13348 results for ""60+mice"+"6+weeks"+diet+study+2014+2017+DOI"

in 35.03 milliseconds.

• CLUSTER consortium RNAseq CD19 B cell dataset of UK JIA patients.

  This study examines B cell transcriptomic profiles in Juvenile Idiopathic Arthritis (JIA) patients to investigate molecular mechanisms underlying disease heterogeneity. CD19+ B cells were isolated from peripheral blood samples and subjected to RNA sequencing to characterise gene expression patterns. The dataset includes patients with documented uveitis status to enable investigation of B cell contributions to the common JIA comorbidity.

  Study EGAS50000001123

• Genetic and Microenvironmental Analysis of Peripheral T-cell Lymphoma

  This study enrolled 129 patients diagnosed with PTCL, comprising 94 cases of nTFHL and 35 cases of PTCL-NOS. Whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed using DNA and RNA of sufficient quality extracted from their tumor specimens. WES was conducted for all 129 cases, while RNA-seq was performed on 57 tumor samples.

  Study EGAS50000001258

• WES Analysis of precancerous lesions in Lynch Syndrome

  The project focuses on identifying the genetic alterations involved in the early stages of tumor development in individuals with Lynch Syndrome. Using Whole Exome Sequencing (WES), the study aims to characterize somatic mutations and molecular pathways that drive the transformation from normal tissue to precancerous lesions. This research contributes to a better understanding of tumorigenesis in hereditary colorectal cancer syndromes.

  Study EGAS50000001546

• EstMB cohort participants sequenced with MGISEQ-2000 platform

  Ensuring the comparability of data generated across different sequencing platforms has become a pressing concern in efforts to uncover robust links between the microbiome and human health. In this study, we conducted a comprehensive comparison of taxonomic and functional profiles from matched human gut microbiome sample pairs, sequenced using both the MGISEQ-2000 (MGI) and NovaSeq 6000 (Illumina NovaSeq) platforms.

  Study EGAS50000001538

• Single-cell multi-omics and mtDNA genotyping of human peripheral blood cells

  In this study, we characterize human peripheral blood cells using mitochondrial single-cell ATAC-seq (mtscATAC-seq), which simultaneously profiles mitochondrial genomes and chromatin accessibility at single-cell resolution. This submission includes PBMCs from one healthy pediatric donor and one 80-year-old patient diagnosed with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome.

  Study EGAS50000001020

• ICARUS-LUNG01-GEOMx

  A GeoMx spatial transcriptomic study using 7 patients from the ICARUS LUNG01 trial focusing on tumour and immune cell compartments. We selected 7 paired baseline and on-treatment patient samples for analysis. We selected up to 4 regions of interest (ROI) per sample tissue. We identified tumour and immune cell areas of illumination (AOI) using CK and CD45 antibodies respectively

  Study EGAS50000001679

• Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

  Normal-cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B-lymphocytes prior to lymphoma remains uncertain. In this study, we sequenced multiple stages of the B-lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of high-prevalence of mutated MYD88.

  Study EGAS00001005656

• Sputum bacterial microbiota in an overall healthy population in Guangdong province, China

  This repository contains raw sequencing data for sputum fungal microbiota in an overall healthy population in Guangdong province, China. The aim of the study is to provide a comprehensive insight on the multi-kingdom airway microbiome, how it may underlie the interplay between exposure and healthy outcomes, and whether it can be employed to inform airway health and diseases.

  Study EGAS00001006721

• Sputum fungal microbiota in an overall healthy population in Guangdong province, China

  This repository contains raw sequencing data for sputum fungal microbiota in an overall healthy population in Guangdong province, China. The aim of the study is to provide a comprehensive insight on the multi-kingdom airway microbiome, how it may underlie the interplay between exposure and healthy outcomes, and whether it can be employed to inform airway health and diseases.

  Study EGAS00001006720

• HipSci HumanHT_12v4 Expression BeadChip analysis-Healthy volunteers

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies from healthy volunteers.

  Study EGAS00001000867

• HipSci RNA sequencing for embryonic stem cell control lines

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNA sequencing on commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines.

