19072 results for "Buy fc coins Buyfc26coins.com is EA Sports official for FC 26 coins They are the best FC seller..nEoY"

in 40.35 milliseconds.

• Genomic sequencing of Pediatric Rhabdomyosarcoma

  Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood accounting for approximately 350 newly diagnosed cases yearly in the United States. With the development of multimodal chemotherapy regimens, relapse-free survival rates have improved to 70-80% in patients with localized disease albeit with significant toxicity. Unfortunately, despite aggressive treatment, patients with metastatic or recurrent disease continue to suffer from high mortality. Further characterization of the genetic events underlying this tumor type is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. In a collaborative effort between the National Cancer Institute, the Children's Oncology Group, and the Broad Institute, we use a combination of whole-genome and whole-exome sequencing to characterize the landscape of somatic alterations in 147 tumor/normal pairs.

  Study phs000720

• H3Africa Chip Design - Aim of designing a cost-effective GWAS chip with content appropriate for use in genomics studies of individuals from the African continent.

  Since it is recognized that currently available chips may not be ideally suited to studying African populations, the H3Africa Genome Analysis working group undertook the task of designing a cost-effective GWAS chip with content appropriate for use in genomics research studies of individuals from the African continent. To address gaps in sequence data for some of the African populations being studied in H3Africa projects, a high coverage whole genome sequence dataset was generated at the Baylor College of Medicine with samples provided by H3Africa PIs and collaborators, funded by the National Institutes of Health. This dataset includes 350 high coverage and 160 medium coverage whole genome sequences from 348 populations. The data is accompanied by minimal metadata, including country, ethnic group and sex.

  Study EGAS00001002976

• Intrapatient tumor heterogeneity and clonal evolution in metastatic salivary gland cancer: an autopsy study: access to data

  Funded by the Radboud Oncology Fund and the Dr. C.J. Vaillant Fund, the Salivary Gland Cancer Autopsy research group (Research Group) has sequenced DNA of 17 salivary gland cancer samples of and three healthy control samples from three patients with salivary gland cancer. This research project is led by Carla M.L. van Herpen from Radboud University Medical Centre in Nijmegen, the Netherlands (“Radboudumc”). The DNA sequencing data have been used for an analysis of intrapatient tumor heterogeneity and clonal evolution of metastatic salivary gland cancer. The Research Group is willing to consider applications from third party researchers for access to the DNA sequence data. Access to the data will be granted to qualified researchers for approved use. Access to DNA Sequencing Data is available by application to the Data Access Committee (DAC). Researchers granted access to DNA Sequencing Data must feedback the results of their research to the Research Group, after publication in accordance with the Research Group publication policy set forth in the Data Access Agreement.

  Dac EGAC50000000792

• Acute Respiratory Distress Network (ARDSNet) Study 02 Late Steroid Rescue Study (LaSRS) (ARDSNet-LaSRS-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Biospecimens: Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from ARDSNet-LaSRS include BAL Slides, Bronchial Lavage, and Plasma. Please note that use of biospecimens in genetic research is subject to a tiered consent.Objectives: Since previous reports suggested that corticosteroids may improve survival, this project was developed as a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.Background: Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death.Participants: There were 180 participants.Conclusions: The results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (NEJM April 20, 2006; Vol 354, No. 16, pp 1671-84).

  Study phs003769

• Patient-derived organoids as predictive models for drug testing and repurposing in glioblastoma therapy

  Glioblastoma multiforme (GBM) remains a highly aggressive brain tumor with limited treatment options and poor prognosis. Temozolomide (TMZ) is the only approved first-line therapy, but frequent resistance limits its efficacy, highlighting the urgent need for alternative treatments. Patient-derived glioblastoma organoids (GBOs) offer a promising preclinical model for personalized drug testing and therapy development.

