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• Benchmarking V(D)J Repertoire Reconstruction: Bulk RNA-Seq vs PCR-Based RepSeq Validated by SMRT Sequencing

  The aim of this study is to benchmark methods for immunoglobulin repertoire profiling using human B-cell samples. We compare targeted VDJ mRNA sequencing and repertoire reconstruction from bulk RNA-seq data to PCR-independent full-length transcript sequencing using Single-Molecule Real-Time technology. The objective is to assess methodological biases and establish a robust reference framework for immunoglobulin repertoire analysis.

  Study EGAS50000001541

• Binding of Epstein Barr Virus EBNA2 Unifies Multiple Sclerosis Genetic Mechanisms

  This study is focused on multiple sclerosis (MS). MS is likely caused by a combination of genetic and environmental factors; however, the mechanisms contributing to these factors remain poorly understood. Epstein-Barr virus (EBV) in particular is a well-established environmental risk factor for MS. We have created a computational algorithm that systematically searches for common molecular mechanisms that might be impacted at multiple MS-associated loci. Using this algorithm, we have discovered that over 40% of MS-associated loci contain MS genetic variants that fall within regions of the human genome occupied by the EBV-encoded EBNA2 protein. The same MS-associated variants also impact gene expression levels of MS-associated genes in EBV-infected B cell lines. Our hypothesis is that allele-dependent binding of EBNA2 and its co-factors explains the allele-dependent risk at many MS genetic loci. Importantly, this hypothesis links the genetic associations of MS to the known molecular roles played by EBV and Notch signaling in disease processes.Subjects with and without MS were recruited into an Institutional Review Board (IRB)-approved protocol through the Cincinnati Autoimmune Registry and Repository. From each subject, DNA from peripheral blood was isolated for whole genome sequencing (WGS). These data will be used to identify genotype-dependent transcriptional regulation in cells assessed from patients and controls. This WGS data was deposited before the full integration of sequence data with other functional genomic data types.From each subject, 90 mL of blood is drawn for isolation of peripheral blood mononuclear cells from which primary B and T cells will be isolated. For each B cell isolation, an EBV-transformed B cell line will be derived.

  Study phs003240

• Somatic_mutation_and_clonal_evolution_in_premalignant_lung_disease___WGS

  Cancer is a genetic disease caused by an accumulations of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from the lung tissue of individuals with a variety of lung diseases (COPD, UIP, IPF, Emphysema, pulmonary hypertension). This will allow us to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. Smoking is a large risk factor for developing many of these lung diseases so we are particularly keen to determining whether there is evidence of a smoking signature in these patients.

  Study EGAS00001002747

• Dissecting_global_protective_immune_response_to_dengue_virus_at_a_single_cell_resolution

  1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001004980

• Genomic Characterization CS-MATCH-0007 Arm Z1D

  The CS-MATCH-0007 protocol is a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing, RNA sequencing and if possible, whole-genome, methylation and miRNA sequencing using pre-and posttreatment tumor biopsy specimens from all patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to their corresponding genomic alterations. Arm Z1D is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with MMR deficiency are treated with nivolumab. This subprotocol is one of the treatment arms in the EAY-131 trial included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood and RNA from tumor tissue. A fuller genomic landscape of tumors from these patients will enable discovery of potential molecular features correlated to clinical outcomes or lay the foundation for future studies leading to new and more effective treatments.

  Study phs001859

• Genomic Characterization CS-MATCH-0007 Arm Y

  The CS-MATCH-0007 protocol is a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing, RNA sequencing and if possible, whole-genome, methylation and miRNA sequencing using pre-and post-treatment tumor biopsy specimens from all patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to their corresponding genomic alterations. Arm Y is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with AKT mutations are treated with AZD5363. This subprotocol is one of the treatment arms in the EAY-131 trial included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood and RNA from tumor tissue. A fuller genomic landscape of tumors from these patients will enable discovery of potential molecular features correlated to clinical outcomes or lay the foundation for future studies leading to new and more effective treatments.

  Study phs001904

• Genomic Characterization CS-MATCH-0007 Arm H

  The CS-MATCH-0007 protocol is a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from all patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to their corresponding genomic alterations. Arm H is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with BRAF V600K/V600E mutations are treated with Dabrafenib and Trametinib. This subprotocol is one of the treatment arms in the EAY-131 trial included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood and RNA from tumor tissue. A fuller genomic landscape of tumors from these patients will enable discovery of potential molecular features correlated to clinical outcomes or lay the foundation for future studies leading to new and more effective treatments.

  Study phs001888

• deCODE Genetics study on genes contributing to nicotine dependence in humans

  A genome-wide association study on smoking behavior and nicotine dependence in Icelandic smokers, assessed by the number of cigarettes smoked per day, smoking initiation and degree of dependence on nicotine. The number of cigarettes smoked per day was ascertained through questionnaires given to individuals participating in multiple disease projects at deCODE Genetics (n=16,483). Smoking initiation was analyzed by comparing those that have ever smoked (n=16,483) versus those that have never smoked (n=21,667). The nicotine dependence analysis included 3,435 nicotine dependent cases (score 4 or higher on Fagerstrom Test for Nicotine Dependence (FTND) or endorsement of at least three of the seven Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria) and 3,344 low-quantity smokers as controls.

  Study phs000393

• Diverse modes of genomic alterations in hepatocellular carcinoma

  Hepatocellular carcinoma is the most prevalent type of liver cancer. We intended to study the genomic landscape of this disease. We conducted whole-genome, exome and transcriptome sequencing for 42 patients. We show diverse modes in which the HCC genome is affected in these patients, including well-known and novel mutations, structural variations, and Hepatitis B-virus integration into the genome.

  Study EGAS00001000824

• NPC Genome Project

  Niemann-Pick disease, type C1 (NPC1) is neurodegenerative disorder due to pathological variants of NPC1. NPC1 is predominately a pediatric/adolescent disorder, although adult onset cases have been described. The NPC1 protein functions to move unesterified cholesterol from the endolysosomal lumen to make it bioavailable for cellular function. Impaired NPC1 function results in endolysosomal accumulation of unesterified cholesterol and other lipids. The NPC1 phenotype is extremely heterogeneous, both with respect to age of onset and sign/symptom complex. Comparison of individuals homozygous for the common p.I1061T variant and affected siblings suggests that other genes can significantly modify the clinical phenotype. The goal of this project is to obtain genome sequencing on ~200 individuals with NPC1 in order to facilitate identifying potential genetic modifiers.

  Study phs003214