  Study EGAS00001001727

• Low_depth_whole_genome_sequencing_across_multiple_isolated_populations

  Isolated populations have unique population genetics characteristics that can help boost power in genetic association studies for complex traits. Leveraging these advantageous characteristics requires an in-depth understanding of parameters that have shaped sequence variation in isolates. This study performs a comprehensive investigation of these parameters using low-depth whole genome sequencing (WGS) across multiple isolates.

  Study EGAS00001001597

• Multiple_Myeloma_Diagnosis_to_Relapse_study_samples

  The study will investigate serial samples from the same patient taken at the time of MGUS or SMM diagnosis, and later at the time of evolution towards MM. Samples will be sequenced by whole genome along with a matched normal to obtain the highest possible amount of information toinvestigate genomic changes at disease evolution.

  Study EGAS00001001299

• HipSci-Whole Exome sequencing-healthy volunteers

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sup-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies from healthy volunteers.

  Study EGAS00001000592

• Whole_exome_sequencing_for_HELIC

  The HELIC study has been whole genome sequencing individuals from 2 Greek isolatedpopulations at 1x depth. The genotype calling process crucially involves a VQSR stepfollowed by imputation-based refinement. We have been investigating optimal ways toincrease calling accuracy. To aid us in setting appropriate parameters for VQSR and otherQC steps, we have carried out whole exome sequencing of a small number ofHELIC samples.

  Study EGAS00001000602

• Multiple Sclerosis ImmunoChip data

  The purpose of this study is to leverage the custom content of the ImmunoChip consortium; incorporating candidate loci from 12 autoimmune diseases, to both fine-map previously identified multiple sclerosis loci and identify new multiple sclerosis candidates. As a fine-mapping array, both common and rare variation are included within a subset of ~180 candidate loci across the genome.

  Study EGAS00001003219

• The Genetic History of Greenlandic-European contact

  The Inuit ancestors of the Greenlandic people arrived in Greenland close to 1000 years ago. Since then, Europeans from many different countries have been present in Greenland. Consequently, the present-day Greenlandic population has ~25% of its genetic ancestry from Europe. In this study, we investigated to what extent different European countries have contributed to this genetic ancestry.

  Study EGAS00001004933

• IL_10_signalling_and_macrophage_gene_expression

  Study to stimulate WT and IL-10RB mutant macrophages with LPS in presence or absence of recombinant IL-10 and compare their gene expression profiles by RNASeqThese data are 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 EGAS00001001283

• Whole Exome Sequencing of High grade T1 non-muscle invasive bladder cancer

  High-grade T1 (HGT1) bladder cancer (BC) is the highest risk subtype of non-muscle-invasive BC with unpredictable outcome and poorly understood risk factors. Here we performed whole exome sequencing across 61 HGT1 samples to identify genomic predictors of good outcome, recurrence or progression. This study includes somatic mutation calls and clinical data for 61 HGT1 tumors.

  Study EGAS00001004603

• RRBS MDACC Lung PreCancer

  To study the evolution of DNA methylation at genome level and methylation intra-tumor heterogeneity (ITH) during early lung carcinogenesis, we performed multiregional reduced representation bisulfite sequencing (RRBS) of 62 resected lung nodules from 39 patients including atypical adenomatous hyperplasia (AAH, n=14), adenocarcinoma in situ (AIS, n=15), minimally invasive adenocarcinoma (MIA, n=22), and invasive adenocarcinoma (ADC, n=11).

  Study EGAS00001004610

• High intensity sequencing of plasma cfDNA and WBC gDNA

  We sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white-blood cell (WBC) DNA covering a large genomic region (508 genes, 2Mb, 60,000x raw-depth) in a prospective study of 124 metastatic cancer patients, with contemporaneous matched metastatic tumor tissue biopsies, and age-matched 47 non-cancer controls.

  Study EGAS00001003755

• Transcriptome sequencing of myelodysplasia

  Transcriptome sequencing was performed on 214 patients with myelodysplasia in this study. RNA was obtained from bone marrow CD34+ cells (n=100) and/or bone marrow mononuclear cells (n=165). Transcriptome sequencing was performed for both cell fractions in 51 patients. We also studied bone marrow CD34+ cells and bone marrow mononuclear cells obtained from three healthy adults each.

