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• IMCISION RNAseq

  RNA sequencing of 32 primary head and neck squamous cell carcinoma (HNSCC) samples prior to treatment with neoadjuvant anti-PD-1 (n=6) or anti-PD-1 + anti-CTLA-4 (n=26) immunotherapy, and 30 paired on-treatment HNSCC samples (i.e. after neoadjuvant immunotherapy). RNA quantity used: 10ng. Library Preparation Kit: SMART Stranded Total RNA Seq Kit (Takara). Sequencing parameters: NovaSeq 6000, 2x 100 bp. File type: fastQ

  Dataset EGAD00001008127

• Germline RUNX1 Variation and Predisposition to Childhood Acute Lymphoblastic

  Somatic mutations of RUNX1, which encodes the myeloid and lymphoid transcriptional factor RUNX1, are common in both B- and T- acute lymphoid leukemia (ALL) and are associated with poor prognosis of T-ALL. However, there has been no comprehensive investigation of the pattern or prevalence of RUNX1 germline mutation in both B- and T-ALL. Here we report germline RUNX1 variants in 1.23% of B-ALL and 2.11% of T-ALL, identifying 31 unique variants in 62 B-ALL and 18 unique variants in 26 T-ALL children. The majority of frameshift and nonsense variants affected RUNX1 function in transcriptional regulation, hematopoiesis, and cellular proliferation. We identified JAK3 as the most frequent somatic mutation in T-ALL with RUNX1 variants. These results not only identify RUNX1 as a leukemia predisposition gene but also further underline the importance of germline genetic variants to the development of ALL

  Dataset EGAD00001007793

• Enrichment of PTPRT and JAK2 mutations in lung cancer from African Americans and evidence for increased GI and HRD in LUSC

  The goal of this study is to compare the somatic mutation landscape between European Americans and African Americans. It includes various histological forms of lung cancer. In LUAD, we find increased prevalence of PTPRT and JAK2 mutations among African Americans. These proteins function in the same pathway and as such, this may be a new actionable target for lung cancer. We have also examined the landscape of copy number profiles in African Americans and European Americans.

  Study phs001895

• GCAT| ICD Disease Diagnoses

  Disease diagnoses of GCAT Cohort participants obtained from electronic health records (EHR), mainly including the time period from 2012 to 2017. Disease diagnoses are codified in ICD-9, and the position of diagnosis refers to primary/secondary diagnoses (up to 14 secondary diagnoses per visit). The date and origin of the visit are also specified (AP: primary care, UGR: emergency, AH: hospital care, SMA: outpatient medical service, SMH: hospital medical service).

  Dataset EGAD00001007731

• C3 SNPs and outcome after lung transplantation

  Background: Development of chronic rejection is still a severe problem and causes high mortality rates after lung transplantation (LTx). Complement activation is important in the development of acute rejection (AR) and bronchiolitis obliterans syndrome, with C3 as a key complement factor. Methods: Since a single nucleotide polymorphism (SNP) in the C3 gene (rs2230199) is associated with long-term outcome after solid organ transplantation, we investigated this SNP in relation to LTx. In addition, we looked at local production of C3 by analyzing bronchoalveolar lavage fluid (BALF) of LTx patients using isoelectric focusing (IEF). Results: We demonstrated the presence of C3 in BALF and showed that this is produced by the donor lung based on the genotype of SNP rs2230199. We also analyzed donor and patient SNP configurations and observed a significant association between the SNP configuration in patients and episodes of AR during 4-years follow-up. Survival analysis showed a lower AR-free survival in homozygous C3 slow patients (p=0.005). Furthermore, we found a significant association between the SNP configuration in donors and BOS development. Patients receiving a graft from a donor with at least one C3 fast variant for rs2230199 had an inferior BOS-free survival (p=0.044). Conclusions: In conclusion, our data indicate local C3 production by donor lung cells. In addition, a single C3 SNP present in recipients affects short-term outcome after LTx, while this SNP in donors has an opposite effect on long-term outcome after LTx. These results could contribute to an improved risk stratification after transplantation.

  Study EGAS00001003843

• Mult-omics Palbociclib Resistance Study in HR+/HER2– Metastatic Breast Cancer

  This study is multi-omics study of a Asian longitudinal metastatic breast cancer (MBC) cohort treated with palbociclib plus endocrine therapy. It contains NGS of baseline (BL) and progressive disease (PD) from 70 patients, consisting of 79 tumor/normal matched whole exome sequencing (WES) from 62 patients and 90 tumor whole transcriptome sequecing samples (WTS) from 70 patients. There were 56 BL biopsies profiled by WES and 64 by WTS; 23 PD biopsies were profiled by WES and 26 by WTS. Twenty and 23 patients had paired BL and PD biopsies profiled by WES and WTS, respectively.

  Dataset EGAD00001008314

• Long-read whole genome sequencing of gastric cancer

  Gastric cancer (GC) remains a significant health challenge globally, with a particularly high incidence in Asia, including Singapore. Understanding the genomic landscape of normal gastric and the different GC subtypes along with its precursor lesions such as intestinal metaplasia (IM) as well as GC metastatic sites is crucial for advancing diagnostics, prognostics, and therapeutics. Long-read sequencing technologies offer an opportunity to delve deeper into the genomic and epigenetic alterations underlying these conditions and to complement existing short-read omics data. By integrating these data with previously generated in-house multi-omics data (such as RNA sequencing and whole exome sequencing), we hope to better elucidate the molecular mechanism underlying GC initiation and progression.

  Study EGAS50000001607

• HGG panel sequencing

  NGS panel sequencing of pediatric high-grade gliomas (HGG), including diffuse midline gliomas and hemispheric HGG. This is a population-based dataset from the Hospital for Sick Children (Toronto, Canada), of patients <18 years of age at diagnosis, and diagnosed between 2000-2022. The goal of the study was to define the genetic drivers in pediatric HGG, including the rates of different genetic drivers, such as H3 and BRAF mutations, in a single-site population based cohort.

  Study EGAS50000000221

• miRNA_expression_in_response_to_LPS_stimulus_in_macrophages

  Our lab is currently using macrophages as a model system for understanding how geneticvariation modulates the response to external environmental stimulus. We want to extend thisbeyond regular polyadenylated RNA to small RNAs such as miRNAs. This project wouldcover the costs of a pilot to study miRNA response to LPS stimulus, and will be performed aspart of a rotation project in the lab. We will require a small number of miRNA libraries and asingle lane of MiSeq

  Study EGAS00001000691

• Bulk-tissue RNA-sequencing paired nuclear and cytoplasmic fractions of anterior prefrontal cortex, cerebellar cortex and putamen tissues from 4 post-mortem neuropathologically-confirmed control individuals ( anterior prefrontal cortex &amp; cerebellar cortex – 4 individuals, putamen- 3 individuals)

  Profiling of paired nuclear and cytoplasmic fractions of anterior prefrontal cortex, cerebellar cortex and putamen samples by bulk-tissue RNA-sequencing. Samples were derived from 4 post-mortem neuropathologically-confirmed control individuals ( anterior prefrontal cortex – 4 individuals, cerebellar cortex – 4 individuals, putamen- 3 individuals). Paired-end FASTQ files for each of the human samples are provided. Fastp (v 0.20.0), a fast all-in-one FASTQ pre-processor, was used for adapter trimming, read filtering and base correction. Fastp default settings were used for quality filtering and base correction. Further details on parameters used are available here: https://github.com/RHReynolds/RNAseqProcessing .