  Study EGAS50000001221

• Genomic Studies of Gilles de la Tourette Syndrome

  This study consists of three components. The first component includes genome-wide association study (GWAS) data on 695 TS cases and 198 ancestry matched controls from the first TS GWAS of 1285 TS cases and 4964 ancestry matched controls. The second component includes genome-wide association study (GWAS) data on 2106 TS cases from the second TS GWAS of 2716 TS cases and 3762 ancestry matched controls. The third component consists of 438 individuals representing 146 probands with DSM-IV-TR diagnosed Tourette Syndrome and their parents (146 complete parent-offspring trios). These individuals are part of the whole exome sequencing study, aiming to use whole exome sequencing of TS parent-offspring to identify de novo protein-truncating variants (PTVs) that are present in the child with TS but not in either parent. All subjects were collected by the Tourette Association of America International Consortium for Genetics (TAAICG) at seven sites in the United States and Canada. Both affected individuals and unaffected relatives were assessed for the presence of Tourette Syndrome and Chronic (Persistent) Tic Disorder (CTD) using a standardized, semi-structured interview, which has high clinical validity and reliability for the diagnoses of TS and CTD (TSAICG, Am J Hum Genet, 2007 (PMID: 17304708)); Darrow et al., Psychiatric Research, 2015 (PMID: 26054936)).

  Study phs001380

• Genomic Evolution of Breast Cancer Metastasis and Relapse

  Recurrent breast cancer is almost universally fatal. We characterize 170 patients locally relapsed or distant metastatic cancers using massively parallel sequencing. We identify that the relapse-seeding clone disseminates late from the primary tumor. TP53 and AKT1 appear to be enriched in ER-positive cancers predisposed to relapse. Mutation acquisition continues at relapse as the same mutation signatures continue to operate and new signatures, such as that caused by radiotherapy appear de novo. In 49% of cases we identify drivers mutations private to the relapse and these are sampled from a wider range of cancer genes, including SWI-SNF complex and JAK-STAT signaling.

  Dataset EGAD00001002697

• RNA_seq_of_Toxoplasma_gondii_response_in_human_macrophages

  Toxoplasmosis is a zoonotic disease caused by a ubiquitous protozoan parasite called Toxoplasma gondii, which caninfect all mammal and bird species throughout the world. seroprevalence varies widely between countries. Studieshave estimated that between 7-34% of people in the UK have been infected with T. gondii. The vast majority of thesepeople will not have noticed any symptoms, however about 10% of people develop a mild to moderate self limitingflu-like illness. Following the acute active stage of the infection the parasite persists in the body in the form of cysts,particularly in heart and skeletal muscle and nervous system tissues, for many years, and usually for life. Inimmunocompetent persons these cysts do not pose a health risk. We will use RNA-seq to quantify the transcriptionalresponse of macrophages to T gondii infection.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001001708

• RNA-seq study of longitudinal blood cell samples from children at risk of type 1 diabetes

  The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding auto-antibody positivity or reflect progressive b-cell destruction. Here we report the mRNA sequencing–based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4, CD8 cell fractions and unfractionated PBMC samples longitudinally collected from seven children who developed beta-cell autoimmunity (Case subjects) at a young age and matched control subjects.

  Study EGAS00001004071

• Profiling of childhood neuroblastoma and the immune microenvironment by single-cell sequencing of RNA and TCR

  Neuroblastoma tumor cells and their tumor microenvironment are studied by single-cell RNA sequencing of primary neuroblastoma tumors and neuroblastoma-infiltrated tissues/metastases. Both diagnostic samples, taken pre-treatment and samples taken after induction chemotherapy at surgical resection and biopsies from relapse samples are included.  For a number of patients single-cell RNA sequencing of blood samples (controls) are included and additionally we performed single-cell T cell receptor sequencing (TCR) on the tumor and blood samples. With this study, we will focus on identifying differences in tumor cells and their (immune) microenvironment 1) before and after treatment or at relapse and 2) between primary tumors and infiltrated tissues/metastases. Moreover, with TCR sequencing we aim to unveil immune cell dynamics in patients with neuroblastoma.

  Study EGAS00001006823

• DAC_For_MPN

  This is the DAC for the MPN data set from Milena Kalmer.