  Study EGAS00001002346

• Phylogenetic reconstruction of breast cancer

  The aim of this study was to identify the evolutionary trajectories of metastatic breast cancer. We present whole genome sequencing data (primary tumours, axillary lymph nodes, distant metastasis and matched normal tissues) from 16 breast cancer patients. This work sheds light on the routes on which tumour cells metastasize and their role in disease progression in ER-positive breast cancer.

  Study EGAS00001004356

• Lymphoctye_colony_WGS

  We study lymphocyte somatic evolution through the sequencing of normal healthy lymphocytes. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth and function.

  Study EGAS00001002948

• Intellance-2: omics data on recurrent glioblastoma patients participating in the Intellance-2 clinical trial, prior to treatment.

  This study contains omics data from patients from the Intellance-2 clinical trial, in which effectiveness of ABT414 in EGFR amplified recurrent glioblastoma patients was tested. Patients were randomly assigned to one of three arms: (1) standard of care treatement (TMZ or CCNU), (2) Only ABT414 and (3) ABT414 + (TMZ|CCNU)

  Study EGAS00001005437

• Bone marrow derived stromal cells from Myelodysplastic Syndromes

  In this study we performed exome sequencing of bone marrow derived, in-vitro expanded mesenchymal stromal cells from patients with Myelodysplastic Syndromes in order to assess clonal mutations in the non hematopoietic compartment. We used bone marrow mononuclear cells as germline controls. Validation was carried out with amplicon based resequencing. Alongside we provide RNA Sequencing of MDS and healthy MSCs.

  Study EGAS00001005051

• Analysis of exonic somatic variants in light-chain amyloidosis (ALA) and ALA concomitant with multiple myeloma

  We aim to provide the very first insight into ALA+MM molecular profiles and compare the results with ALA and with MM. Our detailed study of ALA and ALA+MM represents an important step towards improved understanding of their genetic and transcriptomic background, which is a prerequisite for development of optimal treatment strategies in the future.

  Study EGAS00001004214

• Evolutionary analysis of pancreatic neoplastic cysts through whole-exome and targeted sequencing

  Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyzed 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing.

  Study EGAS00001004473

• Genomic and transcriptomic analysis of baseline PDAC patients' tumors from the OXIRI phase 1b clinical trial

  This study was aimed at investigating the genomic and transcriptomic features associated with response to the OXIRI regimen (oxaliplatin, irinotecan, capecitabine) in pancreatic ductal adenocarcinoma (PDAC) tumors. We performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on baseline tumor samples obtained from 8 patients recruited in the OXIRI phase 1b clinical trial (NCT02368860).

  Study EGAS00001006073

• mutational landscape of normal human breast

  The accumulation of somatic mutations in the healthy breast throughout life and pregnancy is poorly understood. Here we describe whole genome sequencing analysis of epithelial and stromal compartments from the normal breast. We aimed to study how pregnancy and age affect both the mutational burden and the clonality of the healthy breast, and the subsequent implications on breast cancer risk.

  Study EGAS00001004672

• Molecular Phenotype of Constitutional TET2 Haploinsufficiency in Humans

  In this study, we observed the effects of constitutional heterozygous TET2 loss on blood DNA methylation, chromatin activity and gene expression in carriers of truncating TET2 germline mutations. To provide additional context to findings in TET2 mutation carriers, we analysed DNA methylation in four DNMT3A germline mutation carriers and their age-matched controls.

  Study EGAS00001003454

• Separation, characterization, and identification of individuals from multi-person blood mixtures with single cell transcriptome sequencing and a novel bioinformatics pipeline

  We report a deconvolution and identification strategy of scRNA-seq datasets using mixed PMBCs data. After sequencing the data were processed with the de-goulash pipeline and analyzed with aim to identify and aquire biogeogrpahical ancestry of the involved individuals. The study includes samples of biological mixtures and in silico mixtures.

