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• The Natural History of Mucolipidosis Type IV

  Mucolipidosis type IV (MLIV) is an autosomal recessive disorder typically characterized by severe psychomotor delay evident by the end of the first year of life and slowly progressive visual impairment during the first decade as a result of a combination of corneal clouding and retinal degeneration. The purpose of this research study is to look at the brain and eye in patients with mucolipidosis type IV (MLIV). MLIV is a lysosomal storage disease that primarily affects the brain and the eyes. The disease is caused by a defect in a gene called MCLON1 that makes a protein called mucolipin-1. Patients with MLIV do not make enough normal mucolipin. The disease begins early in life and the neurological problems seem to stabilize later in life. On the other hand, the eye abnormalities usually progresses over time. The exact course of the disease has not been determined, and until now, no study has addressed this question carefully. The research objectives are: To learn about the natural history of cognitive function for individuals with mucolipidosis type IV. To measure brain volume over time in individuals with mucolipidosis type IV This is an observational study of individuals with MLIV disorder. Those participating in this study will be evaluated annually for five years following a baseline visit.

  Study phs001329

• Carolina Breast Cancer Study (CBCS)

  The Carolina Breast Cancer Study (CBCS), phase III, is a population-based study aiming to understand the social and molecular correlates of breast cancer outcomes, particularly among Black and young women. CBCS recruited first primary breast cancer cases from 44 North Carolina counties between 2008-2013. All cases were between age 20 and 74 and self-identified as female. Black women and young women were systematically oversampled by randomized recruitment such that the study includes approximately 50% Black women and approximately 50% women diagnosed before age 50. A total of 2,998 participants were enrolled. In the ten years following diagnosis, women completed surveys approximately every 1-2 years and diagnoses of subsequent distant local recurrence and second primary tumors were ascertained via linked medical records. We identified records of women who developed secondary breast tumors (including second primary tumors, contralateral breast cancers, and locoregional recurrences), and these participants were oversampled for targeted DNA sequencing using the UNCseq panel (~1200 genes).CBCS germline pathogenic mutations cannot be investigated because participants were consented between 2008 and 2013 with specific language prohibiting this. However, germline data can be used to call somatic mutations or to standardize somatic genomic data.For sharing of study data not included here, please visit unclineberger.org for instructions on submitting a data use agreement.

  Study phs003725

• Control of Focal Adhesion Kinase Activation by RUNX1-regulated miRNAs in high-risk AML

  We recently described a 16-gene expression signature for improved risk stratification of acute myeloid leukemia (AML) patients called the AML Prognostic Score (APS). A subset of APS high-risk AML patients showed increased levels of focal adhesion kinase (FAK), encoded by the Protein Tyrosine Kinase 2 (PTK2) gene, which was correlated with RUNX1 mutations. RUNX1 mutant cells are more sensitive to PTK2 inhibitors. As we were not able to detect RUNX1 binding sites in the PTK2 promoter, we hypothesized that RUNX1 might regulate micro(mi)RNAs that repress PTK2, such that loss-of-function RUNX1 mutations would result in reduced miRNA expression and derepression of PTK2. Examination of paired RNA-seq and miRNA-seq data from 301 AML cases revealed two miRNAs that positively correlated with RUNX1 expression, contained RUNX1 binding sites in their promoters and were predicted to target PTK2. We show that the hsa-let7a-2-3p and hsa-miR-135a-5p promoters are regulated by RUNX1, and that PTK2 is a direct target of both miRNAs. Even in the absence of RUNX1 mutations, hsa-let7a-2-3p and hsa-miR-135a-5p regulate PTK2 expression, and reduced expression of these two miRNAs sensitizes AML cells to PTK2 inhibition. These data explain how RUNX1 regulates PTK2, and identify potential miRNA biomarkers for targeting AML with PTK2 inhibitors.

  Study EGAS00001006491

• eMERGE: Genetics of Complex Pediatric Disorders from the Center for Applied Genomics

  The Center for Applied Genomics (CAG) is a specialized Center of Emphasis at the Children's Hospital of Philadelphia (CHOP) with the primary goal of translating basic research findings to medical innovations. The mission of CAG is to develop new and better ways to diagnose and treat children affected by rare and complex medical disorders. We aim to discover genetic causes for the most prevalent diseases of childhood including asthma, autism, diabetes, epilepsy, obesity, schizophrenia, pediatric cancer, and a range of rare diseases. Ultimately, our objective is to generate new diagnostic tests and to guide physicians to the most appropriate therapies. The CAG is one of the world's largest genetics research programs in pediatrics, and the only center at a pediatric hospital to have established a large-scale biobank of genotyped samples. The electronic Medical Records and Genomics (eMERGE) Network is a consortium of 9 clinical sites with EMR linked DNA biobanks, including Northwestern University and its NUgene biobank, funded by the NHGRI (National Human Genome Research Institute) to investigate the use of electronic medical record systems for genomic research. The goal of eMERGE is to conduct genome-wide association studies in approximately 100,000 individuals using EMR-derived phenotypes and DNA from linked biorepositories. Using electronic phenotyping methods, the consortium has been and is using DNA samples from all participating sites to explore the genetic determinants of approximately 80 phenotypes, including both diseases and traits, for which the electronic phenotyping algorithms have or are being published on PheKB.org.