  Dac EGAC50000000531

• University of North Carolina at Chapel Hill (UNC) Hepatocellular Carcinoma Study by Exome Sequencing (HCCSES)

  Genetic alterations in specific driver genes lead to disruption of cellular pathways and are critical events in the instigation and progression of hepatocellular carcinoma. As a prerequisite for individualized cancer treatment, we sought to characterize the landscape of recurrent somatic mutations in hepatocellular carcinoma. We performed whole exome sequencing on 87 hepatocellular carcinomas and matched normal adjacent tissues to an average coverage of 59x. The overall mutation rate was roughly 2 mutations per Mb, with a median of 45 non-synonymous mutations that altered the amino acid sequence (range 2 to 381). We found recurrent mutations in several genes with high transcript levels: TP53 (18%), CTNNB1 (10%), KEAP1 (8%), C16orf62 (8%), MLL4 (7%) and RAC2 (5%). Significantly affected gene families include the nucleotide-binding domain and leucine rich repeat containing family, calcium channel subunits, and histone methyltransferases. In particular, the MLL family methyltransferases for histone H3 lysine 4 were mutated in 20% of tumors. Conclusion: The NFE2L2-KEAP1 and MLL pathways are recurrently mutated in multiple cohorts of hepatocellular carcinoma.

  Study phs000627

• Prevalence and Clinical Characteristics of hearing loss caused by MYH14 mutation

  Mutations in MYH14 are reported to cause autosomal dominant nonsyndromic hereditary hearing loss (ADNSHL), and 35 variants have been reported to cause hearing loss in various ethnic groups, but the information on prevalence as well as clinical features are fragmented. In this study, genetic screening for MYH14 variants was carried out using a large series of Japanese hearing loss patients to reveal the information. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 8074 (including 1336 ADNSHL) unrelated Japanese hearing loss patients (probands) to identify genomic variations responsible for hearing loss. We identified 20 patients with 14 mutations from 15 pedigrees. The prevalence was proved to be 0.19% (15/8074) among hearing loss patients, and 1.12% (15/1336) among ADNSHL patients. The 12 mutations out of 14 mutations identified were novel. The patients typically showed late onset, slowly progressive modelate flat-type hearing loss. The clinical information revealed by the present study would contribute to further diagnosis and management of MYH14-associated hearing loss.

  Study JGAS000323

• Copy-number signatures and mutational processes in ovarian carcinoma

  This study contains the data underlying our approach for copy-number signature identification in high-grade serous ovarian cancer. The samples studied are part of the BriTROC-1 consortium, a national study into relapsed high-grade serous ovarian cancer. The dataset consists of shallow-whole genome sequencing of 300 samples from 143 patients with match tagged-amplicon sequencing of TP53. The study also contains deeper whole-genome sequencing of 48 cases.

  Study EGAS00001002557

• Identification of responsible genes and development of standardized medicine for familial breast cancer by genetic analysis with NGS technology

  Aims: To clarify risk of germline variants of known causal genes for Hereditary Breast Ovarian Cancer Syndrome in Japan by combinatorial analysis of somatic and germline variants in the breast cancer tissue. Methods: Target caputure analysis by using Illumina HiSeq 2000; the panel genes are 119 genes including 30 HBOC known causal genes. Participants/Materials: 108 whole blood and 124 primary tumor samples from familial breast cancer patients.

  Study JGAS000224

• WGS of Five Pancreatic Cancer Patients-Tumor and Normal

  We performed whole genome sequence on tumor-derived and normal cell lines from patients who had terminal pancreatic cancer and consented for rapid autopsy upon their death. The 5 samples are from Dr. Christine Iacobuzio-Donahue's rapid autopsy program as reported in Boland et al. (PLOSOne, 2024, In Press, PMID 38352348).