  Study EGAS00001006202

• Finding structural variation and functional consequences from the primary leukemia cells (CLL) at the single-cell level

  In this study, we aimed to identify somatic structural variation of chronic lymphocytic leukemia (CLL) at the single-cell level and investigate its direct consequence on the nucleosome occupancy using scNOVA approach. For this purpose, we performed strand-specific single-cell sequencing of primary leukemia samples from 63-year-old female patient.

  Study EGAS00001004925

• COVID-19 GWAS in Japanese

  The Japan COVID-19 Task Force (JCTF) was established in early 2020 as a nation-wide multicenter consortium to overcome the COVID-19 pandemic in Japan. We conducted a genome-wide association study (GWAS) involving 2,393 Japanese COVID-19 cases collected in initial pandemic waves with 3,289 controls. GWAS genotyping was performed using Infinium Asian Screening Array (Illumina, USA).

  Study EGAS00001006284

• ALLoreactive T-Cell receptOr RePertoire in kidnEy tranSplantation

  A prospective study for investigating the T-cell receptor (TCR) repertoire in T-cell mediated rejection (TCMR) after kidney transplantation. The pre-formed donor-reactive TCR repertoire was tracked in blood and tissue of patients after kidney transplantation and characteristics of TCR repertoires from patients experiencing a rejection were compared to patients with no histopathological signs of rejection.

  Study EGAS00001005299

• cis-eQTL mapping of TB-T2D comorbidity in a five-way admixed SA cohort

  The aim of the study was to identify ancestry-specific genetic variants associated with differentially expressed genes in TB-T2D comorbid patients compared to T2D patients, as well as between TB patients and healthy controls. Both global and local ancestry was incorporated in regression models to account for the genetic heterogeneity in our complex multi-way admixed population.

  Study EGAS00001007059

• Whole-Exome Sequences from Imazighen and non-Imazghen from Algeria

  Study of high-coverage whole-exome sequences from Amazigh (Tamazight-speakers) and non-Amazigh individuals (Arab-speakers) from Algeria to analyze the impact of demography in functional genomic variation in the complex demographic context of North Africa. Amazigh individuals were sampled in Oum El Bouaghi, Batna, Khenchela, and Ghardaïa, and non-Amazigh individuals were sampled in Algiers.

  Study EGAS00001007236

• Study of Addiction: Genetics and Environment (SAGE)

