12501 results for ""non-traditional+communal+storytelling+approach"+novel+segment+noted+in+critical+commentary"

in 20.87 milliseconds.

• Single-cell RNA-seq data of the tumor microenvironment of lymphocyte-rich Hodgkin lymphoma and other Hodgkin lymphoma subtypes

  Lymphocyte-rich classic Hodgkin lymphoma (LR-CHL) is a rare subtype of Hodgkin lymphoma. Recent technical advances have allowed for the characterization of specific crosstalk mechanisms between malignant Hodgkin Reed-Sternberg (HRS) cells and different normal immune cells in the tumor microenvironment (TME) of CHL. However, the TME of LR-CHL has not yet been characterized at single cell resolution. Here, using single cell RNA sequencing, we examined the immune cell profile of 8 cell suspension samples of LR-CHL in comparison to 20 samples of the mixed cellularity (9 cases) and nodular sclerosis (11 cases) subtypes of CHL, as well as 5 reactive lymph node controls.

  Study EGAS00001005541

• Using human induced pluripotent stem cell-derived oligodendrocytes to explore cellular phenotypes associated with t(1;11) translocation.

  Although the underlying neurobiology of major mental illness (MMI) remains unknown, emerging evidence implicates a role for oligodendrocyte-myelin abnormalities. Here, we took advantage of a large family carrying a balanced t(1;11) translocation, which substantially increases risk of MMI, to undertake both diffusion tensor imaging (DTI) and cellular studies to evaluate the consequences of the t(1;11) translocation on white matter structural integrity and oligodendrocyte-myelin biology (this translocation disrupts among others the DISC1 gene which plays a crucial role in brain development). At a cellular level, we observe dysregulation of key pathways controlling oligodendrocyte development and morphogenesis in induced pluripotent stem cell (iPSC) case derived oligodendrocytes.

  Study EGAS00001004595

• Understanding_the_multicellular_dynamics_of_clear_cell_renal_cell_carcinoma___visium

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

  Study EGAS00001006045

• Epiclomal: probabilistic clustering of sparse single-cell DNA methylation data

  We present Epiclomal, a probabilistic clustering method arising from a hierarchical mixture model to simultaneously cluster sparse single-cell DNA methylation data and infer their corresponding hidden methylation profiles. Using synthetic and published single-cell CpG datasets we show that Epiclomal outperforms non-probabilistic methods and is able to handle the inherent missing data feature which dominates single-cell CpG genome sequences. Using a recently published single-cell 5mCpG sequencing method (PBAL), we show that Epiclomal discovers sub-clonal patterns of methylation in aneuploid tumour genomes, thus defining epiclones. We show that epiclones may transcend copy number determined clonal lineages, thus opening this important form of clonal analysis in cancer.

  Study EGAS00001003504

• A standardised framework for robust fragmentomic feature extraction from cell-free DNA sequencing data

  Fragmentomic features of cell-free DNA represent promising non-invasive biomarkers for cancer diagnosis. However, a lack of systematic evaluation of biases in feature quantification has hindered the adoption of such applications. We compared features derived from whole-genome sequencing of ten healthy donors using nine library kits and ten data-processing routes, and validated them in 1,182 plasma samples from published studies. Our results clarify the variations resulting from library preparation and feature quantification methods. We designed the Trim Align Pipeline and the cfDNAPro R package as unified interfaces for data pre-processing, feature extraction, and visualisation, aiming to standardise multimodal feature engineering and integration for machine learning.

  Study EGAS00001008051

• 10X whole single cell RNA-seq from pre-frontal cortex biopsy

  The biopsy procedure was performed by a standard operative procedure under general anaesthesia. The placement of burr hole on the frontal lobe, opening of dura and cortex was performed in a routine fashion for VP shunt or VCS surgery. The biopsy was sharp dissected with knife through the leptomeninges, forming a tissue block consisting of cortex and subcortex, and placed in a sterile tube containing CSF. Fresh tissue sample processing was performed within the hours after surgery. The tissue was dissociated followed by red cell and debris removal and counting of the cells to be sequenced with (scRNA-seq; 10x Genomics). After dissociation only non neuronal cells were retrieved.