  Dataset EGAD00001009264

• Lebanon_HighCov_seq

  We propose to investigate the genomics of a Lebanese sample. we plan (1) genotyping (2.5M) of 120 Lebanese individuals, choosing this platform to allow comparison with the 1000 Genomes and African Genome Variation project populations, (2) 8x sequencing of 100 individuals to provide unbiased population-level sequence information including allele frequencies, and (3) 30x sequencing of four individuals to allow inferences such as from PSMC/MSMC to be obtained. The current form is for the high-coverage sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001002085

• WES analysis in identifying additive genetic factors that may contribute to the occurrence of moyamoya in neurofibromatosis type 1

  Moyamoya is a progressive cerebral vasculopathy, for which genetic susceptibility factors were mainly identified in Asian populations. When associated with other medical conditions, such as neurofibromatosis type 1 (NF1), this vasculopathy is frequently reported as Moyamoya syndrome (MMS). Intriguingly, most cases of MMS-complicated NF1 have been described in Caucasians, inverting the population ratio for moyamoya vasculopathy observed in Asians, despite NF1 prevalence being constant worldwide. This study aims to investigate whether, among Caucasians, additive genetic factors may contribute to the occurrence of MMS in NF1. WES analysis has been carried out on an Italian family with co-occurrence of NF1 and MMS, as well as other cerebral vasculopathies.

  Study EGAS00001003053

• Lebanon_LowCov_seq

  we propose to investigate the genomics of a Lebanese sample. we plan (1) genotyping (2.5M) of 120 Lebanese individuals, choosing this platform to allow comparison with the 1000 Genomes and African Genome Variation project populations, (2) 8x sequencing of 100 individuals to provide unbiased population-level sequence information including allele frequencies, and (3) 30x sequencing of four individuals to allow inferences such as from PSMC/MSMC to be obtained. The current form is for the low-coverage sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001002084

• RNA-seq consisting of FASTQ paired-end reads from cancer samples

  Efforts to precisely identify tumor human leukocyte antigen presented peptides (HLAp) capable of mediating T cell based tumor rejection still face important challenges. Recent reports suggest that non-canonical cancer HLAp could be immunogenic but their identification requires highly sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches. Here, we present a MS-based analytical pipeline that can precisely characterize the non-canonical HLAp repertoire, incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLAp. Albeit often at low levels and in distinct subpopulations of cells, numerous non-canonical HLAp are shared across tumors. This analytical platform holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.

  Study EGAS00001003724

• Cancer and germline exomes consisting of FASTQ paired-end reads from melanoma and lung cancer samples

  Efforts to precisely identify tumor human leukocyte antigen presented peptides (HLAp) capable of mediating T cell based tumor rejection still face important challenges. Recent reports suggest that non-canonical cancer HLAp could be immunogenic but their identification requires highly sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches. Here, we present a MS-based analytical pipeline that can precisely characterize the non-canonical HLAp repertoire, incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLAp. Albeit often at low levels and in distinct subpopulations of cells, numerous non-canonical HLAp are shared across tumors. This analytical platform holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.

  Study EGAS00001003723

• Resuscitation Outcomes Consortium (ROC) Controlled Study of the Clinical Effectiveness of Automated Real-Time Feedback on CPR Process Conducted at a Subset of ROC Sites (CPR) (ROC-CPR-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: A substudy of the ROC PRIMED trial, the ROC CPR trial sought to investigate whether real-time audio and visual feedback during cardiopulmonary resuscitation (CPR) outside a hospital increases the proportion of participants who achieved prehospital return of spontaneous circulation.Background: Cardiopulmonary resuscitation is an essential link in the chain of survival for treating cardiac arrest. However, performance of CPR is highly variable both outside hospital and in hospital. Interruptions in chest compression, inadequate depth of chest compression, and high rates of ventilation adversely affect blood flow during chest compressions and can hinder resuscitation. Suboptimal CPR, particularly time spent without chest compressions (low chest compression fraction), can reduce survival of cardiac arrest patients.Current technology incorporated into a monitor-defibrillator can assess core components of CPR through the use of an accelerometer and impedance changes across the defibrillation electrodes. This technology can also provide real-time audiovisual feedback so that the rescuer is prompted to perform according to guideline specifications. Use of such feedback increases the likelihood of performing CPR in accordance with guidelines during training and simulation. Participants: There were 1586 participants: 771 treated without feedback and 815 with feedback.Design: CPR feedback was provided through proprietary Q-CPR software operating in the Philips MRx monitor-defibrillator. The feedback feature of the defibrillator includes audible voice prompts and visual messages on the monitor screen that are triggered when measured chest compressions or ventilation deviate from guidelines or are interrupted.The study was conducted in 21 emergency medical service (EMS) agencies at three ROC regions in the U.S. and Canada. Randomized treatment clusters, which ranged from individual emergency medical vehicles to groups of emergency agencies, were assigned to feedback-on or feedback-off treatments. Each cluster remained in its assigned mode for two to seven months, after which it switched to the opposite treatment arm. At the end of those two treatment periods, each cluster was again randomly assigned to feedback-on or feedback-off. This cycle continued for the duration of the study. Each cluster switched treatment arms at least once, and up to four times, during the study. Conclusions: Real-time visual and audible feedback during CPR altered performance to more closely conform with CPR guidelines. Clusters assigned to feedback were associated with increased proportion of time in which chest compressions were provided, increased compression depth, and decreased proportion of compressions with incomplete release. However, frequency of prehospital return of spontaneous circulation did not differ according to feedback status, nor did the presence of a pulse at hospital arrival, survival to discharge, or awake at hospital discharge (Hostler, et al., 2011, PMID: 21296838).

  Study phs003818

• Genetic Studies of Chronic Kidney Disease (CKD)

  The Genetic Studies of Chronic Kidney Disease (CKD) is an ongoing genetic research and biobanking protocol which aims to elucidate the genetic basis CKD. The study recruits patients seen at the Columbia University Medical Center (CUMC) Nephrology Division for the evaluation and care of CKD. All patients clinically diagnosed with CKD are eligible to participate; there are no inclusion or exclusion criteria related to age, sex/gender, and/or race/ethnicity. In addition to office visits, patients are recruited in contexts including perinatal care and nonprofit events for patients with various forms of CKD; recruitment tools include bilingual informational brochures, flyers, and consent forms. All individuals provide informed consent; for minors, signature of the parent/guardian is required. Consent includes: use of biosamples given for genetic studies, and the request to be re-contacted if medically actionable genetic findings are identified. In the case of the latter, such research-level findings are first validated in a clinically certified (CLIA) laboratory environment, using a second sample given by the individual at the time of re-contact; following CLIA validation, the individual is once again re-contacted, and, assuming he or she still desires return of these results, they can then be returned. Following the above consent process to participate in the study, individuals provide a single biosample (generally, a venous blood sample), from which DNA is extracted using standard protocols and used for genetic studies, such as exome sequencing. Basic clinical and demographic data, including sex/gender, age, and race/ethnicity are also collected. All data collected is stored in a secure computerized database, with patient samples anonymized using numerical identifiers; the relation of this identifier to patients&#39; names is kept in a locked computer file in a centralized database. Electronic data complies with all HIPAA and other privacy and security regulations, and resides on a firewall server maintained by the CUMC IT department.

  Study phs001828

• Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma

  Glioblastoma patient derived Fast/Slow cycling cancer stem cell RNA sequencing. Consists of 3 patient cell lines and 6 files

  Dataset EGAD00001004380

• The Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project: Defining a Healthy Volunteer Cohort

  The integration of comprehensive genomic and phenotypic data from diverse ethnic populations offers unprecedented opportunities towards advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases are not representative of the global human population, making variant interpretation challenging, especially in underrepresented populations such as the North African population. To address this, the Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project launched a study comprising 1000 individuals free of cardiovascular disease (CVD). Here, we present the first 391 Egyptian healthy volunteers (EHVols) recruited to establish a pilot phenotyped control cohort. All individuals underwent detailed clinical investigation, including cardiac MRI, and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions (ICC). We identified 1,262 variants in 27 cardiomyopathy genes of which 15.1% were not captured in current global and regional genetic reference databases (here: gnomAD and Great Middle Eastern (GME) Variome). The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in CVD and population genetics.

