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• ImmunAID Data Access Committee

  The ImmunAID Data Access Committee (DAC) oversees controlled access to cohort data and samples generated within the project. Access requests must be submitted via a standardized form and are reviewed by a Steering Committee (SC), with potential input from the External Advisory Board (EAB). Requests must include detailed scientific, ethical, and regulatory information, including data protection measures in accordance with the GDPR and French legislation. The SC evaluates proposals based on scientific merit, methodological rigor, ethical considerations, and the availability of cohort resources. Decisions are communicated within 8 weeks. Opinions can be favorable, conditional (requiring modifications), or unfavorable (with one resubmission allowed). Only academic, industrial, or project-affiliated research teams are eligible to apply.

  Dac EGAC50000000654

• 10X CD4 auto-antigens

  Ex vivo CD4 T-cells from 4 donors were stimulated with antigen-coupled beads to aCD3, ABD, EBNA1, ANO2 or CRYAB and the LiveCD3+CD4+CFSEdim cells were sorted by flow cytometry. Cells were labelled with barcoded antibodies to identify the original stimulus. All stimulations from each donor were pooled into four reactions, i.e. one reaction per donor. Libraries were assembled with the 10X Chromium Next GEM Single Cell 5’ Kit for TCR and transcriptome with feature barcodes. Dataset contains raw fastq reads as well as supplementary information needed to link fastq files to modality, i.e. gene-expression, protein or VDJ, and includes supplementary information to de-multiplex the reactions by stimulation condition.

  Dataset EGAD50000002201

• Sequence data to study genomic CNVs that drive apoptotic resistance and relapses on immune checkpoint inhibitors

  The dataset consists of bulk whole exome sequencing (WES) and whole genome sequencing (WGS) data from baseline and disease-progressed tumors after immune checkpoint inhibitor (ICI) treatment, derived from patients, human cell lines, and mouse models. Whole exome sequencing includes 17 clinical cases and one human cell line model with parental and acquired resistant cell lines (n = 5). Whole genome sequencing encompasses the YUMMER mouse model, including vehicle-treated controls (n = 2) and acquired resistant tumors (n = 3). The sequence reads have been aligned to hg19 and mm9 reference genomes, with mapped files (BAM) made available for analysis.

  Dataset EGAD50000001537

• Whole-genome variant calling of individuals from the study of allergic diseases in the Canary Islands

  Research study of genetic susceptibility and analyses of polygenic risk scores in allergic diseases. This dataset consists of variant data derived from whole-genome sequencing in reference samples from one of the parental populations (i.e., North Africans). The dataset consist of 15 VCF files (and corresponding index files) with a total of 1.58 million variants called using GATK v4 and following the Broad Variant Calling Best Practices, from a set of unrelated individuals sequenced in paired-read mode 2x150 bp using an Illumina HiSeq 4000 sequencer.

  Dataset EGAD50000000429

• Dataset of methylation data from whole blood DNA

  This dataset includes raw data (.idat) for the Illumina Human450k beadchip and methylation levels (.txt files). Methylation level were treated for normalization and background substraction. We removed probes with at least one of the following characteristics: (1) weak signal (p > 0.01) (2128 CpG sites), (2) SNP-enriched sites (4100 sites), (3) out of a CpG context (not on a CG) (3149 sites), or (4) located on sex chromosomes (11,129 sites). A total of 465,071 CpG sites were analyzed initially. Signal was then normalized, first by scaling to the internal controls using the methylumi R package, then by applying the method of subset-quantile within array normalization (SWAN) implemented in the minfi R package.

  Dataset EGAD00010001593

• FFPE tumor RNA exome capture sequencing

  This dataset includes raw, untrimmed FASTQ files generated from bulk RNA exome capture sequencing of FFPE tumor samples from 268 stage III colorectal cancer patients, prior to receiving adjuvant chemotherapy treatment. RNA libraries were prepared with the Illumina TruSeq RNA Exome kit and sequenced (PE51bp) using an Illumina NovaSeq 6000 with an S4 flow cell. The metadata file "RNAseq_metadata.tsv" contains columns with relevant quality metrics "DV200" and "cDNA_ng_ul" per sample, and a column indicating whether the sample was part of one or more published analyses: Franken et al., Eur. J. Cancer, 2026. PMID: 41650786. DOI: https://doi.org/10.1016/j.ejca.2026.116262 Crnovrsanin et al., XXX, 2026. PMID: XXX. DOI: XXX

  Dataset EGAD50000002440

• Inter and intra - tumor heterogeneity in Colorectal Cancer

  The dataset consists of two main sample groups. 1) The inter-tumour sample group contains a total of 97 samples from 27 patients. Each patient has a single normal and primary sample as well as one or more metastases. All samples were sequenced using IonTorrent PGM and a custom colorectal cancer (CRC) panel. 2) The intra-tumour sample group contains a total of 68 samples from a single tumour as well as a normal tissue sample. All 68 samples were sequenced using IonTorrent PGM and a custom CRC panel. Shallow whole genome sequencing was additionally applied to 10 of the samples using Illumina HiSeq 4000.

  Dataset EGAD00001003131

• ICR639 CPG NGS Validation series

  The dataset includes sequencing data generated using the TruSight Cancer Panel (TSCP) a targeted NGS assay for analysis of CPGs and orthogonally generated data supporting at least one pathogenic variant in a CPG for a total of 645 pathogenic CPG variants. The set of pathogenic CPG variants includes strong representation of some of the most challenging types of pathogenic variants, with 339 indels, including 16 complex indels and 24 insertions or deletions with length greater than 5bp, and 74 exon CNVs, including 23 single exon CNVs. There are 502 pathogenic variants in BRCA1 or BRCA2, making this an important first-line validation dataset for laboratories performing NGS testing of BRCA1 and BRCA2.

  Dataset EGAD00001004134

• C9orf72 region reads of 3001 samples

  This dataset includes cram files from 3,001 samples. These cram files include all read pairs where at least one of the reads aligns within 1kb of the C9orf72 repeat expansion. Additionally, these cram files also contain reads that are aligned to any of 29 pre-determined off target locations where the aligners are known to mis-align reads associated with this repeat expansion. These samples were sequenced using a combination of 2x100bp reads on an Illumina HiSeq2000 and 2x150bp reads on an Illumina HiSeqX sequencer and aligned using the Isaac aligner.

  Dataset EGAD00001004834

• Whole-exome sequencing of glioblastomas with long-term relapse interval

  Whole-exome sequencing data (Agilent SureSelectXT Human All Exon V7). Retrospective study of matched pairs of initial and post-therapeutic GBM cases treated with temozolomide+radiotherapy with a recurrence period greater than one year. Matched normal, initial and post-therapeutic samples for 27 patients and 1 patient (GBM046) with a matched normal and two post-therapeutic samples.

  Dataset EGAD00001008568

• Single cell RNA-seq, TCR-seq and bulk TCR-seq on HNSCC patients treated with ICB

  We performed single cell RNA- and TCR-sequencing (10x Genomics) on immune infiltrates (CD45+ cells) from 18 HNSCC patients enrolled in the IMCISION trial (Vos et al. 2021). Viable immune cells were isolated from pre-treatment and post-treatment primary tumor biopsies of 10 patients responding (1 partial pathological response and 9 major pathological responses) and 7 patients non-responding to anti-PD-1 and anti-CTLA4 combination immunotherapy. One patient treated with anti-PD-1 monotherapy (1 major pathological response) was included in the dataset. Bulk TCR-seq was performed on the PBMCs of responding patients, pre- and post-treatment.

  Dataset EGAD00001011311

• Regulatory Genomics of Human Embryonic Development

  We used epigenetic profiling to map active enhancers in the developing human limb and cortex as described in two published studies: Cotney J, Leng J, Yin J, Reilly SK et al. The evolution of lineage-specific regulatory activities in the human embryonic limb. Cell 2013;154(1):185-96. Reilly SK, Yin J, Ayoub AE, Emera D et al. Evolutionary changes in promoter and enhancer activity during human corticogenesis. Science 2015;347(6226):1155-9. We also used ChIP-seq to map binding sites for the chromatin modifier CHD8 in the developing human brain, as described in one published study: Cotney J, Muhle RA, Sanders SJ, Liu L et al. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nat Commun 2015;6:6404. We are also depositing primary human sequence reads related to processed datasets in the Gene Expression Omnibus under the following accession numbers: GSE42413 (Cotney et al. 2013); GSE63649 (Reilly et al. 2015); GSE57369 (Cotney et al. 2015).