  This study is part of the Gene Environment Association Studies initiative (GENEVA) funded by the National Human Genome Research Institute. The overarching goal is to identify novel genetic factors that contribute to addiction through a large-scale genome-wide association study of DSM-IV alcohol dependent (and frequently illicit drug dependent) cases and non-dependent, unrelated control subjects of European and African American descent. The focus of this proposal is a case-control design of unrelated individuals for a genetic association study of addiction. Cases are defined as individuals with DSM-IV alcohol dependence (lifetime) and potentially other illicit drug dependence. In addition to the categorical diagnosis, we have data on ordinal measurements of number of DSM-IV symptoms for alcohol, nicotine, marijuana, cocaine, opiates and other drugs so that we will able to construct quantitative measurements of addiction severity over a wide range of substances. Controls are defined as individuals who have been exposed to alcohol (and possibly to other drugs), but have never met lifetime diagnosis for alcohol dependence or dependence on other illicit substances. Analyses that include refinement of the phenotype and incorporation of important demographic and environmental factors into association studies will be pursued. Cases and controls were selected from three large, complementary datasets: the Collaborative Study on the Genetics of Alcoholism (COGA), the Family Study of Cocaine Dependence (FSCD), and the Collaborative Genetic Study of Nicotine Dependence (COGEND). COGA: COGA was initiated in 1989 and is a large-scale family study that has had as its primary aim the identification of genes that contribute to alcoholism susceptibility and related characteristics. COGA is funded through the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Subjects were recruited from 7 sites across the U.S. Alcohol dependent probands were recruited from treatment facilities and assessed by personal interview. After securing permission, other family members were also assessed. A set of comparison families was drawn from the same communities as the families recruited through the alcohol dependent probands. Assessment involved a comprehensive personal interview developed for this project, the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), which gathers detailed information on alcoholism related symptoms along with other drugs and psychiatric symptoms. Families with three or more first-degree relatives who were alcohol dependent were invited for more extensive testing, including neurophysiology evaluations (ERPs and EEGs) and a battery of neuropsychological assessments. Blood was obtained for genetic studies. Institutional Review Boards at all sites approved the protocols, including sharing in the NIAAA national repository. COGA has four Co-Principal Investigators Bernice Porjesz, Victor Hesselbrock, Howard Edenberg, and Laura Bierut. COGA includes nine different centers where data collection, analysis, and storage take place. The nine sites and Principal Investigators and Co-investigators are: University of Connecticut (Victor Hesselbrock); Indiana University (Howard Edenberg, John Nurnberger, Jr., Tatiana Foroud); University of Iowa (Samuel Kuperman); SUNY Downstate (Bernice Porjesz); Washington University in St. Louis (Laura Bierut, Alison Goate, John Rice); University of California at San Diego (Marc Schuckit); Howard University (Robert Taylor); Rutgers University (Jay Tischfield); Southwest Foundation (Laura Almasy). Q. Max Guo serves as the NIAAA Staff Collaborator. This national collaborative study is supported by the NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Family Study of Cocaine Dependence (FSCD): This project was initiated in 2000 as a case-control family study of cocaine dependence funded through the National Institute on Drug Abuse (NIDA; PI: Laura Bierut). The primary goal was to increase the understanding of the familial and non-familial antecedents and consequences of cocaine dependence. Cocaine dependent individuals were systematically recruited from chemical dependency treatment units (both public and private; residential and outpatient) in the greater St. Louis metropolitan area. Community based control subjects were identified through a Missouri Driver's License Registry (maintained at Washington University for research purposes) and matched by age, race, gender, and residential zip code. As a supplement to this project, blood samples were collected for future genetic analysis and were included in the NIDA Genetics Consortium. Phenotypic data, DNA, and cell lines are in the NIDA Center for Genetics Studies. Collaborative Genetic Study of Nicotine Dependence (COGEND): COGEND was initiated in 2001 as a three-part program project grant funded through the National Cancer Institute (NCI; PI: Laura Bierut). The three projects included a study of the familial transmission of nicotine dependence, a genetic study of nicotine dependence, and a study of the relationship of nicotine dependence with nicotine metabolism. The primary goal is to detect, localize, and characterize genes that predispose or protect an individual with respect to heavy tobacco consumption, nicotine dependence, and related phenotypes and to integrate these findings with the family transmission and nicotine metabolism findings. The primary design is a community based case-control family study. All subjects were recruited from Detroit and St. Louis. Nicotine dependent cases and non-dependent smoking controls were identified and recruited. In addition, one sibling for each case and control subject was recruited in a subset of the sample. Over 56,000 subjects aged 25-44 years were screened by telephone, over 3,100 subjects were personally interviewed, and over 2,900 donated blood samples for genetic studies. All three studies (COGA, COGEND, FSCD) include measures of basic socio-demographic variables, including age, sex, race/ethnicity, family income, educational attainment, religious participation, and family structure. Other important covariates and/or potential moderators of genetic effects include comorbid addictions and age at initiation of use for cigarettes, alcohol and drugs. The assessments also include measures of various life stressors, such as physical and sexual abuse, which have been implicated in gene-environment interactions for several disorders. Coding for both individual variables and indices has been standardized across studies. All subjects were assessed in person by trained research assistants. Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR), was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease"(HHSN268200782096C). Note for Publications Related to Study: The Study of Addiction: Genetics and Environment (SAGE) has not yet generated publications. Below is a listing of publications related to the three studies from which the SAGE sample was selected. COGA has over 228 publications listed at www.niaaagenetics.org 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 addiction through a large-scale genome-wide association study of DSM-IV alcohol dependent (and frequently illicit drug dependent) cases and non-dependent, unrelated control subjects of European and African American descent. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000092

• Age related Macular Degeneration (AMD) - Michigan, Mayo, AREDS, Pennsylvania (MMAP) Cohort Study: Association and Sequencing Studies