  Study phs003775

• Center for Craniofacial and Dental Genetics: Exome Sequencing of Orofacial Cleft Families

  Orofacial Clefts (OFCs) are genetically complex structural birth defects caused by genetic factors, environmental exposures, and their interactions. OFCs are the most common craniofacial anomalies in humans. Affect about 1 in 800 newborns, OFCs are also one of the most common structural birth defects worldwide. OFCs can impose a substantial personal cost resulting from the associated emotional and financial burden. On average a child undergoes 6 surgeries, spends 30 days in hospital, receives 5 years of orthodontic treatment, and participates in ongoing speech therapy, leading to an estimated total lifetime treatment cost of about $200,000. Individuals born with an OFC have higher infant mortality (especially in developing countries with limited access to care), higher mortality rates at all other stages of life, increased incidence of mental health problems, and higher risk for other disorders (notably including breast, brain, and colon cancers). Prior genetic studies have focused on the contribution of common genetic variants through genome-wide linkage and association studies. These studies have revealed a significant etiologic heterogeneity. One promising approach to dissect the etiology of OFCs into focus on subclinical phenotypic features present in the non-cleft family members of affected individuals. These subclinical features are subtle phenotypic features that may represent mild manifestations of the same risk genes; thus, their inclusion in family-based studies may clarify the inheritance patterns in OFC families. In this project, we conducted whole exome sequencing in multiplex families with both overt OFCs and subclinical phenotypes to identify high-impact genes causing OFCs.

  Study phs001675

• Illumina RNA sequencing for HLA expression qauntification

  In this study, we quantified mRNA expression levels of HLA class I and II genes from peripheral blood samples of 50 healthy individuals. The gene- and allele-specific mRNA expression was assessed using unique molecular identifiers, which enabled PCR bias removal and calculation of the number of original mRNA transcripts. We identified differences in mRNA expression between different HLA genes and alleles. Our results suggest that HLA alleles are differentially expressed and these differences in expression levels are quantifiable using RNA sequencing technology.

  Study EGAS00001004931

• RNA sequencing of end-stage kidney disease patients with COVID-19

  This dataset contains paired RNA sequencing data for end-stage kidney disease (ESKD) patients on dialysis. There are two cohorts. The first includes 179 samples from 51 COVID-19 patients recruited during the initial phase of the COVID-19 pandemic (April-May 2020) and 55 non-infected ESKD patients as controls. 17 patients initially recruited as controls as part of the Wave 1 cohort were later infected with COVID-19 in January-March 2021. We acquired a total of 90 samples during the acute infection and convalescent samples for 12 of the 17 patients following the acute COVID-19 episode. RNA-seq counts and full clinical metadata for these cohorts are available without restriction from Zenodo (https://doi.org/10.5281/zenodo.6497251).

  Dataset EGAD00001009752

• WES sequencing of metastatic colorectal cancer patient-derived xenografts with known response to irinotecan.

  Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we expand a pre-existing collection (https://doi.org/10.1158/2159-8290.CD-24-0556) of molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. We complemented previous mutational profiles with whole exome sequencing for 46 xenografts with known response to irinotecan.

  Study EGAS50000001484

• Bulk RNA sequencing of metastatic colorectal cancer patient-derived xenografts with known response to irinotecan

  Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we expand a pre-existing collection (https://doi.org/10.1158/2159-8290.CD-24-0556) of molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. We complemented previous expression profiles with bulk RNAseq for 38 xenografts with known response to irinotecan.

  Study EGAS50000001485

• Molecular analysis of cancer genomes in children with Lynch syndrome: exploring causal associations

  Lynch syndrome (LS) predisposes to cancer in adulthood and is caused by heterozygous germline variants in a mismatch repair (MMR) gene. Recent studies show an increased prevalence of LS among children with cancer, suggesting a causal relationship. For LS-spectrum (LSS) cancers, including high-grade gliomas and colorectal cancer, causality has been supported by typical MMR-related tumor characteristics, but for non-LSS cancers, causality is unclear. This dataset contains 5 patients with Lynch Syndrome from the INFORM registry.

  Study EGAS00001007146

• Metastatic Colorectal Adenocarcinoma Tumor Purity Assessment from Whole Exome Sequencing Data

  As molecular medicine wields greater and greater influence on cancer patient care, including therapeutic selection, it becomes increasingly important to understand the power and deficiencies of computational tools used in decision making processes. Here we use a set of unselected metastatic colorectal tumor samples in a head-to-head comparison between the calculation of stromal content by a board certified pathologist, versus that derived from whole exome sequencing and purity assessment by a variety of common computational methods. We find that in about 1/2 of the samples the computational methods each do a poor job of assessing the percent stromal contamination, and as a result, tumor variant allele frequencies (VAFs) are low or undetected, whereas analysis of organoids derived from the same tumors yielded much higher VAFs in keeping with their lower stromal content. The whole exome sequence of our samples is available via dbGaP, accession phs003059.v1.p1.

