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• Genes-Environments and Admixture in Latino Asthmatics (GALA II) Study

  A case-control pharmacogenetic study of bronchodilator drug response among racially admixed Latino children with asthma. Each participant had two spirometry measurements using the KoKo PFT System. With the first spirometry test, participant was administered with 4 puffs of HFA Albuterol. The second albuterol measurement was based on age, for participants under 16 years of age, additional 2 puffs were administered and for those over 16 years of age, additional 4 puffs were administered. The overall goal is to identify genetic factors which are predictive of drug response in children with asthma. The principal tools include a questionnaire and biological specimen collection. Participants are 8-21 years old at time of recruitment. Children with asthma have physician-diagnosed asthma, symptoms and medications. The GALAII Study is utilized in the following dbGaP substudies. To view genotypes, analysis, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" box located on the right hand side of this top-level study page phs001180 GALAII Study. phs001274phs001274 GALAII GWAS

  Study phs001180

• Anti-myeloperoxidase IgM B cells in anti-neutrophil cytoplasmic antibody-associated vasculitis

  Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a prototypic autoimmune disease, with a subset of AAV patients manifesting anti-myeloperoxidase (MPO) IgG. Patients with AAV respond positively to B cell-targeting and complement-targeting therapies, but disease flares are not uncommon. Here, by comparing samples from healthy individuals and MPO+ AVV patients, we show that B cell autoreactivity against MPO in the circulation of patients is dominated by CD27+IgM+ B cells whereas MPO-specific IgG+ cells are infrequent. Additionally, while naive anti-MPO-IgM B cells are present in both patients and controls and produce anti-MPO IgM upon stimulation, anti-MPO-IgM memory B cells and serum anti-MPO IgM are features of patients. Our results thus hint that defective elimination of B cell reactivity to MPO in the human repertoire, the presence of activated IgM+ anti-MPO B cells in disease, and a dominant role for anti-MPO IgM in complement activation, may all contribute to MPO+ AAV etiology and thereby serve as potential target for therapy.

  Study EGAS50000000753

• LEF1 knockdown effects on human T cell transcriptome and chromatin accessibility profiles.

  LEF1 (Lymphoid Enhancer-Binding Factor 1) is a key transcription factor in T cell development and function, and its dysregulation has been implicated in various immune-related disorders. This study aimed to comprehensively characterize the transcriptional and epigenetic changes induced by LEF1 knockdown in human T cells. CD3+ T cells isolated from three healthy donors were transfected with either LEF1-specific siRNA or control siRNA, followed by activation with CD3/CD28 Dynabeads and culture in IL-2-containing media. Cells were harvested at 24, 48 and 72 hours post-transfection for multi-omics analysis including bulk RNA-seq, bulk ATAC-seq, single-cell CITE-seq (For CITE-seq, 48 and 72 hours only). This dataset provides insights into LEF1-dependent gene regulatory networks and chromatin accessibility patterns in activated human T cells, contributing to our understanding of T cell biology and potential therapeutic targets. This dataset is part of a comprehensive study investigating functional roles of risk polymorphisms in autoimmune diseases, particularly focusing on the rs58107865 variant at the LEF1 locus.

  Study JGAS000818

• Single-Cell Multiomics of the Immune Microenvironment in T-Cell Acute Lymphoblastic Leukemia

  We present single-cell transcriptome and surface protein expression (CITE-seq) data from four healthy donors and fifteen pediatric T cell acute lymphoblastic leukemia (T-ALL) patients at diagnosis and at different treatment timepoints (days 1 – 6 and at time of remission). Mononuclear cells from peripheral blood (PB; longitudinal) or bone marrow (BM; diagnosis only) were isolated and CD45high immune cells and CD45dimCD7+ malignant cells were sorted and subsequently pooled to enrich for immune cells. For comparison,CD45high immune cells from four healthy donors were also sorted. Single-cell sequencing of the transcriptome and surface protein expression (204 antibodies) was performed using the 10x Genomics platform.Multiomics analyses resulted in the identification of a T-ALL subgroup characterized by a remodeled immune microenvironment at initial diagnosis. This immune landscape is dominated by the presence of non-malignant CD4-CD8-TCRab T cells that interact with CXCL16 expressing non-classical monocytes. Leukemia cell intrinsic transcriptional rewiring in these patients is associated with activation of Rap1 signaling.