  Study phs001165

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

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

  Study phs001292

• Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS)

  This pharmacogenomic study focused on the response of patients with MDD to an 8-week course of treatment with citalopram or escitalopram. Briefly, clinical assessments and research assessments were performed at each study visit as summarized in Table 1. Many patients continued on antidepressant medication after the 8 week study. Table 1: Study timeline and patient contacts. Week Consent/Med Hx Write Rx SI Qx SCID HRS-D17 QIDSC16 CGI-I 0 SC RC RC SC SC SC 4 RC RC SC SC RC 8 RC RC SC SC RC HRS-D17=Hamilton Rating Scale for Depression, QIDS-C16=Quick Inventory of Depressive Symptomatology, CGI-I=Clinical Global Impression-Improvement, SCID=Structured Clinical Interview for DSM-IV, SC=Study Coordinator, RC=Research Clinician. Enrollment and baseline assessment. Upon initial intake, the Study Coordinator (SC) obtained informed consent as well as clinical and demographic information, including history of bone marrow or liver transplant or blood transfusion within the previous 6 weeks, and prior history of treatment during the current major depressive episode. The SC completed the Structured Clinical Interview for DSM-IV (SCID), the HRS-D17 (17-item Hamilton Rating Scale for Depression) and the QIDS-C16 (Quick Inventory of Depressive Symptomatology) and reviewed the inclusion/exclusion criteria. After review with the Research Clinician (RC) and when appropriate, after a negative pregnancy test, the SC invited the subject to participate in the study if entry criteria were met. If the subject agreed, he/she received treatment according to the study protocol. Treatment schedule. Participants selected for inclusion in the study were seen at weeks 0, 4, and 8. The appropriate treatment antidepressant (citalopram or escitalopram) was determined following discussion between the patient and RC concerning medical, financial, and insurance considerations. The study medication citalopram was given in tablet or liquid form, depending on the patient's need. A fixed-flexible dose schedule was employed with the possibility of a dose escalation. In particular, the initial dose of citalopram was 20 mg and escitalopram was 10 mg. This dose was increased to 40 mg and 20 mg, respectively, after 4 weeks if the subject had a score of >/= 6 on the QIDS-C16 and the RC concluded that the subject could tolerate the increase. If necessary, dose was reduced at the discretion of the RC. The importance of medication compliance was discussed with the subject, and subjects were asked to bring in the medication at each visit for the purpose of counting remaining pills to assess compliance. Participants may have had an abbreviated course of therapy if they were clearly intolerant of the drug or failed to respond to a 40 mg dose of citalopram or a 20 mg dose of escitalopram. They then received standard treatment from a primary physician or psychiatrist with different medications and/or therapeutic modalities (e.g. psychotherapy). Special attention was given to subjects with suicidal ideation. Those subjects were offered additional appointments as needed to ensure their safety. Participants were also contacted by telephone at week 1 and week 2 by the Clinical Nurse Specialist (CNS) or other study personnel to ensure medication compliance and patient safety. The CNS was supervised by the study psychiatrist and principal investigator and deferred to the physician's judgment as needed. The SC was trained to notify the RC at the time of the clinical visits or the phone interviews if the subject endorsed any suicidal ideation or plans. For those subjects who were unable to attend the follow-up visits as scheduled, the patient was contacted by phone to complete the HRS-D17/QIDS-C16. The participant was also asked to return to the clinic to complete a final blood draw for the study. Adjunctive and concurrent medications. Adjunctive treatments were those used to manage transient associated symptoms (e.g., insomnia) or transient or longer-term medication side effects (e.g., sexual dysfunction). Adjunctive treatments that were not used to treat depression were allowed during the study. However, drugs in the exclusion criteria for this study were not used as adjunctive therapies. Subjects were allowed to participate in the study while receiving concurrent medications for general medical conditions as long as there was no contraindication to use while taking citalopram or escitalopram. Drug efficacy phenotype evaluation. The change in QIDS-C16 score and change in HRS-D17 score were used as the major research outcome measures to assess drug response. At each clinical research visit, the RC also completed the Clinician Global Impression of Improvement (CGI-I) scale. For the primary genome-wide association analyses, dichotomous outcome variables, remission and response, were defined based on the QIDS-C16 last visit score. Remission was defined as a QIDS-C16 score of 5 or less, while response was defined as at least a 50% reduction in the QIDS-C16 score from baseline. Specimen collection. Specimen collections were obtained by the General Clinical Research Center (GCRC) at St. Mary's Hospital (SMH). Subjects had blood drawn on an outpatient basis at GCRC-SMH on three separate occasions - baseline (0), week 4 and week 8 visits. Prior to sample collection, date and time of last dose of study medication was gathered at the 4 and 8 week visits. For those patients who were unable to complete the regularly scheduled visits, a dismissal blood draw was requested. GCRC then shipped samples to Mayo Clinic's Biospecimens Accessioning and Processing Lab. Genotyping and biomarker assays. DNA from 529 patients was genotyped by the RIKEN Center for Genomic Medicine (Yokohama, Japan) using Illumina Human610-Quad BeadChips (Illumina, San Diego, CA). The study also included the determination of plasma drug levels at weeks 4 and 8, and metabolite levels at baseline and weeks 4 and 8 for a subset of subjects. The primary genome-wide association study based on these data, which includes a summary of the protocol, subject description, selection of subjects for genetic analyses, and definitions of clinical outcomes, was published in the Pharmacogenomics Journal (Ji et al., 2012).