  Study phs003059

• Gain of function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions

  DNA methylation and Polycomb are key factors in the establishment of vertebrate cellular identity and fate. Here we report de novo missense mutations in DNMT3A, encoding the DNA methyltransferase DNMT3A, that cause microcephalic dwarfism, a hypocellular disorder of extreme global growth failure. Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2/3, and alter DNA methylation in patient cells. Polycomb-associated DNA methylation canyons/valleys, hypomethylated domains encompassing developmental genes, become methylated with concomitant depletion of H3K27me3 and H3K4me3 bivalent marks. Such de novo DNA methylation occurs during differentiation of Dnmt3aW326R pluripotent cells in vitro, and is also evident in Dnmt3aW326R/+ dwarf mice. We therefore propose that the interaction of the DNMT3A PWWP domain with H3K36me2/3 normally limits DNA methylation of polycomb-marked regions. Our findings implicate the interplay between DNA methylation and polycomb at key developmental regulators as a determinant of organism size in mammals.

  Study EGAS00001003231

• Gain of function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions

  DNA methylation and Polycomb are key factors in the establishment of vertebrate cellular identity and fate. Here we report de novo missense mutations in DNMT3A, encoding the DNA methyltransferase DNMT3A, that cause microcephalic dwarfism, a hypocellular disorder of extreme global growth failure. Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2/3, and alter DNA methylation in patient cells. Polycomb-associated DNA methylation canyons/valleys, hypomethylated domains encompassing developmental genes, become methylated with concomitant depletion of H3K27me3 and H3K4me3 bivalent marks. Such de novo DNA methylation occurs during differentiation of Dnmt3aW326R pluripotent cells in vitro, and is also evident in Dnmt3aW326R/+ dwarf mice. We therefore propose that the interaction of the DNMT3A PWWP domain with H3K36me2/3 normally limits DNA methylation of polycomb-marked regions. Our findings implicate the interplay between DNA methylation and polycomb at key developmental regulators as a determinant of organism size in mammals.

  Study EGAS00001003232

• Biomarker Research for Anti EGFR Monoclonal Antibodies by Comprehensive Cancer Genomics

  The purpose of this study is to explore new biomarkers for predicting the effectiveness of an anti-epidermal growth factor receptor (anti-EGFR) antibody in patients with advanced colorectal cancer. The investigation involves analyzing the entire exome, conducting a genome-wide association study (GWAS), and analyzing copy number variations (CNVs) using single nucleotide polymorphism (SNP) arrays. Genetic material from both cancerous and non-cancerous tissues, as well as blood samples from patients who received the antibody treatment, will be used. The goal is to identify genetic mutations and SNPs associated with treatment efficacy and adverse events, and to assess the correlation between their presence and treatment effectiveness using statistical methods.

  Study JGAS000779

• The Innate Immune Response as a Therapeutic Target for Cutaneous Leishmaniasis

  The overall goal of the proposed project is to identify innate host functions that contribute to cure or failure during antileishmanial drug therapy, and their related biomarkers. Results from this project enabled the identification of host-specific predictive and prognostic signatures of therapeutic responsiveness, and the bases for rational selection of host-targeted therapeutics that redirect inflammation and revert pathogenicity. Through sequential transcriptomic profiling of blood monocytes (Mo), neutrophils (Nφ), and eosinophils (Eφ) over the course of systemic treatment with meglumine antimoniate, we discovered that a heightened and sustained Type I interferon (IFN) response signature is a hallmark of treatment failure (TF) in Cutaneous Leishmaniasis (CL) patients. The transcriptomes of pre-treatment, mid-treatment and end-of-treatment samples were interrogated to identify predictive and prognostic biomarkers of TF. Results from this study instigate the evaluation of Type-I IFN responses as new immunological targets for host-directed therapies for treatment of CL, and highlight the feasibility of using transcriptional signatures as predictive biomarkers of outcome for therapeutic decision making.