  Study phs004269

• Uveal melanoma patient with germline MBD4 nonsense mutation

  There is currently no effective treatment for metastasised uveal melanoma (UM). Recently, it was reported that a UM patient was responsive to checkpoint inhibitor (CI) treatment, due to a high tumour mutation burden correlated with a germline loss-of-function MBD4 mutation. Here, we report on another UM patient who carried an MBD4 germline nonsense variant (p.Leu563Ter) and her tumour showed a 5-fold higher than average mutation burden. We confirmed the association between germline loss-of-function variant in MBD4 and CI response. The patient experienced stable disease (10 months) and survived two years with metastatic disease, which is twice as long as median survival. Additionally, the frequency of MBD4 loss-of-function variants in reported UM cohorts was >20 times higher than in an aggregated population genome database (P < 5x10-5), implying a potential role as UM predisposition gene. These findings provide a strong basis for the inclusion of MBD4 in screening of potential UM-prone families as well as stratification of immunotherapy.

  Study EGAS00001003362

• Pilot_experiment_on_functional_genomics_in_osteoarthritis

  The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). In this pilot we will assess the feasibility of the approach in the relevant tissue. We will obtain diseased and non-diseased tissue (cartilage and endochondral bone) following TJR, coupled with a blood sample, from 12 patients. We will generate genotype data on the HumanCoreExome array and will characterise the 12 pairs of diseased and non-diseased tissue samples in terms of methylation (Illumina 450k array), transcription (RNASeq) and expression (quantitative proteomics). The pilot will help assess the feasibility of isolating sufficient levels of starting material for the different approaches, and will instigate the development of analytical approaches to synthesising the resulting data. If successful, it is envisaged that we will proceed with expanding the work to 500 patients in the first year, with a target total sample size of 3,000 in the longer term. The key collaborators in this work are Mark Wilkinson (Sheffield) and Jyoti Choudhary

  Study EGAS00001001212

• Pilot_experiment_on_functional_genomics_in_osteoarthritis

  The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). In this pilot we will assess the feasibility of the approach in the relevant tissue. We will obtain diseased and non-diseased tissue (cartilage and endochondral bone) following TJR, coupled with a blood sample, from 12 patients. We will generate genotype data on the HumanCoreExome array and will characterise the 12 pairs of diseased and non-diseased tissue samples in terms of methylation (Illumina 450k array), transcription (RNASeq) and expression (quantitative proteomics). The pilot will help assess the feasibility of isolating sufficient levels of starting material for the different approaches, and will instigate the development of analytical approaches to synthesising the resulting data. If successful, it is envisaged that we will proceed with expanding the work to 500 patients in the first year, with a target total sample size of 3,000 in the longer term. The key collaborators in this work are Mark Wilkinson (Sheffield) and Jyoti Choudhary

  Study EGAS00001001213

• Salivary Gland Cancer TSO500 dataset

  Salivary gland cancer (SGC) is a rare cancer for which systemic treatment options are limited. Therefore, it is important to characterize its genetic landscape in search for actionable aberrations. This research aimed to identify these actionable aberrations by NGS-based analysis of DNA (single and multiple nucleotide variants, copy number variants, microsatellite instability and tumor mutational burden) in a large cohort of SGC patients. DNA was extracted from archival tissue of 119 patients with various SGC subtypes and sequenced using a targeted NGS panel encompassing 523 cancer related genes (TruSight Oncology 500, TSO500). The 119 patients included 46 AdCC patients, 43 SDC patients, 15 MEC patients, 9 AciCC patients and 6 patients with other subtypes (1 secretory carcinoma, 1 polymorphic adenocarcinoma (PAC), 1 adenocarcinoma NOS, 1 myoepithelial carcinoma, 1 epithelial/myoepithelial carcinoma and 1 mixed PAC/myoepithelial carcinoma). Median exon coverage ranged from 80-904 (median 308) unique reads and the median percentage of exon coverage with at least 100 unique reads was median 96.6% in these 119 samples.

