6257 results for "fc 26 ultimate team coins buy Buyfc26coins.com is FC 26 coins official site..E4Pd"

in 34.10 milliseconds.

• Resource for Genetic Epidemiology Research on Adult Health and Aging (GERA)

  The Resource for Genetic Epidemiology Research on Aging (GERA) Cohort was created by a RC2 "Grand Opportunity" grant that was awarded to the Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) and the UCSF Institute for Human Genetics (AG036607; Schaefer/Risch, PIs). The RC2 project enabled genome-wide SNP genotyping (GWAS) to be conducted on a cohort of over 100,000 adults who are members of the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC), and participating in its RPGEH. The purpose of the RPGEH is to facilitate research on the genetic and environmental factors that affect health and disease by linking together clinical data from electronic health records, survey data on demographic and behavioral factors, and environmental data from various sources, with genetic data derived from biospecimens collected from participants. At the time of the award of the RC2 project in late 2009, the RPGEH had established a cohort of about 140,000 individuals who had answered a detailed survey, provided saliva samples for extraction of DNA, and given broad consent for the use of their data in studies of health and disease. To maximize the diversity of the resulting sample, the GERA cohort was formed by including all racial and ethnic minority participants with saliva samples (N = 20,925; 19%); the remaining participants were drawn sequentially and randomly from white non-Hispanic participants (89,341; 81%). A total of 110,266 participant samples were included to ensure that at least 100,000 were successfully assayed. The resulting GERA cohort is 42% male, 58% female, and ranges in age from 18 to over 100 years old with an average age of 63 years at the time of the RPGEH survey (2007). The sample is ethnically diverse, generally well-educated with above average income. Approximately 69% of the participants are married or living with a partner. Length of membership in KPNC averages 23.5 years. UCSF and RPGEH investigators worked with the genomics company Affymetrix to design four custom microarrays for genotyping each of the four major race-ethnicity groups included in the GERA Cohort, described in detail in Hoffmann et al., 2011a and 2011b. Following genotyping and quality control procedures, and after removal of invalid, discordant, or withdrawn samples, about 103,000 participants were successfully genotyped. The resulting genotypic data were linked to survey data and data abstracted from the electronic medical records. As described below, all RPGEH participants were mailed new consent forms with explicit discussion of the placement of data in the NIH-maintained dbGaP. About 77% of participants returned completed consent forms, resulting in a final sample size of 78,486 participants in the GERA Cohort with data for deposit into dbGaP. Origins of the RPGEH GERA Cohort The goal in creating the RPGEH GERA cohort was to create a large, multiethnic, and comprehensive population-based resource for research into the genetic and environmental basis of common age-related diseases and their treatment, and factors influencing healthy aging and longevity. The GERA Cohort consists of a diverse cohort of more than 100,000 adults who are members of the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC), and participating in its Research Program on Genes, Environment and Health (RPGEH). KPNC is an integrated health care delivery system with a population of about 3.3 million people in northern California. The membership of KPNC is representative of the general population in the 14 county area in which facilities are located, although the membership is underrepresented for the extremes of income at both ends of the spectrum. The RPGEH utilizes the longitudinal electronic health records (EHR) of KPNC to obtain clinical, laboratory, imaging and pharmacy information on all cohort members, to which personal demographic, behavioral and health characteristics have been added through member surveys. The GERA Cohort comprises a subsample of the RPGEH participant cohort, and was created through the RC2 award from the NIA, NIMH, and NIH Common Fund as described above. GERA Study Design The GERA Cohort is a subsample, as described above, of the longitudinal cohort enrolled in the Kaiser Permanente RPGEH. The RPGEH cohort includes about 400,000 survey participants of whom about 200,000 have provided broad consent and a sample of saliva or blood for use in studies of genetic and environmental factors in health and disease. The GERA Cohort was developed from a mailed survey sent to all adult members of KPNC who had been members for two years or more in 2007. All survey respondents were contacted and asked to complete a consent form; those who completed consent forms were asked to provide a saliva sample. Additional male participants were added to the RPGEH through inclusion of the Northern California sample of the California Men's Health Study (CMHS) cohort of about 40,000 men from KPNC, ages 45-69 years old at the time of the CMHS survey in 2002-2003. The CMHS participants contributed about 15,400 saliva samples to the RPGEH and were eligible for inclusion in the GERA Cohort. CMHS participants were included according to the same sampling design as for the RPGEH cohort as a whole. Specifically, all minority participants were selected for inclusion in order to maximize representation of minorities in the GERA Cohort, and Non-Hispanic White participants were selected at random to complete the sample of 110,266 GERA Cohort participants. GERA Genotypic Data High-density genotyping was conducted at UCSF using custom designed Affymetrix Axiom arrays, as described in Hoffmann et al. (2011a; 2011b). To maximize genome-wide coverage of common and less common variants, four specific arrays were designed for individuals of Non-Hispanic White (EUR), East Asian (EAS), African-American (AFR), and Latino (LAT) race/ethnicity. There was broad overlap among the SNPs on the arrays, which were designed using a hybrid greedy imputation algorithm (Hoffmann et al., 2011b) applied to genotype information validated by Affymetrix from the 1000 Genomes Project. However, in order to capture low frequency variants specific to particular race-ethnicity groups, SNP content varies between arrays. A more detailed description of the process of genotyping and results is included in Genotyping of DNA Samples. Description of the analyses of population structure and development of principal components for adjustment of population structure is included in Population Structure Analysis. GERA Phenotypic Data RPGEH and CMHS Survey Data. The sources of data on demographic and behavioral factors deposited in dbGaP for the GERA Cohort are the RPGEH and CMHS surveys. Data on common demographic factors such as gender, race/ethnicity, marital status, and education and on behavioral factors such as smoking, alcohol consumption, and body mass index, have been cleaned, edited, reconciled between the two surveys, and compiled into summary indices, where appropriate, for deposition into dbGaP. A more complete description of the survey variables is included in Survey Variables Documentation. Please note that the terms of use of the GERA Cohort Data, as specified in the Data Use Certification (DUC), prohibit the use of survey variables as outcomes in analyses. For example, a genome-wide association study (GWAS) of education or smoking is not permitted as specified by the DUC. Only health conditions can be used as outcome variables in analyses. Health Conditions derived from Kaiser Permanente Electronic Medical Records. Data on the occurrence of health conditions in participants in the GERA Cohort have been derived from summarizing ICD-9 coded diagnoses in Kaiser Permanente's electronic medical records. An algorithm that aggregates specific ICD-9 codes into appropriate diagnostic groups for selected conditions is applied to outpatient and inpatient databases; see Disease and Conditions Definitions Documentation for details. The criterion for including a condition as "present" for a participant is the occurrence of two or more diagnoses within a diagnostic category occurring on separate days. Two or more is used as the criterion in order to reduce false positives due to mistakes or rule-out diagnoses. When compared with validated disease registries, the criterion of 2+ diagnoses yields high specificity and good sensitivity. ICD-9 codes in the electronic records are specified in several ways. For outpatient visits occurring during the period 1995 to 2006, diagnoses were assigned by the treating physician who endorsed specific diagnoses on an optically scanned list that varied by specialty. Beginning in 2006 with the advent of an integrated, fully electronic medical record, outpatient diagnoses are made by physicians/ providers using a pull down menu. Discharge diagnoses from inpatient stays are specified by physicians and coded by specially trained coders. Databases of ICD-9 codes for diagnoses assigned at outpatient visits, or as one of the discharge diagnoses following inpatient stays, are complete and available for all KPNC members dating back to 1995. Although the average length of KPNC membership among GERA cohort members is 23.5 years in 2007, not all have been members since 1995, so the history for some conditions, such as those that are not chronic or recurrent, may not be complete for all cohort members. The year of first membership in KPNC is included as a variable in the list of survey variables, enabling investigators to estimate the number of years of observation of each Cohort member. RPGEH Access and Collaborations Website and Procedures The RPGEH maintains a web portal for inquiries and applications for collaboration and access to data. The url is: https://rpgehportal.kaiser.org/. RPGEH has an application process and an Access Review Committee that reviews applications for collaboration and use. For more details, please contact RPGEH through the website.