  Study phs000670

• Neuroblastoma_MP-PCR_MultiplexPCR_TargetedSequencing_BAMs

  This dataset contains raw sequencing data (BAM/BAI files) generated from human neuroblastoma patient samples. The data were produced using targeted high-throughput next-generation sequencing and are intended to support genomic analyses of tumor-associated alterations. All files are provided under controlled access in accordance with EGA data protection requirements.

  Dataset EGAD50000002260

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 8a)

  Whole genome sequencing data of 26 high-grade serous carcinoma (HGSC) patients (87 samples) sequenced with MGISEQ-2000 and HiSeq X Ten.

  Dataset EGAD00001011304

• Verification of BCR reconstruction from single-cell RNA-seq using BraCeR

  This dataset was made to verify the computational reconstruction of B cell reseptors from single-cell RNA-seq using BraCeR. The dataset contains BCR-derived reads from single-cell RNA-seq from 13 cells using the Smart-seq2 protocol, as well as targeted BCR-sequencing data from the same cells.

  Dataset EGAD00001004199

• Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT-BioLINCC)

  Data Access NOTEPlease refer to the "Authorized Access" section below for information about how access to the data from this accession. Access differs from many other dbGaP accessions. BiospecimensAccess to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from TOPCAT include Buffy Coat, DNA, Plasma, Serum, Urine, and Whole Blood. Please note that use of biospecimens in genetic research is subject to a tiered consent. Objectives The TOPCAT trial evaluated the effectiveness of aldosterone antagonist therapy in reducing cardiovascular mortality, aborted cardiac arrest, and heart failure hospitalization in patients who have heart failure with preserved systolic function. Background Many patients with heart failure have a normal, or near-normal, left ventricular ejection fraction (LVEF). Such patients share similar signs and symptoms as patients who have heart failure and a reduced LVEF, as well as an impaired quality of life and a poor prognosis. However, at the time of TOPCAT, the benefit of medical therapies for heart failure were limited to those with a reduced LVEF. Due to a lack of favorable evidence from clinical trials, clinical guidelines offered no specific recommendations for the management of heart failure in patients with preserved LVEF, except for attention to coexisting conditions. Among patients with heart failure and a reduced LVEF and those with myocardial infarction complicated by heart failure and left ventricular dysfunction, mineralocorticoid receptor antagonists have been shown to be effective in reducing overall mortality and hospitalizations for heart failure. In small mechanistic studies involving patients with heart failure and preserved left ventricular function, mineralocorticoid receptor antagonists improved measures of diastolic function. However, rigorous testing was needed regarding their effect on clinical outcomes in patients with preserved LVEF. Therefore, the TOPCAT trial was initiated to determine whether treatment with spironolactone, an aldosterone antagonist, would improve clinical outcomes in patients with symptomatic heart failure and a relatively preserved LVEF. Participants A total of 3445 participants were enrolled, with 1722 assigned to the spironolactone group and 1723 assigned to the placebo group. Among these, 2464 participants were enrolled via the hospitalization stratum and 981 were enrolled via the BNP stratum. Design TOPCAT was a phase 3, multicenter, international, randomized, double-blind, and placebo controlled trial. Eligible participants were randomly assigned to receive either spironolactone or placebo in a 1:1 ratio. Randomization was stratified according to whether the patient met the criterion for previous hospitalization or BNP elevation. The baseline visit included assessment of socio-demographics, physical characteristics, medical history, lifestyle factors, laboratory measures, electrocardiography variables and health-related quality of life and functional status. Study drugs were initially administered at a dose of 15 mg once daily, which was increased as tolerated to a maximum of 45 mg daily during the first four months after randomization. Subsequent dose adjustments were made as required and subjects continued to receive other treatments for heart failure and co-existing illnesses. Measurement of potassium and creatinine levels was required within 1 week after a change in the study-drug dose and at each scheduled study visit. Follow-up visits to monitor symptoms, medications, and events and to dispense study drug were scheduled every four months during the subject's first year on the study, and every six months thereafter. The mean follow-up interval was 3.3 years in each study group. Repository blood and urine samples were collected at the baseline and 1 year visits from consenting subjects. The primary endpoint was a composite of cardiovascular mortality, aborted cardiac arrest or hospitalization for the management of heart failure. Secondary endpoints included all-cause mortality, hospitalization for heart failure management, new onset of diabetes mellitus or atrial fibrillation, and quality of life. A subset of subjects also participated in the Echocardiography or Echocardiography and Vascular Stiffness ancillary studies. Echocardiography, and additionally tonometry in the Echocardiography and Vascular Stiffness study, were performed at baseline and at either 12 or 18 months following randomization. If the subject was already enrolled in the TOPCAT trial at the time the ancillary study was initiated, but had not yet reached the 18 month visit, baseline was determined via a retrospective analysis performed on any echocardiographic images completed within 60 days prior to TOPCAT enrollment and no tonometry was performed if applicable. Conclusions In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. However, the drug reduced the secondary endpoint of heart failure hospitalization incidence.