  Study EGAS00001006232

• RNA sequencing data of 257 samples from 106 patients with HR+/HER2- breast cancer treated with AC plus paclitaxel or letrozole plus ribociclib (SOLTI-1402 CORALLEEN trial)

  Early-stage Luminal B breast cancer is frequent and is a major cause of breast cancer death due to its poor prognosis. Our proposal aims to study the biology behind the sensitivity and resistance of Luminal B breast cancer to chemotherapy (CHT) or a non-CHT regimen composed of hormone therapy in combination with ribociclib, a CDK4/6 inhibitor. To accomplish this, we first completed the SOLTI-1402 CORALLEEN phase II trial, a study where 106 patients with early-stage Luminal B breast cancer were randomized to standard neoadjuvant CHT for 6 months, or neoadjuvant letrozole and ribociclib for 6 months. After treatment, patients underwent surgery. The primary results of the study, which showed that the response rate to letrozole+ribociclib was similar to CHT, was reported (Prat et al; Lancet Oncol). Tumor biopsies were available at baseline, week 3 and surgery. A total of 257 samples were analyzed using the Illumina TruSeq Stranded Total RNA w/Ribo Zero Gold with MiSeq in TGL (Sequencer NovaSeq S4/PE/100x).

  Study EGAS00001007060

• MP2PRT: Genomic and Molecular Characterization of Biomarkers Associated with Tumor Angiogenesis, DNA Repair, and Immunologic Tolerance using Samples from the NRG Oncology Phase 3 Randomized Trial, GOG-0240 (NCT00803062)

  The Molecular Profiling to Predict Response to Treatment (MP2PRT) program is part of the NCI's Cancer Moonshot Initiative. The aim of this program is the retrospective characterization and analysis of biospecimens collected from completed NCI-sponsored trials of the National Clinical Trials Network and the NCI Community Oncology Research Program. This study is one of the selected studies under this program. For this study, genomic characterization (WGS, WXS, Total RNAseq, miRNAseq) has been performed on cervical tumor tissue from patients with advanced disease (persistent, recurrent, and metastatic) and matching germline samples. It is hypothesized that the characterization of these tissues using next generation sequencing will lead to the identification of relevant novel genetic aberrations within the immunologic, DNA repair, and tumor angiogenesis domains that dichotomize the study population into exceptional responders and non-responders to systemic therapy, with a spectrum of response manifesting between the two extremes.

  Study phs002293

• Single cell sequencing data of PBMC and CSF from a cohort of Multiple Sclerosis patients and other neurological disease controls

  Neuroinflammation is often characterised by immune cell infiltrates in the cerebrospinal fluid (CSF). Here we apply single-cell RNA sequencing to explore the functional characteristics of these cells in patients with various inflammatory, infectious and non-inflammatory neurological disorders. We show that CSF is distinct from the peripheral blood in terms of both cellular composition and gene expression. We report that the cellular and transcriptional landscape of CSF is altered in neuroinflammation, but is strikingly similar across different neuroinflammatory disorders. We find clonal expansion of CSF B and T cells in all disorders but most pronounced in inflammatory diseases, and we functionally characterise the transcriptional features of these cells. Finally, we explore the genetic control of gene expression in CSF lymphocytes. Our results highlight the common features of immune cells in the CSF compartment across diverse neurological diseases and may help to identify new targets for drug development or repurposing in Multiple Sclerosis.

  Study EGAS50000000739

• Starting Treatment with Agonist Replacement Therapies (START): A Randomized Trial of Methadone vs Buprenorphine/Naloxone for the Treatment of Opioid Dependence

  The Starting Treatment with Agonist Replacement Therapy (START) study was a 24-week, open-label, randomized trial of methadone versus Suboxone (buprenorphine/naloxone) for the treatment of opioid dependence. Patients were over the age of 18 and met DSM-IV qualifications for opioid dependence. The primary goal of the study was to determine if either medicine was associated with liver toxicity issues in this vulnerable patient population. Liver enzymes were measured at four time points. Urinalysis for opioids, cocaine, cannabis, benzodiazepines, and methamphetamine were performed on a weekly basis. A flexible dosing scheme was used during which physicians could alter medication dose based on withdrawal symptoms and urinalysis results. Neither medication was found to be associated with liver enzyme levels. In version 2 of this study, a text file containing 7704 SNPs with large allele frequency discrepancy as compared to 1000 Genomes is included. Users have the option to exlude these 7704 SNPs.