  Study EGAS00001004434

• Foregut Microbiome and Risk of Gastric Intestinal Metaplasia, and Gastric Cancer Risk

  The study is composed of two sub-studies. The first study, conducted by NYU Grossman School of Medicine, is a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. Shotgun metagenomic sequencing using oral wash samples from the 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs were conducted. The other study, conducted by Vanderbilt University Medical Center, is a prospective case-control study on the oral microbiome and gastric cancer risk, utilizing shotgun metagenomic sequencing data of pre-diagnostic buccal samples from 319 Asians, 118 African Americans and 51 European Americans. This study includes data from three population-based studies: the Southern Community Cohort Study (SCCS), the Shanghai Women's Health Study (SWHS), and the Shanghai Men's Health Study (SMHS). The SWHS and SMHS include 74,941 women aged 40-70 years and 61,480 men aged 40-74 years, respectively, who were permanent residents of Shanghai and recruited to the cohorts between 1997 and 2006. The SCCS is an ongoing prospective cohort study, including ~86,000 participants recruited during 2002 and 2009 from 12 Southeastern states. Nearly 67% of study participants are African Americans (AAs) and the remaining are European American (EA) subjects.

  Study phs002566

• MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas

  Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas1. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients2. Here we show that a subset of recurrent gliomas carry MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that they lead to TMZ resistance both in vitro and in vivo. Lastly we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.

  Study EGAS00001004544

• Center for Sub-Cellular Genomics

  A cell is a highly complex system with distributed molecular physiologies in structured sub-cellular compartments whose interplay with the nuclear genome determine the functional characteristics of the cell. A classic example of distributed genomic processes is found in neurons. Learning and memory require modulation of individual synapses through RNA localization, localized translation, and localized metabolites, such as those from dendritic mitochondria. Dendrites of neurons integrate distributed synaptic signals into both electrical and nuclear transcriptional response. Dysfunction of these distributed genomic functions in neurons can result in a broad spectrum of neuropsychiatric diseases such as bipolar and depressive disorders, autism, among others. The Center for Sub-Cellular Genomics' (CSG) mission is to develop new technologies to enable the dissection of complex genomic interactions within a single cell. New technologies include methods to target DNA and RNA sampling at sub-cellular resolution in live cells; high-throughput isolation and microfluidics chemistry for sub-cellular fractions; sub-cellular resolution mass-spectrometry; and computational tools for analysis of sub-cellular genomics data. The new technologies developed by CSG will enable the broader genomics community to associate sub-cellular processes to cell function and dysfunction. These technologies will be utilized in the center to generate a comprehensive atlas of genomic signatures of sub-cellular compartments in the mammalian neuron system. The technologies and neuron-focused data obtained here will be relevant to neurodegenerative and neuropsychiatric diseases including schizophrenia, depression, autism spectrum disorder, traumatic brain injury, and Alzheimer's.

  Study phs002120

• Genome sequencing identifies splice-disrupting variants in childhood heart disease

  We used genome sequencing (GS) to identify cardiac specific splice disrupting variants that were subsequently validated in a subset of participants. In turn, we developed a heart-specific model for canonical and non-canonical splice variants, which was applied to patients with congenital heart disease (CHD). These included patients with two of the most common forms of cyanotic CHD i.e. tetralogy of Fallot (TOF) and dextro-transposition of the great arteries (TGA). In addition to identifying canonical splice-disrupting variants in known CHD-related genes in 1% cases, this approach identified putatively damaging non-canonical splice-disrupting variants in 11% of isolated CHD, with deeply intronic variants representing 53% of non-canonical splice-disrupting variants in CHD genes. GS was critical for the identification of variants that would not be captured by routine clinical genetic tests including exome sequencing, while cardiac RNA-Seq allowed for high specificity in the interpretation of splice-disrupting effects in the heart.

  Study EGAS50000000586

• Identification of Modifiers of 22q11.2 Deletion Syndrome in Whole Genome Sequence - CIDR

  This project aims to identify genetic modifiers of congenital heart disease (CHD), which occurs among 22q11.2 deletion syndrome (22q11.2DS; also known as DiGeorge syndrome/velo-cardio-facial syndrome) patients. In contrast to the prevalence of ~0.8% in the general population, about 60%-70% of 22q11.2DS patients have CHD, of which most are conotruncal heart defects, making 22q11.2DS a very ideal model to study the genetic underpins of CHD. The chromosome 22q11.2 region is susceptible to meiotic chromosome rearrangements leading to hemizygous deletions, because there are large blocks of low copy repeats, termed LCR22s, that are dispersed in the region. Non-allelic homologous recombination during meiosis can lead to specific-sized deletions. Approximately 90% have a typical hemizygous 3 million base pair (Mb) deletion between LCR22-A and -D, while some have nested deletions between LCR22-A and B or LCR22-A and C. Our goal is to perform a case-control association study, in which cases have CHD, while controls have normal heart structures, all with 22q11.2DS. All individuals are unrelated and have been collected from collaborators in the US, Canada and Europe. All subjects received a clinical diagnosis of 22q11.2DS and signed informed consent to allow a blood sample to be collected for research. The DNA samples were de-identified in 2 steps to protect their privacy. We then determined deletion type using multiplex ligation-dependent probe amplification (MLPA). This information is provided for the great majority of subjects. We also obtained cardiac phenotype information from echocardiogram reports as well as reported race and ethnicity (Hispanic vs. non-Hispanic information), which is required for the analysis. We will obtain 30X whole-genome sequence data from NIH CIDR. We will first annotate the sequence variants identified to uncover rare ( For genotype data, we will provide the raw fastq data from whole-genome sequencing as well as the called variants file in a VCF file. For phenotype data, we will provide the sample relationship files (ped files), CHD affection status, deletion type, and race.

  Study phs002514

• Genome Variation among HIV-Resistant People with Hemophilia

  Rare individuals are highly resistant to infection with human immunodeficiency virus (HIV). Studies of candidate genes resulted in the discovery of a 32bp deletion in the CC-chemokine receptor 5 gene (CCR5&#916;32), which rendered this critical co-receptor for primary HIV infection to be non-functional. Pharmacologic and vaccine-induced blockade of CCR5 is being pursued to treat and prevent HIV infection and other conditions. The allele frequency of CCR5&#916;32 among persons of European ancestry is approximately 10%. CCR5&#916;32/&#916;32 homozygotes are almost totally resistant to HIV infection. People with severe hemophilia A require frequent replacement with clotting Factor VIII (FVIII) to control hemorrhage. Prior to the discovery of HIV in 1984 and licensure of recombinant FVIII in the late 1980s, people with severe hemophilia A were treated with plasma-derived FVIII and thus were intensively exposed to HIV. Only 5% of such patients were not infected with HIV. Of these, approximately 1/3 were CCR5&#916;32/&#916;32 homozygotes. The remaining 2/3 of these people who were highly resistant to HIV remain unexplained. This project seeks to discover genome variations among people who are highly resistant to HIV infection. Such variation is likely to serve as a target for reducing the morbidity and incidence of HIV.