  Study phs003545

• Research Study into The Molecular Genetics of Hereditary Neuropathies

  Identification of genes implicated in inherited neuropathy through collecting and sequencing multiple generation families with inherited neuropathy. Patients in this study have been evaluated for demyelinating peripheral neuropathy as determined by decreased motor nerve conduction velocities in the sural nerve. Patients have also been screened for mutations in all genes implicated in demyelinating peripheral neuropathy and are expected to have previously unidentified mutations. Exome (WES) sequencing for two patients affected with inherited neuropathy. VCF files with called variants for each de-identified patient have been submitted.

  Study phs001351

• Single cell transcriptome sequencing of the developing human embryonic meninges

  There are no effective medical therapies for meningiomas, partly due to our limited understanding of their cellular origin and composition For this purpose, we generated data to make a comprehensive reference single cell and spatial transcriptomic atlas of human fetal meninges. Samples of meninges from human embryos of post-conceptional week (PCW) 5.0-13.0 were dissected and subject to 10Xgenomics chromium single cell RNA sequencing with the purpose of identifying cell types and gene expression programs for normal meninges development, Furthermore, this dataset should help discover cells of origin for meningiomas.

  Study EGAS50000000980

• Development of blood-based biomarkers for precision medicine in castration-resistant prostate cancer

  Cell-free DNA (cfDNA) testing is emerging as a tool for cancer precision medicine. However, little is known about the clinical significance of low-frequency variants detected in circulating cell-free tumor DNA (ctDNA) from castration-resistant prostate cancer (CRPC) patients. We conducted targeted sequencing of cfDNA and paired leukocyte DNA from CRPC patients using molecular barcodes, and ctDNA variants with a variant allele frequency ??? 0.1% were detected using an in-house pipeline.

  Study JGAS000330

• Medulloblastoma exome sequence analysis

  Medulloblastomas are the most common malignant brain tumors in children. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles. Here, we utilized whole exome hybrid capture and Illumina sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, to our knowledge novel findings in medulloblastoma and all cancer. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma. "Reprinted from 'MEDULLOBLASTOMA EXOME SEQUENCING UNCOVERS SUBTYPE-SPECIFIC SOMATIC MUTATION', with permission from Nature"

  Study phs000504

• 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

• Pharmacogenomics of Metformin Dose Response in T2DM Patients

  Type 2 Diabetes Mellitus (T2DM) is a chronic and sometimes debilitating disease that affects millions of adults in the USA. Metformin is commonly prescribed for T2DM; yet some T2DM patients do not tolerate it or respond well. This pharmacogenomics study will examine response, as both change in T2DM patients' weight and hemoglobin A1c (HbA1c) levels, to different doses of metformin, by extracting this data from the electronic health record (EHR), for T2DM subjects taking metformin found by prescription orders in the EHR, and identified as cases with the EHR phenotype algorithm published by Kho et. al. in 2012 (PMID: 22101970 as part of the eMERGE (electronic Medical Records and Genomics; dbGaP phs000237, phs000297, phs000360, phs000368, phs000888, and phs000948) project.

  Study phs000984

• GATCI whole genome somatic variants (MuTect)

  Sequence data in fastq format was aligned to the GRCh38 reference genome with BWA-MEM and preprocessed with GATK for indel realignment and base quality score recalibration. Aligned sequence was analyzed with MuTect to generate somatic variant calls. Variant calls are in VCF format. In total, there are 60 tumour samples from 38 patients, all with matched normal. Further details can be found in the vcf headers.