  Study phs001135

• ucfDNA workflows for molecular profiling of malignant disease

  Urinary cell-free DNA (ucfDNA) is a promising liquid biopsy analyte obtained by a non-invasive sampling method, particularly valuable in urological cancers due to the proximity of biofluids to the tumor site. However, extremely high fragmentation and low abundance of ucfDNA pose significant analytical challenges. Improper handling and storage can severely affect ucfDNA quality, necessitating optimized pre-analytical workflows for clinical applications. We evaluated multiple pre-analytical workflows, including urine stabilization approaches against unstabilized urine samples. Our results demonstrated that without stabilization, ucfDNA degraded rapidly and minimal quantities remaining after 72 hours. In contrast, urine stabilization preserved ucfDNA integrity, enabling successful downstream analyses, including digital PCR and next-generation sequencing, for mutation detection in cancer-related genes and genome wide copy number profiling. These findings underscore the critical role of stabilization for a reliable ucfDNA analysis and highlight its potential in molecular diagnostics as a complementary tool to plasma-based liquid biopsies.

  Study EGAS50000001093

• The ICGC-TCGA DREAM Somatic Mutation Calling - Tumour Heterogeneity Challenge

  Tumors are composed of many different cell types, ranging from the normal tissue micro-environment, infiltrating immune cells and tumour cells. This group of tumour cells is itself intrinsically highly heterogeneous, driven by the rapid mutation rate of cancer cells to become a mixture of different sub-populations. These different types of cells, called subclones, have different sets of mutations in their DNA. Because some subclones evolve from others, many subclones share mutations. While it is increasingly easy to determine what mutations are present in the tumor, it remains very difficult to determine which subclones have which mutations. The task of assigning mutations to subclones is called subclonal reconstruction.The ICGC-TCGA DREAM Somatic Mutation Calling - Tumour Heterogeneity Challenge (SMC-Het) is an international effort to improve standard methods for subclonal reconstruction: to quantify and genotype each individual cell population present within a tumor. The goal of this challenge is to identify the best subclonal reconstruction algorithms and to identify the conditions that affect their performance.

  Study EGAS00001002092

• Successful Clinical Response in Pneumonia Therapy (SCRIPT)

  The goal of this study is to iteratively identify, validate and refine biomarkers to predict clinical failure, and identify novel targets for therapy, beyond traditional antibiotics, for patients with severe pneumonia requiring intubation, including severe community-acquired pneumonia (CAP), hospital-acquired pneumonia, and ventilator-associated pneumonia (HAP/VAP). We hypothesize that factors within the alveolar microenvironment in many patients with pneumonia prevent the active process of pneumonia resolution.The major emphasis will be on HAP. Mechanically ventilated CAP patients are a very high-risk group for subsequent VAP, and therefore CAP samples will be included to determine baseline bacteria, microbiome, and host defense patterns for those that do or do not develop HAP/VAP. Hospital-acquired pneumonia is the leading cause of death from nosocomial infections. Even in patients receiving pathogen-appropriate therapy, reported clinical failure rates are increasing, approaching 50% in recent clinical trials. Current approaches to improve outcomes in patients with pneumonia almost exclusively focus on the development of antibiotics to address the problem of resistance. However, the prevalence of antibiotic-resistant pathogens is insufficient to explain the high rates of clinical failure. Instead, we hypothesize that factors within the alveolar microenvironment in many patients with pneumonia prevent the active process of pneumonia resolution. These factors include pathogen-specific adaptations to the injured lung that modulate the innate and adaptive immune response, as well as changes to the alveolar microbiome, driven by selective pressure within our modern intensive care units. Understanding this complex adaptive system requires the integration of clinical information with unbiased measures of the host, pathogen, and microbiome changes within the alveolar microenvironment. These measures must be repeated over time to identify factors that distinguish successful from failed therapy for pneumonia sufficiently early during the clinical course to allow for effective interventions. To address this challenge, we have assembled a talented group of investigators in the Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center. We will leverage our routine clinical practice of safe alveolar sampling in mechanically ventilated patients with pneumonia with repeated non-bronchoscopic bronchoalveolar lavage (NBBAL) sampling over the course of pneumonia. From this fluid, we will combine flow cytometry with multi-omic technologies (cell population-specific transcriptomics, epigenomics, shotgun microbiome sequencing, and pathogen-specific sequencing). Our systems scientists will integrate these genomic data with robust clinical -omics with the goal of identifying biomarkers that can be prospectively tested in patients and causally evaluated in humanized mouse models.The addition of a pooled sample artificially increases the number of automatically computed subjects by one.