  Study EGAS50000001058

• TCR- and BCR-sequencing data for The interface of malignant and immunologic clonal dynamics in high-grade serous ovarian cancer

  Each tumor sample was cut into three pieces, yielding two end-pieces for cryovials and a middle portion placed in 10% buffered formalin. End pieces were homogenized manually and with a paddle blender (Stomacher). All paraffin-embedded blocks, including formalin-fixed tumor samples and molecular-fixed fallopian tubes, were sectioned and stained with hematoxylin and eosin prior to expert histopathological review to confirm the presence of high grade serous carcinoma. Homogenized end pieces were then flash frozen, and RNA was extracted using the miRNeasy Mini kit. Nanodrop was used to assess quality (260/280) and quantity. Total RNA samples were also QC checked using the Caliper HT RNA HiSens assay. Samples ranging from 60-255ng RNA were re-arrayed into a 96-well plate. 5'-RACE PCR was carried out as described in "The interface of malignant and immunologic clonal dynamics in high-grade serous ovarian cancer" (Zhang et al.). Briefly, this involved first round and nested PCR with TRB (TCR beta chain) and IGH (immunoglobulin heavy chain) gene-specific primers. The indexed libraries were sequenced on the Illumina HiSeq platform with paired-end 250bp reads using v2 chemistry reagents.

  Dataset EGAD00001003985

• CINECA synthetic data.Please note: This study contains synthetic data (with cohort “participants” / ”subjects” marked with FAKE) has no identifiable data and cannot be used to make any inference about cohort data or results.

  Please note: This study contains synthetic data (with cohort “participants” / ”subjects” marked with FAKE) has no identifiable data and cannot be used to make any inference about cohort data or results. The purpose of this dataset is to aid development of technical implementations for cohort data discovery, harmonization, access, and federated analysis. In support of FAIRness in data sharing, this dataset is made freely available under the Creative Commons Licence (CC-BY). Please ensure this preamble is included with this dataset and that the CINECA project (funding: EC H2020 grant 825775) is acknowledged. For any questions please contact isuru@ebi.ac.uk or cthomas@ebi.ac.uk

  Study EGAS00001002472

• Integrated single-cell profiling dissects cell-state-specific enhancer landscapes of human tumor infiltrating T cells.

  Despite extensive studies on the chromatin landscape of exhausted T cells, the transcriptional wiring underlying functional and dysfunctional states of human tumor infiltrating lymphocytes (TILs) is incompletely understood. Here, we identify tissue-specific and general gene-regulatory landscapes in the wide breadth of CD8+ TIL functional states covering four cancer entities using single-cell chromatin profiling. We map enhancer-promoter interactions in human TILs by integrating single-cell chromatin accessibility with single-cell RNA-seq data from tumor entity-matching samples and prioritize key elements by super enhancer analysis. Our analysis reveals a human core chromatin trajectory to TIL dysfunction and identifies key enhancers, transcriptional regulators, and deregulated target genes involved in this process. Finally, we validate enhancer regulation at loci encoding PD1, TCF1, and TIM3 by targeting non-coding regulatory elements with potent CRISPR activators and repressors. In summary, our study advances the understanding of molecular regulation of TIL (dys-)function and provides a framework for modulating immunotherapeutic relevant TIL genes via their enhancers.