  Age-related Macular Degeneration (AMD) is a leading cause of incurable blindness in people over the age of 65. AMD is a late-onset multi-factorial neurodegenerative disease and its pathogenesis involves interaction of genetic and environmental factors. Several chromosomal regions have been associated with AMD susceptibility through linkage analysis (Swaroop et al., 2009). More recent studies provide strong evidence that variants within the CFH gene cluster on chromosome 1 and at/near LOC387715/ARMS2 on chromosome 10 are strongly associated with the disease. Variants at other genes including C2/BF, C3, CFI and APOE4, also contribute to AMD susceptibility. Our primary goals are to identify genetic variants and haplotypes that are associated with AMD. The underlying hypothesis is that DNA variation(s) in multiple genetic susceptibility loci will predispose individuals to AMD pathogenesis, and comparison of DNA of cases and controls should identify these susceptibility variants. Our studies are focused on the genetic analysis of advanced AMD and should provide novel insights into disease diagnosis, progression and pathology. We have assembled a collaborative group of researchers from the University of Michigan, Mayo Clinic, University of Pennsylvania, and the AREDS group including National Eye Institute intramural investigators, who collected clinical data and DNA from a large number of patients affected with AMD and from unaffected controls. The primary source of funding was National Eye Institute. Study 1: To identify genetic variants and haplotypes that are associated with AMD, we submitted and obtained usable genotyping data on 2185 patients and 1155 controls from the Center for Inherited Disease Research (CIDR). Study 2: To identify rare coding variants associated with a large increase in risk of AMD, 10 candidate loci spanning 57 genes were sequenced in 2,335 cases and 789 controls. Probes were designed to capture 96.5% of the coding sequence and 35% of total locus sequence, generating an average 123Mb of on-target sequence per individual at 127x average depth. Substudies: phs000182 AMD-MMAP Cohort Study: A Joint Genome-Wide Asscociation Study phs000246 Fuchs' Corneal Dystrophy GWAS phs000457 MMAP Methylation in AMD phs000685 Age-Related Macular Degeneration Targeted Sequencing Study

  Study phs000684

• Diabetic Retinopathy Genomics Study (DRGen) - Genetic Biomarkers of Diabetic Retinopathy

  Using a well-defined, clinically supported phenotypic strategy, we seek to better understand the role of common and rare genetic variants in the progression of diabetic retinopathy (DR). Whole exome/whole genome sequencing (WES/WGS) was used to systematically search the human genome to detect DR susceptibility genes or genes that protect people from developing advanced DR. Clinical data and bio specimens were obtained from clinically defined DR phenotypes such as, (i) No/Mild NPDR (non-proliferative DR) with a subset of extreme phenotype, ii) Diabetic macular edema (DME) alone and iii) Proliferative diabetic retinopathy (PDR) alone. In this ongoing comprehensive genomic study, we wish to i) Identify potential common and rare variants that may influence the phenotypic differentiation of DR into DME or PDR, ii) Define genetic variants stratified based on the "extreme phenotype," and iii) Characterize genetic factors that determine the differential response to anti-VEGF drugs in DME patients. Definition of Diabetic Retinopathy and classification of groups Study 1. Proliferative diabetic retinopathy (PDR). Anybody showing evidence of retinal neovascularization on the disc (NVD) or elsewhere (NVE) with or without pre-retinal and vitreous hemorrhage will be considered PDR. We will include only those "active" PDR patients. The total number of consented subjects in this study is 182. Study 2. Isolated Phenotype: Varied response with anti-VEGF treatment is a significant limiting factor for better clinical outcomes. We quantify the response to anti-VEGF treatment based on visual acuity changes and anatomic features of DME assessed by optical coherence tomography (OCT). Depending on the response at one month following three monthly intravitreal anti-VEGF injections, we have observed two phenotypes: 1) Good responders: Participants were considered "good responders" if the anatomical outcome to anti-VEGF treatment resulted in a significant reduction of baseline central retinal thickness (CRT) > 25% after three anti-VEGF injections. 2) Poor Responders: Participants were classified as "poor responders" if the outcome of anti-VEGF treatment resulted in a reduction of CRT < 20% or in any increase in CRT after three monthly injections. The total number of consented subjects in this study is 17.