  Study phs002300

• Genetic defects in familial renal disorders

  Several different genes cause, when mutated, increased urinary phosphate excretion and hypophosphatemia leading to rickets/osteomalacia; however, the majority of phosphate-wasting disorders has not yet been defined at the molecular level. Identification of phosphate-regulating genes has provided important novel insights into the mechanism contributing to phosphate homeostasis, which remains incompletely understood. We therefore pursue exome-wide nucleotide sequence analysis to define the underlying mutations, which is expected to provide novel insights into the regulation of this important mineral. Virtually nothing is known about the genetic mutations that cause non-syndromic structural abnormalities involving the urinary tract, which represent about 50% of the causes of end-stage renal disease (ESRD). The completion of the human genome project and the technological advances that allow low cost whole exome sequencing have now made it feasible to readily search for the cause of different inherited disorders in humans, particularly if clinical information and genomic DNA is available from larger kindreds with multiple affected members that can be used for mapping the disease-causing genetic locus. Furthermore, catalogs were generated that document the expression profiles of numerous genes during embryonic, fetal, and postnatal development, thereby supporting the exploration of kidney involvement in animal models of different diseases and in human genetic syndromes. We therefore plan to define the mechanisms leading to inherited disorders of the urogenital tract and the kidneys by establishing the causative genetic defects through a combination of genetic mapping and whole exome sequencing. Hajdu-Cheney Syndrome (HCS) is a rare autosomal-dominant skeletal disorder characterized by severe osteoporosis, acroosteolysis of the distal phalanges, renal cysts and other abnormalities. Our goal is to identify the genetic cause of HCS using exome sequencing. Opsismodysplasia is a very rare recessive spondylometaphyseal dysplasia characterized by delayed epiphyseal ossification, shortness of bones and sometimes low serum phosphate levels. Discovery of the causing mutation will give us insights into the pathogenesis of this often lethal disease.

  Study phs000477

• Genomics of Hepatocellular Carcinoma

  Despite the growing incidence of hepatocellular carcinoma (HCC) due to increased hepatitis C virus infection and non-alcoholic steatohepatitis in Western populations, the genetic determinants of this cancer have yet to be established. A minority (15-20%) of HCC occurs in livers without cirrhosis or other chronic disease. Because the liver is functionally preserved in these patients and surgical resection of the tumor may be performed safely, and because of the scarcity of livers available for transplantation, non-cirrhotic patients undergo surgical resection for HCC treatment. These resected tumors present investigatory opportunities in two ways: First, they provide tumor specimen which have not been treated with chemotherapy and embolization. Second, the absence of cirrhosis may provide an unconfounded background from which to investigate the genetic tumorigenesis of HCC. In livers with cirrhosis, genetic instability is prevalent as assessed by assays for microsatellite instability, loss of heterozygosity and aberrant DNA methylation. In contrast, in livers without cirrhosis, the non-tumor tissue surrounding HCC have been found to have fewer genetic aberrations. It has been postulated that the pathologic process of cirrhosis may result in the accumulation of many "passenger"; as well as "driver" mutations, and that the examination of the HCC cancer genome may be facilitated in non-cirrhotic livers because of the absence of an accumulated background noise of mutations.

  Study phs001106

• Whole exome and transcriptome analysis of UV-exposed epidermis and carcinoma in situ reveals early drivers of carcinogenesis