  Study phs003665

• Characterization of the molecular signature of human monocytes in aging and myelodysplastic syndrome

  Deep immunophenotypic profiling of peripheral blood immune cells from young and older control subjects as well as patients with MDS was initially performed, using mass cytometry to identify monocyte subpopulations. Abundance of monocyte subpopulations separated the samples from patients with MDS from elderly control subjects was identified. Therefore, targeted immunophenotyping of monocytes was also performed with flow cytometry and RNA sequencing from isolated CD14+ peripheral blood longitudinally in 26 subjects, six young healthy individuals, nine older healthy individuals and eleven patients with MDS.

  Study EGAS00001007676

• Whole Exome Sequencing of Human Gastro-esophageal Cancer PDXs

  The current study investigates biomarkers of response to anti-EGFR therapies in gastro-esophageal cancer. Whole exome sequencing was performed on 26 tumors to explore potential factors influencing treatment outcomes. As part of the analysis, somatic mutations in EGFR, ERBB2, and key downstream signaling genes (KRAS and PIK3CA) were examined to exclude the presence of known mutations conferring sensitivity/resistance. The study aims to contribute to the identification of patients who may benefit from lower-toxicity regimens, improving treatment personalization and minimizing adverse effects.

  Study EGAS50000000966

• Datasets of RNA-seq of tumor samples from clear cell renal cell carcinoma patients included in the Translational Program of the NIVOREN GETUG-AFU-26 trial

  RNA-seq analyses were performed on tumor tissue samples of 115 advanced clear cell renal cell carcinoma patients who participated in the NIVOREN GETUG-AFU-26 trial. The samples were obtained prior to treatment initiation. RNA-seq was performed to evaluate previously published gene expression signatures. These included: the IMmotion T effector (CD8A, EOMES, PRF1, IFNG and CD274) and the IMmotion Myeloid (IL-6, CXCL1, CXCL2, CXCL3, CXCL8, and PTGS2) gene signatures represent gene expression patterns associated with T effector cells and myeloid cells, respectively, while JAVELIN Renal 101 Immuno (T-cell receptor signaling: CD3G, CD3E, CD8B, THEMIS, TRAT1, GRAP2, CD247; T-cell activation, proliferation, and differentiation: CD2, CD96, PRF1, CD6, IL7R, ITK, GPR18, EOMES, SIT1, NLRC3; Natural killer cell mediated cytotoxicity: D2, CD96, PRF1, CD244, KLRD1, SH2D1A; Chemokine: CCL5, XCL2; and Other immune response genes: CST7, GFI1, KCNA3, PSTPIP1) represents gene expression patterns associated with both innate and adaptive immune response.