  Study phs001226

• NHLBI TOPMed: Pediatric Asthma Controller Trial (PACT)

  After a 2-4 week assessment/characterization run-in period, 6-14 year-old children who met NAEPP criteria for mild-moderate persistent asthma specifically based on symptom criteria and methacholine PC20 ≤ 12.5 mg/ml and FEV1 ≥ 80% were randomized to one of the three active treatment arms for 12 months. Randomization was stratified according to clinical center, bronchodilator response (< 12% or ≥ 12%), race (Caucasian or non-Caucasian), and methacholine PC20 (< 2 or ≥ 2 mg/ml). The primary outcome variable was the proportion of asthma-free days during the 12-month treatment period. Secondary outcomes included other measures of asthma control (percentage of rescue-free days, albuterol-free days, and episode-free days; the number of asthma exacerbations requiring prednisone therapy and the time to the first asthma exacerbation), forced oscillation and spirometry, reversibility (FEV1 pre- and post 2 puffs of albuterol MDI), methacholine PC20, exhaled nitric oxide, and asthma-related quality of life.

  Study phs001730

• Functional Dynamics of the Elderly Gut Microbiome During Probiotic Consumption

  A mechanistic understanding of the health benefits conferred by consumption of probiotic bacteria has been limited by our knowledge of the resident gut microbiota and its interaction with the host. We used fecal samples from a study of twelve healthy individuals aged 65-80 to characterize the structure and functional dynamics of the gut microbiota associated with consumption of the single-organism probiotic, Lactobacillus rhamnosus GG ATCC 53103 (LGG). Samples were collected prior to probiotic consumption (day 0), on day 28 immediately after consuming 10^10 CFU of LGG twice daily for 28 days and day 56, one month after stopping LGG consumption. Our integrative approach incorporated bacterial 16S rRNA gene sequencing, whole-community expression profiling using RNA-seq, and metagenomic sequencing. We highlight the value of combinatorial 'omics methods and concomitant high-resolution informatics to probe the role that probiotics may play on the structure and function of the resident microbiota.

  Study phs000896

• Integrative Somatic and Germline Computational Biology to Redefine Clinical Actionability in Solid Tumors

  Neuroendocrine tumors (NETs) are rare cancers that arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic NETs (GEP-NETs) growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we performed single-cell RNA-sequencing (scRNA-seq) of fresh resections of GEP-NETs, including four pancreatic NETs, three small intestinal NETs, and one perigastric NET. We used single-cell sequencing to investigate the tumor and immune cellular landscapes of GEP-NET patients. Malignant GEP-NET gene and regulon expression was compared with normal, gastrointestinal endocrine cell differentiation and fate determination stages. We further characterized immune-immune and immune-tumor interaction networks within GEP-NETs, identifying novel therapeutic opportunities in the myeloid compartment of the microenvironment. Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

  Study phs003141

• Spatial Transcriptomics Reveals Discrete Tumor Microenvironments and Autocrine Loops Within Ovarian Cancer Subclones

  Ovarian masses from patients with high grade serous ovarian carcinoma undergoing debulking surgery were subjected to spatial transcriptomics profiling using the 10x Genomics Visium (fresh frozen) platform. Copy number inference using inferCNV predicted the presence of subclones with mutually exclusive copy number alterations (CNAs) in 5 of the 8 patient samples studied. In one patient, 3 subclones were predicted. For this patient sample, a serial section of the same tumor was used to microdissect regions corresponding to each of these subclones, and a 'normal' region predicted to contain only fibroblasts and no tumor cells. These microdissected regions were processed for low pass whole genome sequencing (WGS) and CNAs recorded using ichorCNA. An oral biopsy lacking tumor cells from an unrelated donor was used as a negative control for CNA inference. The CNAs predicted by inferCNV for the three subclones were validated by the low pass WGS and no CNAs were observed in the normal region containing fibroblasts.

  Study phs003561

• Type I Interferon Exacerbates Mycobacterium Tuberculosis Induced Human Macrophage Death

  In this study, we tested whether type I interferons (IFN-I), namely IFN-alpha and IFN-beta, may promote Mycobacterium tuberculosis (Mtb) pathogenesis by exacerbating cell death of human monocyte-derived macrophages (MDM) infected with Mtb. We differentiated the MDM under two different published methods (see Document Method.pdf for Table 1 of Methods). To determine if MDM infected with Mtb upregulates IFN-I transcripts, signaling factors, or IFN-I stimulated genes (ISGs), the MDM were infected with Mtb or treated with an activator of stimulator of IFN genes (STING), diamidobenzimidazole (di-ABZI). STING activation acted as a positive control for IFN-I induction and ISG upregulation. Indeed, di-ABZI treated MDM differentiated under both methods upregulated ISGs 24 hpi. At 24 hour post treatment, MDM differentiated under one method, but not under another method, upregulated ISGs, such as ISG15, IFITM3, and CXCL10, upon Mtb infection. MDM differentiated under both methods upregulated ISGs upon di-ABZI treatment.

  Study phs003607

• Childhood Cancer Data Initiative (CCDI): NCI-COG Pediatric MATCH Precision Medicine Clinical Trial

  The National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial provides a framework for biomarker-driven early phase trials of targeted therapies in pediatric and young adult cancer patients across the United States. Pediatric MATCH enrolled more than 1,300 patients with treatment-refractory cancers, offering access to molecular screening and investigational targeted therapies. To further advance this, matched diagnostic, refractory tumor, and normal samples from Pediatric MATCH cases were molecularly characterized, creating one of the largest comprehensive data sets available for childhood cancers. This analysis has the potential to provide novel insights into the genetics of refractory pediatric, adolescent, and young adult cancers, as well as inform potential therapeutic strategies. The following molecular characterization assays were performed: Tumor whole exome sequencing (WES) Tumor whole genome sequencing (WGS) Tumor RNA sequencing (RNA-seq) Blood whole exome sequencing (WES) Blood whole genome sequencing (WGS)

  Study phs002883

• High Resolution Maps of the HeLa 3D Genome Using Hi-C

  We use in situ Hi-C to probe the three-dimensional architecture of genomes, constructing haploid and diploid maps of nine cell types (including HeLa). The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1-kilobase resolution. We find that genomes are partitioned into contact domains (median length, 185kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ~10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs 'facing' one another. The inactive X-chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats. The data for the other (non-HeLa) cell types has been uploaded to GEO.

  Study phs001010

• A Genomics-Based Classification of Human Lung Tumors

  We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.

  Study EGAS00001000647

• Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation

  Induced Pluripotent Stem Cells (iPSC) derived from healthy individuals are important controls for disease modeling studies. To create a resource of genetically annotated iPSC, we reprogrammed footprint-free lines from four volunteers in the Personal Genome Project Canada (PGPC). Multilineage directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users further demonstrated line versatility by generating kidney organoids, T-cells and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited a hypertrophic phenotype as expected. WGS annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harboured at least one pre-existing or acquired variant with cardiac, neurological or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cell types found in six tissues for disease modelling, and clinical annotation highlighted variant-preferred lines for use as unaffected controls in specific disease settings.

  Study EGAS00001003684

• 65 prostate cancer cases WGS and transcriptome sequencing project

  We obtained whole-genome and transcriptome sequencing of tumor-benign pairs from 65 Asian prostate cancer (PCa) patients. Taken together with the TCGA PCa cohort, our integration analysis provides the first comprehensive mutational landscape of PCas across major ethnics worldwide and reveals potential novel role of frequent altered chromatin remodeler genes in PCas without androgen receptor (AR) alteration and complex rearrangements derived from Chromoplexy. In addition, we identified 5 putative tumor suppressor genes (TSGs) chains including one on chromosome 13q with novel findings of PCDH9 (deletions in 15/65 tumors) which was implicated in aggressive progression of prostate cancer. Finally, the integrative pathway and co-expression network analysis followed by the functional study indicated the frequent altered genes, particularly focal amplifications of PLXNA1 (11/65), in semaphoring signaling of axon guidance pathway may interact with PI3K/AKT and AR signaling and also contribute to the aggressiveness and progression of prostate cancer.

  Study EGAS00001000888

• Familial adult myoclonic epilepsy in Sri Lankan and Indian families

  Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA repeat insertion in intron 4 of SAMD12 on chromosome 8. We performed whole genome sequencing on two families with FAME, one of Sri Lankan origin and the other of Indian origin, and identified a TTTCA repeat insertion in SAMD12 in both families. Haplotype analysis revealed that both families shared the same core ancestral haplotype reported in Japanese and Chinese families with FAME1. Mutation dating, based on the length of shared haplotypes, estimated the age of the ancestral haplotype to be approximately 670 generations, or 17,000 years old. Our data extend the geographic range of this repeat expansion to Southern Asia and potentially implicate an even broader regional distribution given the age of the variant. This finding suggests patients of Asian ancestry with suspected FAME should be screened for the SAMD12 TTTCA expansion.