  Dataset EGAD00001005822

• GATCI whole genome somatic variants (SomaticSniper)

  Sequence data in fastq format was aligned to the GRCh38 reference genome with BWA-MEM and preprocessed with GATK for indel realignment and base quality score recalibration. Aligned sequence was analyzed with SomaticSniper to generate somatic variant calls. Variant calls are in VCF format. In total, there are 60 tumour samples from 38 patients, all with matched normal. Further details can be found in the vcf headers

  Dataset EGAD00001005818

• GATCI whole genome germline variants

  Sequence data in fastq format was aligned to the GRCh38 reference genome with BWA-MEM and preprocessed with GATK for indel realignment and base quality score recalibration. Aligned sequence was analyzed with GATK HaplotypeCaller to generate germline variant calls. Variant calls are in VCF format. In total, there are 60 tumour samples from 38 patients, all with matched normal. Further details can be found in the vcf headers

  Dataset EGAD00001005817

• NHLBI TOPMed: The Genetics and Epidemiology of Asthma in Barbados

  Asthma is a complex disease where the interplay between genetic factors and environmental exposures influences susceptibility and disease prognosis. Asthmatics of African descent tend to have more severe asthma and more severe clinical symptoms than individuals of European ancestry. The baseline prevalence of asthma in Barbados is high (~20%), and from admixture analyses, we have determined that the proportion of African ancestry among Barbadian founders is similar to U.S. African Americans, rendering this a unique population to disentangle the genetic basis for asthma disparities among African ancestry populations in general. We therefore performed whole genome sequencing on 1,100 individuals from the Barbados Genetics of Asthma Study (BAGS), in order to generate additional discovery of rare and structural variants that may control risk to asthma.

  Study phs001143

• Exploring the Microbiome-Gut-Brain Axis with Respect to Psychoneurological Symptoms for Children with Solid Tumors

  The human body hosts tens of trillions of microbes, a number 10 times greater than the number of human body cells. The collection of these human-associated microbes and their genomes is called the “human microbiome”. More than 90% of these microbes live in the gastrointestinal (GI) tract, representing 500 species on average. With the development of high-throughput sequencing technology and bioinformatics tools (e.g., 16S ribosomal RNA or 16S rRNA sequencing and shotgun metagenomics analysis), recent progress has been made to elaborate the critical role that the gut microbiome plays in human health and disease. A significant disruption (dysbiosis) of the composition and function of the gut microbiome is associated with carcinogenesis, chemotherapeutic metabolism, and treatment-related symptom toxicities. The current state of science on the gut microbiome in cancer has only recently started in animal models and adults, and has not been well investigated in children diagnosed and treated for cancer, nor with respect to associations with cancer treatment-related toxicities. This proposed study will explore the hypothesis that dysbiosis of the gut microbiome is associated with cancer treatment-related GI and psychoneurological symptoms. We will collect both stool samples (for the gut microbiome) and patient-reported outcomes across chemotherapy.

  Study phs002960

• Highly prevalent NF-kappa B signaling pathway-activating somatic mutations in intracranial aneurysms

  Intracranial aneurysms (IAs) are a high-risk factor for life-threatening subarachnoid hemorrhage. Their etiology, however, remains mostly unknown. We conducted screening for somatic mutations in 65 IA tissues and identified 16 genes that were mutated with a high prevalence (92%). In particular, six genes, including PDGFRB, were mutated commonly in fusiform and saccular IAs and are linked to the NF-kappa B signaling pathway. Mutant PDGFRBs constitutively activate NF-kappa B signaling and induce inflammation-related gene expression in vitro. Spatial transcriptomics also detected similar changes in IA tissues. Virus-mediated expression of a mutant PDGFRB induces a fusiform-like dilatation of the basilar artery in mice. This study reveals a high prevalence of somatic mutations in NF-kappa B signaling genes in IAs and opens a new avenue of research toward development of its pharmacological interventions.

  Study JGAS000591

• NHLBI TOPMed: Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE)

  Started in 2007, the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) is one of the largest asthma cohort studies in the United States. Its overarching goal is to elucidate the genetic underpinnings of asthma and asthma medication treatment response. The cohort was recruited from a large health care system serving southeast Michigan and the Detroit metropolitan area, and the participants broadly represent the demographic and socioeconomic diversity of the region. Control participants (i.e., patients without a diagnosis with asthma) were recruited from the same health system and geographic region. By virtue of their health system enrollment, both asthma case and control patients have longitudinal clinical information which was routinely collected as part of their care. Both case and control patients underwent at detailed evaluation at the time of enrollment which included lung function testing and bronchodilator response. The SAPPHIRE cohort is a member of the Asthma Translational Genomics Collaborative (ATGC). The latter was selected for whole genome sequencing in Phase 3 of the National Heart Lung and Blood Institute's TOPMed Program. The SAPPHIRE sample selected for sequencing includes African American and/or Latino individuals with and without asthma.