  Dataset EGAD00001008662

• NHLBI TOPMed: Genome-Wide Association Study of Adiposity in Samoans

  The individuals sequenced here represent a small subset of the parent study (described below) and were carefully selected for the purpose of creating a Samoan-specific reference panel for imputation back into the parent study. The INFOSTIP algorithm of Gusev et. al. (2012) (PMID: 22135348) was used to optimally choose the individuals for sequencing. The research goal of the parent study (dbGaP ID phs000914) is to identify genetic variation that increases susceptibility to obesity and cardiometabolic phenotypes among adult Samoans using genome-wide association (GWAS) methods. DNA from peripheral blood and phenotypic information were collected from 3,119 adult Samoans, 23 to 70 years of age. The participants reside throughout the independent nation of Samoa, which is experiencing economic development and the nutrition transition. Genotyping was performed with the Affymetrix Genome-Wide Human SNP 6.0 Array using a panel of approximately 900,000 SNPs. Anthropometric, fasting blood biomarkers and detailed dietary, physical activity, health and socio-demographic variables were collected. We are replicating the GWAS findings in an independent sample of 2,500 Samoans from earlier studies. After replication of genomic regions and informative SNPs in those regions, we will determine sequences of the important genes, and determine the specific genetic variants in the sequenced genes that are associated with adiposity and related cardiometabolic conditions. We will also identify gene by environment interactions, focusing on dietary intake patterns and nutrients.

  Study phs000972

• ApoA-1 and Atherosclerosis in Psoriasis

  Apolipoprotein A-1 is a protein localized to high-density lipoprotein that functions to remove cholesterol from tissues for transport back to the liver. Psoriasis is a systemic inflammatory disease associated with poor high-density lipoprotein function and accelerated non-calcified burden by coronary computed tomographic angiography. In this study, 310 psoriasis patients from The Psoriasis, Atherosclerosis, and Cardiometabolic Disease Initiative (PACI) were studied at baseline to determine if levels of circulating apolipoprotein A-1 predict early onset coronary artery disease in inflammatory conditions. Of the 310 participants, 124 were followed for four years to determine if apolipoprotein A-1 predicts non-calcified coronary burden over time. The primary outcome of this study was non-calcified coronary burden by coronary computed tomography angiography. To assess non-calcified coronary burden, participants underwent coronary computed tomography angiography using the same scanner (320-detector row Aquilion ONE ViSION, Toshiba, Japan). For ApoA-1 quantification, fasting blood draw was performed the same day as the coronary computed tomography angiography. The 400MHz proton Vantera Clinical Analyzer was used to quantify Plasma apolipoprotein A-1. The study determined that low levels of apolipoprotein A-1 are associated with increased coronary artery burden and that this relationship persists over time. The data are available through dbGaP and the dataset includes all variables reported in the manuscript.

  Study phs003231

• Symptom Clusters in Oncology Patients Receiving Chemotherapy

  The parent longitudinal study evaluated the symptom experience of oncology outpatients receiving chemotherapy. Patients completed questionnaires in their homes a total of six times (assessments 1 through 6). The questionnaires were timed to evaluate symptoms associated with the receipt of two cycles of chemotherapy that were administered approximately a month apart. Assessments 1 and 4 evaluated symptoms prior to the receipt of chemotherapy. Assessments 2 and 5 evaluated symptoms in the week following the administration of chemotherapy. Assessments 3 and 6 evaluated symptoms two weeks following the administration of chemotherapy. For this analysis, morning and evening fatigue data from the enrollment assessment (i.e., prior to the second or third cycle of chemotherapy) and the assessment that was done approximately 1 week after administration of chemotherapy were evaluated. Patients completed the Lee Fatigue Scale to obtain information on morning and evening fatigue severity. For the morning fatigue assessment, patients were asked to describe how they “felt over the past week when they woke up in the morning”. For the evening fatigue assessment, they were asked to describe how they felt over the past week “before they went to bed at night”. Medical records were reviewed for disease and treatment information. Epigenome assays (microarray) were completed for 1170 patients. Whole transcriptome sequencing (bulk RNA-Seq) was completed for 651 patients.