  Study EGAS00001004012

• Circulating tumor cells for comprehensive and multiregional non-invasive genetic characterization of multiple myeloma (arrays set)

  Multiple myeloma (MM) patients undergo repetitive bone marrow (BM) aspirates for genetic characterization. Circulating tumor cells (CTCs) are detectable in peripheral blood of virtually all MM cases and are prognostic, but their applicability for non-invasive screening has been poorly investigated. Here, we used next-generation flow cytometry to isolate matched CTCs and BM tumor cells from 42 patients and compare their genetic profile. In 8 cases, tumor cells from extramedullary plasmacytomas were also sorted and whole-exome sequencing performed in the three spatially-distributed clones. Noteworthy, ≥84% mutations present in BM and extramedullary clones were detectable in CTCs. Concordance between BM tumor cells and CTCs was high for chromosome arm-level copy-number alterations (≥94%) though not for translocations (43%). All high-risk genetic abnormalities except one t(4;14) were detected in CTCs whenever present in BM tumor cells. Altogether, these results support CTCs for non-invasive risk-stratification of MM patients based on their numbers and genetic profile.

  Study EGAS00001004314

• Oncogenic cooperation in a human de novo T-ALL model

  We previously modelled T-cell acute lymphoblastic leukemia (T-ALL) by over-expressing four oncogenes (activated NOTCH1, LMO2, TAL1, and BMI1) in healthy human umbilical cord blood cells through lentiviral transduction (Kusakabe et al, Nat Commun 10, 2913 (2019). https://doi.org/10.1038/s41467-019-10510-8). We have now tested individual effects of the four oncogenes by transducing human cells with all possible combinations of one, two, three, and four oncogenes. We also tested the effects of additional known T-ALL oncogenes including HOXA9, LYL1, MEF2C, NXK2.1, TLX1, and TLX3. In addition to culture in vitro on OP9-DL1 feeders, we also injected transduced cells into immunodeficient NSG mice. We observed differing abilities of the various oncogene combinations to support growth in vitro and frank leukemia in vivo. This study includes RNA-seq data from samples of transduced cells cultured in vitro as well as cells harvested from clinically moribund mice after development of leukemia in vivo.

  Study EGAS00001006055

• Single-cell RNA-seq and spatial transcriptomics data for the sarcoidosis baseline project

  Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid organ formation. To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on granulomas from patients with sarcoidosis and bioinformatically reconstructed the underlying gene-regulatory networks. We discovered an immune stimulatory environment in granulomas that repurposed transcriptional programs associated with lymphoid organ development. Granuloma formation followed characteristic spatial patterns and involved genes linked to immunometabolism, cytokine and chemokine signaling, and extracellular matrix remodeling. Three cell types emerged as key players in granuloma formation: metabolically reprogrammed macrophages, cytokine-producing Th17.1 cells, and fibroblasts with inflammatory and tissue remodeling phenotypes. Pharmacological inhibition of one of the identified processes attenuated granuloma formation in a sarcoidosis mouse model. We show that human granulomas adopt characteristic aspects of normal lymphoid organ development in aberrant combinations, indicating that granulomas constitute aberrant lymphoid organs.

  Study EGAS00001006970

• Transcriptome of CD4+ T cells and CD8+ T cells in glioblastoma multiforme

  Patients included in this study were over 18 years of age and had a histology-confirmed diagnosis of glioblastoma multiforme (GBM). Exclusion criteria were the previous administration of any anti-tumor therapy including radiation therapy. All patients gave written informed consent. The study was approved by the local ethics committee (TUM Medical school) and conducted following the Declaration of Helsinki. During resection of the tumors, tumor tissue and tissue from normal appearing brain within the operative channel was collected. Blood was drawn during the surgical procedure. Single cell suspensions were prepared from the tumor tissue, the normal appearing brain, and the blood. CD4+ T cells and CD8+ T cells were sorted by flow cytometry. Only patients with a complete set of specimens (CD4+ tumor infiltrating lymphocytes (TIL), CD8+ TIL, CD4+ T cells from normal appearing brain, CD8+ T cells from normal appearing brain, blood-derived CD4+ and CD8+ T cells) containing a minimum of 1000 cells in each sorted sample were further analyzed (n=9). Total RNA was isolated from sorted cell populations using the RNAeasy Plus micro kit (Qiagen, 74034). Quality and integrity of total RNA was controlled on a Bioanalyzer 2100 (Agilent Technologies). Library preparation for bulk-sequencing of poly(A)-RNA was done as described previously (Parekh et al., 2016). Briefly, barcoded cDNA of each sample was generated with a Maxima RT polymerase (ThermoFisher Scientific, EP0742) using oligo-dT primer containing barcodes, unique molecular identifiers (UMIs) and an adaptor. Ends of the cDNAs were extended by a template switch oligo (TSO) and full-length cDNA was amplified with primers binding to the TSO-site and the adaptor. NEB UltraII FS kit was used to fragment cDNA. After end repair and A-tailing, a TruSeq adapter was ligated and 3'-end-fragments were finally amplified using primers with Illumina P5 and P7 overhangs. In comparison to previous descriptions (Parekh et al., 2016), the P5 and P7 sites were exchanged to allow sequencing of the cDNA in read 1 and barcodes and UMIs in read 2 to achieve a better cluster recognition. The library was sequenced on a NextSeq 500 (Illumina) with 59 cycles for the cDNA in read 1 and 16 cycles for the barcodes and UMIs in read 2. Data were processed using the published Drop-seq pipeline (v1.0) to generate sample- and gene-wise UMI tables (Macosko et al., 2015). Reference genome (GRCh38) was used for alignment. Transcript and gene definitions were used according to the Genecode Annotation Version 35.

  Study EGAS50000000156

• Resuscitation Outcomes Consortium (ROC) Prehospital Resuscitation Using an Impedance Valve and Early Versus Delayed Analysis (PRIMED) (ROC-PRIMED-BioLINCC)

  Accessing Data: Please refer to “Authorized Access” below regarding accessing data through the BioData Catalyst ecosystem. The data from this accession is not available for download through dbGaP.Objective: The purpose of this study was to examine two different treatments during a cardiac arrest that occurs outside of the hospital and whether either or both treatments would increase the number of people who lived to hospital discharge with satisfactory functional status. The first treatment involved using a device called the Impedance Threshold Device (ITD). The other treatment involved the amount of CPR given before the emergency medical services (EMS) providers first looked at the heart rhythm to determine if a shock is needed.Background: Out-of-hospital cardiac arrest is a common and lethal problem with a low survival rate, leading to an estimated 330,000 deaths each year in the United States and Canada. The traditional approach to out-of-hospital cardiac arrest has been to emphasize early analysis of cardiac rhythm, with delivery of defibrillatory shocks, if indicated, as quickly as possible. It has been suggested, however, that many participants may benefit from a period of CPR before the first analysis of rhythm.The impedance threshold device (ITD) is designed to enhance venous return and cardiac output during CPR by increasing the degree of negative intrathoracic pressure. Previous studies have suggested that the use of an ITD during CPR may improve survival rates after cardiac arrest. This effect is achieved by preventing the passive inflow of air into the chest during chest recoil between chest compressions without impeding active ventilation. The ITD has been found to improve hemodynamics, the perfusion of vital organs, and neurologically intact survival in studies in animals. The results of small, short-term clinical trials have suggested that the ITD can increase systolic blood pressure during resuscitation and improve short-term survival rates. Participants: In the ITD study, 4,345 participants were assigned to sham ITD and 4,373 to active ITD, while in the early versus later rhythm analysis, 5,290 participants were assigned to early cardiac rhythm analysis, and 4,643 were assigned to later cardiac rhythm analysis. This study qualified for exception from informed consent required for emergency research.Design: Most participants were enrolled simultaneously in both the early analysis versus later analysis component and the active ITD versus sham ITD component of the trial.The use of an active ITD was compared with that of a sham ITD in participants at 10 ROC sites in the United States and Canada. Participants, investigators, study coordinators, and all care providers were unaware of the treatment assignments. EMS personnel were trained in ITD function, proper use of the ITD, and all aspects of protocol implementation, with an emphasis on the optimal performance of CPR according to local guidelines. The first EMS responders to arrive at the scene of the arrest who were equipped with a randomly assigned ITD (active or sham) attached the device between the ventilation bag and face mask or between the bag and an advanced airway. Responders were encouraged to implement use of the device within 5 minutes after their arrival or as soon as clinically possible. Each of the 10 participating ROC centers was also divided into approximately 20 clusters. All episodes of cardiac arrest in a cluster were randomly assigned to one CPR strategy; after a set period of time, ranging from 3 to 12 months, all episodes in that cluster were then assigned to the other strategy. Participants in the early-analysis group were assigned to receive 30 to 60 seconds of chest compressions and ventilations (sufficient time to place defibrillator electrodes) before electrocardiographic (ECG) analysis, and those in the late-analysis group were assigned to receive 3 minutes of chest compressions and ventilations before ECG analysis. The start and stop times for CPR were recorded by the responders, and the information was supplemented by the recording of defibrillator time. Conclusions: All 10 sites halted enrollment in November 2009 when the data and safety monitoring board recommended termination because interim analysis showed that the findings were not likely to change with continuation of the study. Neither use of the ITD nor the amount of CPR given before cardiac rhythm analysis significantly improved survival with satisfactory function (i.e., a score of ≤3 on the modified Rankin scale) among participants with out-of-hospital cardiac arrest receiving standard CPR. There were also no significant differences in the secondary outcomes, including rates of return of spontaneous circulation on arrival at the emergency department, survival to hospital admission, and survival to hospital discharge.