  Study phs002501

• Predicting Chemotherapy-Induced Mucositis with Genetic and Clinical Factors

  We hypothesized that genetic variability in the enzymes/proteins involved in drug metabolism, inflammation, and immune function is a major underlying contributor to mucositis incidence and progression and that, based on this variability we can identify variants that influence risk, and develop a mucositis progression prediction model that improves on existing models by incorporating genetic variability along with clinical factors. Using genome wide association study (GWAS) combined with a pathway candidate gene approach and a modified case-control study method, we investigated the hypothesis in a sample of 1092 patients who received a myeloablative dose of melphalan (MEL) followed by autologous hematopoietic stem cell (ASCT) transplantation as treatment for multiple myeloma and for whom banked blood stem cell samples and clinical data were available.

  Study phs000545

• SNP array analysis of spondylocostal dysostosis patient iPSCs and gene edited isogenic controls

  This study, "SNP Array Analysis of Gene Edited SDV Patient iPSCs" is part of a larger study where we applied our recently established experimental in vitro model system of the human segmentation clock, for the analysis of human segmentation defects of the vertebrae (SDV) including spondylocostal dysostosis (SCD). To this end we generated patient-derived iPSC lines, identified putative disease-causing mutations and corrected these mutations using CRISPR/Cas9-based genome editing technology. We identified in the patient-sample originally obtained from the NIGMS Human Genetic Cell Repository at the Coriell Institute for Medical Research (#: GM13539) heterozygous compound mutations in MESP2. These mutations were corrected accordingly and the resulting clones were genotyped by SNP array analysis.

  Study phs001975

• Exome Sequencing of a family with thrombocytopenia, red cell macrocytosis, and lymphoblastic leukemia predisposition

  A family with a history of bleeding, variable thrombocytopenia, red cell macrocytosis and two cases of pre B-cell acute lymphoblastic leukemia was studied in a single visit. The family was assessed for bleeding history using a bleeding questionnaire. Additionally, complete blood counts were measured and whole blood was collected from five affected individuals and three unaffected individuals for DNA extraction and whole exome sequencing. The goal of this study is to determine the genetic cause of thrombocytopenia, red cell macrocytosis, and predisposition to leukemia in a family. It is hoped that the information obtained from this study will help researchers understand the genetic and molecular basis of platelet and red cell production, as well as leukemia predisposition.

  Study phs000873

• Genomics of Pediatric Renal Medullary Carcinomas

  Version 1We derived faithful cancer cell lines from patients with a diagnosis of renal medullary carcinomas (RMC). These models have been sequenced with whole genome, exome and transcriptome technologies along with the patient's primary germline and tumor samples. We took these faithful models and performed loss-of-function genetic perturbation screens (e.g. RNAi and CRISPR-Cas9) along with an orthogonal small molecule screen. We identified the ubiquitin-proteasome system as an important target in RMC as well as other SMARCB1 deficient cancers.Version 2We have collaborated with the Children's Oncology Group and the study AREN03B2 to study the cohort of patients with a central diagnosis of RMC. Here, we used 10x linked read sequencing along with RNA-sequencing to profile these matched tumor-normal pairs.

  Study phs001800

• Genetic Association Studies in the Solomon Islanders

  The goal of this study was to determine the genetics underlying blond hair in the Solomon Islands, which has the highest prevalence of blondism outside of Europe. Participants in the study were of self-reported Solomon Islands ancestry and were 6-36 years of age at enrollment. Individuals with blond (N = 43) and dark hair (N = 42) were selected, approximately matched for age, sex and local geography, and spectrophometric measurements of hair pigmentation were made as a single measurement taken from hair at the crown. Individuals with gray, white, thin, bleached or artificially colored hair were excluded from analysis. All 85 participants were evaluated in a genome-wide scan to detected association to hair pigmentation in the Solomon Islands.