  Study phs000674

• National Eye Institute (NEI) Age-Related Eye Disease Study (AREDS)

  The Age-Related Eye Disease Study (AREDS) was initially designed as a long-term multi-center, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. In addition to collecting natural history data, AREDS included a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. AREDS participants were 55 to 80 years of age at enrollment and had to be free of any illness or condition that would make long-term follow-up or compliance with study medications unlikely or difficult. On the basis of fundus photographs graded by a central reading center, best-corrected visual acuity and ophthalmologic evaluations, 4,757 participants were enrolled in one of several AMD categories, including persons with no AMD. The clinical trials for AMD and cataract were conducted concurrently. AREDS participants were followed on the clinical trials for a median time of 6.5 years. Subsequent to the conclusion of the clinical trials, participants were followed for an additional 5 years and natural history data were collected. The AREDS research design is detailed in AREDS Report 1. AREDS Report 8 contains the mainline results from the AMD trial; AREDS Report 9 contains the results of the cataract trial. Blood samples were also collected from 3,700+ AREDS participants for genetic research. Genetic samples from 600 AREDS participants (200 controls, 200 Neovascular AMD cases, and 200 Geographic Atrophy cases) were selected using data available in March 2005 and then were evaluated with a genome-wide scan. These data, as well as selected phenotypic data, were made available in the dbGaP. DNA from AREDS participants, which is currently being stored in the AREDS Genetic Repository, is available for research purposes. However, not all of the 3,700+ AREDS participants who submitted a blood sample currently have DNA available. In addition to including the data from the genome-wide scan on the 600 original samples, this second version of the AREDS dbGaP database provides a comprehensive set of data tables with extensive clinical information collected for the 4,757 participants who participated in AREDS. The tables include information collected at enrollment/baseline, during study follow-up, fundus and lens pathology, nutritional estimates, quality of life measures and measures of morbidity and mortality. In November 2010, over 72,000 high quality fundus and lens photographs of 595 AREDS participants (of the original 600 selected for the genome-wide scan) were made available in the AREDS dbGaP. In addition to the genome-wide scan data, the fundus and lens grading data for these participants are also available through the AREDS dbGaP. Details about the ocular photographs that are available may be found in the document "Age-Related Eye Disease Study (AREDS) Ocular Photographs". In January 2012, a measure of daily sunlight exposure was added in a separate "sunlight" table. Furthermore, the "followup" table has been revised. The visual acuity for the right eye was inadvertently missing at odd-numbered visits (01, 03, 05, etc.). This data is now part of the table. In February 2014 over 134,500 high-quality fundus photographs (macular field F2) of 4613 AREDS participants were added to the existing AREDS dbGaP resource. The AREDS dbGaP image archive already contains over 72,000 high quality fundus and lens photographs of 595 AREDS participants for whom dbGaP-accessible genotype data exist. Information about the available ocular photographs found in the document "Age-Related Eye Disease Study (AREDS) Ocular Photographs" has been updated with an addendum. It is hoped that this resource will better help researchers understand two important diseases that affect an aging population. These data may be applied to examination and inference on genetic and genetic-environmental bases for age-related diseases of public health significance and may also help elucidate the clinical course of both conditions, generate hypotheses, and aid in the design of clinical trials of preventive interventions. Definitions of Final AMD Phenotype Categories Please see phd001138.1 for a detailed description of how AREDS participants' final AMD phenotype was categorized. User's Guide for AREDS Phenotype Data A detailed User's Guide for the AREDS phenotype data is available. This User's Guide is meant to be a comprehensive document which explains the complexities of the AREDS data. It is recommended that all researchers using AREDS phenotype data make use of this User's Guide.

  Study phs000001

• A Randomized, Double-Blind, Crossover Study of Sodium Phenylbutyrate (Buphenyl) and Low-Dose Arginine (100 mg/kg/day) Compared to High-Dose Arginine (500 mg/kg/day) Alone on Liver Function, Ureagenesis and Subsequent Nitric Oxide Production in Patients with Argininosuccinic Aciduria (ASA)

  Individuals with Urea Cycle Disorders (UCD) cannot remove ammonia, a waste product, from the blood. At present there is little information on the use of sodium phenylbutyrate (Buphenyl™) in children with argininosuccinic aciduria (ASA). It is hoped that this drug may help lower ammonia and argininosuccinic acid levels in patients with ASA. Through this study we hope to learn whether the use of sodium phenylbutyrate (Buphenyl™) in patients with ASA, in addition to diet and arginine therapy, will decrease liver damage and the number of periods during which ammonia levels are high. The primary study objective is to determine if the treatment of ASA patients with sodium phenylbutyrate (Buphenyl™) in conjunction with lowered doses of arginine improves liver function as measured by short-term assessment of synthetic activity and the use of stable isotope tracers to assess ureagenesis and nitric oxide production. Twelve patients with ASA will be studied using a randomized, cross-over design. Medical records will be reviewed to confirm the diagnosis prior to enrollment. Patients will be on the each arm of the study for one week each preceded by a three day washout period. Patients will come to the Baylor College of Medicine General Clinical Research Center in Texas Children's Hospital for an inpatient hospitalization. This hospitalization is for diet control, clinical evaluation, and stable isotope infusions for measurement of in vivo rates of ureagenesis and nitric oxide production. During the washout periods Buphenyl™ or other alternative route medications, e.g., benzoate, will be discontinued and arginine will be administered at the standard therapeutic dose of 500 mg/kg/day or 10 grams/m2. Following randomization, subjects will be maintained on either high-dose arginine (500 mg/kg/day or 10 grams/m2) alone, or the alternative of low-dose arginine (100 mg/kg/d or 2 grams/m2) along with sodium phenylbutyrate (500 mg/kg/day or 10 grams/m2). For the second week they will be crossed over to the other arm of the study preceded by another three day washout. Previous medications and dietary protein intake (0.6 g/kg/day or current metabolic diet) will be continued during both arms of the study. The two arms may be performed as separate ten-day admissions. The decision to design the study with two arms, high-dose arginine and low-dose arginine/Buphenyl™, was reached after weighing several considerations. First, the current accepted practice for treatment of ASA is high-dose arginine. Based on metabolic flux studies, we have quantified the effects of this dose of arginine as compared to standard doses of Buphenyl™/phenylacetate on ureagenesis. Since the study is not designed or intended to address the independent effects of Buphenyl™ as compared to arginine alone, Buphenyl™ was added for safety reasons to accommodate loss of clearance of nitrogen by decreasing the arginine dose. Moreover, based on our experience with recruiting for previous versions of this study, most ASA patients with liver dysfunction are on an alternative route ammonia scavenger medication in addition to arginine. We found that this has in fact become an accepted practice. Hence, when considering study design from both a safety and recruitment perspective, it was most reasonable to design the study to investigate specifically the hypothesis that the production and presence of argininosuccinic acid leads to liver dysfunction. Since both low-dose arginine with Buphenyl™ and high-dose arginine alone lead to a decreased production of argininosuccinic acid, and both are currently accepted therapies in ASA and UCDs in general, the need to address their effects distinctly is not being investigated at this time. Sodium phenylbutyrate dosage will be 500 mg/kg/day in patients weighing less than 20kg and 10 g/m2/day in larger patients. Daily dosage will be given in equally divided doses 4 times per day. In order to ensure that the study remains double-blind to investigators, study staff and subjects, the Investigational Pharmacy Service at Texas Children's Hospital will dispense both the Buphenyl™ and arginine in powder form which is compounded into capsules or will be mixed with syrpalta (up to 5 grams will dissolve in 10cc liquid) and administered orally or through nasogastric or gastrostomy tube. No nasogastric tube should be placed or gastrostomy performed solely for the purpose of inclusion in this study. Because the reported adverse effects of sodium phenylbutyrate include gastritis, participants will be started on a standard dose of ranitidine (Zantac™), or comparable drug, during both arms of the study.

  Study phs001305

• Neurodevelopmental Genomics: Trajectories of Complex Phenotypes

  This study is a collaboration between the Center for Applied Genomics (CAG) at Children's Hospital of Philadelphia (CHOP) and the Brain Behavior Laboratory at the University of Pennsylvania (Penn). The cohort consists of youths aged 8-21 years who consulted the CHOP network and volunteered to participate in genomic studies of complex pediatric disorders. All participants underwent clinical assessment, including a neuropsychiatric structured interview and review of electronic medical records. They were also administered a neuroscience based computerized neurocognitive battery (CNB) and a subsample underwent neuroimaging. These are described separately below. Clinical Testing: GOASSESS, a computerized, structured screener developed from a modified version of the Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS, Kaufman et al. 1997, PMID: 9204677). Components of the interview include a timeline of life events, demographics and medical history, Global Assessment of Functioning, and Interviewer Observations. A psychopathology symptom and criterion-related assessment of mood disorders (depression, mania/hypomania), anxiety disorders (overanxious/generalized-, separation-, social-anxiety, specific phobia, panic disorder, agoraphobia, obsessive compulsive disorder, post-traumatic stress disorder), behavioral disorders (attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder), psychosis spectrum (psychosis and prodromal symptoms), eating disorders, suicidal thinking and behavior, and treatment history. This is also based on K-SADS. An abbreviated Family Interview for Genetics Studies (FIGS) to assess major domains of psychopathology in the proband's first-degree relatives. Computerized Neurocognitive Battery: The CNB, developed for large-scale studies, yields measures of accuracy and speed for domains of executive-control functions (abstraction, attention, working memory), episodic memory (verbal, facial, spatial), complex cognitive processing (language reasoning, nonverbal reasoning, spatial processing), social cognition (emotion identification, emotion intensity differentiation, age differentiation) and sensorimotor and motor speed. The following neurobehavioral domains were assessed: Penn Conditional Exclusion Test is a measure of abstraction and concept formation. Participants decide which of 4 objects does not belong with the other 3, based on one of three sorting principles, which change. Feedback is used. Attention: The Penn Continuous Performance Test. Participants respond to a set of 7-segment displays whenever they form a digit or letter. Working Memory: The Letter N-back Test displays sequences of uppercase letters with a stimulus duration of 500 ms (ISI 2,500 ms.) In the 0-back condition, participants respond to a single target (i.e., X). In the 1-back condition they respond if the letter is identical to that preceding it. In the 2-back condition, they respond if the letter is identical to that presented two trials back. Verbal Memory: The Penn Word Memory Test presents 20 target words that are then mixed with 20 distracters equated for frequency, length, concreteness and low imageability. A 20 min delayed recall procedure is also administered. Face Memory: The Penn Face Memory Test presents 20 digitized faces that are then mixed with 20 distracters equated for age, gender and ethnicity. The procedure is repeated at 20 min delay. Spatial Memory: The Visual Object Learning Test uses Euclidean shapes as stimuli with the same paradigm as the word and face. Language and Analogical Reasoning: The Penn Verbal Reasoning consists of verbal analogy problems. Spatial Processing: Penn Line Orientation Test presents two lines at an angle, and participants click on a button that makes one line rotate until it has the same angle as the other. Emotion Processing: Facial displays of 4 emotions (Happy, Sad, Anger, Fear) and Neutral faces, 8 each, are presented and the subject identifies the emotion in a multiple-choice format. The facial stimuli are balanced for gender, age, and ethnicity. Sensory-motor Processing Speed: The task requires moving the mouse and clicking on a green square that disappears after the click. The square gets increasingly small and appears in unpredictable locations. Neuroimaging Protocol: Studies were performed at Penn using a Siemens Trio (Erlangen, Germany) 3T scanner equipped with 40mT/m gradients and 200 mT/m/s slew-rates. RF transmission utilized a quadrature body-coil, and reception a 12-channel head coil optimized for parallel imaging. Total image acquisition time was about 45 min. Structural Imaging: The T1-weighted protocol utilized a 3D, inversion-recovery, and magnetization-prepared rapid acquisition gradient echo. Relevant imaging procedures include: Structural magnetic imaging Diffusion tensor imaging ASL perfusion BOLD fMRI Neuroimaging tasks: Fractal N-Back Task of Spatial Working Memory Face Emotion Identification Task Neuroimages: The current data release includes over 9700 MRI images that may be downloaded through Authorized Access.