  Study phs003863

• Single-Cell RNA-Seq Profiling of Peripheral Immune Responses to Severe Infection in Uganda

  We conducted a prospective observational study (RESERVE-U-2-TOR) of adults admitted to Tororo General Hospital in eastern Uganda with severe, undifferentiated infection (i.e., suspected sepsis). Peripheral blood mononuclear cells (PBMCs) were isolated from freshly collected heparinized whole-blood samples (4 - 5 mL) using a standard density-gradient protocol (STEMCELL Technologies). PBMCs were aliquoted, cryopreserved in CryoStor CS10 (STEMCELL Technologies), stored overnight at -80°C, and transferred to liquid nitrogen for longer-term storage. Upon thawing, viability was assessed using the Nexcelom Cellaca Cell Counter, and cells were diluted to optimal concentrations for loading onto the Chromium Controller (10X Genomics). Each sample targeted the capture of ~10,000 GEMs (gel bead-in-emulsions). Single-cell RNA libraries were prepared using the Chromium Single Cell 3' Reagent Kit v3.1 following the manufacturer's standard protocol. Libraries were quality-assessed using an Agilent TapeStation and quantified using both Qubit 2.0 Fluorometer (Invitrogen) and qPCR (Applied Biosystems). Sequencing was performed on the NovaSeq X Plus platform (Illumina) using a 28×91 read configuration per 10X guidelines, targeting ~50,000 reads per cell. Data from this study available through dbGaP include raw single-cell RNA-seq data generated from PBMC samples collected from a subset of RESERVE-U-2-TOR participants at study enrollment (N=8).

  Study phs004100

• Identification of RNA biomarkers in Parkinson's disease iPSC-derived neuronal cells

  Parkinson?s disease (PD) is an age-related, chronic and progressive neurodegenerative disorder characterized by a loss of multifocal neurons and subsequent motor symptoms. These overt motor symptoms are often preceded by prodromal non-motor symptoms. Though a number of genetic and environmental factors have been identified to play a role in PD, more exact methods for both diagnosing and assessing prognosis are yet to be discovered. Probing the transcriptomes of control and PD cells can give some interesting insight into changes caused by the disease (in both coding and non-coding gene expression), highlighting potential RNA biomarkers that may be used for PD diagnosis and as new drug targets. The study consists of two main sources of data: matched neural stem cell (NSC) and fully differentiated dopaminergic neurons derived from iPS cells. Both sets of data are made up of three samples from a control cell line, and five samples carrying a mutation in one of several genes known to be linked to heritable PD: PARK2, PARK22 or PARK9. All transcriptome libraries were synthesized and sequenced using no-amplification non-tagging cap analysis of gene expression (nAnT-iCAGE) on the Illumina HiSeq 2500 platform. Resulting data was mapped to the human genome annotation (hg38) and processed CAGE tags were clustered ready for differential expression analyses. The 16 samples here described were sequenced across two lanes.

  Study JGAS000142

• Identification of RNA biomarkers in Parkinson's disease iPSC-derived neuronal cells

  Parkinson���s disease (PD) is an age-related, chronic and progressive neurodegenerative disorder characterized by a loss of multifocal neurons and subsequent motor symptoms. These overt motor symptoms are often preceded by prodromal non-motor symptoms. Though a number of genetic and environmental factors have been identified to play a role in PD, more exact methods for both diagnosing and assessing prognosis are yet to be discovered. Probing the transcriptomes of control and PD cells can give some interesting insight into changes caused by the disease (in both coding and non-coding gene expression), highlighting potential RNA biomarkers that may be used for PD diagnosis and as new drug targets. The study consists of two main sources of data: matched neural stem cell (NSC) and fully differentiated dopaminergic neurons derived from iPS cells. Both sets of data are made up of three samples from a control cell line, and five samples carrying a mutation in one of several genes known to be linked to heritable PD: PARK2, PARK22 or PARK9. All transcriptome libraries were synthesized and sequenced using no-amplification non-tagging cap analysis of gene expression (nAnT-iCAGE) on the Illumina HiSeq 2500 platform. Resulting data was mapped to the human genome annotation (hg38) and processed CAGE tags were clustered ready for differential expression analyses. The 16 samples here described were sequenced across two lanes.

  Study JGAS000318

• Epigenetic profiling of human CD4+ memory T cells reveals their proliferative history and argues in favor of a progressive differentiation model driven by epigenetically controlled master regulators.