  Study phs000493

• Single Cell Genomic Analysis of Lymphoma

  Our study aimed to define the extent of heterogeneity between anatomically separated tumor manifestations in follicular lymphoma at single-cell resolution. We subjected single-cell suspensions derived from nodal, synchronously-acquired fine needle aspirations from two distinct tumor sites to high-throughput microfluidics-based single-cell RNA sequencing. By comparing the relative composition of the tumor subpopulations between the two tumor sites, we found that some patients can exhibit site-to-site differences. While the overall composition of the tumor microenvironment did not differ significantly between sites, we did detect a specific correlation between site-to-site tumor heterogeneity and T follicular helper cell abundance. Our study demonstrates the significant limitations of a solitary biopsy in defining the full scope of a patient's disease.

  Study phs002188

• DNA Methylation Characterization of Fusion-Positive and Fusion-Negative Rhabdomyosarcoma

  Rhabdomyosacoma (RMS) is a common pediatric soft tissue tumor that is associated with the skeletal muscle lineage. RMS comprises two major subtypes: fusion-positive (FP, most commonly PAX3- FOXO1 or PAX7-FOXO1) and fusion-negative (FN, frequently associated with mutations in RAS pathway). Our previous study demonstrated that FP and FN tumors exhibit distinct DNA methylation profiles. In this study, further investigation of genome-wide DNA methylation profiles in RMS tumors revealed DNA methylation differences between AX3-FOXO1 and PAX7-FOXO1 subsets in FP RMS, and between RAS mutation and RAS wild-type subsets in FN RMS. These data provide new insight into the relationship of DNA methylation with mutational changes and transcriptional organization in FP and FN RMS.

  Study phs001970

• VCRC Genetic Repository One Time DNA Protocol

  The purpose of this study is to identify genes that increase the risk of developing vasculitis, a group of severe diseases that feature inflammation of blood vessels. Better methods are needed to recruit patients with these rare diseases into cohorts of adequate size for high-quality genetics studies, and the existing infrastructure of the Vasculitis Clinical Research Consortium (VCRC) provides the means for such recruitment. Results of these studies will provide vasculitis researchers with insight into the causes of these diseases and generate new ideas for diagnostic tests and therapies, and will be of great interest to the larger communities of researchers investigating vasculitis and other autoimmune, inflammatory, and vascular diseases. This study will enhance the VCRC Data and Specimen Repository.

  Study phs001712

• Genomics of Glomerular Disorders

  The purpose of the "Genomics of Glomerular Disorders" study is to identify genetic contributions to primary glomerulopathies. This repository includes a total of N = 4,238 patients with a kidney biopsy diagnosis of a primary glomerular disorder across the following categories: focal segmental glomerulosclerosis (FSGS, N = 583), Henoch-Schönlein purpura nephritis (HSPN, N = 403), IgA nephropathy (IgAN, N = 1,555), membranous nephropathy (MN, N = 1,003), and minimal change disease (MCD, N = 694). The dataset includes a total of 2,290 patients recruited into the Cure Glomerulonephropathy (CureGN) study and another 1,948 patients from the Columbia University CKD Biobank (i.e., non-CureGN patients). The sample sizes by phenotype are counted based on enrollment diagnoses. The repository includes 3,958 WGS samples and 2,129 RNA-seq samples.

  Study phs002480

• Clinical Outcomes of 344 Diffuse Large B-Cell Lymphoma patients

  This study examines clinical outcomes of patients with diffuse large B-cell lymphoma (DLBCL). We analyzed a cohort of 344 patients from the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). To protect patient confidentiality, all samples were pseudonymized. The dataset includes clinical key characteristics, such as patient age at diagnosis, sex, ECOG performance status, disease stage, serum lactate dehydrogenase levels, bulky disease, bone marrow involvement, extranodal involvement, and B-symptoms. We used these data alongside proteomic and transcriptomic profiles to explore relationships between clinical features and molecular signatures, reconstructing regulatory networks. Insights from this integrative analysis aim to identify key pathological drivers and biomarkers of DLBCL progression, ultimately informing improved risk stratification and targeted therapeutic approaches.

  Study EGAS50000001054