  Study phs003825

• Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)

  Subpopulations and Intermediate Outcome Measures in COPD Study Description Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) supports the prospective collection and analysis of phenotypic, biomarker, genetic, genomic, and clinical data from subjects with COPD for the purpose of identifying subpopulations and intermediate outcome measures. It is funded by the National Heart, Lung, and Blood Institute and is coordinated by the University of North Carolina at Chapel Hill. Molecular fingerprinting and extensive subject phenotyping will be performed to identify disease subpopulations and to identify and validate surrogate markers of disease severity which will be useful as intermediate outcome measures for future clinical trials. Secondary aims are to clarify the natural history of COPD, to develop bioinformatic resources that will enable the utilization and sharing of data in studies of COPD and related diseases, and to create a collection of clinical, biomarker, radiographic, and genetic data that can be used by external investigators for other studies of COPD. Participating Institutions: Research participants for SPIROMICS will be enrolled, phenotyped, and followed at twelve SPIROMICS Clinical Centers: Columbia University, Temple University, Johns Hopkins University, Wake Forest University, University of Michigan, University of Illinois at Chicago, University of Iowa, University of Utah, National Jewish Health, University of Alabama at Birmingham, University of California at San Francisco, and University of California at Los Angeles. The University of North Carolina at Chapel Hill serves as the Genomics and Informatics Center. The Radiology Reading Center is based at the University of Iowa. The PFT Reading Center is based at the University of California at Los Angeles. Study Design: SPIROMICS is a prospective cohort study that enrolled approximately 2,981 participants at twelve clinical centers over five years. Participants are distributed across four enrollment strata (i.e., Never-smokers, Smokers without COPD, Mild/Moderate COPD, and Severe COPD). Study Visits: Participants have up to four in-person visits (Baseline and Annual Clinic Visits at years 1, 2, 3 after Baseline). Study questionnaires and spirometry are completed at all main study visits. Blood and urine samples are collected at visits 1, 2, and 4. Sputum samples are collected at Visit 1. The CT scans are completed and Baseline and Visit 2. Participants also receive quarterly follow-up calls to assess health status and determine if an exacerbation has occurred. Substudies A. Bronchoscopy and Immunophenotyping Substudy The Bronchoscopy Substudy enrolled a total of 251 participants. These participants will be recruited across all four study strata. This substudy includes two study visits. During the first visit sputum samples are collected for Immunophenotyping analysis at the Immunophenotyping Core Lab based at the University of Michigan. Participants then return for a second visit during which samples are collected via bronchoscopy, including bronchoalveolar lavage, epithelial brushings and bronchial biopsies. Immunophenotyping analysis is also conducted on BAL and blood collected during the bronchoscopy study visit. B. Repeatability Substudy The entire baseline clinic visit was repeated on 98 volunteers to determine reliability of measurement procedures. All baseline study-related procedures and questionnaires, including the CT scan, was re-administered and new samples of blood, urine, saliva, and sputum was collected. Field center staff processed these biospecimen samples according to the same protocol. C. Exacerbation Substudy The Exacerbation Substudy is a prospective, longitudinal observational study of 204 participants, which will allow the assessment of participant driven health care utilization (HCU) events and symptom-defined exacerbation events over time. HCU driven events are defined by change in medical treatment in response to a perceived COPD Exacerbation. Symptom-based events will be defined by using EXACT-PRO (EXacerbations of Chronic Pulmonary Disease Tool - Patient Reported Outcome) a daily symptom diary developed to measure the frequency, severity, and duration of exacerbations in clinical trials. All participants are provided with a PDA on which to complete the diary. Participants reporting a possible COPD exacerbation will be brought into the study clinic for a study visit to collect biological specimens and questionnaire data. The overall objectives of the exacerbation substudy are to: Obtain clinical data and specimens on SPIROMICS participants before and during an acute COPD exacerbation defined by: Health care utilization triggered by the subject, or Symptomatic change (triggered by an EXACT defined threshold) Describe symptomatic changes occurring around HCU and symptom-defined (EXACT) events and their relationship to clinical and specimen data Characterize the non-exacerbation "stable" state in COPD using the EXACT, including: Symptom variability (EXACT), Clinical data and specimen parameters during a stable state (baseline), The relationship between clinical and specimen data and symptom severity and variability. Explore the characteristics of stable patients, defined as those who do not experience HCU or symptom-defined (EXACT) events during the sub-study period, using baseline clinical data and specimens and compare these characteristics with patients who experience HCU and/or symptom-defined events. Examine the relationship between HCU and symptom-defined exacerbation frequency during the first one-year period of follow-up for exacerbations and health outcomes, including 12-month change in lung function and COPD health status, and longer term morbidity and mortality, with the latter derived from long-term data from the larger SPIROMICS study.

  Study phs001119

• A Case-Controlled Study for Genotype-Phenotype Associations in Multiple Sclerosis (MS)

  This is a multi-centre, case-controlled study to develop a dataset containing 1000 MS cases and 1000 matched controls and to associate DNA sequence (allelic) variations with MS phenotypes. Study subjects were enrolled through a prospective effort initiated in 2003. Three MS clinical centres were involved in subject recruitment and biological specimen collection using identical inclusion/exclusion criteria, two in Europe (Vrije Universiteit Medical Center, Amsterdam; and University Hospital Basel) and one in the US (University of California San Francisco). This study recruited subjects of northern-European ancestry with a diagnosis of MS (McDonald et al., 2001), with dissemination in time and space. Patients with Clinically Isolated Syndromes (CIS) were also included if they fulfilled 3 of the 4 Barkhof criteria for dissemination in space as per application of the McDonald criteria (McDonald et al., 2001). While recruitment predominantly included subjects with a relapsing onset of MS, individuals with all clinical subtypes of the disease participated, including clinically isolated syndrome (CIS), relapsing remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and progressive relapsing MS (PRMS). The control group consisted of unrelated individuals, primarily spouses/partners, friends, and other volunteers. Control subjects were of northern-European ancestry and matched as a group, proportionally with cases according to age (±5 years) and gender. A familial history or current diagnosis of MS as well as a relation to another case or control subject were considered exclusionary for this group. Protocols were approved by the Committees on Human Research at all Institutions and informed consent was obtained from all participants prior to participation in the study. Primary Study Objective:To identify DNA sequence variations (genotype) and flanking sequences that are associated with clinical factors (phenotype) which differ between study subjects with and without MS. Secondary Study Objectives: To develop a clinical dataset including quantitative measures of 1000 well-characterized cases with MS, and 1000 ethnically matched controls. To identify other genotype-phenotype associations in MS study subjects such as magnetic resonance imaging (MRI) measures of disease burden and/or severity. To identify or confirm candidate surrogate markers of neurodegeneration using a variety of techniques including biochemical assays, blood transcriptome analysis, plasma proteomics and MRI*. GenotypingGenotyping of the complete dataset was performed at the Illumina facilities using the Sentrix® HumanHap550 BeadChip. *MRI results are not available on dbGaP.

  Study phs000171

• Phase II Study of Cryoablation and Post-Progression Immune Checkpoint Inhibition in Metastatic Melanoma

  Percutaneous cryoablation guided by imaging is a well-established, minimally invasive treatment for oncological conditions. We posited that cryoablation could alter the immune microenvironment by directly influencing the tumor, potentially eliciting an anti-tumor response in cases resistant to immune checkpoint inhibition (ICI). In this non-randomized phase II single-center study (NCT03290677), individuals with unresectable melanoma experiencing progression on ICI underwent cryoablation in a single progressing metastasis, while ICI was continued for at least two additional cycles. The main objectives were to assess safety and feasibility and to evaluate tumor response in non-ablated lesions. Between May 2018 and July 2020, 17 patients participated in the study. The treatment regimen proved safe, revealing an objective response rate of 23.5% and a disease control rate of 41% (comprising 4 partial responses and 3 stable diseases). In our investigation into the factors influencing response to cryoablation therapy in ICI-resistant melanoma, we conducted single-cell RNA sequencing (scRNA-seq) using both 10x Genomics and Smart-seq2 technologies on biopsies from metastatic sites of 15 patients. We collected pre-treatment samples from all patients and post-treatment samples from 5 patients, totaling 20 samples. After quality control, excluding cells specific to anatomical sites or rare cell types (e.g., alveolar type II, neurons), and batch correction, we analyzed 49,071 single cells spanning melanocyte, endothelial, stromal, T, myeloid, and B/plasma cell lineages. Differential gene expression (DGE) analysis between myeloid cells identified the genes MARCKS and IL10, two genes involved in anti-inflammatory responses that can inhibit macrophages activation to be associated with failed response. Moreover, DGE analysis of T cells identified the gene TXK, which acts as a Th1 transcription factor, and the gene CMKLR1 (chemerin-like-receptor-1), which triggers migration of CD8 T-cells to be upregulated in patients who benefited from cryoablation treatment. In contrast, MTHFD2 and GGH, two genes involved in one-carbon metabolism and the folate cycle, were upregulated in T cells from patients who did not respond to therapy. Our analysis revealed a significant increase in B/plasma cells in patients who responded positively to the therapy combination, along with an enrichment of oxidative phosphorylation in T cells among non-responsive patients with progressive disease. These findings advocate for further investigation into this innovative and synergistic therapeutic approach.