  Dataset EGAD50000001541

• Wilm's tumor sequencing data

  No. of samples: 80 (28 ULP-WGS, 26 WES, 26 RNA-SEQ) File types: FASTQ (28 ULP-WGS, 19 WES, 18 RNA) and BAM (7 WES, 8 RNA) Technology used: Sequencing - Illumina Novoseq 6000; Map/Align - Illumina DRAGEN v3.7.5; Genome assembly - GrCh38p13 Filename nomenclature: - SampleName_Passage_SampleType_TissueType_SequencingType - Passage of: PX = unknown; PZ = from patient; P0 = first passage from patient on plastic; P1 = first passage from plastic/PDX/organoid - SampleType: STN = normal; STT = tumor - SampleType STN: 00 = tissue unknown; 01 = adjacent normal; 02 = fibroblast; 03 = germline blood; 21 = cell line from patient tissue; 22 = cell line from PDX; 23 = cell line from patient fibroblast - SampleType STT: 00 = tissue unknown; 01 = primary tumor; 21 = cell line from patient; 22 = cell line from PDX - TissueType: WT = Wilm's tumor; 00 = kidney unknown; 01 = kidney left; 02 = kidney right - SequencingType: 00 = unknown; 02 = ultra-low pass whole-genome sequencing; 20 = whole-exome; 61 = bulk RNA-sequencing

  Dataset EGAD00001011111

• Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis

  This longitudinal observational study will investigate the natural history and progression of four genetic causes of intrahepatic cholestasis of childhood, including alpha-1 antitrypsin deficiency (α1-AT), Alagille syndrome (AGS), progressive familial intrahepatic cholestasis (PFIC), and bile acid synthesis defects (BAD). This study will be conducted as part of the Cholestatic Liver Disease Consortium (CLiC), an NIH-funded multi-centered Rare Disease Clinical Research Consortium. In this study, we will collect defined data elements in a uniform fashion at fixed intervals for five years over a relatively large number of patients with these rare disorders. In addition, a biobank of patient specimens and DNA samples will be established for use in ancillary studies to be performed in addition to this study. By comparing outcome measures between the four liver diseases (i.e., using each disorder as a disease-control for the other disorders), the full impact of each disorder can best be determined in comparison to the other liver diseases. Using the longitudinal database in this fashion, this study will provide an improved understanding of the effects of the cholestatic liver during childhood irrespective of the underlying etiology as well as to the pathophysiology, outcome, and complications of each of the disorders. This initial characterization will allow calculation of sample sizes for future therapeutic intervention clinical trials and provide the baseline to which interventions should be compared.

  Study phs001288

• Uncovering tumor intrinsic and extrinsic factors that regulate hepatocellular carcinoma growth using patient derived xenograft assays

  Several major factors limit our understanding of hepatocellular carcinoma (HCC). First, human HCCs are infrequently biopsied for diagnosis and thus are not often biologically interrogated. Second, HCC initiation and progression are strongly influenced by the cirrhotic microenvironment, and the exact contributions of intrinsic and extrinsic tumor factors are unclear. A powerful approach to examine the personalized biology of liver cancers and the influence of host tissues is with patient derived xenograft (PDX) models. In Asia, HCCs from hepatitis B virus patients have been efficiently converted into PDXs, but few parallel efforts from the west have been reported. In a large-scale analysis, we implanted 93 HCCs and 8 cholangiocarcinomas (CCAs) to systematically analyze host factors and to define an optimized platform for PDX development from both surgical and biopsy samples. NSG mice that had undergone partial hepatectomy (PHx) represented the best combination of engraftability, growth, and passageability, but overall rates were low and indicative of a unique intrinsic biology for HCCs in the US. PDX models preserved the histology and genetic features of parental tumors, and ultimately, 9 new models were usable for pre-clinical studies. Intriguingly, HCC PDXs were differentially sensitive to regorafenib and sorafenib and CCA PDXs were also highly sensitive to regorafenib. PDX models functionalize early and advanced stage HCCs and revealed unique biological features of liver cancers from the US.

  Study EGAS00001004020

• NAR-GAB 2025 deposit data

  Paired-end whole-exome sequencing data derived from Illumina hybrid-capture experiments (Agilent SureSelect Human All Exon kits). Six human probands with rare diseases; one sample per subject. Sequencing reads from each individual were processed into analysis-ready gVCF files following standard best-practice pipelines, including alignment, duplicate marking, base quality calibration, and variant calling. All gVCF files are encrypted using Crypt4GH and are available under controlled access through our DAC in accordance with a strict DUO-based policy.