  Study phs000445

• EGAD00000000058

  Aggregate results from 22 Carbamazepine-induced hypersensitivity syndrome patients and 2691 UK National Blood Service (NBS) control samples

  Dataset EGAD00000000058

• Virginia PrIMeD Study

  The goal of this study was to determine whether screening children (2-16 yrs) in pediatric waiting rooms for genetic risk of type 1 diabetes (T1D) could be applied to diverse (by geography, genetic ancestry) communities, and for those at "high genetic risk," if barriers prevent subsequent screening for presence of islet autoantibodies. A total of 3,818 children were recruited from eight general pediatric and specialty clinics across Virginia. Clinical Research Coordinators were stationed at each clinic and obtained informed consent/assent, a brief medical history, and a saliva sample for DNA extraction and determination of their genetic risk using a T1D Genetic Risk Score (T1D GRS). Children were present in the clinic for a "healthy" visit, although children with and without a history of T1D were recruited into the study. Age, sex, self-reported ancestry/race, T1D history, and other medical history information was obtained. DNA was extracted from the saliva samples and genotyping with a T1D-focused array using 74 SNPs (including 26 SNPs in the HLA region) provided data to generate a T1D GRS for each individual. Of the 3,818 children recruited, there was a slight excess of males (1,959, 51.3%), a majority of white and Hispanic/Latino ancestry (82.8%), and 91 (2.4%) with prevalent T1D. A total of 542 (14.2%) had "high T1D genetic risk" (T1D GRS > 5). Although the T1D GRS included non-HLA genetic variants, 80% of those with "high genetic risk" would have been classified using only those SNPs in the HLA region alone. Of children with "high genetic risk" and without pre-existing T1D (n=494), 7.0% (34/494) consented for islet autoantibody screening. Among children with pre-existing T1D (n=91), 52% (n=48) also had a "high genetic risk." The HLA-focused T1D GRS was not significantly associated with age at onset of T1D. Of those at high genetic risk that consented for autoantibody testing (n=34) and completed the blood collection (n=28), two (2/28, 7.1%) tested positive for multiple autoantibodies and were at significant risk of developing T1D. Follow up of 55% of parents/guardians identified 2 (of 2,096, 0.095%) participants who developed T1D, one at "high genetic risk" and one with a first-degree relative with T1D. A major factor in obtaining islet autoantibody testing was concern over SARS-Cov-2 exposure and an independent non-scheduled blood collection.Individual-level data at each SNP (genotyped and imputed) for T1D genetic risk and affiliated data are provided in dbGaP.

  Study phs003609

• Host genotyping data from Dutch adult bacterial meningitis patients and linked bacterial genome sequences

  Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. This study includes 1146 samples of host genotyping data (genotyped and imputed) from Illumina Omni arrays. Samples were collected from adults (&gt;16 yrs) patients with CSF confirmed bacterial meningitis in the Netherlands between 2006 and 2015. Metadata includes patient outcome, species of bacteria, and for 467 samples a link to an ENA run with the associated bacterial genome (S. pneumoniae only).

  Study EGAS00001005993

• Genomic Regions Associated with Susceptibility to Barrett's Esophagus and Esophageal Adenocarcinoma in African Americans: The Cross BETRNet Admixture Study

  Differences in rates of diseases between different populations with similar environments are presumed to be secondary to variability in population frequencies of disease causing alleles. Recently admixed populations such as African Americans (AAs) provide a natural opportunity to identify disease-causing variants by examining the ancestry of long chromosomal haplotypes. Admixture mapping approach can be successful in locating genes for diseases such as EAC whose rates varies markedly between the ancestral populations. This is a case only study with 54 African American cases and also on a subset of 28 cases with high genotyping quality. We seek to identify chromosome regions that have excess European ancestry and contrasting it to excess African ancestry.

  Study phs001454

• Genomics of Opioid Pharmacogenomics and Acute/Chronic Postsurgical Pain after Major Surgery in Children

  Pain management after surgery is not optimal, partly due to great interindividual variability in pain perception and coping. This can lead to persistent pain beyond the healing period and disability. Up to two-thirds of the inter-individual variability results from genetic variations in pain perception as well as response to the pain medicine. The investigators aim to identify genomic (genetic/epigenetic), psychological and drug profiles contributing to this variability. Opioids are the mainstay for treatment of postoperative pain in children. Experience dictates that opioids have narrow therapeutic indices and large inter-patient variability in response. This leads to serious side effects like respiratory depression in up to 50% of children undergoing invasive surgery, which can be fatal. It is evident that there are particular children who are more susceptible to suffering side effects and having inadequate pain relief from opioids.It is hypothesized that much of the genetic variability can be explained by gene function which is modulated by a) Single Nucleotide Polymorphisms (SNPs) in genes that encode proteins involved in pain perception, opioid transport/metabolism (pharmacokinetics), and opioid receptor signaling (pharmacodynamics); b) epigenetics which modify gene expression without structural changes to the DNA, and c) genes that influence psychological factors.The purpose of this research study is to identify factors and genes that may be associated with acute and chronic post-surgical pain, and to develop pharmacometric models for response to opioids, like morphine and hydromorphone. While children undergoing different surgeries will be recruited for acute outcomes, children undergoing spine fusion will be followed for 10-12 months for evaluation of psychological and genomic factors affecting chronic post-surgical pain, with a goal of identifying genetic and epigenetic risk models for prediction of acute and chronic post-surgical pain. Although opioids are used every day, some children have bad reactions from their use, like breathing problems, sedation, etc. The investigators want to study factors that may be associated with pain sensitivity, opioid requirements after surgery, their metabolism, efficacy and their side-effects. The investigators expect that the information obtained in this research study will help to develop effective, safer, and tailored treatment options in the future.

  Study phs002105

• sWGS of HGSOC samples for fixative comparison study

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

  Dataset EGAD00001001938

• Evidence for Enhancer Activity in Intron 1 of TNFRSF1A Using CRISPR/Cas9 in Human Induced Pluripotent Stem Cell-derived Macrophages

  Use of CRISPR/Cas9 technology to study the TNFRSF1A gene, which plays a key role in autoimmune diseases such as ankylosing spondylitis, multiple sclerosis, and inflammatory bowel disease. By editing a specific regulatory element within the TNFRSF1A locus, we have identified the role of an enhancer element that is not well understood.

  Study EGAS50000000703

• Cancer genomics for elucidation of molecular mechanisms of carcinogenecis and progression in lung cancer

  The objective of this project is to analyze genomic aberrations and gene expression changes such as mutations, deletions, amplifications, and hypermethylation in human lung cancer cells at the somatic cell level, and to contrast these with clinicopathological information to elucidate the molecular mechanisms and characteristics of lung cancer development and progression at the genetic level.

  Study JGAS000756

• A PROSTATE TUMORGRAFT PANEL TO ACCELERATE PRECISION MEDICINE

  The management of advanced prostate cancer (PCa) has strongly evolved in the last decade with the introduction of the next generation of androgen receptor pathway inhibitors which have considerably improved patient outcomes. Most recently, the investigation of genomic landscape has provided targetable molecular alterations such as homologous gene DNA repair defects correlated with response to PARP inhibitors. Despite these significant advances, while localized PCa is generally associated with favorable outcome, metastatic PCa is currently considered incurable. For further investigations in precision treatment, the development of preclinical models representing the complex prostate tumor heterogeneity are mandatory. Accordingly, we aimed to establish a resource of patient-derived xenograft (PDX) models that exemplify each phase of this multistage disease for accurate and rapid evaluation of candidate therapies.