  A key element of adaptive immunity is the development of long-lived memory cells, which protect against recurring infection by providing a highly enriched pool of antigen-specific cells ready to react to the pathogen. Different classes of memory T cells occur upon primary activation of naive T cells, however, their detailed differentiation pathway is not entirely clear. As part of the IHEC consortium, we generated genome-wide epigenetic maps of a number of CD4+ T cell memory (Tmem) stages including rare subsets such as terminally differentiated (TEMRA) and bone marrow-resident Tmem. We found that CD4+ T cells show progressive global DNA demethylation with differentiation into memory stages, which reflects their proliferative history and likely indicates their decline in differentiation and proliferation potential. Furthermore, transcriptomic profiling combined with co-regulation network analyses arranged different Tmem subsets into a successive differentiation pathway. In addition, we identified a number of epigenetically controlled candidate master regulators for Tmem formation, of which we functionally validated a new methylation-sensitive promoter for the known 'naive-keeper' transcription factor Foxp1. Our study highlights the power of epigenomic datasets in the elucidation of the cellular history but also of the functional potential of T cell populations including the identification of epigenetically controlled master regulators.

  Study EGAS00001001624

• Spatial concordance of DNA methylation classification in diffuse glioma

  Background: Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence. Methods: We used neuronavigation to acquire 133 image-guided and spatially-separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast enhanced T1 weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a three-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites. Results: Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account. Conclusion: Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists.

  Study EGAS00001005434

• Genome wide variation in the Angolan Namib desert reveals unique Pre-Bantu ancestry

  The populations of the Angolan Namib Desert have been largely neglected in previous surveys of the genomic landscape of southern Africa. Although at present, the Namib is culturally dominated by Southwest Bantu-speaking cattle-herders, the region exhibits an extraordinary ethnographic diversity which includes an array of semi-nomadic peoples whose subsistence strategies fall outside the traditional division between foraging and food production and can thus be referred to as “peripatetic”. Among these small-scale populations are the last speakers of the Kwadi branch of the Khoe-Kwadi language family associated with the introduction of pastoralism into southern Africa (Kwepe), as well as a range of groups whose origins remain enigmatic (Kwisi, Twa and Tjimba). Using genome-wide data from 208 individuals belonging to nine ethnically diverse groups from the Angolan Namib and adjacent areas (Kwepe, Kwisi, Twa, Tjimba, !Xun, Kuvale, Himba, Nyaneka, Ovimbundu) in combination with published data from other regions of Africa, we reconstruct in detail the histories of contact emerging from pre-historic migrations to southern Africa and show that peripatetic groups from southwestern Angola stand out for exhibiting elevated levels of an unique, regionally-specific and highly divergent Pre-Bantu ancestry. These findings highlight the importance of the Namib for understanding the deep genetic structure of Africa.