  Study phs003579

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

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

  Study EGAS00001000949

• scCRISPRi/a-seq Control and IFN treated iPS derived human GPC/OPCs

  Datasets consists of 2 batches of human glial progenitors (iPS), cells were sequenced as controls and IFN treated. Using the 10Genomics platform from the samples 2 libraries were built forgene expression libraries (scRNA-seq) and captured guides sequencing library (gRNA) on a set of Multiple Sclerosis associated SNPs. Batch one includes KRAB and P300 perturbed cells in 2 rounds sequenced RNA libraries for Ctrl and IFN and 1 round of capture guides for Ctrl and IFN. Batch 2 includes 1 round of both RNA expresison library and captures guides for KRAB and P300 perturbations in Ctrl and IFN treated cells.

  Dataset EGAD50000002053

• LuCaP cell line ChIP-seq

  ChIP-seq of 2 LuCaP cell lines with different factors. LuCaP cell line 189.4 was ChIP-sequenced for 6 factors with different conditions as well as the input DNA (n=31 in total). LuCaP 189.4 ChIP-sequence experiments include; 3 H3K27ac/DMSO, 3 H3K27ac/vorinostat, 3 H3K27ac/dexamethasone, 3 H3K27ac/dexamethasone/vorinostat, 3 GR dexamethasone, 3 GR dexamethasone/vorinostat, 3 HDAC3/DMSO, 3 AR, 3 FOXA1, 3 H3K27ac and 1 input sample. LuCaP 35 ChIP-sequence experiments as well as input include (n=10 in total); 3 H3K27ac, 3 AR, 3 FOXA1 and 1 input sample. All 41 samples were sequenced using paired-end reads on Illumina NovaSeq 6000. Each sample has 2 fastq files, one for the forward and reverse read, respectively.

  Dataset EGAD50000001345

• Determining off-target effects of splice-switching antisense oligonucleotides using short read RNAseq in neuronally differentiated human induced pluripotent stem cells

  Neuronal cells derived from female healthy control hiPSC lines LUMCi003-A, LUMCi003-B and LUMCi023-A were transfected with in total four different splice-switching AONs targeting three different human transcripts. Untransfected samples as well as samples transfected with a scrambled AON were included as controls. Three days after transfection, RNA was isolated for sequencing using Illumina Novaseq6000 in order to perform differential gene expression analysis and differential splicing analysis to determine off-target effects. Sequencing was performed in two batches: one containing the samples from cell line LUMCi003-A and the other containing cell lines LUMCi003-B and LUMCi023-A.

  Dataset EGAD50000001742

• ATAC sequencing raw data files of human Treg cell subsets

  Assay for Transposase-Accessible Chromatin using sequencing (ATAC) sequencing of human CD38+, HLA-DR+, CD38+ HLA-DR+, and CD38- HLA-DR- regulatory T (Treg) cell subsets sorted from peripheral blood pooled from 4 healthy donors. After isolation and purification of Treg cell subsets with flow cytometry, samples were frozen and transferred to Active Motif for ATAC sequencing. The dataset contains one raw sequencing file (fastq) of accesible regions for each of the above-mentioned Treg cell subsets.

  Dataset EGAD50000000664

• HiDEF-seq single-molecule sequencing of single-strand mismatches and damage

  Our study sought to resolve, with single-molecule fidelity, the mismatches and damage events that precede DNA mutations. Using a novel single-molecule, long-read sequencing method (HiDEF-seq) we detect base substitutions when present in either one or both DNA strands. We also detect cytosine deamination, a common type of DNA damage, with single-molecule fidelity. This study profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes. These samples revealed single-strand mismatch and damage signatures. Since double-strand DNA mutations are only the endpoint of the mutation process, our approach enables new studies of how mutations arise in a variety of contexts, especially in cancer and aging.

  Dataset EGAD50000000460

• WGS data for MMML for Study EGAS00001002199

  Whole genome sequencing data for MMML (tumor/control pairs and one cell_line)

  Dataset EGAD00001003274

• Whole genome sequencing of multiple myeloma patient samples.

  Tumor (CD138+ plasma cells) and non-tumor (peripheral blood white cells or stem cell harvest) DNA from patients with a plasma cell dyscrasias were sequenced. Whole genome sequencing using high molecular weight DNA was performed using the 10X Genomics Chromium platform on either a HiSeq4000 or NovaSeq (Illumina) using 100 to 150 bp paired-end reads. The dataset consists of 111 patients, and 223 samples in total (matched tumor and control per patient; one patient had 2 tumor samples sequenced). Diseases consisted of 2 MGUS patients, 8 SMM patients, 91 newly diagnosed myeloma patients, 1 previously treated patient, 4 relapsed MM patients, and 5 PCL patients. Paired RNA-seq data are available for 81 of the samples under study EGAS00001003411.

  Dataset EGAD00001004452

• Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES)

  The T2D-GENES/GoT2D 13K exome sequencing study includes ~13,000 samples, half T2D cases and half T2D controls, from five ancestries (~5K Europeans, ~2K each of African-American, East-Asian, South-Asian, and Hispanic). Samples underwent deep exome sequencing, with SNVs and INDEls called according to GATK best practices; variant sites were then filtered according to the GATK best practices, and then samples and variants underwent further filtering based on aggregate genotype quality as described in Fuchsberger et al. (e.g. low call rate, excess heterozygosity for samples, low call rate or coverage for variants). Please note that one of the samples in the T2D-GENES vcf does not have phenotype data.

  Dataset EGAD00001002246

• Exome sequencing of a Novel Primary T Cell Immunodeficiency Kindred (2019-08-19)

  Primary T cell immunodeficiency disorders have a heterogeneous genetic basis. This study will focus on one case characterised by severe T cell lymphopenia in the index case. We aim to sequence the complete exomes of this individual, her three unaffected siblings and parents in an effort to identify the causative genetic mutation responsible for this disorder. We will perform exome capture using Agilent SureSelect system, followed by sequencing on the HiSeq platform. Our study has the potential to uncover genes important for T cell development and novel therapeutic strategies to treat T cell immunodeficiencies. . This dataset contains all the data available for this study on 2019-08-19.

  Dataset EGAD00001005263

• WES and RNAseq of Simultaneous Bilateral Breast Cancer

  This dataset includes NGS profiling of 13 women with simultaneous bilateral breast cancer. Seven women have WES of untreated surgical resections and matched healthy tissue. The six other women have WES of healthy tissue, WES+RNAseq of pre-neoadjuvant tumor biopsies, and when residual disease was present (6 tumors in 4 patients), WES+RNAseq of residual disease from post-neoadjuvant therapy surgery. One patient from the WES+RNAseq cohort had multifocal bilateral disease at diagnosis so there are 2 pre-neoadjuvant biopsy samples from each breast.