  Study phs000607

• Data generated by the Drier Lab at HUJI

  This Data Access Committee is responsible to all data generated by and deposited by the Drier Lab at the Faculty of Medicine of the Hebrew University of Jerusalem (http://yotamdrier.ekmd.huji.ac.il/)

  Dac EGAC50000000060

• Haukeland University Hospital Data Access Committee for STRAT-PARK datasets archived in Federated EGA Norway

  This is the Data Access Committee mandated by Haukeland University Hospital for the STRAT-PARK cohort: an initiative to stratify Parkinson's disease.

  Dac EGAC50000000428

• DAC for "Identification and characterization of tertiary lymphoid structures in brain metastases"

  This is the DAC for the study "Identification and characterization of tertiary lymphoid structures in brain metastases" of Prof. Dr. Guido Reifenberger (Guido.Reifenberger@med.uni-duesseldorf.de)

  Dac EGAC50000000369

• Data Access Committee for Translational analyses from a phase II study of pembrolizumab and epigenetic modification with azacitidine in platinum-resistant epithelial ovarian cancer

  This DAC is responsible for request review and handling related to the study above.

  Dac EGAC50000000697

• Policy to access RNAseq Patient Derived Sézary syndrome cells

  This is the policy for accessing the RNAseq raw data associated to the project 'Diverse transcriptomic and mutational patterns but limited functional pathway alterations in patient-derived SS cells'

  Dac EGAC50000000693

• DAC for "Drug Development against Tumor Microtube Networks in Glioblastoma"

  This is the DAC for the study "Drug Development against Tumor Microtube Networks in Glioblastoma" of Dirk C. Hoffmann, Dirk.Hoffmann@dkfz.de and Frank Winkler, Frank.Winkler@med.uni-heidelberg.de

  Dac EGAC50000000326

• CRC and UC WES samples

  This is the dataset used to produce results for the report "NOUS-209 off-the-shelf immunotherapy has the potential to hit primary and metachronous colorectal and urothelial cancer in Lynch syndrome"

  Dac EGAC50000000782

• Leptomeningeal melanocytic tumour

  This is the first whole exome sequencing analysis of a primary meningeal melanocytic tumour (MMT) alongside the patients germline. Here we report the CRAM files from the tumour and germline.

  Dataset EGAD00001003750

• HEMOGLOBIN HAPLOTYPES IN ABIDJAN

  This is a prospective study with 100 participants. The enzymatic digestion profiles after conventional PCR allowed the identification of different haplotypes of hemoglobin in Abidjan.

  Dataset EGAD00001008546

• Transcriptomic profiling of human small intestine macrophage and DC subsets

  Using low input SMART-seq protocol, the whole transcriptome of human small intestine macrophage subtypes is characterized.

  Dataset EGAD00001003581

• danMAC5

  Three whole genome sequecing of three independent cohorts. The three cohorts derives from projects including samples of inviduals with Danish origin. Data is deviden into males and female and compiled.

  Dataset EGAD00001009756

• PacBio data of de novo assembly individual EGYPT

  This is the PacBio long read data used for performing de novo assembly of the EGYPT individual (mapped against GRCh38).

  Dataset EGAD00001006034

• Whole Genome Sequencing of Asian Lung Cancers: Second Hand Smoke is Not Responsible for Higher Incidence of Lung Cancer Among Asian Never-Smokers

  Background Asian nonsmoking populations have a higher incidence of lung cancer compared to their European counterparts. There is a long-standing hypothesis that the increase of lung cancer in Asian never-smokers is due to environmental factors such as second-hand smoke. Results We analyzed whole-genome sequencing of 30 Asian lung cancers. Unsupervised clustering of mutational signatures separated the patients into two categories: i) all of the never-smokers, and ii) only smokers or ex-smokers. Half of the ex-smokers / smokers were in the never-smoker-like cluster. The overall somatic variant profiles of Asian lung cancers were similar to that of European origin with G.C>T.A being predominant in smokers. We found EGFR and TP53 are the most frequently mutated genes with mutations in 50% and 27% of individuals, respectively. Among these Asian never-smokers, 71% had an EGFR mutation compared to 20% of the smokers in the smoking cluster. Other frequently mutated genes include RYR2, SATB2, C1orf88, FERMT1 and CTNNB1. Somatic alterations occurred in WNT signaling pathway genes, suggesting this pathway plays a role in both Western and Asian lung cancers. Conclusions Asian never-smokers have lung cancer signatures distinct from the smoker signature and their mutation profiles are similar to that of European never-smokers. The profiles of Asian and European smokers are also similar. This suggests that the same mutational mechanisms underlie the etiology for both ethnic groups, and the high incidence of lung cancer in Asian never-smokers might not be due to second hand smoke or other carcinogens that cause oxidative DNA damage. Half of the ex-smokers/smokers have a molecular phenotype similar to never-smokers; of which, 50% had EGFR mutations. This suggests that routine EGFR testing is warranted in the Asian population, regardless of smoking status.

  Study EGAS00001000621

• Whole_Genome_Sequencing_of_hiPS_cells

  Human induced pluripotent stem (hiPS) cells hold great promise for regenerative medicine. Safety issues of use of hiPS cells however remain to be addressed. One of such issues is mutations derived from somatic donor cells and introduced during genome manipulation. We sequence whole genomes of hiPS cells and analyzed mutations. Our study brings hiPS cell technology one step closer to application to regenerative medicine.

  Study EGAS00001000008

• The mutational landscape and its longitudinal dynamics in relapsed and refractory Hodgkin lymphoma

  In classical Hodgkin-lymphoma (cHL), only a few cases recur, and only a limited fraction of patients is primary-refractory to standard-polychemotherapy. Underlying genomic features of unfavorable clinical courses remain sparsely characterized. Here, we investigated the genomic characteristics of primary-refractory/relapsed cHL in contrast with long-term-responders (LTR). In total, data from 84 samples were submitted.

  Study EGAS50000000149

• Myocardial Infarction Genetics Exome Sequencing Consortium: Precocious Coronary Artery Disease Study

  The Precocious Coronary Artery Disease (PROCARDIS) study is an international, multicenter case-control study aimed at discovering the genetic contributors to premature coronary artery disease. All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Agilent SureSelect Human All Exon Kit v2 and sequencing was performed on an Illumina HiSeq 2000 or 2500.

  Study phs000883

• The Incidence of Thromboembolic Events in Patients with Antibodies to Heparin-PF4 after Cardiac Bypass

  The purpose of this study is to determine how often heart surgery patients who receive heparin develop an immune response (heparin-induced thrombocytopenia) that leads to clots forming in different parts of the body. These clots usually occur in the legs (deep venous thrombosis or DVT) or lungs (pulmonary embolism or PE) or cause heart attacks (myocardial infarction or MI) and strokes.

  Study phs000606

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

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

  Study phs001855

• Genetic Analysis of Limb Malformation Disorders: Freeman Sheldon Syndrome Exome Sequencing Study (LMD-FSS)

  The overall goal of this project is to investigate the etiology and pathogenesis of malformations (i.e., birth defects) of the limb, concentrating on abnormalities of limb patterning such as limb deficiency/duplications and multiple congenital contractures. The exome sequences of four unrelated individuals were obtained by massively parallel DNA sequencing. The three individuals were affected with Freeman Sheldon syndrome (OMIM: 193700).

  Study phs000204

• Investigating Human Placentation and Pregnancy Using First Trimester Chorionic Villi

  Chorionic villus sampling (CVS) is routinely used for prenatal diagnosis of cytogenetic disorders, but also possesses great potential for studying placentation. To better understand villi biology, human placentation, and how these relate to pregnancy outcomes, we examined the morphology and transcriptomes of villi obtained via CVS from 10-14 weeks of pregnancy and correlated these with pregnancy attributes and clinical outcomes.

  Study phs001320

• Family Genomics of Congenital Heart Defects

  The study identified the causal mutation in a five-generation pedigree harboring a cardiac septal defect. The inheritance pattern is consistent with an autosomal dominant mutation with high penetrance. We performed whole-genome sequencing (Complete Genomics) on 21 individuals in the pedigree, of which 11 individuals are affected. We identified a single gene, GATA4, as primarily responsible for this cardiac phenotype in this pedigree.