  Squamous cell carcinoma in situ (SCCIS) is a prevalent precancerous lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Although SCCIS is common, its pathogenesis remains poorly understood. To better understand SCCIS development, we performed laser-captured microdissection of human SCCIS and adjacent epidermis to isolate genomic DNA and RNA for next generation sequencing. Whole exome sequencing (WES) identified UV-signature mutations in multiple genes including Notch 1-3 (GeneID:4851, GeneID:4853, GeneID:4854) in the epidermis and SCCIS and oncogenic TP53 (GeneID:7157) mutations in SCCIS. Novel gene families, including SCHLAFEN genes, contained UV/oxidative-signature disruptive (UVD) epidermal mutations that manifested positive selection in SCCIS. The frequency and distribution of NOTCH and TP53 mutations indicate that NOTCH mutations may precede TP53 mutations. RNA sequencing identified 1166 differentially expressed genes; the top 5 enriched GO biological processes included: 1) immune response, 2) epidermal development, 3) protein phosphorylation, 4) regulation of catalytic activity, and 5) cytoskeletal regulation. The NEURL1 ubiquitin ligase, which targets Notch ligands for degradation, was upregulated in SCCIS. Neuralized 1 protein was found to be elevated in SCCIS suggesting that increased levels could represent a novel mechanism for downregulating Notch during UV-induced carcinogenesis. The data from DNA and RNA sequencing of epidermis and SCCIS provide insights regarding SCCIS formation.

  Study phs002019

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

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

  Study phs000972

• ApoA-1 and Atherosclerosis in Psoriasis

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

  Study phs003231

• Selenium Chemoprevention: Benefits and Harms

  Selenium is a trace element that may have anti-carcinogenetic effect, but heterogenous treatment effects have been observed. This genome-wide association study investigates if genetic variation modifies the effect of selenium chemoprevention in the Selenium and Celecoxib Trial, a randomized, double-blind, placebo-controlled trial conducted at the University of Arizona Cancer Center. The objective of the clinical trial was to determine whether daily intake of 200 µg/d of selenium as a supplement could reduce the risk for developing metachronous colorectal adenomas. The study participants were recruited between 2001 and 2011. Genome-wide association study was performed for 1,323 study participants who provided blood sample at the time of study entry.

  Study phs002283

• The Genomic Analysis of Medulloblastoma

  Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children's Research Hospital. We have found several novel mutations which appear subtype specific. These mutations were checked for frequency in a separate tumor cohort of 56 children with medulloblastoma, also treated on the St. Jude Medulloblastoma 2003 trial, and were tested in several animal models of medulloblastoma for proof of oncogenic potential.

  Study phs000409

• Genomic Psychiatry Cohort (GPC) Whole Genome Sequencing and Genotyping Study

  The Center for Genomic Psychiatry at the University of Southern California (USC), SUNY Downstate and an extensive network of academic medical centers have created the Genomic Psychiatry Cohort (GPC). The GPC consists of a large clinical cohort of patients with schizophrenia, bipolar disorder, and healthy controls. The data generation of genotyping and whole genome sequencing of the GPC has been done in collaboration with the USC and the Broad Institute of MIT and Harvard. Genome-wide association studies are being performed with the samples to identify genetic risks for psychiatric disease. Genotyping is also being used to determine ancestry informative markers and replication of candidate genes. Whole genome sequencing identifies functional variants associated with disease risk.

  Study phs001020

• Genomic Landscape of High-Grade Neuroendocrine Neoplasms

  This project is a multi-omics study of high grade (grade 3) neuroendocrine neoplasms across diverse organs. Genomic analysis using low-pass whole genome sequencing for copy number analysis, whole exome sequencing and whole transcriptomic sequencing using RNAseq were performed. As high grade neuroendocrine neoplasms are highly lethal with a median survival of approximately 7 months, new insights are urgently needed for better prognosis, diagnosis and management. This study focuses on gene and pathway discoveries in this cancer, and includes samples from a diverse set of organs, including the lungs, gastroenteropancreatic tract, breast, prostate, head and neck and bladder. This study was made possible by a generous donation from The Helen B. Rodde Fund.

  Study phs002070

• Improved Detection and Identification of Microsatellite Instability Features in Colorectal Cancer

  In this study, we analyzed a series of colorectal cancers using a new sequencing technology that sequences more than 200 microsatellite regions in parallel. With this technology, we evaluated mono-, di- , tri- and tetranucleotide repeats to provide a broad spectrum of microsatellite instability (MSI) events. This deep sequencing technology provides greater than 2000X coverage and eliminates the need for PCR amplification. Because every read corresponds to a single DNA molecule, we eliminated artifacts introduced by PCR that obscured true MSI events. Also included in our analysis is a new method for detection of somatic copy number changes in 83 cancer genes, with which we can infer chromosomal instability (CIN) status.

  Study phs001914