  Study EGAS00001007011

• From research to data sharing: exploring EGA user's experiences

  The Cell Plasticity and Regeneration Group at the Bellvitge Biomedical Research Institute-IDIBELL focuses on the process of recruitment of macrophages that takes place in the small intestine during injury and healing. They recently published a paper titled “Mucosal Macrophages Govern Intestinal Regeneration in Response to Injury" in Gastroenterology Journal. As part of the research, some experiments were conducted using human intestinal organoid lines. These cells were processed for RNA sequencing, and the sequencing data were deposited at the EGA to be made available to the scientific community. When dealing with human genomic information, repositories must ensure the availability of the datasets while ensuring data protection. In this context, the European Genome-phenome Archive stands as a service for secure archiving and sharing of genetic, phenotypic and clinical data resulting from biomedical research. Following the recent publication of their paper, we took the opportunity to talk to Ilias Moraitis, first author, and Jordi Guiu, group leader, to find out about their experience with data sharing. Could you explain the focus of your research? In the lab, we study intestinal regeneration and how immune cells participate in this process. We use several techniques: engineered mouse models, image tracing, as well as mouse and human cells intestinal organoids. What challenges do you face regarding data management? We didn’t have a lot of problems. Always the informatic part, the data analysis, can give problems. But everything was smooth and working. We think it’s very important to deposit the data in repositories. For the mouse data it is very straightforward, but for us it was the first time depositing human data, which is sensitive because it comes from patients, and this is legally regulated. That’s why we thought about the EGA, and it was our first time. Why do you think it is important to submit data to repositories such as EGA? Because we think data is important for the science. Nowadays, we are sequencing a lot everywhere worldwide and having these resources shared with the scientific community it’s not only good for science, but it is also saving money and reducing costs. And there is so much data in there that can be used for other projects and for other questions. And it saves time! How was the process of submitting the data to the EGA? The communication worked very well but it was slower than we would like. But I think this is something we learn on the way. People usually wait until the last minute to do this before publication but if you know it in advance, you can start the process earlier. If you had to repeat the process, would you do anything differently? It’s like everything, isn’t it? For the first time you don’t know, you aren’t sure, but for the second time you know the steps, you know what to do and it’s faster. Of course, we would to do it earlier. Also, there were some things related to the control access that we didn’t know how to manage, but it was something more internal to us. Who is going to receive the communications and when, is our ethical committee going to evaluate this? All these technicalities that we didn’t know before starting this process, so we had to think about all these things. Next time it will be faster on our side. Do you have any suggestions for us to improve the submission process? Maybe we’ll need to ask our bioinformatician who did it! He was in charge of this part. Besides that, we think if the process were faster, it would be better for everyone. Also, in science a lot of times you have to do a lot of things at the very last minute, because of the nature of the experiments, or the need to accomplish for submitting a paper. Being faster in the process would be a plus. On your side, we went through the process and were able to find some information, but there were aspects we weren't aware of and weren't sure how to handle. I'm not sure if other institutes have different protocols for managing data requests or how they handle these internally. We believe the main issue lies in how the forms are filled out. Do you have any recommendations for other submitters? The main advice is to do this with enough time. Submit the data when you have the sequences, and don’t wait until the last minute. And then it can be under embargo, so you don’t need to make it public at that moment. As soon as you sequence, upload it and then it will be there for whenever you need to publish. How do you think we could encourage other researchers to submit their data? There are different layers here. One is that it is mandatory. You have to do this. The other is that we belong to a research community, to the same community and sharing this is making our research community stronger and more efficient. And then, also because this gives you visibility. The data is there, other people can analyse your data, and this also will bring citations to your papers. It has many advantages.

  Blog from-research-to-data-sharing

• Osteoporotic Fractures in Men (MrOS)