  Study phs000758

• Harnessing the Electronic Health Record to Predict Risk of Cardiovascular Disease: Sangre Por Salud (SPS) Biobank GWAS Data

  These data are from subjects in the Sangre Por Salud (SPS) Biobank, a Latino population from the Southwest United States. Subjects were genotyped in 2 batches on the Illumina Multi-ethnic Global Array. Data from this study were used for testing a new cardiovascular risk score and evaluating polygenic risk scores. SPS biobank GWAS data is available on 3699 subjects.

  Study phs003553

• FluOMICS

  The FluOMICS project is to generate predictive models of influenza virus pathogenesis, leveraging previous collaborations that generated global datasets and models that predict the severity of disease caused by three influenza virus strains with different levels of virulence. This case-control study of patients diagnosed with severe and mild influenza virus disease evaluates associations between potential molecular regulators of the host response and determinants of disease outcome.

  Study phs003407

• Constrained hypermutation and absence of TERT promoter mutations in Lynch syndrome-associated urothelial cancer

  Lynch syndrome is a hereditary condition characterized by defective DNA mismatch repair and high incidence of several cancers, including urothelial cancers (UC) of the upper urinary tract and bladder. We set out to study the somatic landscape of LS-associated urothelial cancer (LS-UC) by analyzing 41 surgical tumor samples and 3 urine DNA samples from 34 LS-UC patients.

  Study EGAS50000000831

• Tumor-resident T-cell regulate responses to checkpoint blockade immunotherapies

  In cancer models, CD103+CD8 TRM cells are implicated in the response to anti-PD-1 immunotherapy, and a subset of CD4 TRM cells expressing the integrin CD49a is required for response to anti-CTLA-4 immunotherapy. We performed single-cell RNA sequencing on tumour-infiltrating T lymphocytes (TILs) isolated from colon carcinoma et unsupervised analyses reveal several TRM populations.

  Study EGAS50000000826

• Collagen Proteostasis in Health and Disease

  This study uses human iPSC-derived cartilage to investigate the effects of the p.Arg719Cys mutation in the COL2A1 gene, which is linked to precocious osteoarthritis. Using a CRISPR-edited isogenic cell line pair, we compared wild-type and mutant cartilage for matrix defects and cellular stress responses. We performed RNA-sequencing and quantitative proteomics to characterize changes in gene expression, protein interactions, and collagen folding.

  Study phs004112

• Evaluation of novel therapies using primary cultured gynecological cancer cells and search for predictors of efficacy

  The objective of this study is to establish an optimal method to evaluate the anti-tumor efficacy and biological activity of the novel therapies under investigation in our department using cancer tissues and cells derived from patients with gynecological malignancies in vitro and to evaluate them in practice. This research will contribute to the development of new treatments for gynecological cancer.

  Study JGAS000809

• Differentiation-associated ISG expression of NK cells in chronic viral hepatitis

  Little is known about the effects of ISGs on NK cell responses in chronic viral hepatitis. Here, we determined the expression, regulation and function of ISGs in NK cells with respect to phenotype and function, we performed high-throughput single cell RNA sequencing of circulating CD3-CD56+ NK cells from healthy donors (HD) and patients with chronic HBV or HCV infections.

  Study EGAS00001007771

• Bevacizumab plus erlotinib in advanced solid cancers with Krebs cycle gene mutations: A multicenter phase II study

  Targeting aberrant metabolism in tumors with alterations in genes encoding Krebs cycle enzymes, a central component of glucose metabolism, is a promising therapeutic strategy. These tumors rely on aerobic glycolysis and promote VEGF-dependent angiogenesis; furthermore, EGFR signaling enhances aerobic glycolysis. This phase 2 trial evaluated bevacizumab and erlotinib in patients with solid tumors harboring Krebs cycle gene mutations.

  Study EGAS50000001243

• Targeted sequencing data of regulatory regions in 200 Spanish ASD trios

  This study consists of genomic sequencing data obtained through targeted sequencing of regulatory regions (85,394 human cCREs from ENCODE v2, version 2, https://screenv2.wenglab.org/) in 200 ASD (Autism Spectrum Disorder) trios (father and mother unaffected and proband affected). The aim of the project is to detect genomic variants (rare and inherited variants) in regulatory regions that contribute to autism.

  Study EGAS50000001395

• Comprehensive molecular profiling for breast cancer patients and high-risk individuals.

  Although germ-line mutations in BRCA1 and BRCA2 gene are responsible for familial breast and ovarian cancer, the detailed mechanism of tumorigenesis is yet unknown. Here, we performed next-generation sequencing to determine the genomic profiles of familial breast cancer tumorigenesis. Target-capture sequencing of fresh-frozen or formalin-fixed-paraffin-embedded (FFPE) samples of breast cancer or normal breast tissue were performed.

  Study JGAS000368

• Identification of New Therapeutic Targets for Renal Medullary Carcinoma via Integrated Genomic and Transcriptomic Profiling

  Renal medullary carcinoma (RMC) is a rare, aggressive kidney cancer associated with sickle cell trait, characterized by SMARCB1 loss and resistance to conventional therapies used for other renal cell carcinomas (RCC). We conducted whole exome sequencing (WES) on RMC samples. This study provides a large molecular characterization of RMC, highlighting TROP2 and other cell surface markers as promising therapeutic targets.

  Study EGAS50000001280

• The_Little_Princess_Knowledge_Bank_RNAseq

  The purpose of the knowledge bank is to serve as a community resource and to address the following specific questions about Wilms tumour: (1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to treatment stratification? (2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of Wilms tumour including the most common subtypes classified as intermediate risk?

  Study EGAS00001005244

• Myelodysplastic_Syndrome_Exome_Sequnecing

  Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Myelodysplastic Syndrome development.

  Study EGAS00001000089

• Genetic_screening__of_GPI_anchor_protein_synthesis__

  This study will analyse the guide sequence which were used for making mutations in the Cas9-expressing cells. We used GeCKO v2 library which were released by Feng Zhang, 2014. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001001256

• Transcriptomes_of_human_lymphocytes

  In this study we will compare the single cell transcriptomes of immune cells from asthmatics responding to steroids, those refractory to steroids, and a control population.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001001755

• Determination of the molecular nature of the Vel blood group by exome sequencing

  The genetic basis of the Vel group is yet to be determined. We have collected DNA samples from about 90 Vel negative blood donors by phenotyping 270,000 donors. Understanding the genetic basis of the Vel group could have clinical significance as transfusion of Vel positive blood to Vel negative recipients with anti-Vel can cause severe and acute haemolytic transfusion reactions.

  Study EGAS00001000069

• Whole-exome sequencing of extranodal NK/T cell lymphoma

  Extranodal NK/T cell lymphoma (ENKTCL) is an aggressive Epstein-Barr virus-associated T/NK neoplasm that predominantly affects Asians. To explore the causative somatic events, we conducted a comprehensive genetic analysis of 19 ENKTCL patients including whole-exome sequencing (N = 16). Commonly deregulated gene pathways in ENKTCL included epigenetic modifiers followed by human leukocyte antigen (HLA) and related genes and JAK-STAT pathway.

  Study EGAS00001004357

• Amplicon_based_sequencing_of_drug_resistant_lung_cancer_cell_lines

  A EGFR mutant NSCLC cell line which is sensitive to AZD9291 inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a AZD9291. Single cell derived colonies were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors hypothesised from currently available literature.

  Study EGAS00001001675

• Genome_Diversity_in_Africa_Project___GemCode_libraries_

  High depth whole genome sequencing from GemCode (10x Genomics) DNA libraries containing long range linkage information for one Baganda trio and one Baganda child (parent already sequenced at high depth). This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001001828

• Whole transcriptome and exome sequencing of childhood ALL

  Gene fusion is a major class of genomic abnormalities in childhood acute lymphoblastic leukemia (ALL) and sentinel chromosomal rearrangements involving EP300 and CREBBP may cause global epigenetic deregulation during leukemogenesis with potentials for therapeutic targeting. This dataset includes whole transcriptome sequencing of 231 children with acute lymphoblastic leukemia from a Singapore-Malaysia frontline clinical treatment protocol.

  Study EGAS00001001858

• Mapping_genetic_variants_underlying_gene_regulation_in_inflammed_intestinal_cell_types_to_identify_novel_IBD_drug_targets

  Biopsies from the terminal ileum and rectum of individuals with Crohn's disease are digested on ice to single cells and processed for single-cell RNA-sequencing (10X Genomics and Illumina) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001003770

• Whole-genome bisulfite sequencing analysis of low-grade astrocytomas in the ICGC PedBrain Tumor Project

  Pilocytic Astrocytoma (PA) is the most common pediatric brain tumor. While genome and transcriptome landscapes are well-studied, data of the complete methylome, tumor cell composition and immune infiltration are scarce. We generated whole genome bisulfite sequence data (WGBS) of nine PAs to find evidence for a link of focal methylation differences and differential gene expression to immune infiltration.

  Study EGAS00001004019

• Brain transcriptome of hereditary cerebral haemorrhage with amyloidosis–Dutch type (HCHWA-D)

  HCHWA-D is an early onset hereditary form of Cerebral Amyloid Angiopathy (CAA) caused by a point mutation resulting in an amino acid change (NP_000475.1:p.Glu693Gln) in the Amyloid Precursor Protein (APP). Post-mortem brain tissue (9 patients and 9 age-related controls; frontal and occipital cortex) was used for next generation sequencing of RNA (RNA-Seq with ribosomal RNA depletion).