  Dataset EGAD00001009987

• IL-17 Signaling in Human iPSC-derived Midbrain Neurons in Parkinson's Disease

  To determine IL-17-induced global transcriptome changes in midbrain neurons derived from induced pluripotent stem cells (iPSC) from three sporadic Parkinson's disease (PD) patients and three age- and sex-machted controls, deep RNA sequencing (RNA-Seq) of IL-17-treated and untreated PD and control iPSC-dderived midbrain neurons was performed. Total RNA was isolated from untreated and IL-17-treated cells with the TruSeq RNA Sample Preparation Kit v2 (Illumina). RNA libraries were quantified using the KAPA SYBR FAST ABI Prism Library Quantification Kit (Kapa Biosystems) and cluster generation was performed on the cBot with the TruSeq SR Cluster Kit v3 (Illumina). The sequencing run was performed on a HiSeq 1000 instrument (Illumina) using the indexed, 50 cycles single read (SR) protocol and the TruSeq SBS v3 Kit (Illumina). Image analysis and base calling resulted in .bcl files that were then converted into .fastQ files by the CASAVA1.8.2 software. FastQ files were aligned to the human genome (hg19) using STAR.and annotated with gencode.v19. DESeq2 was used to determine differential expression. Criteria to determine significantly dysregulated genes were as follows: adjusted p-value below 0.05 and log2FC (fold change) of greater than one. Only genes with a mean expression value of greater than one RPKM (reads per kilobase per million mapped reads) throughout the dataset were considered. Control and PD samples were analyzed as two independent datasets. Upon IL-17 treatment only 17 genes were found to be dysregulated in controls but 125 genes were dysregulated in iPSC-derived midbrain neurons from PD patients. The 125 IL-17-dependent genes in PD iPSC-derived neurons separated the treated from untreated PD samples using an unsupervised, hierarchical clustering applying an Euclidean distance metric. More detailed study information can be found in Sommer A, Maxreiter F, Krach F, Fadler T, Grosch J, Maroni M, Graef D, Eberhardt E, Riemenschneider MJ, Yeo GW, Kohl Z, Xiang W, Gage FH, Winkler J, Prots I, Winner B. Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease. Cell Stem Cell. 2018 Jul 5;23(1):123-131.e6. doi: 10.1016/j.stem.2018.06.015. PMID: 29979986

  Study phs001686

• eMERGE Network Imputed GWAS for 41 Phenotypes

  The electronic Medical Records and Genomics (eMERGE) Network is a consortium of ten participating sites (Cincinnati Children's Hospital Medical Center/Boston Children's Hospital, Children's Hospital of Philadelphia, Essentia Institute of Rural Health, Marshfield Clinic Research Foundation and Pennsylvania State University, Geisinger Clinic, Group Health Cooperative/University of Washington, Mayo Clinic, Icahn School of Medicine at Mount Sinai, Northwestern University, Vanderbilt University Medical Center) funded by the NHGRI to investigate the use of electronic medical record (EMR) systems for genomic research. The goal of eMERGE is to conduct genome-wide association studies in approximately 55,000 individuals using EMR-derived phenotypes and DNA from linked Biorepositories. Using electronic phenotyping methods, the consortium used DNA samples from all participating sites to explore the genetic determinants of over forty phenotypes, including Abdominal aortic aneurysm; Ace-Inhibitor/Cough; Attention Deficit Hyperactivity Disorder; Age-related macular disease; Appendicitis; Asthma; Atopic Dermatitis; Autism; Benign Prostatic Hyperplasia; Carotid artery disease as a Quantitative Measure; caMRSA; Cataract; Clostridium difficile colitis; Extreme Obesity; Chronic Kidney Disease; Chronic Kidney Disease and Type 2 Diabetes; Chronic Kidney Disease, Type 2 Diabetes and Hypertension; Colon Polyps; Cardiorespiratory Fitness; Dementia; Diverticulosis; Diabetic retinopathy; Gastroesophageal Reflux Disease; Glaucoma; Height; Heart failure; Hypothyroidism; Lipids; Ocular hypertension; Peripheral Arterial Disease; QRS duration; Red blood cell indices; Remission of Diabetes after ROUX-EN-Y gastric bypass surgery; Resistant hypertension; MACE while on Statins; Type 2 Diabetes; Venous Thromboembolism; White blood cell indices; and Zoster virus infection, as well as using the phenome-wide association study (PheWAS) paradigm to replicate and discover relationships between targeted genotypes with multiple phenotypes. Sites and participants include: Children's Hospital of Pennsylvania (CHOP): The Center for Applied Genomics (CAG) at the Children's Hospital of Philadelphia (CHOP) is a high-throughput, highly automated genotyping and sequencing facility equipped with state-of-the-art genotyping and sequencing platforms. Children who are treated at the Children's Hospital Healthcare Network and their parents may be eligible to take part in a major initiative to collect more than 100,000 blood samples, covering a wide range of pediatric diseases. A large majority of participants consenting to prospective genomic analyses also consent to analysis of their de-identified electronic medical records (EMRs). EMRs are longitudinal, with a mean duration of 6.5 years. Cincinnati Children's Hospital Medical Center/Boston's Children's Hospital (CCHMC/BCH): Cincinnati Children's Hospital Medical Center (CCHMC) and Boston Children's Hospital (BCH) are pediatric institutions dedicated to improving health and welfare of children and to the shared purpose of discovery and practical application of new genomic information to the ordinary care of children. The CCHMC/BCH site has been built on a five-year history of collaboration, particularly in patient electronic record (ERM)-related informatics, the basis of much of eMERGE II. CCHMC and BCH together bring an extraordinary faculty to eMERGE II who are committed to diseases that afflict children, specifically phenotypes that focus upon diseases of children in ways that will leverage the available eMERGE adult GWAS and EMRs to discover meaningful use results. CCHMC/BCH plans to demonstrate real-time execution of phenotypic selection across their two distinct pediatric institutions as a model for ensuring phenotypic standardization and for national scalability. They will also look carefully at parents' responses to results and use of their children's research results and better understand the factors that influence their decisions about learning incidental findings. In addition to patient and parent perceptions CCHMC/BCH will also explore clinician perceptions of pharmacogenetic research results after EMR integration. Geisinger Health System: A research cohort of adult Geisinger Clinic patients was enrolled from community-based primary care clinics of the Geisinger Health System. Patients were eligible for enrollment if they were a primary care patient of a Geisinger Clinic physician and were scheduled for a non-emergent clinic visit. All participants provided written informed consent and HIPAA authorization. Consenting patients agreed to provide blood samples for broad biomedical research use, and permission to access data in their Geisinger electronic medical record for research. The enrollment rate was 90% of patients approached. The demographics of the cohort approximate those of the Geisinger Clinic outpatient population. Research blood samples were collected during an outpatient clinical phlebotomy encounter. Research blood samples are coded and stored in a central biorepository. Samples are linkable to clinical data in a de-identified manner for research via an IRB-approved data broker process. For genomic analysis, DNA is extracted from EDTA-anticoagulated whole blood. Group Health(GH)/University of Washington (UW): GH participants for the PGx project were enrolled in the eMERGE Network through the Northwest Institute of Genetic Medicine (NWIGM) biorepository, and provided the appropriate consent to receive clinically relevant genetic results (N~6300.) Participants were eligible if aged 50 - 65 years old at the time of their enrollment into the NWIGM repository, living, enrolled in GH's integrated group practice, and had completed an online Health Risk Appraisal. The selection algorithm was based on several data sources from the EHR at Group Health: 1. Demographics - participants with self-reported race as Asian or African ancestry were prioritized and selected to enrich for non-European ancestry; 2. Diagnosis and procedure codes - participants were selected if found to have a history of hypertension, atrial fibrillation (AF), or congestive heart failure (CHF). Participants with a history of arrhythmia were added if the entire selection algorithm did not generate 900 individuals. We also enriched for participants with EHR evidence of actionable indications related to PGRNSeq genes. Participants were selected if found to have an ICD9 code for malignant hyperthermia, hypertension, atrial fibrillation, congestive heart failure or long QT syndrome (LQTS); 3. Laboratory values - if participants had any laboratory event of creatine kinase (CK) >1000, and were dispensed statins within 6 months of the event, then they were selected; and 4. Medications - participants were excluded if ever on carbamazepine or had a current regimen of warfarin. Essentia Institute of Rural Health, Marshfield Clinic, Pennsylvania State University (Marshfield): The Marshfield Clinic Personalized Medicine Research Project is a population-based biobank in central Wisconsin with more than 20,000 adult subjects who provided written, informed consent to access their medical records and provided a blood sample from which DNA was extracted and plasma and serum stored. In addition to an average of 30 years of medical history data, a questionnaire about environmental exposures, including a detailed food frequency questionnaire, is available to facilitate gene/environment studies. Mayo Clinic: The Mayo biobank is a disease-specific biobank for vascular diseases including peripheral arterial disease (PAD). PAD patients were identified from individuals referred to the non-invasive vascular laboratory for lower extremity arterial evaluation. Since 1997, laboratory findings have been recorded into an electronic database employing an in-house software package for data archiving and retrieval; this data becomes part of the Mayo EMR. Patients referred to the center with suspected PAD undergo a comprehensive non-invasive evaluation including the ankle-brachial index (ABI) - the ratio of blood pressure measured in the upper arms divided by blood pressure measured at the ankles. Controls subjects are identified from patients referred to the Cardiovascular Health Clinic for stress ECG. The prevalence of PAD in patients with normal exercise capacity who do not have inducible ischemia on the stress ECG , was <1%. Data regarding risk factors for atherosclerosis such as diabetes, dyslipidemia, hypertension, and smoking are ascertained from the EMR. Icahn School of Medicine at Mount Sinai School (Mt. Sinai): The Institute for Personalized Medicine (IPM) Biobank Project 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 Biobank populations include 28% African American (AA), 38% Hispanic Latino (HL) predominantly of Caribbean origin, 23% Caucasian/White (CW). IPM Biobank disease burden is reflective of health disparities with broad public health impact: average body mass index of 28.9 and frequencies of hypertension (55%), hypercholesterolemia (32%), diabetes (30%), coronary artery disease (25%), chronic kidney disease (23%), among others. 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. Northwestern University: The NUgene Project is a repository with longitudinal medical information from participating patients at affiliated hospitals and outpatient clinics from the Northwestern University Medical Center. Participants' DNA samples are coupled with data from a self-reported questionnaire and continuously updated data from our Electronic Medical Record (EMR) representing actual clinical care events. Northwestern has a state-of-the art, comprehensive inpatient and outpatient EMR system of over 2 million patients. NUgene has broad access to participant data for all outpatient visits as well as inpatient data via a consolidated data warehouse. NUgene participants consent to distribution and use of their coded DNA samples and data for a broad range of genetic research by third-party investigators. Vanderbilt University: BioVU, Vanderbilt's DNA databank, is an enabling resource for exploration of the relationships among genetic variation, disease susceptibility, and variable drug responses, and represents a key first step in moving the emerging sciences of genomics and pharmacogenomics from research tools to clinical practice. BioVU acquires DNA from discarded blood samples collected from routine patient care. The biobank is linked to de-identified clinical data extracted from Vanderbilt's EMR, which forms the basis for phenotype definitions used in genotype-phenotype correlations.