  The Osteoporotic Fractures in Men Study (MrOS) is a multi-center prospective, longitudinal, observational study of risk factors for vertebral and all non-vertebral fractures in older men, and of the sequelae of fractures in men. The original specific aims of the study include: (1) to define the skeletal determinants of fracture risk in older men, (2) to define lifestyle and medical factors related to fracture risk, (3) to establish the contribution of fall frequency to fracture risk in older men, (4) to determine to what extent androgen and estrogen concentrations influence fracture risk, (5) to examine the effects of fractures on quality of life, (6) to identify sex differences in the predictors and outcomes of fracture, (7) to collect and store serum, urine and DNA for future analyses as directed by emerging evidence in the fields of aging and skeletal health, and (8) define the extent to which bone mass/fracture risk and prostate diseases are linked. The MrOS study population consists of 5,994 community dwelling, ambulatory men aged 65 years or older from six communities in the United States (Birmingham, AL; Minneapolis, MN; Palo Alto, CA; Monongahela Valley near Pittsburgh, PA; Portland, OR; and San Diego, CA). Inclusion criteria were designed to provide a study cohort that is representative of the broad population of older men. The inclusion criteria were: (1) ability to walk without the assistance of another, (2) absence of bilateral hip replacements, (3) ability to provide self-reported data, (4) residence near a clinical site for the duration of the study, (5) absence of a medical condition that (in the judgment of the investigator) would result in imminent death, and (6) ability to understand and sign an informed consent. To qualify as an enrollee, the participant had to provide written informed consent, complete the self-administered questionnaire (SAQ), attend the clinic visit, and complete at least the anthropometric, DEXA, and vertebral X-ray procedures. There were no other exclusion criteria. The baseline examination was completed over a 25-month period from March 2000 to April 2002. Participants completed questionnaires regarding medical history, medications, physical activity, diet, alcohol intake, and cigarette smoking. Objective measures of anthropometric, neuromuscular, vision, strength, and cognitive variables were obtained at a clinic visit. Skeletal assessments included DEXA, calcaneal ultrasound, and vertebral radiographs. Vertebral and proximal femoral QCT was performed on a subset (65%) of participants. Serum, urine, and whole blood specimens were collected. During the study period, participants complete a tri-annual questionnaire every four months that obtains information concerning the occurrence of incident falls and fractures. Follow-up is over 99% complete. All reported fractures are confirmed using physician review of radiology reports or study radiologist review of x-rays. All deaths are also centrally adjudicated using death certificates and recent hospitalization records. In additional to the baseline study visit and tri-annual questionnaires, all surviving active participants were invited to follow-up visits and questionnaires. A second comprehensive clinic visit was completed between March 2005 and May 2006 or about 4.5 years after baseline. Most baseline measures, including vertebral radiographs, were repeated at the second visit. A third comprehensive clinic visit was completed between March 2007 and March 2009 or about 7.0 years after baseline. Many baseline measures were repeated at the third visit. A measure of energy expenditure was also obtained utilizing an accelerometer based armband device. Surviving participants have also completed two extensive mailed questionnaires designed to updated information obtained at clinic visits. The first questionnaire was mailed between baseline and visit 2 between July 2002 and March 2004. The second questionnaire was mailed after the third questionnaire between March 2009 and February 2011. The MrOS Sleep Study, an ancillary study of the parent MrOS cohort, was conducted between December 2003 and March 2005 and recruited 3,135 MrOS participants for a comprehensive sleep assessment. Men were screened for nightly use of mechanical devices during sleep including pressure mask for sleep apnea (CPAP or BiPAP), mouthpiece for snoring or sleep apnea, or oxygen therapy and were generally excluded. The sleep visit included objective measures of sleep using actigraphy and polysomnography. Other measures at the sleep visit include neuropsychiatric measures, performance measures, health related questionnaires, routine exam measures previously completed at MrOS clinic visits and a urine and serum specimen collection. During the sleep study period, participants complete a tri-annual questionnaire every four months that contains information about incident cardiovascular events. All reported events are centrally adjudicated utilizing hospital records, study ECGs and other supporting documentation. The Hip Osteoarthritis study, another ancillary study of the parent MrOS cohort, was completed at the second clinic visit between March 2005 and May 2006. Participants were asked for consent for a hip x-ray and osteoarthritis measurements were obtained from these x-rays. DNA was extracted from baseline whole blood samples for use in genetic research. Consent for use of DNA was obtained through written consent. Raw GWAS data is housed at the study's coordinating center and not released as part of the dbGAP release. The raw data can be requested from the study's coordinating center. Only QC cleaned Plink files are available on dbGAP.

  Study phs000373

• DATA ACCESS WITH REGARDS TO EXOME-WIDE ASSOCIATION ANALYSIS OF CORONARY ARTERY DISEASE IN THE KINGDOM OF SAUDI ARABIA POPULATION

  Dac EGAC00001000420

• Transcriptional and DNA binding profiling of CEBPE in REH acute lymphoblastic leukaemia cells using shRNA RNA-Seq and ChIP-Seq

  Dac EGAC00001000891

• The data access committee for Multimodal Genomic Features Predict Outcome of Immune Checkpoint Blockade in Non-small Cell Lung Cancer

  Dac EGAC00001001331

• Data access committee for white blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer

  Dac EGAC00001001435

• Data Access Commitee for study Fine-Scale Genomic Analyses Of Admixed Individuals Reveal Unrecognized Genetic Ancestry Components In Argentina

  Dac EGAC00001001634