  Study EGAS00001007033

• Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling

  The four main medulloblastoma subgroups are characterized by distinct biology, clinicopathological features and clinical outcomes. While the WNT and SHH subgroups are characterized by clearly defined aberrant signaling of developmental pathways, the underlying biology of Group 3 and 4 remains poorly understood. Here, we delineate distinct post-translational regulation orchestrating active oncogenic signaling networks in Groups 3 and 4. Specifically, aberrant ERBB4-SRC signaling constitutes a novel hallmark feature of Group 4, with great promise as a novel oncogenic mechanism and potential vulnerability for therapeutic intervention in the most common subgroup. Altogether, this novel integrative proteogenomic landscape demonstrates the added value of proteomics and phosphoproteomics analysis to discover and exploit unexpected oncogenic mechanisms in medulloblastoma and beyond.

  Study EGAS00001002757

• Evaluation of protocols for rRNA depletion-based RNA sequencing of nanogram inputs of mammalian total RNA

  Next generation RNA-Sequencing (RNA-seq) is a flexible approach that can be applied to e.g. global quantification of transcript expression, the characterization of RNA structure such as splicing patterns and profiling of expressed mutations. Many RNA-seq protocols require up to microgram levels of total RNA input amounts to generate high quality data, and thus remain impractical for the limited starting material amounts typically obtained from rare cell populations, such as those from early developmental stages or from laser micro-dissected clinical samples. Here, we present an assessment of the contemporary ribosomal RNA depletion-based protocols, and identify those that are suitable for inputs as low as 1-10 ng of intact total RNA and 100-500 ng of partially degraded RNA from formalin-fixed paraffin-embedded tissues.

  Dataset EGAD00001005316

• Genetic Study of Vascular Anomalies

  Vascular anomalies are malformations or tumors of the vasculature that can result in significant morbidity and mortality. Vascular anomalies are caused by germline or post-zygotic pathogenic variants in genes that regulate cell growth and vascular development. Complex or extensive vascular anomalies are often intractable despite interventions such as sclerotherapy, embolization, or surgery. In recent years, targeted therapy has played an increasingly crucial role in the management of these diseases. Identification of the molecular causes of vascular anomalies is essential to provide efficacious therapy; however, genetic profiling is often limited by difficulty obtaining affected tissues and limited sequencing depth. The lack of this information limits treatment options and the precision of targeted therapy, especially for primary complex lymphatic anomalies. To address these limitations, we have applied novel techniques, including analysis of unconventional samples such as endothelial cells isolated from lymphatic fluid and cell-free DNA, deep coverage exome sequencing, and unique molecular identifier ultra-deep targeted sequencing, in the molecular profiling of these diseases.

  Study phs003197

• RNAseq of MCL cell lines

  This study provides bulk RNA sequencing data from Mino and Jeko-1 mantle cell lymphoma (MCL) cell lines treated with CDK9 inhibitors, including the novel compound YX0798. CDK9 is a key regulator of RNA polymerase II–mediated transcription, and its inhibition disrupts transcriptional programs critical for tumor survival. The dataset captures transcriptomic changes associated with CDK9 inhibition, including downregulation of oncogenic drivers such as MYC and MCL-1. These data support mechanistic studies of transcriptional reprogramming and therapeutic vulnerability in aggressive MCL.

  Study EGAS50000001089

• Elucidation of genomic pathology of a patient with concurrent acute myeloid leukemia and mediastinal germ cell tumor

  The occurrence of a mediastinal germ cell tumor (GCT) and hematological malignancy in the same patient is very rare. Whole exome sequencing was performed for concurrent acute myeloid leukemia (acute megakaryoblastic leukemia) and mediastinal germ cell tumor. Somatic mutations, such as TP53 or PTEN, were commonly identified in both acute myeloid leukemia and mediastinal germ cell tumor, suggesting the common founder clone. Normal buccal cells were used as a control. Illumina NextSeq 500 platform were used.

  Study JGAS000211

• Investigation_of_mutational_signatures_associated_with_DNMT3A_deficiency_

  Mutational signatures have been shown to be attributable to specific genetic contexts, such as mutations in DNA repair genes. DNMT3A is a DNA methyltransferase that helps maintain the DNA methylation pattern in a site-specific manner and may participate in DNA repair or the stress response. We have identified an adult individual who is a germline mosaic for a DNMT3A mutation. We have obtained clonal lymphoblastoid cells (LCLs) from the subject representing both WT and mutant lines grown in the same individual for &gt;50 years. These clones represent a unique opportunity to examine the mutational impact of the DNMT3A mutation in a well-controlled setting. Our goal is to perform WGS on whole blood, representing the pool, as well as several WT and several mutant clones, in order to investigate the contribution of DNMT3A to mutation rates and signatures.

  Study EGAS00001002329

• SudanMitoSeq: Sudanese mitochondrial sequencing

  In various contexts, mitochondrial function or dysfunction can be linked to mitochondrial genome variations. The use of mitochondrial genetics thus promises personalized diagnostics and treatments. In order to devise specific precision medicine approaches based on mitochondrial genetic variation and to test them within clinical studies, control data is indispensable. Such control data needs to comprehensively cover genetic variation commonly observed and thus expected. In the context of this study we assessed whether current, world-wide mitochondrial data sufficiently represents the region of North and East Africa, that is, whether current reference data is ready for precision medicine in this region. Towards this, we sequenced mitochondrial genomes of 159 Sudanese individuals provided as part of this EGA study and analyzed them together with various other, publicly available data concerning mitochondrial variation. For details, please refer to the publication.

  Study EGAS00001005669

• Ecological Stressors, PTSD, and Drug Use in Detroit: The Detroit Neighborhood Health Study (DNHS)

  The Detroit Neighborhood Health Study (DNHS) is a prospective, representative longitudinal cohort study of predominantly African American adults living in Detroit, Michigan. The overall goal of the DNHS is to identify how genetic variation, lifetime experience of stressful and traumatic events, and features of the neighborhood environment predict psychopathology and behavior. Cohort participants were selected with a dual-frame probability design, using telephone numbers obtained from the U.S. Postal Service Delivery Sequence Files as well as a listed-assisted random-digit-dial frame. Individuals without listed landlines or telephones and individuals with only a cell phone listed were invited to participate through a postal mail effort. Participants completed a 40 minute, structured telephone interview annually between 2008-2012 to assess perceptions of participants' neighborhoods, mental and physical health status, social support, exposure to traumatic events, and alcohol and tobacco use; each participant was compensated $25USD. All survey participants were offered the opportunity to provide a specimen (venipuncture, blood spot, or saliva) for immune and inflammatory marker testing as well as genetic testing of DNA. Participants received an additional $25USD if they elected to give a sample. Informed consent was obtained at the beginning of each interview and again at specimen collection. The Institutional Review Board of the University of Michigan reviewed and approved the study protocol. The DNHS submission to dbGaP includes phenotype data from all five survey waves (n=856), all available GWAS data for participants who completed wave 4 (n=507), and methylation data for wave 1, wave 2, wave 4, and wave 5 participants (n = 456).

