e.g. filename.fastq.gz.unavailable.c4gh). If you encounter an unavailable file that you need, please reach out to our Helpdesk. We'll promptly work on making the file accessible for download as soon as possible. Specific to using keys Can I access one EGA account from different devices? Yes, you can access your account from different devices by linking several public keys to your EGA account. Each device can generate a unique public-private key pair, and the corresponding public keys can be linked to the same account. This way, you can use different public keys on different devices and still have access to the same account and data. I have several keys and I don't remember which one is which When generating SSH keys, it's a good practice to add a comment using the -C flag. This will allow you to add a descriptive tag to your key, making it easier to identify later on. Here's an example command that generates an SSH key with a comment: ssh-keygen -t ed25519 -C work-pass In this example, we're generating an ed25519 SSH key with the comment work-pass. Once you have multiple keys with different comments, you can use the comments to easily identify each key. To view the comments for your existing SSH keys, you can use the following command: ssh-keygen -l -f /path/to/key This will display the key fingerprint and the associated comment. By checking the comments, you should be able to identify which key is which. What if I can't find my SSH keys for uploading files with a key file, and how can I use new keys? If you can't find your SSH keys, don't worry - you can make new ones. To do this, open your terminal or command prompt and type a command to make a new SSH key. You can pick a name for the key, and choose a password to keep it safe. After making the key, you can add the new key to your account or server where you want to upload files using the key file. This usually involves copying and pasting the key's "public" (e.g. file.pub) part to the right place. If you lose track of the key again, just make a new one and add it again. Keep in mind that SSH keys belong to you and your computer, so if you switch computers or accounts, you'll need to make new keys. I don't want to type the passphrase every time I use the key. What can I do? You can use an ssh-agent to avoid typing the passphrase every time you use the key. An ssh-agent is a program that stores your private keys in memory and provides them to ssh when needed. You can add your key to the ssh-agent using the command ssh-add followed by the path to your key file.Here's an example of the steps to follow: Open a terminal window.Start the ssh-agent by typing the command eval $(ssh-agent).Add your key to the ssh-agent by typing the command ssh-add [key filepath]. For instance, if your key file is located in the home directory with the name mykey, the command will look like this: ssh-add ~/mykey After adding your, key to the ssh-agent, you should be able to use ssh without having to enter your passphrase every time. Can I use my password for authentication (without my private key)? If you prefer to use your username and password for authentication instead of your private key, you can still do so. When using a Graphical User Interface (GUI) such as FileZilla, you can select Ask for password as your Logon Type (Figure 3). This option will prompt you to enter your password when you click Connect, instead of using your private key. Figure 3: This option will prompt you to enter your password when you click "Connect", instead of using your private key. Figure 3: Process of establishing a new connection to __EGA_OUTBOX_DOMAIN__ using your password as the logon method in FileZilla. The figure showcases the FileZilla version 3.52.2 operating on IOS v11.2.3. By following the depicted steps, users can create a secure and efficient connection to the inbox, ensuring seamless data transfers. It's worth noting that using a password for authentication can be less secure than using an SSH key, as passwords can be more easily compromised through various means. However, if you choose to use your password for authentication, selecting "Ask for password" as your Logon Type is a good way to do so securely via a GUI. Why is it better to use my key and not my password? SSH keys for authentication is generally considered to be more secure and convenient than using passwords. SSH keys are more difficult to crack than passwords, and they can be restricted to specific users and machines, giving you more control over access. Once you set up your SSH keys, you can use them to authenticate quickly and easily, without having to enter a password every time. This makes automation of tasks, such as uploading encrypted files, much simpler. Additionally, SSH keys provide better logging, allowing you to keep track of who is accessing your systems and when. All in all, using SSH keys is a good practice for improving security and convenience in your authentication process.

  Documentation access/download/files/live-outbox

• Transcriptome profiling of human lung fibroblasts in COPD

  Primary lung fibroblast were isolated from well-matched control donors (no COPD, n=3) and patients with COPD (GOLD stage I-IV, n=8). Total RNA of cultured human lung fibroblast were isolated at passage 3 and rRNA was depleted. 75 bp single-end reads were generated from RNA libraries on Illumina NextSeq 500.

  Dataset EGAD00001009405