  Study phs000888

• REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE)

  Leveraging access to the blood supply and blood donors, the REDS-IV-P program began conducting the RESPONSE study (REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic) in early 2020 in order to 1) evaluate if SARS-CoV-2 RNA was found in blood donations in the U.S. using an assay that could potentially be used to screen the blood supply if evidence of SARS-CoV-2 transfusion-transmission became apparent 2) conduct serosurveys using optimized assays/algorithms to monitor antibody reactivity in blood donor populations over time, 3) enroll SARS-CoV-2 positive donors and others into a longitudinal cohort study to answer fundamental questions about the evolution of viremia and immune responses, and 4) establish a sharable biorepository that includes specimens collected early on in the infection and potentially large volumes of plasma from infected/convalescent donors.Screening for SARS-CoV-2 RNAemia was completed using a SARS-CoV-2 nucleic acid test (NAT) performed on retained blood donor minipool samples from six geographic regions in the US. The study also included serosurveillance (i.e. testing for antibody directed against the SARS-CoV2 spike protein) of donations from the same six regions to document accruing seroincidence in blood donor populations and to project these rates in the general population. To enrich for donors with acute SARS-CoV-2 infection, another part of the study focused on donors reporting post-donation information (PDI) consistent with COVID-19 by testing plasma from all available PDI donations for SARS-CoV-2 RNA by NAT. Subjects who were diagnosed with COVID-19 based on PDI reports or who tested positive by SARS-CoV-2 NAT on index donation plasma were enrolled into a longitudinal follow-up study which collected multiple samples for up to one-year post-infection. The longitudinal follow-up study also enrolled community members who reported a new positive SARS-CoV-2 NAT test in the prior 7-14 days. The specific aims of the RESPONSE study were to: Establish the incidence of SARS-CoV-2 RNAemia in blood donations from the American Red Cross (ARC) regions in Los Angeles, Boston, and Minneapolis metropolitan areas, Bloodworks Northwest (BWNW), New York Blood Center (NYBC), and Vitalant San Francisco Bay Area, monthly between March and September of 2020 Conduct serosurveys to study antibody reactivity in same six areas as above monthly for March to August 2020 Document rates of Post Donation Information (PDI) reports to determine PDI rates relevant to SARS-CoV-2 clinical disease and test index donation plasma from PDI donors for SARS-CoV-2 RNA Enroll SARS-CoV-2 infected subjects into a longitudinal cohort study to answer fundamental questions on the evolution of viremia, early immune responses and waning of immunity over 3-12 months of follow-up Establish a sharable biorepository of samples from all of the above Aims for future research The data from Aims 3 and 4 above is being made available in BioData Catalyst.Biospecimens for these Aims are managed by Vitalant Research Institute (VRI). More information on biospecimens is available.

  Study phs003578

• BLUE CORAL: Biology and Longitudinal Epidemiology of PETAL COVID-19 Observational Study

  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.Available Data: Long Term Follow-up data has been added with version 2. Biospecimens: Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from PETAL BLUE CORAL include: Bronchial Lavage, Plasma, Tracheal Aspirate, Urine, Whole Blood Buffy Coat, DNA, Plasma, Serum, Urine, and Whole Blood. Please note that use of biospecimens is tiered for both non-genetic and genetic research.Objectives: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19–related hospitalization.Background: For many individuals, the effects of COVID-19 persist after the acute phase and result in prolonged symptoms and disability. This has led to widespread efforts to characterize the epidemiologic characteristics of such post-COVID-19 sequelae. However, accurate data were limited, hindering the ability to counsel patients, caregivers, and policy makers and to plan relevant recovery-focused clinical research. Thus, the BLUE CORAL study was intended to address the knowledge gaps and provide critical data to help guide clinical care, public health, and scientific efforts.Participants: A total of 1376 COVID-19 patents were enrolled, with 825 (444 male, and 379 female) that completed at least one follow-up survey.A subset of the BLUE CORAL adult participants were enrolled in the extension study, FIRE CORAL. FIRE CORAL was a multicenter prospective cohort study of participants recovering from COVID-19 disease after discharge from the hospital. Design: BLUE CORAL was a prospective cohort study. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Posthospital surveys were administered by trained interviewers in English or Spanish to patients or their proxies at 1, 3, and 6 months after enrollment. Cardiopulmonary symptoms were assessed using the Airways Questionnaire 20, the Kansas City Cardiomyopathy Questionnaire, and the Seattle Angina Questionnaire. Fatigue was assessed using the Patient Health Questionnaire-9. Disability was assessed by self-report of limitations in activities of daily living (ADLs) or instrumental activities of daily living (IADLs). Financial problems were assessed using the World Health Organization Disability Assessment Schedule 2.0 question and questions regarding job changes, time off work, and insurance coverage developed with the Mi-COVID-19 study using qualitative interviews. Quality of life was measured using the European Quality of Life 5-dimension 5-level instrument.The primary outcomes were new or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Symptoms that were not present before hospitalization or specifically reported as increased in severity were counted as new or worsened. Conclusions: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.

  Study phs003419

• Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-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. ObjectivesHypertension Study: To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic.Lipid Study: To determine whether pravastatin compared with usual care reduces all-cause mortality in older, moderately hypercholesterolemic, hypertensive participants with at least an additional CHD risk factor. BackgroundHypertension Study: Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown.Lipid Study: Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease (CHD) reduce CHD events. However, many of these studies were too small to assess all-cause mortality or outcomes in important subgroups.ParticipantsHypertension Study: A total of 33,357 participants. Lipid Study: A total of 10,355 participants. Baseline mean total cholesterol was 224 mg/dL; LDL-C, 146 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL; and triglycerides, 152 mg/dL. Mean age was 66 years; 49% were women, 38% black and 23% Hispanic, 14% had a history of CHD, and 35% had type 2 diabetes. DesignHypertension Study: A randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15,255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure (HF), and peripheral arterial disease).Lipid Study: Multicenter (513 primarily community-based North American clinical centers), randomized, non-blinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The interventions in the trial were pravastatin, 40 mg/d, vs usual care. The primary outcome was all-cause mortality, with follow-up for up to 8 years. Secondary outcomes included non-fatal myocardial infarction or fatal CHD (CHD events) combined, cause-specific mortality, and cancer.ConclusionsHypertension Study: Thiazide-type diuretics are superior in preventing one or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.Lipid Study: Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol (9.6%) and LDL-C (16.7%) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention.