  Dataset EGAD50000002100

• National Institute of Dental and Craniofacial Research (NIDCR) Sjögren's International Collaborative Clinical Alliance (SICCA): Center for Inherited Disease Research (CIDR) Genome-Wide Genotyping

  The Sjögren's International Collaborative Clinical Alliance (SICCA) is a multisite observational cohort study that recruited a large cohort of geographically diverse participants. Enrollment of participants began in late 2004 at five (one domestic and four international) sites, in which all groups used the same protocol-directed methods to provide uniform evaluations; collect oral, ocular, and rheumatologic data; and collect specimens. The sites were located at the University of Buenos Aires, Argentina; Peking Union Medical College, Beijing, China; Rigshopitalet (formerly at Glostrup Hospital), Copenhagen, Denmark; Kanazawa Medical University, Ishikawa, Japan; King's College, London, UK (joined in 2007); and the University of California, San Francisco (UCSF). In 2009, Aravind Eye Hospital, Madurai, India; Johns Hopkins University, Baltimore, MD; and University of Pennsylvania, Philadelphia, PA were added as additional SICCA sites. UCSF is the coordinating center for SICCA. All specimens and data collected for SICCA are housed at UCSF. To facilitate the research focused on understanding the genetics of Sjögren'sSjögren's syndrome, high-density SNP genotype data and SICCA clinical information are being made available to the research community. This includes participants recruited from all SICCA research groups (RG). These participants (3,382), blood relatives (439), and unrelated healthy controls (25) had their whole blood or saliva sample (Oragene) extracted for DNA for the GWAS at the UCSF DNA Bank. Eighty eight percent of the participants are women, most are of European or Asian ancestry and the median age is 55. To assess potential batch effects when doing case-control comparisons using planned external controls, 30 DNA samples from each of three studies were genotyped with SICCA DNA samples: The Genetic Architecture of Smoking and Smoking Cessation - Collaborative Genetic Study of Nicotine Dependence (COGEND) - PI: Laura Bierut. NEI-Age-related disease study (AREDS) - Genetic Variation in Refractive Error Substudy - PI: Dwight Stambolian. Controls from the National Institute of Mental Health's (NIMH's) Human Genetics Initiative. Genome-Wide Association Study of Schizophrenia - PI: Pablo V. Gejman. Molecular Genetics of Schizophrenia - nonGAIN Sample (MGS_nonGAIN) - PI: Pablo V. Gejman. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data quality control, dbGaP preparation and posting, and imputation to 1000 Genomes to increase SNP density was performed by the Center for Biomedical Statistics at the University of Washington. Data analysis was performed at UCSF using software PLINK, EIGENSOFT, and SNPTEST.

  Study phs000672

• The Placenta Harbors a Unique Microbiome

  This study is to investigate placental microbiome through 16S rDNA-based and whole genome shotgun metagenomic sequencing. Identified taxa and their gene carriage patterns were compared to other human body sites niches. The placental microbiome profiles were most akin to the human oral microbiome.

  Study phs000735

• bulk RNA-Seq samples of CRC patients

  The dataset contains samples of 30 CRC patients (3 samples for each patient, tumor and 2 normal adjacent tissue sites, 90 samples in total). Dataset is composed by fastq file (paired end) type from bulk RNA-Seq.

  Dataset EGAD00001009635

• MorphoITH: A Framework for Deconvolving Intra-Tumor Heterogeneity Using Tissue Morphology

  This study introduces MorphoITH, a framework for deconvolving intra-tumor heterogeneity (ITH) in clear cell renal cell carcinoma (ccRCC) based on tissue morphology from histopathological slides. The study tested MorphoITH's ability to capture different aspects of morphology and to reflect genetic ITH. The data deposited here is derived from a morphology guided multi-regional sequencing dataset used to study the relationship between morphology and genetic evolution. This dataset consists of whole exome sequencing of tumor from multiple sites and adjacent normal samples which were collected from two patients treated in affiliated hospitals of the University of Texas Southwestern Medical Center (UTSW), including Parkland Hospital.