  Study phs000560

• NIDA Genetic Epidemiology of Opioid Dependence in Bulgaria (GEODB)

  The study was conducted in Bulgaria as a collaboration between the Molecular Medicine Center (Medical University, Sofia), the Bulgarian Addictions Institute (Sofia), the Initiative for Health Foundation (Sofia) and Washington University School of Medicine (Saint Louis, MO, USA). This is a case-population control study. Participants (N=2,499 interviews; N=1,995 with GWAS data) in our study are primarily active heroin users (78%) aged 18 and over, with a median 8.9 years of daily heroin use (minimum of 12 months). Virtually all participants (99.1%) qualified for a lifetime DSM-IV diagnosis of dependence, symptom endorsement probabilities ranging from 77% to 99.3%; and 61% endorsing all symptoms. 85% were heroin injectors and 97% reported using (or having used) heroin daily. Anonymized, population-representative control samples (no phenotypic data, N = 1,062 with GWAS data) were drawn from the MMC repository. Unlike other studies, where samples are clinically ascertained (e.g., from ORT programs), our participants are primarily untreated. PTSD, major depression, suicidality, mania, alcohol, nicotine and substance dependence (separating heroin and opioids) were assessed using the MAGIC (Todd et al., 2003, PMID: 14627881), a broad semi-structured psychiatric assessment tool with good reliability and prospective stability. The onset of (any) illicit drug use in this sample is not particularly remarkable (age~16), but the age of onset of heroin use is much lower than in the USA: 25% by age 16; 50% by age 19, with no differences between ethnicities or gender. This is consistent with findings from other studies in Bulgaria. In contrast, in 2008, SAMHSA estimated an average age of 23.4 for new heroin initiates in the USA. Further, progression from first use to regular use appears to be more rapid, with the majority of participants reporting onset of dependence problems within one year of initiation. Another unique aspect of this study population are the comparatively low levels of polysubstance use (outside of nicotine and alcohol). This early-use, fast-transition and monosubstance heroin pattern stands in sharp contrast to what is reported in many studies in the Western World. In our study, 47% of Ethnic Bulgarians and 66% of Roma used only opioids, even years after the onset of drug use. 15.4% of Ethnic Bulgarians and 66.2% of Roma reported heroin as the very first illicit drug used. Lifetime, 12.5% of Ethnic Bulgarians and 52.8% of Roma report never having used another illicit drug other than heroin more than five times. While both Roma and Ethnic Bulgarians certainly experiment with other drugs, abuse/dependence rates for these drugs are low in Ethnic Bulgarians (from 8.4% for inhalants to 28% for stimulants) and in the Roma population (from 1.3% for hallucinogens to 11.2% for stimulants).

  Study phs001804

• HCA_Thymus_Disease

  Single cell RNA sequencing on thymic cells from children with syndromic diseases such as Trisomy 21 and inflammatory/autoimmune diseases such as myasthenia gravis. Our group has previously performed atlasing of the healthy human thymus using single cell transcriptomics and obtained an unprecedented understanding of human thymus throughout development. In this study, we intend to survey diseased human thymus and compare this to healthy to obtain a better understanding of thymic dysfunction in human diseases. The diseases we will survey include congenital conditions such as Down's syndrome, CHARGE syndrome, DiGeorge syndrome as well as acquired diseases such as myasthenia gravis and thymic hyperplasia. We intend to perform genetic and genomic study on the samples, including expression analysis. This will not only help us to understand the cells and molecular pathways affected in dysfunctional thymus; but may also lead to generalisable understandings in human genetic diseases and inflammatory/autoimmune diseases. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001004310

• How to upload GPG files

  Uploading files Users that holds an ega-box-XXX account can upload files using either INBOX or FTP. Users who have a Submitter role associated with their email will only be able to upload files using INBOX. Before uploading your files please make sure that any files that will be uploaded to EGA do not use special characters in their naming convention such as # ? ( ) [ ] / \ = + < > : ; " ' , * ^ | &. This can cause issues with the archiving process, leading to problems for end users. The EGA is a shared, public service with limited storage. In order to manage the available resources, we enforce a limit of 10Tb per submission account at any one time. Please do not exceed this limit. INBOX FTP The FTP is only compatible with files encrypted using the EGACryptor tool Before uploading Once your submission files have been prepared using the EGAryptor, the resulting encrypted files and associated md5sum files can be uploaded to your submission account using Aspera or FTP. The EGA is a shared, public service with limited resources. In order to manage the available resources, EGA submission boxes should not exceed 8Tb in size, and cannot exceed 12Tb. If you are approaching this limit please contact contact EGA Helpdesk so that we can advise on how to register the associated metadata and trigger the archiving of files, so that you can continue with your submission. If we note that your submission account increases above 10Tb on a consistent base your password will be changed until metadata is associated. Aspera Download Aspera Using Aspera FTP FTP windows FTP Linux / Unix FTP client (Filezilla) FTP and TLS Troubleshooting Troubleshooting Aspera Download Aspera is a commercial file transfer protocol that may provide faster transfer speeds than ftp especially over longer distances. The Aspera ascp command line client. Please select Aspera Connect. The ascp command line client is distributed as part of the aspera connect highperformance transfer browser plugin and is free to use, without registration. The minimum required version of the IBM Aspera Cli is V4. Further instructions. Using the Aspera ascp command line program The location of the ascp program in the filesystem: Mac: on the desktop go cd /Applications/Aspera\ Connect.app/Contents/Resources/ there you'll see the command line utilities where you're going to use ascp. Windows: the downloaded files are a bit hidden. For instance, in Windows 7 the ascp.exe is located in the users home directory in: AppData\Local\Programs\Aspera\Aspera Connect\bin\ascp.exe Linux: should be in your user's home directory, cd /home/username/.aspera/connect/bin/ there you'll see the command line utilities where you're going to use ascp. Your command should look similar to this: ascp -P33001 -O33001 -QT -l300M -L- /path/file ega-box-N@fasp.ega.ebi.ac.uk:/path If you wish to upload several files without being requested the password, please use the below command : ASPERA_SCP_PASS=ega-box-password ascp -P33001 -O33001 -QT -l300M /path/file ega-box-N@fasp.ega.ebi.ac.uk:/path/ Explanation of parameters l300M option sets the upload speed limit to 30MB/s. You may wish to lower this value to increase the reliability of the transfer. L option is for printing logs out while transferring files to upload can be a file mask (e.g. '/homes/submitter/*.srf) or a list of files. ega-box-N is your submission account login. Add k2 switch for transfer restarts Check the command line transfer usage for more configuration details. Using FTP to upload your prepared files Use your preferred ftp client. For example, lftp is a popular choice for Linux and Mac users. Use binary mode for file transfers. Use ftp.ega.ebi.ac.uk as the target host. Login with your ega-box username and password. Upload files to your private ega-box upload area. Depending on your network setting you might wish to start FTP in passive or active mode. Using default FTP command line client in Windows Start the command line interpreter: press WinR, type cmd, hit enter Enter ftp ftp.ega.ebi.ac.uk Enter your submission username Enter your submission password Type binary to enter binary mode for transfer To see a list of available ftp commands type help. Type ls command to check the content of your submission account. Type prompt to switch off confirmation for each file uploaded. Use mput command to upload files: mput *.bam* Use bye command to exit the ftp client. Use exit command to exit the command line interpreter. Using default FTP command line client in Linux / Unix Open a terminal and type ftp ftp.ega.ebi.ac.uk Enter your submission username Enter your submission password Type binary to enter binary mode for transfer To see a list of available ftp commands type help. Type ls command to check the content of your submission account. Type prompt to switch off confirmation for each file uploaded. Use mput command to upload files: mput *.bam* Use bye command to exit the ftp client. Using FTP client FileZilla We recommend the use of FileZilla, a free FTP client . FileZilla is open source software distributed free of charge under the terms of the GNU General Public License. Use the following connection details (File - Site Manager) and add yoursubmission account username and password: Using FTP client FileZilla Select the files you wish to upload and then select upload: Using FTP client Filezilla Using LFTP with TLS We recommend the following to force the use of a secure connection. lftp > set ftp:ssl-force yes We also recommend setting the following for not encrypting the bulk data itself for performance reasons (theauthentication will still be encrypted): lftp > ftp:ssl-protect-data no In order to verify the certificate,the recommended way would be to use the CA certificates from your machine. To do that use this command in lftp adjusting the path to your ca-certificates location. lftp > ssl:ca-file "/etc/ssl/certs/ca-certificates.crt" If that is not possible or certificates are old and you can't update them, you can download the certificates needed from Quo Vadis Digital Repository The two certificates to download in PEM format are: QuoVadis Root CA2 G3 QuoVadis EV SSL ICA G3 Then you can concatenate them in a file one after the other and save it as lftp-certificates.pem Once this is done you have to point the ssl:ca-file variable to the path lftp > set ssl:ca-file "/path/to/lftp-certificates.pem" Also note that you can save this configuration at ~/.lftp/rc Another option is to download the certificates and add them to the ca-certificates of your machine. For example: In RHEL7 and cenots and others box the process to add the certificates globally is: Download the two certificates (in PEM or DER format, doesn't matter) and save them to "/etc/pki/ca-trust/source/anchors/" Run "update-ca-trust extract" Another less secure option is to turn off certificate verification with the following command: lftp > set ssl:verify-certificate false Troubleshooting If you are having problems with Aspera connection timeouts, it can be down to either one of the following. Transfers cannot start the connection fails instantly. Ensure that TCP traffic on port 33001 is allowed (open) for outbound connections through your computer's firewall and network's firewall. The connection is made, transfers are started, but 0 bytes (0%) are uploaded for each file. Ensure that UDP traffic on port 33001 is allowed (open) for outbound connections through your computer's firewall and network's firewal