  Study phs004021

• Submitter Portal API

  Submitter Portal API The metadata submission process can be difficult and time-consuming. For this reason, the EGA has developed the Submitter Portal, a tool that was created to offer a simplified and user-friendly method of registering metadata. Our portal provides features that are intended to make the input of metadata easier, ensuring that your data is registered correctly and effectively. Our page is divided into logical sections and includes a helpful video instruction to further assist you as you complete the submission process. With the Submitter Portal, you can rest assured that the submission of your data is in good hands. For those that want a more flexible and automated approach, we also provide a programmatic approach using the Submitter Portal AP in addition to the user interface of the Submitter Portal. With the help of our API, you can quickly include the submission of metadata into your own workflow for a more effective and individualised experience. Previous steps Create your EGA account To submit data you first need to create your EGA user. Then, once your account has been verified, you will have to request a submitter role and sign the EGA Data Processing Agreement (DPA). When the DPA is signed, you must send it to EGA Helpdesk for further validation. Please, note that if you already have an EGA account, or you have an ega-box (submission account), you can skip this step.  Upload your files Please note that all your files must be encrypted using the Crypt4GH tool before upload them.As soon as you are assigned with a submitter role, you will be able to connect to the EGA inbox and upload your files. Understand the EGA metadata schema It's crucial to comprehend the EGA metadata schema, a set of rules that specify how data is organised, described, and shared inside the EGA, in order to get the most out of this resource. Learn all about EGA metadata schema! Register your DAC and policy There are two objects in the EGA metadata schema that are registered in a separate portal. All DACs and policy objects are registered using the DAC Portal, a tool developed by EGA to help data controllers manage their data stored at the EGA. You can find the relevant information in the DAC Portal Guide. Programmatic submission All the calls to the API need to be Authenticated. We use the OpenID Connect protocol. API Usage Flow: Click here to check the API usage flow schema Obtain Access and Refresh Token: The first step to using the API is to obtain an access and refresh token. These tokens are required for authentication and authorisation of API requests. To obtain these tokens, you need to log in using your EGA credentials. Example: curl "https://idp.ega-archive.org/realms/EGA/protocol/openid-connect/token" \ -d "grant_type=password" \ -d "client_id=sp-api" \ -d "username=your-username" \ --data-urlencode "password=your-password" Use Access Token in API Calls: Once you have obtained the access token, you must use it in all the calls to the API. The access token is valid for a limited time period. When it expires, you will need to use the refresh token to obtain a new access token. Create Submission Object: After authentication, you can start creating a submission object. This object will be used to store all the metadata objects and files related to the submission. Example: curl "https://submission.ega-archive.org/api/submissions" \ -H "Authorization: Bearer your-access-token" \ -H "Content-Type: application/json" \ -d "{ \"title\":\"My submission title\", \"description\":\"My submission description\" }" Create EGA Metadata Objects: Within the submission object, you can create other metadata objects required for the submission. These objects may include information about the submitter, study, sample, experiment, and run. Example of study creation: curl "https://submission.ega-archive.org/api/submissions/{submisison-id}/studies" \ -H "Authorization: Bearer your-access-token" \ -H "Content-Type: application/json" \ -d "{ \"title\":\"My study title\", \"description\":\"My study description\", \"study_type\":\"Metagenomics\" }" If you would like to reuse already registered objects in new submissions, bear in mind that they must have an accession which you must use to reference them. You cannot reuse objects that have not been finalised and accepted yet.For example, when creating a new run which is reusing a previously submitted experiment, instead of using experiment_provisional_id, you must use experiment_accession_id. Enums There are some fields that only accept specific values, i.e. study_type. The API provides several enumerations to list these values. You can list all the enumerations, or a specific one, for example, study_types. Obtain IDs of files You can list the files available in your inbox and filter by a prefix by adding the prefix param, i.e. &prefix=/my_folder/abc Example: curl "https://submission.ega-archive.org/api/files?status=inbox&prefix=/my_folder/abc" \ -H "Authorization: Bearer your-access-token" \ -H "Content-Type: application/json" To improve performance and manageability, we have limited the number of files that the Submitter Portal API can return in a response. If a given call exceeds this limit, user will be asked to narrow down the search by using the query parameters already available in this endpoint. Finalise Submission: Once all the metadata objects are created and linked to the submission, you can finalise the submission. Finalising the submission sends it to the Helpdesk team for review. Please, note that all files linked to the submission must be ingested, and all objects created in a submission must be linked before you can finalise the submission. API Reference: For a full API reference, please check our specification documentation.

  Documentation submission/metadata/submission/sequencing-phenotype/submitter-portal-api

• Women's Health Initiative Clinical Trial and Observational Study

  The Women's Health Initiative (WHI) is a long-term national health study that has focused on strategies for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women. The original WHI study included 161,808 postmenopausal women enrolled between 1993 and 1998. The Fred Hutchinson Cancer Research Center in Seattle, WA serves as the WHI Clinical Coordinating Center for data collection, management, and analysis of the WHI. The WHI has two major parts: a partial factorial randomized Clinical Trial (CT) and an Observational Study (OS); both were conducted at 40 Clinical Centers nationwide. The CT enrolled 68,132 postmenopausal women between the ages of 50-79 into trials testing three prevention strategies. If eligible, women could choose to enroll in one, two, or all three of the trial components. The components are: Hormone Therapy Trials (HT): This double-blind component examined the effects of combined hormones or estrogen alone on the prevention of coronary heart disease and osteoporotic fractures, and associated risk for breast cancer. Women participating in this component with an intact uterus were randomized to estrogen plus progestin (conjugated equine estrogens [CEE], 0.625 mg/d plus medroxyprogesterone acetate [MPA] 2.5 mg/d] or a matching placebo. Women with prior hysterectomy were randomized to CEE or placebo. Both trials were stopped early, in July 2002 and March 2004, respectively, based on adverse effects. All HT participants continued to be followed without intervention until close-out. Dietary Modification Trial (DM): The Dietary Modification component evaluated the effect of a low-fat and high fruit, vegetable and grain diet on the prevention of breast and colorectal cancers and coronary heart disease. Study participants were randomized to either their usual eating pattern or a low-fat dietary pattern. Calcium/Vitamin D Trial (CaD): This double-blind component began 1 to 2 years after a woman joined one or both of the other clinical trial components. It evaluated the effect of calcium and vitamin D supplementation on the prevention of osteoporotic fractures and colorectal cancer. Women in this component were randomized to calcium (1000 mg/d) and vitamin D (400 IU/d) supplements or a matching placebo. The Observational Study (OS) examines the relationship between lifestyle, environmental, medical and molecular risk factors and specific measures of health or disease outcomes. This component involves tracking the medical history and health habits of 93,676 women not participating in the CT. Recruitment for the observational study was completed in 1998 and participants were followed annually for 8 to 12 years. Extension Studies: The original protocol allowed for follow-up until March 2005, after which participants were invited to enroll in the first WHI Extension Study for follow-up through 2010. Participants were invited again to participate in the second WHI Extension Study with continued follow up from 2010 to at least 2015. As of March 31, 2011 there were 93,122 women enrolled in the second extension. In Extension Study 2, the overall WHI study population was divided into two new subsamples, the Medical Records Cohort (MRC) and the Self-Report Cohort (SRC). The MRC consists of all former hormone trial participants and all African American and Hispanic participants from all study components. The SRC consists of the remaining participants. The extent of outcome information collected differs between the two cohorts, with more extensive outcomes information collection on the MRC. As part of Extension Study 2, selected older WHI participants were invited to participate in an In Person Visit (a.k.a., Long Life Study) at their homes during which additional blood samples were collected and various measurements were taken (such as blood pressure, height, weight, waist circumference, grip strength, etc.). In October 2015, Extension Study 2 was renewed with continued follow-up planned through October 2020, pending annual contract review and renewal. Additional Information: The WHI website, https://www.whi.org/about/SitePages/About%20WHI.aspx has much more information about the study. For WHI data collection forms used over the years, please see https://www.whi.org/researchers/studydoc/SitePages/Forms.aspx. For additional dataset documentation, see https://www.whi.org/researchers/data/Pages/Available%20Data.aspx. For data preparation and use, please refer to 'WHI dbGaP Cohort Data Release Data Preparation Guide May 2018' for additional details about the WHI data. The WHI Cohort is utilized in the following dbGaP substudies. To view genotypes, analysis, expression data, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" box located on the right hand side of this top-level study page phs000200 WHI Cohort. phs000386 WHI SHARe phs000281 GO-ESP WHISP phs000315 WHI GARNET phs000503 WHISE phs000227 PAGE WHI phs000675 WHIMS+ phs000746 WHI Harmonized and Imputed GWAS phs001334 WHI Metabolomics of CHD phs001335 WHI BA23 phs001614 WHI LLS Phase III GWAS

  Study phs000200

• Five Mantle Cell Lymphoma Patients Before and After Failure of Standard Chemotherapy

  MCL cells were isolated from different tissues of five patients with MCL at diagnosis, and at the time of the first clinical relapse after failure of standard immunochemotherapy based on alternation of R(ituximab)-CHOP and R-high-dose-araC. All patients signed informed consent according to the Declaration of Helsinki. Four patients were diagnosed with classical nodal aggressive MCL, and all these patients experienced early relapse (i.e., progression of disease POD < 12 months). One patient was diagnosed with indolent non-nodal MCL and relapsed 9 years after initial MCL diagnosis. The dataset presents single cell RNA sequencing data as well as whole exome sequencing data for these five patients.

  Dataset EGAD50000001213