  Study EGAS00001002730

• INSIGHT: VHL Case Report

  The overall goal of this study is to uncover contributors to inherited cancer through analysis of individuals and families with, or at risk of, a hereditary cancer syndrome. In addition, we hope to elucidate novel mechanisms of tumourigenesis in hereditary cancer patients. This specific report highlights a rare case of VHL mosaicism and shows the value of tissue testing in VHL variant negative cases.

  Study EGAS00001005895

• Exome sequencing of Fibromyalgia patients

  Fibromyalgia is a complex disorder characterized by increased sensitivity to pain and extreme tiredness. It affects mostly women, and its causes are unknown. In this study we have performed exome sequencing of 87 fibromyalgia cases, including some sibling pairs, to perform rare variant association analysis and identify fibromyalgia risk factors. A few of the included samples have been also included in a previous GWAS study.

  Study EGAS00001003826

• Whole-exome sequencing of intravascular large B-Cell lymphoma

  Intravascular large B-cell lymphoma (IVLBCL) is a unique form of diffuse large B-cell lymphoma (DLBCL) characterized by extranodal cell growth especially in small vessels without systemic lymphadenopathy. The limitation in obtaining sufficient tumor materials hampers understanding the molecular pathogenesis of IVLBCL. We performed whole-exome sequencing of IVLBCL using plasma-derived cell-free DNA (cfDNA) and patient-derived xenograft (PDX) samples.

  Study EGAS00001003970

• Drug-induced epigenomic plasticity reprograms circadian rhythm regulation to drive prostate cancer towards androgen-independence (RNA-seq)

  Understanding how prostate cancer cells adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenetic plasticity towards pro-survival signaling, and uncovered circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel clinical lead for therapeutic development.

  Study EGAS00001006016

• Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

  ABACUS is a single arm phase 2 study that investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in 95 patients with muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint.

  Study EGAS00001004445

• Molecular landscape of blastic plasmacytoid dendritic cell neoplasm

  Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignancy assumed to originate from plasmacytoid dendritic cells (pDCs), which mostly affects the skin, bone marrow and lymph nodes and sequentially other organ systems. We applied paired WES/RNA-seq combined with genome-wide copy-number analysis to characterize 47 BPDCN patients regarding mutational drivers, cytogenetic aberrations and gene-expression profiles.

  Study EGAS00001006166

• Drug-induced epigenomic plasticity reprograms circadian rhythm regulation to drive prostate cancer towards androgen-independence (ChIP-seq)

  Understanding how prostate cancer cells adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenetic plasticity towards pro-survival signaling, and uncovered circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel clinical lead for therapeutic development.

  Study EGAS00001006017

• Human pan-genome analysis

  The reference human genome is still incomplete, and several non-reference sequences have derived from diverse populations. With the available of whole genome sequencing data from multiple individuals, we could construct the pan-genome sequence. Here we provide high quality genome sequencing (~30x coverage) from 185 Han Chinese individuals. All samples were sequenced using Illumina HiSeq X10 sequencer and paired-end 150-bp reads were produced.

  Study EGAS00001003657

• Benchmarking dataset for ProSolo, a probabilistic single nucleotide caller for single cell DNA sequencing data

  This is the dataset used in the benchmarking of ProSolo, a new probabilistic single nucleotide variant caller for single cell DNA sequencing data that provides control over the false discovery rate of different single cell events at genomic sites (e.g. alternative allele presence or allele dropout). It provides the whole exome sequencing data used in assessing ProSolo's performance that is not available elsewhere, namely bulk whole exome sequencing data of a patient with a constitutional mismatch repair defect (MSH6-) and their parents and siblings, a bulk whole exome sample of granulocytes from that patient and 5 single granulocytes whole exome sequenced after whole genome amplification.

  Dataset EGAD00001005929

• Massive parallel RNA sequencing of highly purified mesenchymal cells derived from bone marrow specimens of 3 Diamond-Blackfan anemia cases

  Highly purified mesenchymal cells (CD45-/7AAD-/CD235a-/CD31-/CD271+/CD105+) were prospectively FACS-isolated from bone marrow specimens of 3 Diamond-Blackfan anemia (DBA) cases. This data set, comprising 3 DBA cases, is used as complement to 45 low-risk myelodysplastic syndrome (LRMDS) and 4 Shwachman-Diamond syndrome (SDS) cases to demonstrate aberrant inflammatory signaling as a common mechanism in pre-leukemia syndromes to induce genotoxic stress in hematopoietic stem cells. In addition, this data set is used to determine different overlapping gene expression signatures in pre-leukemia syndromes compared to gene expression profiles of highly purified mesenchymal cells of healthy donors.

  Dataset EGAD00001002661

• Massive parallel RNA sequencing of highly purified mesenchymal cells derived from bone marrow specimens of 4 Shwachman-Diamond syndrome cases

  Highly purified mesenchymal cells (CD45-/7AAD-/CD235a-/CD31-/CD271+/CD105+) were prospectively FACS-isolated from bone marrow specimens of 4 Shwachman-Diamond syndrome (SDS) cases. This data set, comprising 4 SDS cases, is used as complement to 45 low-risk myelodysplastic syndrome (LRMDS) and 3 Diamond-Blackfan anemia (DBA) cases to demonstrate aberrant inflammatory signaling as a common mechanism in pre-leukemia syndromes to induce genotoxic stress in hematopoietic stem cells. In addition this data set is used to determine different overlapping gene expression signatures in pre-leukemia syndromes compared to gene expression profiles of highly purified mesenchymal cells of healthy donors.

  Dataset EGAD00001002660

• Comprehensive genetic analysis of uveal melanoma heterogeneity during metastatic progression

  Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite improvement of diagnosis and treatment of the primary tumor, there is no effective treatment of metastatic disease and approximately half of patients will die within one year or less following metastases detection. Tumor heterogeneity has been proposed as a key factor of drug resistance. However, it has been scarcely studied in UM. The present project aims searching for specific drivers of the metastatic progression, describing the genomic and transcriptomic landscape of metastatic UM, exploring tumor heterogeneity and investigating its role in drug resistance. Thus whole exome sequencing and transcriptomics have been performed on constitutional, primary tumor and metastatic samples from 28 UM patients.

  Dataset EGAD00001004554

• Analysis of Loose Ends in Cancer Genome Structure

  Short-read sequencing (SRS) forms the basis of our understanding of cancer genome evolution, yet it is widely thought to be inadequate for detecting structural variants (SVs). To understand the nature of cancer SVs missed by SRS, we introduce the concept of "loose ends" - sites of missing rearrangements revealed by balancing copy number (CN) across the genomic intervals and adjacencies of a genome graph.

  Study EGAS00001007324

• Efficacy of two different FGFR-inhibitors in a patient with extrahepatic cholangiocarcinoma harboring an FGFR2 mutation

  Cholangiocarcinomas (CCAs) is a type of cancer with few effective systemic therapies. Elucidation of the molecular landscape of the disease from genomic studies based on next generation sequencing (NGS) has contributed to the introduction of new targeted therapies. One of these treatments consists of a class of small molecules that target members of the FGFR family of receptor tyrosine kinases. These drugs are effective and have been approved for cholangiocarcinomas with fusions or rearrangements of FGFR genes. In contrast, the role of these inhibitors in cholangiocarcinomas with mutations in FGFR genes is less well defined. We report here a patient with a cholangiocarcinoma bearing a FGFR2 p.Ser252Trp mutation. The patient was treated with two different FGFR inhibitors, as the first caused ocular toxicity. She obtained clinical benefit from both. This case illustrates the efficacy of FGFR inhibitors on cholangiocarcinoma with specific point mutations. This is the first case to report the clinical benefit of these drugs in FGFR2 p.Ser252Trp mutation. Clinical benefit can be sustained, as seen in our patient. Our case also shows that FGFR inhibitors-induced adverse effects, such as ocular toxicities, may not recur after re-challenge with an alternative drug of the same class.

  Dataset EGAD50000000021

• Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

  In a genome-wide genetic study of early progression to active tuberculosis (TB), we genotyped 4,002 active TB cases and their household contacts in Lima, Peru. We first established TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases (h2g=0.212). We identified a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 x 10-8). With in silico and in vitro analyses we identified genetic variant rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function.

  Study phs002025

• EGA FUSE Client

  EGA FUSE Client What is EGA FUSE Client? The EGA FUSE Client is a Java Native Runtime (JNR) based Filesystem in Userspace (FUSE) client that allows users to access authorised EGA files by presenting them in a virtual directory. This means that users can use authorised EGA files like regular files without having to download them first. The EGA FUSE Client is a useful tool for researchers who need to access and work with large amounts of EGA data. Why use EGA FUSE Client? The EGA FUSE Client provides several benefits for researchers working with EGA data: Efficient use of storage space: With the EGA FUSE Client, users can access authorised EGA files without having to download them first. This means that users can save storage space on their local machines. Faster access to data: Since users can access authorised EGA files directly through the EGA FUSE Client, they can work with the data more quickly than if they had to download the files first. Simplified workflow: The EGA FUSE Client presents authorised EGA files in a virtual directory, allowing users to work with the files like regular files. This simplifies the workflow for researchers who need to access and work with large amounts of EGA data. Get started with EGA FUSE Client To get started with EGA FUSE Client visit the EGA FUSE Client GitHub repository for more information and installation instructions.