  Study EGAS50000001064

• Development and Use of Network Infrastructure for High-Throughput GWA Studies

  The "Development and Use of Network Infrastructure for High-Throughput GWA Studies" project is collaboration between Group Health Cooperative (GH), the University of Washington (UW), and the Fred Hutchinson Cancer Research Center (FHCRC). It is one of 5 sites participating in The Electronic Medical Records and Genomics (eMERGE) Network funded by the National Human Genome Research Institute (NHGRI) with additional funding from the National Institute of General Medical Sciences (NIGMS). The overall eMERGE project is designed to assess whether linking biorepositories of patients in healthcare delivery systems with electronic medical records (EMRs) is an efficient strategy for high-throughput genome wide association (GWA) studies and whether information can be pooled across sites. The primary phenotype in the Group Health/UW Aging and Dementia eMERGE study project is dementia. Phenotyped participants originated from four population-based sources. Seattle-area members of GH (a large integrated health care system in Washington State) consented and enrolled in 1) the University of Washington Alzheimer's Disease Patient Registry (ADPR) and 2) the Adult Changes in Thought (ACT) study, 3) Marshfield Clinic Personalized Medicine Research Project (PMRP), a population-based DNA, plasma and serum biobank of 20,000 adults, 4) Vanderbilt's BioVU, a de-identified DNA biobank. The ADPR (PI: Eric B. Larson; NIH/NIA U01 AG 006781) is a population-based registry of incident dementia cases designed to identify all new dementia cases within GH from 1987 to 1996. Potential dementia cases were identified through referrals from primary care physicians, mental health services, and neurologists, as well as review of CT scans, neurology, emergency room, geriatrician, and mental health clinic logs, and hospital discharge diagnoses. Medical history, physical, laboratory testing, and neuropsychological testing were performed on all consenting potential cases. These data were reviewed by a consensus conference including a neuropsychologist, study physicians, and an epidemiologist. After discussion of the case, dementia status is assigned using DSM-III-R criteria. Alzheimer's disease status was assigned using the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. The study base of the ADPR population was stable with an attrition rate of less than 1%/year. The ACT study (PI: Eric B. Larson; NIH/NIA U01 AG 006781) is an ongoing community-based cohort study designed to determine the incidence of Alzheimer's Disease (AD), other types of dementia, and cognitive impairment and to determine risk factors for these conditions. The original cohort of 2,581 was enrolled in 1994-1996. An expansion cohort of 811 was enrolled in 2000-2002. Continuous enrollment to keep 2,000 persons enrolled and at-risk for dementia outcomes was begun in 2005. To date the study has accrued more than 4,000 participants. Dementia-free participants are enrolled in this cohort and evaluated every two years by study personnel with many evaluations including an assessment of cognitive functioning using the Cognitive Abilities Screening Instrument (CASI), which is an extended version of the Mini-Mental State Examination that has been widely used in epidemiological studies of the elderly. Persons with CASI scores lower than 86 or in whom interviewers suspect unusual cognitive decline are followed up with dementia diagnostic evaluations which include physical and neurological examinations and neuropsychological tests. Medical records are reviewed, and laboratory tests and neuroimaging are obtained if not available. The dementia diagnoses and dementia subtypes are determined during a consensus conference attended by the examining clinicians and other study physicians, a neuropsychologist, and research nurse. After discussion of the case, dementia status is assigned using DSM-IV criteria. Alzheimer's disease status was assigned using NINCDS-ADRDA criteria. Individuals diagnosed with dementia are seen again one year following diagnosis using the same procedures. Individuals not diagnosed with dementia are returned to the pool of at-risk individuals and are seen at their next routinely scheduled biennial visit. The ACT sub-sample is stable; for the original cohort, median enrollment in GH was 19 years prior to joining the ACT study, and 85% of the cohort has ≥ 10 years of GH enrollment. DNA for the ADPR participants were obtained through a companion study, Genetic Differences in Cases and Controls (PI: Walter Kukull; NIH/NIA R01 AG007584). DNA obtained through both studies were extracted from blood using Gentra Systems Puregene methods. DNA concentration is determined by UV optical density. All samples are checked for quality by OD 260/280 ratio. For long-term storage, samples are aliquoted and stored at -70°C. The Marshfield study, Personalized Medicine Research Project (PMRP), a population-based DNA, plasma and serum biobank of 20,000 adults. PMRP was started in 2002 as a 3 Phase project. Completed in April 2004, the objectives of Phase I were to build and develop a large population-based biobank with DNA, plasma and serum samples to facilitate genomics research. Phase 1 was also to educate, inform and consult with the Marshfield Epidemiologic Study Area population and communities concerning potential studies, create the DNA foundation of the personalized medicine database and build the bioinformatics tools to store securely and analyze genotypic and phenotypic data. Phase I tasks included operation of the ethics and security advisory board, scientific advisory board and community advisory group. More than 18,000 residents aged 18 and above from 19 different zip codes surrounding Marshfield, WI were invited to participate in Phase I. After providing written informed consent, participants completed brief questionnaires that included questions about demographics, some environmental exposures, family history of disease, and adverse drug reactions, as well as family members living in the area. Participants provided 50ml of blood from which DNA was extracted and plasma and serum samples were stored. The informed consent process allowed access to electronic medical records and included language about non-disclosure of personal research results. A tick-off box was included so that participants could either allow or decline subsequent recontact for future research studied. The objectives of Phase II are to create the phenotypic database, establish the scientific and administrative infrastructure to support genetic mapping of the DNA and the initial discovery projects and genotype a sufficient portion of the genetic material to support these discovery projects. The objectives of Phase III are to expand the discovery projects, complete the genotyping of the genetic database and expand physician/health care provider education and community consultation. The Vanderbilt BioVU model uses discarded blood leftover from clinical care and de-identified clinical information, both of which are tracked with a Research Unique Identifier that is permanently disconnected from the medical record number used to generate it. The Vanderbilt IRB determined that the project does not qualify as "human subject" research under §46.102(f)(1)(2). The program has been reviewed by OHRP twice (the latest immediately prior to launch), and the determination of the Vanderbilt IRB that the project is consistent with the 8/10/2004 guidance has been validated. The model includes a simple opt out mechanism developed for patients who do not wish to have their samples included. Planning (including community involvement, ethics and IRB discussions, focus groups, development of operating procedures and pilot studies to assess them) began in May 2004, and the resource commenced sample collection in February 2007 and as of May 2009 contains approximately 56,000 samples. The current resource will be available to all Vanderbilt investigators who sign a Data Use Agreement. The resource represents Vanderbilt's broad patient population and thus provides a potential resource for research in a range of common and rare diseases as well as drug response or medication safety. BioVU patient protection model: There has been extensive involvement by the ethics community and the IRB to put in place procedures to provide privacy protection. The overall protection plan is multifaceted and includes a combination of technology and policy: (1) creation of the SD described above; (2) return of only the specific clinical data items requested by investigators (rather than the complete de-identified chart); (3) submission of any specific proposed project to the IRB and to a separate protocol review committee, both of which must approve; (4) implementing a Data Use Agreement that permits only approved queries and data analyses, specifically prohibits attempts at re-identification (at the risk of institutional sanctions), and mandates redeposit of all genetic information generated in a research study back into a genomic database; and (5) tracking and auditing all use.