  Documentation submission/data/uploading-files/ftp

• A unidirectional histone code in bidirectional promoters across cell types

  Recent studies indicate that thousands of genes are expressed from bidirectional promoters (BDPs). Gene regulation at BDPs is poorly understood, in particular how the cell is able to regulate them differently. Here we investigate the effect of histone Modifications in BDP regulation. In this study, we model the gene activity using different gene expression assays, such as RNA-Seq, GRO-cap, and CAGE around the BDP transcription start sites (TSSs) using different histone modifications in various cell types. We develop a new statistical approach that links histone modifications to gene expression at BDPs. It improves over previous methods, because it is able to capture spatial dependencies of histone modifications along a promoter and leads to more interpretable results. We predict a general histone code that is independent of transcript orientation, cell type, and promoter configuration. The histone code at BDPs reveals that promoters are regulated unidirectionally, such that the majority of histone marks associated with gene expression occur downstream of the gene's TSS. By contrasting associations of histone marks with steady-state levels of capped RNAs in CAGE and nascent capped RNAs in GRO-cap, we show which histone marks have a preference for initiating polymerases and actively elongating polymerases. Using single-cell data we show that the bidirectional histone signal of activating marks is often due averaging of a heterogeneous cell population. Our results have implications for other experiments where the relationship between histone modification and gene initiation or gene elongation is investigated on a genome-wide scale.

  Study EGAS00001001656

• What is a DAC?

  What is a DAC? Given the complexity, scale, and diversity of global submitters and studies, the EGA operates a distributed data access model in which requests are made to the data controller, not to the EGA. The European Commission defines a data controller, in the General Data Protection Regulation (GDPR), as the person that determines the purposes for which and the means by which personal data is processed. A Data Access Committees, commonly referred to as DACs, comprise on or more individuals (or data controllers) that review data access requests and make decisions on who can access personally identifiable genetic, phenotypic, and clinical data deposited at the EGA. Therefore, the members of a DAC should be individuals who have the authority to approve data access requests. The animation describes how you can authorise access to your sensitive data with the help of Data Access Committee and Authorisation tool. Acknowledgement to CSC - IT Center for Finland, Elixir Finland, Elixir Europe. Frequently Asked Questions How can I create a Data Access Committee? How can I create a Data Access Committee? The members of a DAC can come from different areas of expertise, such as data management, data analysis, information technology, legal and compliance, subject matter experts, privacy and security, and representatives from the organisations or individuals that provide data to the DAC. The specific members of a DAC can vary depending on the needs of the organisation and the type of data being managed. The EGA strongly suggests checking with your organisation to align with its regulations How should a DAC be named? The chosen name must be informative to the applicant.  For example, internal identifiers, such as grant numbers, should not be used. Individual PI names should also not be used. DAC's are often named after the organisation or department of the data source.  Browse the full list of DAC names currently in the EGA. How can I become an EGA DAC contact? To register a DAC at the EGA you must create first as an EGA user. Once your EGA user has been approved by the Helpdesk team, you will be able to log in to the DAC Portal. How can I register a DAC? To register a DAC, follow the DAC Portal instructions.  You will be required to provide a DAC name, name of the individual(s) that make up your DAC and contact details for your DAC including your Institutional email(s). Wherever possible, the DAC should make sure that all points of contact are readily available and able to answer any initial data requests/queries in < 2 weeks.  Once your DAC is registered, you will have to wait upon the validation from our Helpdesk team. As soon as all the validations have been completed, your DAC will be activated. Alternatively, you can also establish a DAC at the EGA during a programmatic submission through Webin API. Which are the possible roles of a DAC contact? There are two possible roles for DAC contacts: member and admin. An admin has additional privileges compared to a member: An “admin” can manage data requests, create and edit policies, edit the content of the DAC, add or remove contacts, and decide the role of each contact. A “member” can manage data requests and create policies. However, a member does not have permission to modify DAC details, edit information from policies where they are not admins, or add/remove contacts. There is no limit to the number of admins in a DAC, and each admin is responsible for deciding who should have editing privileges. This allows for a more decentralised and democratic approach to managing the DAC. How can I modify the information of a DAC? To modify a DAC, follow the instructions here. Keep in mind that only DAC contact with an admin role can modify the information of a DAC. If your DAC was registered before the lauch of the DAC Portal, and its ID is EGAC0 (not EGAC5), you must use the programmatic submission to modify it. Please, do not hesitate to contact our Helpdesk team if you need help with this! To prevent potential data breaches and ensure adherence to GDPR regulations, it is essential that the European Genome-Phenome Archive (EGA) is informed via the Helpdesk team of any changes to the Data Access Committee (DAC). This should be done in addition to any changes being made on the DAC portal. Data Controllers (as per the definition in the DPA) are also responsible for notifying the previous DAC of any modifications. Without proper notification, changes might not be automatically updated in our system, leading to the risk of incorrect permissions being applied and potential data access issues. Therefore, it is imperative that all Data Controllers follow this protocol to maintain data integrity and security. What’s the link between DAC, policy and dataset? A dataset is linked to one single policy. At the same time, one policy has a one to one relationship with a DAC. In this example, you can see that in this dataset page, we are only showing the information of one DAC (1 dataset - 1 DAC). However, the ratio of objects does not work the same in the other direction. One DAC can own multiple policy objects. And each policy object can be reused in several datasets. Thus, one DAC can manage one or more datasets. In this example, you can see that in this DAC page, we are showing all the datasets that are managed by one DAC (1 DAC - >400 datasets). EGA Data Access Committee Best Practices Which are the EGA DAC best practices? Refer to DAC Best Practices What happens if a DAC member changes institutions? EGA is committed to the protection and ownership of the data stored in our systems. We respect the institution's ownership of the data, and as such, if a DAC member changes institutions, the ownership of the data will not be transferred to the new institution. Therefore, before changing institutions, we request that the DAC contact add a new member who will replace them once they no longer work at the institution. This ensures that the data remains protected and is accessible to authorised personnel at the institution. To prevent potential data breaches and ensure adherence to GDPR regulations, it is essential that the European Genome-Phenome Archive (EGA) is informed via the Helpdesk team of any changes to the Data Access Committee (DAC). This should be done in addition to any changes being made on the DAC portal. Data Controllers (as per the definition in the DPA) are also responsible for notifying the previous DAC of any modifications. Without proper notification, changes might not be automatically updated in our system, leading to the risk of incorrect permissions being applied and potential data access issues. Therefore, it is imperative that all Data Controllers follow this protocol to maintain data integrity and security. What happens if EGA detects an unresponsive DAC? EGA defines an unresponsive DAC as a DAC with one or more contacts who do not respond to data access requests. EGA has procedures in place to identify these types of DACs, escalate the issue, and attempt to reassign the DAC to a responsive contact. This is a crucial step in ensuring that data can be accessed and utilised by researchers. If EGA identifies an unresponsive DAC, the organisation will first try to resolve the issue by escalating it to the appropriate parties. This may involve attempting to reassign the DAC to a more responsive contact. Unfortunately, in situations where we cannot reassign the DAC, the dataset will be withdrawn from the public website and the files will be removed from our system. If an EGA ID is referenced in a publication, the EGA will take extra steps to ensure that the public is made aware of the data's unavailability. I don't want to receive an email notification for pending requests. How can I do that? If you are an EGA DAC with pending requests, you will always receive emails for new data access requests. However, the EGA understands that a request resolution can take some time, for this reason, if you add a comment (make sure you save it by clicking the APPLY button!) we will filter those requests at the time of sending the notification! How can I manage data access requests? What documentation does the DAC need to provide? Each dataset that is submitted to the EGA must be linked to a policy object. The policy is a Data Access Agreement (DAA), which defines the terms and conditions of using the dataset, such as how the data files should be stored once downloaded or details of publication embargoes that should be observed by the approved user. As part of the Data Access Agreement, information regarding the application can be captured to help inform the DAC when making its decision. For example, requestors could be asked to provide a proposed title for their research and a proposal of how the data will be used. By asking for provision of such information the DAC can be assured that the requestor fully understands any consents associated with the data. It is important that accounts created at the EGA, are created solely for those individuals that will be downloading the data from the EGA. As part of the data access request, we strongly encourage you to identify individuals that will need an account at the EGA in order to prevent sharing of login details, which is strictly prohibited under EGA user account policy. Such information can easily be captured in the DAA. NOTICE The data access agreement template below is provided for guidance only and should be adapted as you see fit to suit your own purpose. In the interest of promoting data sharing, we suggest that if an agreement cannot be met around clause 19 in this example that both parties should agree to remain silent, and that the clause should be removed from the agreement. Example DAA How can the DAC provide the DAA? The DAC should provide their own DAA when registering a policy. Data requestors will download this document and should fill it in and send it back to the DAC. Data access decisions should be based on such documentation. The DAA can be downloaded through the request data webpage. Once it has been filled in, the signed copy of the DAA can be uploaded back to the request data webpage and sent to the DAC for review. How can I grant access to the data? Once you receive a data access request, you can login to the DAC Portal. In this portal you will see all your pending requests and will be able to grant or decline access to the requestors. I am a member of the Data Access Committee. Could I approve somebody else to deal with the requests on my behalf? If you want to delegate data access decisions to someone else, make sure that the individual's account is officially registered as a member of the DAC. Remember that a DAC contact with an "admin" role can always add new members to an existing DAC, remove members, and modify contact details through the DAC Portal. Can I automatise the process of managing data access requests? The answer is yes! You can use a programmatic approach using our DAC API! Check out the DAC API specification! Data Breach What should a DAC do if they suspect a breach? If a DAC suspects a data breach of one or more of their datasets, they should immediately contact the EGA Helpdesk team at this link. The DAC must provide the following information when contacting the EGA Helpdesk team: A list of affected datasets An estimated date of the data breach (or interval of dates) A list of unauthorised users who accessed the data (if available). Otherwise, they can provide a list of authorised users for the affected datasets Any observations they would like to raise to the EGA team Once the DAC has contacted the EGA team, we will respond within 48 hours (please allow some leeway during peak times) and activate our data breach protocol. What can I expect from the EGA if they detect a breach? Once the EGA determines that a security incident has occurred, we will notify all DAC members that a data breach has been detected, and take steps to contain the incident. Containment approaches may include: Revoking a data provider's access to the EGA resources, such as by changing passwords. Removing affected EGA datasets from distribution, such as by withdrawing a dataset. Disabling certain functions or services, such as the EGA ingestion pipeline. Shutting down the system or disconnecting it from the network. After the incident has been contained, the EGA will determine whether it is necessary to eradicate components related to the incident. Finally, the EGA will enable recovery of the service to normal operation and confirm that all services are functioning normally.