  Documentation access/download/visualisation/fuse-client

• An exome sequencing study of the HIV elite-long term non progressors and rapid progressors (CASCADE cohorts)

  Background: A rare subgroup of HIV infected individuals naturally controls infection without treatment. These ?elite controllers? constitute an important model for the natural control of HIV infection. Indeed, the study of these individuals may provide insights into strategies for the development of HIV vaccines. Although several HLA and chemokine alleles are known to be over-represented in elite controllers, only a small portion of HIV phenotypic variation is explained by known genetic variants. The elite controller phenotype is rare and distinct, representing the extreme of an infectious disease trait. As such, this phenotype may be partly explained by variation in host immune control, which may be characterized by differences in rare functional genetic variants. Genomic regions underlying elite control can be potentially identified by comparing the presence or frequency of variants in this group to that representing the opposite extreme. In this context, ?rapid progressors? is a group defined by its rapid immunological and clinical disease progression. Aim: To extend an existing study, in order to identify DNA sequence variants involved in the control of HIV infection with greater statistical resolution. Specifically, we aim to sequence up to 200 exomes from multiple cohort studies within the EuroCoord CASCADE collaboration (a collaboration of 25 HIV seroconversion cohort studies across Europe).

  Dataset EGAD00001002179

• Clonal haematopoiesis in patients with AAA (2019-04-03)

  Recent advances in genomics have demonstrated that clonal haemopoiesis driven by leukaemia associated somatic mutations is a relatively common phenomenon that increases in frequency with advancing age. Whilst individuals with clonal haemopoiesis have an increased risk of developing haematological malignancies, they also have an increased mortality from other causes. Additionally, certain mutations are almost exclusively seen in individuals aged 70 years or older, whilst others are seen in individuals with non-haematological cancers including breast and ovarian. Recently, clonal haemopoiesis was found to be associated with a significantly increased risk of atherosclerotic cardiovascular disease. This association is thought to be causative with clonally-derived macrophages showing elevated expression of several chemokine and cytokine genes that contribute to atherosclerosis. Another vascular pathology, abdominal aortic aneurysm (AAA), increases with age and shares risk factors with atherosclerosis (including smoking, male sex, high cholesterol). However, the impact of these risk factors and the overlap between AAA and atherosclerosis is poorly understood. To investigate a possible link between clonal haemopoiesis and AAA, we will study DNA samples from 300 patients with AAA and up to 200 controls for evidence of clonal haemopoiesis. This will be done using target DNA enrichment with biotinylated RNA baits followed by high throughput sequencing. . This dataset contains all the data available for this study on 2019-04-03.

  Dataset EGAD00001004895

• Helleday_HRAS Project

  This experiment is looking at the mutational signatures generated by engineered HRAS mutations by using whole genome sequence generated on massively parallel next generation sequencers.

  Dataset EGAD00001000302

• UniKilinikum Wuerzburg MSNZ AGRasche/AG Riedel EMD DAC

  This is a Data access committee for the Data presented in the paper tilted "Spatially resolved transcriptomics reveals profound subclonal heterogeneity and T cell dysfunction in extramedullary myeloma"

  Dac EGAC50000000173

• Helse Bergen HF Data Access Committee for the MetBreCS trial dataset submitted to Federated EGA Norway

  This Data Access Committee is appointed by Helse Bergen HF to administer access requests for the MetBreCS trial dataset submitted to Federated EGA Norway.

  Dac EGAC50000000523

• GEOCODE data access policy

  The GEOCODE Data Access Policy ensures the responsible use, security, and compliance of GEOCODE data. Access to GEOCODE data is restricted to authorized users based on role-based permissions, ensuring compliance with data protection regulations.

  Dac EGAC50000000574

• Legal Notice EGA is a joint effort by the EBI and CRG. Please, check their terms of use and legal notice in order to follow them in the usage of the EGA website. EBI terms of use CRG terms of use

  Documentation legal-notice

• CHEWIE ctDNA in Rhabdomyosarcoma

  Targeted DNA based panel of multiple ctDNA samples from 10 patients througout clinical care to assess treatment response. The panel is custom-designed and property of UGS, IC.

  Dataset EGAD00001011127

• Liver Tumours WGS (2020-02-20)

  The aim of this study is to define the mutational landscape of human liver tumours. . This dataset contains all the data available for this study on 2020-02-20.

  Dataset EGAD00001005993

• TCRab sequencing of CML patients

  This dataset contains 15 TCRab sequencing samples from 6 CML patients before and after TKI-cessation. The raw data is available as fastq files.

  Dataset EGAD00001012841

• Paediatric glioma cell line WGS

  Whole genome sequencing of 5 paediatric glioma cells lines - KNS42, SF188, UW479, RES186 and RES259. Illumina paired end sequencing is provided as 5 BAM files aligned to hg19 with bwa.

  Dataset EGAD00001004123

• Res1_H23_exp1_MC_04.03.22

  1 sample is pure plasmid DNA and 8 samples are cell pellets for genomic DNA extraction. CRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.

  Dataset EGAD00001012229

• Res1_HT29_exp1_MC_02.03.22

  1 sample is pure plasmid DNA and 10 samples are cell pellets for genomic DNA extraction. CRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.

  Dataset EGAD00001012230

• Res1_HT29_exp2_MC_03.03.22

  1 sample is pure plasmid DNA and 10 samples are cell pellets for genomic DNA extraction. CRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.

  Dataset EGAD00001012231

• TCRab sequencing of RCC patients

  TCRab sequencing was performed on viable frozen tumor dissociated cells from three RCC patients. The raw data is available as fastq files.

  Dataset EGAD00001011046

• DAC for "HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling"

  This is the DAC for the study "HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling" of PD Dr. Aurélie Ernst (a.ernst@dkfz.de) B420, DKFZ.

  Dac EGAC50000000452

• Akershus University Hospital Data Access Committee for Immunoglobulin Heavy-Chain locus in Multiple Sclerosis datasets in FEGA Norway

  This is the Data Access Committee appointed by Akershus University Hospital (AHUS) for datasets from Immunoglobulin Heavy-Chain locus in Multiple Sclerosis studies.

  Dac EGAC50000000659

• DAC for lymphoma IFZ Essen

  This DAC is set in place to handle acess to data on lymphomas and immune cells submitted by scientists from the Institute of Cell Biology (Cancer Research) at the University of Duisburg-Essen in Essen, Germany.

  Dac EGAC50000000521

• Whole Exome Sequencing of gliomas

  15 whole exome sequencing datasets from five patients. Data is provided as bam files. Libraries were generated using the SeqCap EZ Exome v3.0 kit and sequenced on an Illumina sequencer

  Dataset EGAD00001003763

• WGS Study From Pediatrics

  This is a set of 20 10X Genomics Chromium WGS

  Dataset EGAD00001008011

• Whole genome sequencing in myasthenia gravis

  This dataset contains whole genome sequencing data on 25 individuals with myasthenia gravis. The data was generated using Illumina sequencing technology and is presented as BAM files for each sample.

  Dataset EGAD00001005262

• RNA-Seq data of de novo assembly individual EGYPT

  This is the blood RNA-Seq read data used for expression analysis such as haplotypic expression (mapped against GRCh38).

  Dataset EGAD00001006036

• Esophageal Adenocarcinoma Organoid scRNAseq data

  This is 10X single cell RNA-seq data of esophageal adenocarcinoma organoids.

  Dataset EGAD00001007525

• WES data

  This is the Whole Exome Sequencing (WES) data from 59 samples from 11 patients with lung adenocarcinomas including 48 tumor samples and 11 peripheral white blood cell samples

  Dataset EGAD00001000984

• Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study - Maternal Glycemia and Birthweight GEI Study