  Study phs000234

• Investigating Host Genetic Risk Factors for Tuberculosis in Highly Endemic South African Populations

  It is apparent from our recent population genetic and admixture mapping work 1–3 that a substantial part of the ancestral input into the South African Coloured (SAC) population is from the San or Khoe groups, which are not well represented in publicly available genetic databases. It is a reasonable assumption that the SAC population in the Western Cape may have derived more genetic input from the present KhoeSan population in the Northern Cape than the San residing in Namibia. It was concluded by our group that it is indeed the southern African KhoeSan group, the ≠Khomani, that best represent the KhoeSan contribution seen in the SAC 4. More recently, it has been shown that there are ancestry related increases in TB susceptibility, especially with increased Bantu-speaking African and KhoeSan ancestry 5. We aim to elucidate the epidemiological and human-host genetic risk factors for TB and the immunological pathways modulating TB infection. The proposed sub-study will enroll people evaluated for TB at Northern Cape community health clinics and their contacts from their households and/or community. We will conduct a demographic interview, collect saliva, which will be used for genetic analysis, and blood to determine latent TB infection status and capture immunological responses to mycobacterial infections at the cellular level and RNA sequencing.

  Study EGAS00001007850

• A Cancer Cell-Line Titration Series for Evaluating Somatic Classification

  Accurate detection of somatic single nucleotide variants and small insertions and deletions from DNA sequencing experiments of tumour-normal pairs is a challenging task. Tumour samples are often contaminated with normal cells confounding the available evidence for the somatic variants. Furthermore, tumours are heterogeneous so sub-clonal variants are observed at reduced allele frequencies. We present here a cell-line titration series dataset that can be used to evaluate somatic variant calling pipelines with the goal of reliably calling true somatic mutations at low allele frequencies. Cell-line DNA was mixed with matched normal DNA at 8 different ratios to generate samples with known tumour cellularities, and exome sequenced on Illumina HiSeq to depths of >300x. The data was processed with several different variant calling pipelines and verification experiments were performed to assay >1,500 somatic variant candidates using Ion Torrent PGM as an orthogonal technology. By examining the variants called at varying cellularities and depths of coverage, we show that the best performing pipelines are able to maintain a high level of precision at any cellularity. In addition, we estimate the number of true somatic variants undetected as cellularity and coverage decrease. Our cell-line titration series dataset, along with the associated verification results, is effective for this evaluation and will serve as a valuable dataset for future somatic calling algorithm development.

  Study EGAS00001001016

• IMPRESS_all

  Dataset containing tumor, normal and blood sample data, for various tissue and tumor types. Data is targeted methylation data, using smMIP probes to target informative CpG sites in the genome. Sample type can be inferred from the name, with 'W' being normal samples and 'TC' tumor samples. Dataset contains 259 samples in duplicate, with one half of the runs being cut by MSRE's, and the other not. For every sample paired fastq files are present.

  Dataset EGAD50000000882