  Documentation access/data-access-committee/what-is-dac

• GWAS in African Americans, Latinos and Japanese

  The Multiethnic Cohort Study is a population-based prospective cohort study (n=215,251) that was initiated between 1993 and 1996 and includes subjects from various ethnic groups - African Americans and Latinos primarily from Californian (great Los Angeles area) and Native Hawaiians, Japanese-Americans, and European Americans primarily from Hawaii. State drivers&#39; license files were the primary sources used to identify study subjects in Hawaii and California. Additionally, in Hawaii, state voter&#39;s registration files were used, and, in California, Health Care Financing Administration (HCFA) files were used to identify additional African American study subjects. In the cohort, incident cancer cases are identified annually through cohort linkage to population-based cancer Surveillance, Epidemiology, and End Results (SEER) registries in Hawaii and Los Angeles County as well as to the California State cancer registry. Information on estrogen receptor status is also obtained through these registries. Blood sample collection in the MEC began in 1994 and targeted incident breast cancer cases and a random sample of study participants to serve as controls for genetic analyses. Subjects are frequency matched on age at blood draw and ethnicity. The following number of breast cancer cases and controls were genome-wide scanned as part of this study: African Americans, 473 cases and 464 controls; Japanese: 885 cases and 822 controls; Latinos, 520 cases and 544 controls.

  Study phs000517

• Bulk-tissue paired-end RNA-sequencing of anterior cingulate cortex samples derived from Lewy body disease patients

  Profiling of 24 human anterior cingulate cortex samples by bulk-tissue RNA-sequencing. Samples were derived from 5 non-neurological control individuals and 19 individuals with Lewy body disease (Parkinson’s disease = 7 individuals; Parkinson’s disease with dementia = 6 individuals; dementia with Lewy bodies = 6 individuals). Paired-end FASTQ files for each of the human samples are provided and are denoted by the suffixes R1 (read 1) and R3 (read 2). Fastp (v 0.20.0), a fast all-in-one FASTQ pre-processor, was used for adapter trimming, read filtering and base correction. Fastp default settings were used for quality filtering and base correction. Further details on parameters used are available here: https://github.com/RHReynolds/RNAseqProcessing/blob/master/QC/prealignmentQC_fastp_PEadapters.R.

  Dataset EGAD00001007698

• Kidney Two-Hit Mapping

  Germ-line genetic variants identified thus far generally account for only part of the genetic risk predicted for most cancers. A component of the remaining risk may be explained by functionally consequent genetic variants that are individually very rare (or private to that individual's family). While their identification may be highly informative for cancer etiology and biological knowledge, strategies that allow for agnostic (genome-wide) identification of such genes are not straight forward. This is particularly true for rare cancers where sufficient numbers of patients may simply not be available for appropriate statistically powered studies. In this project we have explored a study design based around the concept of "two-hit mapping" using the co-occurrence of germ-line and somatic mutations in the same gene to assist in the identification of susceptibility genes. The dataset includes 54 kidney cancer patients selected for enrichment of genetic disease, that is patients with: early age of onset and/or family history and/or bilateral disease. Germ-line and somatic (kidney cancer) tumor sequencing was carried out. These data may improve our understanding of kidney cancer.

  Study phs001971