  Low and high birth weight are not only major causes of neonatal morbidity and mortality, but epidemiological data have established an association between birth weight and later life risk of adult metabolic diseases. Fetal growth is determined by complex interactions between fetal genes and the maternal uterine environment. Subtle or overt variation in maternal glucose tolerance, which is, in part, genetically determined, is related to fetal size at birth. Moreover, new emerging data suggest that genetic variation in the fetus can impact maternal metabolism (e.g., blood pressure and glucose tolerance). Given the above, we are addressing the hypothesis that, during pregnancy, gene-environment interactions in the context of the maternal-fetal unit impact fetal size at birth and maternal metabolism. Genes that control fetal growth or maternal metabolism during pregnancy are largely unknown, so the first step to address our hypothesis will be to identify genetic variation that impacts fetal growth and maternal metabolism and to determine the interaction of that variation with the intrauterine and fetal environment. To accomplish this, we are performing genome wide association (GWA) mapping on a subset of ~37,000 DNA samples that were collected from mothers and their offspring as part of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. HAPO is a multicenter, international study in which high quality phenotypic data related to fetal growth and maternal glucose metabolism has been collected from 25,000 pregnant women of varied racial and socio-demographic backgrounds using standardized protocols that were uniform across centers. For these studies, we are genotyping 1,500 infants and their mothers of European descent, 1,250 Afro-Caribbean infants and mothers, 800 Hispanic (Mexican-American) infants and mothers, and 1200 Thai infants and mothers. Genotyping is being performed using the Illumina Human610 Quad (European ancestry participants), Human1M Duo (Afro-Caribbean and Hispanic participants), and Omni1-Quad_v1-0_B (Thai participants). The specific aims for the project are as follows: (1) To apply analytic approaches for conducting GWA mapping studies on quantitative phenotypes related to offspring size at birth (birth weight, ponderal index, head circumference and adiposity) allowing for other known influences such as gestational age, parity, and maternal weight gain. (2) To apply the above approaches to identify genetic variation that impacts maternal glucose tolerance at ~28 weeks of gestation (fasting glucose, glucose during an oral glucose tolerance test, and insulin sensitivity expressed as quantitative traits) allowing for other known influences such as maternal weight gain, parity and age. (3) To examine the interaction between maternal genes, the intrauterine environment, and fetal genes to identify interactions that modulate genetic regulation of size at birth and fetal genetic variation that impacts on maternal glucose tolerance. GWA mapping will provide initial evidence for association of specific SNPs with the quantitative traits outlined above. As low and high birth weight are not only major causes of neonatal morbidity and mortality but have also been associated with increased risk of metabolic diseases in adults, identification of genes that regulate fetal growth and maternal metabolism will provide novel information about the pathways that regulate these processes as well as important insight into susceptibility genes for chronic diseases like type 2 diabetes. The Version 1 (v1) dbGaP release will include data only from the Hispanic study participants. The Version 2 (v2) dbGaP release will include data from the Hispanic and European ancestry study participants. The Version 3 (v3) dbGaP release will include data from the Afro-Caribbean, Hispanic and European ancestry participants. The Version 4 (v4) dbGaP release will include data from all participants (i.e., Afro-Caribbean, Hispanic, European ancestry, and Thai participants). This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to maternal metabolism and birthweight through large-scale genome-wide association studies of infants and their mothers at multiple international sites. Genotyping was performed at the Broad Institute of MIT and Harvard, and at CIDR of Johns Hopkins University, GENEVA genotyping centers. Data cleaning and harmonization was performed at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000096

• Whole-Genome Sequencing in Multiplex Epilepsy Families

  Epilepsy is one of the most common neurologic disorders, affecting approximately 4% of individuals at some time in their lives. More than 30% of people with epilepsy continue to have seizures despite treatment, and improved approaches to treatment and prevention are sorely needed. In the search for new strategies to reduce the burden of disease, the discovery of specific genes that influence risk offers a novel opportunity to clarify pathogenic mechanisms, identify susceptible individuals prior to seizure onset, and treat and prevent seizures in people at risk. Despite clear evidence of the importance of genetics in susceptibility to epilepsy, only limited progress has been made in identifying the specific genes that influence risk. One of the greatest challenges for genetic research on this disorder is its extreme clinical and genetic heterogeneity. Although epilepsy is broadly defined by recurrent unprovoked seizures, it is so variable in its clinical manifestations, natural history, and treatment response that most epileptologists view it as a collection of different syndromes ("epilepsies") with distinct etiologies. The genetic effects on susceptibility are also likely to be extremely variable, ranging from rare variants with high penetrance (some of which produce Mendelian patterns of inheritance) to common variants with low penetrance. Recent findings strongly suggest that rare gene variants play a major role in the genetic architecture of the epilepsies. The purpose of this study was to discover new genetic risk factors for epilepsy. The primary approach was to use whole-genome sequencing to interrogate classes of genetic variants, including very rare variants, in multiplex families. Our main hypothesis was that, in at least some proportion of these families, a single variant would explain all instances of epilepsy. Variants identified within the families could then be tested for cosegregation within the family and also validated by seeing enrichment in sporadic epilepsy cases. Furthermore, understanding the impact of rare variation in epilepsy also has the potential to provide insight into the genetic architecture of other complex human diseases. Our analysis focused on families containing multiple individuals with non-acquired (idiopathic or unknown cause) epilepsy under the hypothesis that these would be enriched for genetic control. The families studied had been previously collected and phenotyped in detail, and contain an average of 3.8 individuals per family with a range of different types of epilepsy. We selected one or two affected individuals from each family for sequencing. This work has generated NGS data on 60 samples from 29 multiplex epilepsy families. We have established that, under a monogenic model of inheritance, sequencing pairs of distantly related relatives is an effective method for reducing the number of candidate variants. Critically, we have found that no single variant can explain a large proportion of these epilepsy families. This work emphasizes that identifying causal variants among the many genetic candidates found in this work will require very large sample sizes and gene-based analyses.

  Study phs000690

• INCLUDE Data Hub: NDA GUIDs for Down Syndrome Research

  The INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project is an NIH-wide collaboration that seeks to improve health and quality of life for people with Down syndrome. The INCLUDE Project Data Coordinating Center (DCC) and partners created the INCLUDE Data Hub, a centralized data resource that allows access to large-scale clinical and multi-omics datasets specific to Down syndrome and supports collaborative, cloud-based analysis to accelerate scientific discoveries related to Down syndrome and its co-occurring conditions. The INCLUDE Data Hub includes an innovative researcher data repository, a portal, and a cloud-based platform for data analysis. The portal provides access to de-identified demographics and clinical metadata, as well as multi-omics datasets, including whole genome sequences, transcriptomes, proteomes, and metabolomes. The INCLUDE Data Hub uses a 'registered access' model, whereby users can access the portal and associated data after agreeing to terms of use. From the Data Hub, users can also reach 'controlled access' data (e.g., whole genome sequences) only for those studies for which they have obtained approval by an NIH Data Access Committee through the corresponding dbGaP study. A thoughtful linkage strategy to identify duplicate participants across studies enables researchers to merge multiple datasets and data types to create richer datasets and reduce costly redundancies in large-scale data generation (e.g., -omics) while mitigating potential risks introduced by linkage.Based on recommendations from the NICHD Office of Data Science and Sharing, which completed a comprehensive assessment of existing Privacy Protecting Record Linkage (PPRL) and associated data governance solutions, the INCLUDE DCC and the associated NIH Steering Committee have implemented NIMH Data Archive Global Unique Identifiers (NDA GUIDs) in the INCLUDE Data Hub. The NDA GUID Tool is a government-owned and operated PPRL technology that enables researchers to link data from multiple sources to the same individual without revealing personally identifiable information (PII). With the NDA GUID Tool, the same participant information will return the same GUID whenever or wherever it is entered. The GUID itself is not personally identifiable information or protected health information. Sharing data with NDA GUIDs allows approved researchers to link together data on a single participant, even if the data were collected at different locations or through different studies or are distributed from different data repositories. This dbGaP study enables researchers to access an INCLUDE GUID Mapping File that includes all available NDA GUIDs and their associations to study-specific Participant IDs across studies in the INCLUDE Data Hub. This dbGaP study only distributes NDA GUIDs associated with the INCLUDE Data Hub datasets. To access the associated controlled-access datasets, add the corresponding dbGaP studies to your Data Access Request. A list of these studies is available on the INCLUDE Data Hub Portal: https://portal.includedcc.org/studies.

  Study phs003678

• Kids First: Whole Genome Sequencing in Structural Defects of the Neural Tube

  Myelomeningocele (aka meningomyelocele, MM) is the most severe form of spina bifida, a neural tube defect (NTD) in humans and the most common CNS birth defect. MM is considered a genetically complex disease, and occurs in 3.72/10,000 live US birth, and is partly preventable with prenatal folate, but the genetic basis and the mechanisms by which folate work to reduce disease incidence remain obscure. MM is associated nearly uniformly with prenatal hydrocephalus and the Arnold-Chiari malformation, as well as paraplegia and lifelong neuromotor disability. The genes for several rare syndromic forms of NTDs are known, but the causes for the majority with sporadic MM remain unknown. Despite the importance of MM, most previous research has been limited to targeted sequencing and association studies of folate metabolism genes, or very small-scale exome sequencing. We hypothesize that de novo mutations (DNMs) produce likely gene disrupting (LGD) events that contribution to MM risk. Using conservative estimates of between 50-100 recurrently mutated discoverable genes contributing to risk, and our preliminary data demonstrating an excess of LGD DNMs in MM compared with control individuals, we estimate that with a cohort size of 1000 trios, we should uncover between 5-20 new recurrently mutated genes underlying MM, with minimal false-discovery. With this in mind, we formed the Spina Bifida Sequencing Consortium, and established a platform for data and sample sharing. Preliminary analysis of our first batch of 100 trios analyzed by WGS from GMKF suggests a wealth of important gene mutations. We have embarked on a new recruitment effort of an additional cohort of 400 new simplex MM trios, in collaboration with the US Spina Bifida Association, consented trios to allow for data sharing, and have performed detailed sample quality control. We also have preliminary data that use of dried bloodspot DNA from trios performs comparably to whole blood DNA, so will be happy to swap saliva for bloodspot recruitment at NIH's preference. This cohort is now half-way assembled, with the remaining cohort to be ascertained in the next 6 months. We have established a workflow for de novo SNP/INDEL/SV detection from WGS and have ample computer storage and nodes to see the project to completion. We also plan to continue recruitment into the future with the goal of 2000 trios in the next 5 years. We propose a detailed bioinformatics workflow to identify gene mutations within a statistical framework, considering detailed scRNA expression profiling from developing mammalian neural tube, and have developed a robust functional validation workflow using Xenopus and mouse gene targeting. Our project has the potential to uncover a host of causes for this most common of the CNS birth defects, paving the way for future breakthroughs in detection, treatment, and prevention.

  Study phs002591

• Warm_autopsy__mutational_signatures_and_clonal_units

  Aims and objectives 1. To produce a ‘first generation map’ of mutational burdens and mutational processes that operate in normal human tissues. 2. To examine clonal units and their distribution across normal human tissues with the emphasis on these particular areas: a) Tissues with an architecturally defined unit: Are architectural structures populated by a progeny derived from a single stem cell? Are clonal units confined to a given architectural structure? Examples of tissues where such approach will be used include prostate gland (acini and ducts), small bowel (crypts), thyroid gland (follicles) and others. b) Tissues without an architecturally defined unit: What is the average size of clonal populations? This group includes stratified/pseudostratified epithelia with a basal layer within which there are stem cells that give rise to a progeny of cells showing upwards migration and lateral expansion (e.g. urothelium, cervical squamous epithelium, respiratory epithelium). This approach can also be used in tissues with a sheet-like cell arrangement, for example brain and adrenal gland. Methods To answer these questions, we will use a range of normal human tissue samples which have already been collected from a single deceased individual. The samples are currently stored in a -80C freezer. Ethanol fixed frozen sections will be prepared from these biopsies. Putative clonal units will be identified and dissected out using laser capture microscopy. DNA extraction will be performed using the in-house (CGP) protease based method. In terms of sequencing methods, the project will be split into 2 phases (2 different approaches): - Phase 1: This part of the project will utilise a combination of low input library preparation (developed by Peter Ellis) and standard whole genome sequencing (HiSeqX). The phase has already started (December 2016). This approach will be particularly useful in investigation of mitotically active tissues. - Phase 2: This part of the project will utilise a combination of low input library method (Peter Ellis) and Bottle-neck sequencing (BotSeqS). BotSeqS is a type of duplex sequencing method that offers a more accurate variant calling and allows genome interrogation at a single cell level. This method is currently being developed and is expected to be implemented in 3-6 months (March-April 2017). This approach will be particularly useful for post-mitotic tissues and tissues without pre-defined architectural units.

  Study EGAS00001002216

• Genetic Testing to Understand and Address Renal Disease Disparities

  People of African ancestry (Blacks) have increased risk of kidney failure due to numerous socioeconomic, environmental, and clinical factors. Two variants in the APOL1 gene (GeneID: 8542) are now thought to account for much of the racial disparity associated with hypertensive kidney failure in Blacks. One in 7 AAs carry this risk allele, but it is nearly absent in other populations; the variants protect against infection with African trypanosomiasis which is endemic to Africa. However, this knowledge has not been translated into clinical care to help improve patient outcomes and address disparities. It is unknown whether patient or clinician knowledge of genetic risk impacts patient care (i.e., renal surveillance, BP medication use/intensification) or outcomes such as BP control and CKD. GUARDD is a randomized trial to evaluate the effects and challenges of incorporating genetic risk information into primary care. Hypertensive, nondiabetic, adults with self-reported African ancestry, without kidney dysfunction, are recruited from diverse clinical settings and randomized to undergo APOL1 genetic testing at baseline (intervention) or at one year (waitlist control). Prior to enrolling their patients, providers are educated about genomics and APOL1. Guided by a genetic counselor, trained staff return APOL1 results to patients and provide low-literacy educational materials. Real-time clinical decision support tools alert clinicians of their patients' APOL1 results and associated risk status at the point of care. Our academic - community clinical partnership designed a study to generate information about the impact of genetic risk information on our primary outcome - patient care (renal surveillance by clinicians, of serum creatinine and/or urine albumin tests. with a sub-aim of reduction of systolic blood pressure). Secondary outcomes include impact on primary outcomes at 12 months, psycho-behavioral differences of patients between groups and over time, clinician knowledge, attitudes and beliefs at baseline and 12 months, and differences in outcomes between those tested and not tested. GUARDD will help establish the effective implementation of APOL1 risk informed management of hypertensive patients at high risk of CKD, and will provide a robust framework for future endeavors to implement genomic medicine in diverse clinical practices. It will also add to the important dialog about factors that contribute to and may help eliminate racial disparities in kidney disease.

  Study phs001620

• Region-specific Transcriptome Analysis of the Human Retina and Retinal Pigment Epithelium (RPE)/Choroid

  Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. Reprinted from Whitmore, S.S., Wagner, A.H., DeLuca, A.P., Drack, A.V., Stone, E.M., Tucker, B.A., Zeng, S., Braun, T.A., Mullins, R.F., Scheetz, T.E., 2014. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq. Experimental Eye Research. Used under Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license. Additional RNA sequencing was performed on temporal, macular, nasal, inferior, and superior retina from a fifth subject and is included in this dataset. See original publication for details.

  Study phs001151

• Discovery of Colorectal Cancer Susceptibility Genes in High-Risk Families

  Colorectal cancer remains one of the most common cancers in the US with 146,970 new diagnoses and 49,920 deaths estimated for 2009. Colon cancer is also one of the most familial of cancers. Individuals with a first-degree relative with colon cancer have a 2- to 3-fold increased risk, and those with more than one first-degree relative with colon cancer, or a single first-degree relative affected at age 50 years, have a 3- to 6-fold greater risk than those with no family history. The most prominent high-risk colorectal cancer susceptibility genes, APC, MLH1, MSH2, MSH6, and PTEN, were all discovered more than a decade ago. Currently, mutation screening of these genes, plus a short list of additional genes that are responsible for a very small fraction of colorectal cancer, plays an important role in the clinical management of individuals with a strong family history of the disease or syndromic evidence for the presence of a gene mutation. At the other end of the risk spectrum, genome-wide association studies have identified a number of common alleles with very modest effects on colorectal cancer risk; their clinical utility has yet to be established. However, taken together, the known spectrum of genetic effects only explain about one quarter of the overall familial excess of colorectal cancer. It should be emphasized that, at present, the vast majority of individuals seen at familial cancer clinics are counseled on the basis of their family history alone because they do not have mutations in the known susceptibility genes. Accordingly, the long-term objective of this project is to identify the majority of genes responsible for the unexplained component of inherited colorectal cancer risk. Nextgen DNA sequencing is well suited for application to research questions in genetic susceptibility for which linkage analysis is confounded by extensive genetic heterogeneity. Taking advantage of unparalleled familial cancer genetics resources available through the Utah Population Database, candidate genes have been identified by sequencing all of the gene exons in the human genome from a series of colorectal cancer cases with a very strong family history of colorectal cancer not explained by one of the currently known high-risk susceptibility genes.

  Study phs001787

• Genetic Epidemiology of COPD (COPDGene) Funded by the National Heart, Lung, and Blood Institute

  Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States and the only leading cause of death that is steadily increasing in frequency. This project will establish a racially diverse cohort that is sufficiently large and appropriately designed for genome-wide association analysis of COPD. A total of 10,000 subjects will be recruited, including control smokers, definite COPD cases (GOLD Stage 2 to 4), and subjects not included in either group (GOLD 1 or GOLD-Unclassified). This cohort will be used for cross-sectional analysis, although long-term longitudinal follow-up will be a future goal. The primary focus of the study will be genome-wide association analysis to identify the genetic risk factors that determine susceptibility for COPD and COPD-related phenotypes. Detailed phenotyping of both cases and controls, including chest CT scan assessment of emphysema and airway disease, will allow identification of genetic determinants for the heterogeneous components of the COPD syndrome. The hypotheses to be studied are: 1) Precise phenotypic characterization of COPD subjects using computed tomography, as well as clinical and physiological measures, will provide data that will enable the broad COPD syndrome to be decomposed into clinically significant subtypes. 2) Genome-wide association studies will identify genetic determinants for COPD susceptibility that will provide insight into clinically relevant COPD subtypes. 3) Distinct genetic determinants influence the development of emphysema and airway disease. The initial phase of genome-wide association analysis included 500 COPD cases and 500 control subjects (all non-Hispanic White) genotyped with the Illumina Omni-1 chip. The second phase genotyped the entire study cohort using the Illumina Omni-Express chip. Unique aspects of the study include: 1) Inclusion of large numbers of African American subjects (approximately 1/3 of the cohort); 2) Obtaining chest CT scans (including inspiratory and expiratory images); and 3) Inclusion of the full range of disease severity. The COPDGene_v6 Cohort is utilized in the following dbGaP sub-studies. To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" box located on the right hand side of this top-level study page phs000179 COPDGene_v6 Cohort. phs000296 ESP LungGO COPDGene phs000765 COPDGene_Geno

  Study phs000179

• SCANDARE MACARON project

  Among gynecological cancers, high-grade serous ovarian cancer has the highest prevalence and more than 75% of patients have advanced stage at diagnosis with a 5-year survival of 40%. When the initial complete surgical removal is not possible (60% of patients), an interval surgery can be considered after three to four cycles of neoadjuvant chemotherapy to reduce the tumor mass. However, in approximately 50% of cases the tumor has little or no response to neoadjuvant chemotherapy. Therefore, identification of potential drug targets, biomarkers and/or pathways whose modulation can help in the prevention, interception, or curing of the disease is essential to address the unmet need. Therefore, MACARON project aims to address these issues through the identification of shared neoantigens arising out of somatic alterations and aberrant transcriptional programs in ovarian cancer DNA/RNA datasets.

  Dac EGAC50000000104

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

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

  Dataset EGAD50000000266

• Type 2 Diabetes Starr County GWAS and Exome Sequencing

  The T2D Seq GWAS Starr County Cohort is utilized in the following dbGaP sub-studies. To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" section of this top-level study page phs001166 T2D Seq GWAS Starr County Cohort. phs000143 CIDR T2D Hanis phs001099 T2D GENES Starr County

  Study phs001166