  Study phs001467

• PIVUS study - Longitudinal transcriptomics - Advanced aging

  We performed RNA sequencing in whole-blood from the same 65 individuals from the PIVUS study at ages 70 and 80 (130 samples) to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging. Each individual has four fastq files, two for each age. Consecutive sample IDs refer to the sample individual, e.g. PIVUS003 and PIVUS004 are the age 70 and age 80 samples of the first individual.

  Dataset EGAD00001004965

• neoALTTO

  RNAseq fastq files for 254 samples for the neoALTTO study of lapatinib, trastuzumab or combination in HER2+ breast cancer patients. Those are pre-treatment baseline samples.

  Dataset EGAD00001011354

• Understanding the Biology of Language Impairment through Whole Genome Sequencing

  This study involves the whole genome sequencing of a cohort of 390 individuals assessed for language ability, IQ, and behavior as schoolchildren. The primary goal of the study is to identify genes, regulatory elements, and pathways which may underlie variation in language ability within an average population. 

  Study phs002255

• Investigation of the keratinocytic gene expression pattern in Hidradenitis suppurativa

  The underlying pathogenetic factors generating the innate immune signal necessary for T cell activation, initiation and chronification of Hidradenitis suppurativa (HS, also known as Acne inversa) are still poorly understood. Emerging evidence suggests that defective keratinocyte function critically contributes to HS disease development and progression. To elucidate the role of keratinocytes in HS lesion formation, we compared the transcriptomes of isolated lesional and perilesional HS epidermis by RNA sequencing.

  Study EGAS00001005544

• L1-Architect Project DAC

  This Data Access Committee and policies are for controlling the correct use of the omics datasets generated within the L1-Architect Project, to investigate the impact of L1 transposable elements in tumours with high and ultrahigh rates of somatic retrotransposition

  Dac EGAC50000000289

• FetalQuant-SD: Accurate quantification of fetal DNA fraction by shallow-depth sequencing of maternal plasma DNA

  Noninvasive prenatal testing using massively parallel sequencing of maternal plasma DNA has been rapidly adopted in clinical use worldwide. Fetal DNA fraction in a maternal plasma sample is an important parameter for accurate interpretations of these tests. However, there is a lack of methods involving low-sequencing depth and yet would allow a robust and accurate determination of fetal DNA fraction in maternal plasma for all pregnancies. In this study, we have developed a new method to accurately quantify the fetal DNA fraction by analysing the maternal genotypes and sequencing data of maternal plasma DNA. Fetal DNA fraction was calculated based on the proportion of non-maternal alleles at single-nucleotide polymorphisms where the mother is homozygous. This new approach achieves a median deviation of 0.6% between predicted fetal DNA fraction and the actual fetal DNA fraction using as low as 0.03-fold sequencing coverage of the human genome. We believe that this method will further enhance the clinical interpretations of noninvasive prenatal testing using genome-wide random sequencing.

  Study EGAS00001001611

• Lethal malformation syndrome

  Identification of the genetic basis of rare monogenic diseases can provide insights into disease mechanisms, biological pathways and potential therapeutic targets. Exome sequencing has proven to be a powerful, efficient strategy for the identification of the genes underlying rare Mendelian disorders. The genetic defect behind the lethal malformation syndrome under study is known in some cases and has proven useful in revealing the primary underlying defect. We have six typical unrelated families with no known mutation. The aim of this study is to identify the locus associated with this lethal malformation syndrome in these families using exome sequencing.

  Study EGAS00001000061

• Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) - OncoArray Genotypes

  Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) was one of five projects funded in 2010 as part of the NCI's Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (http://epi.grants.cancer.gov/gameon/). GAME-ON's overall goal was to foster an intra-disciplinary and collaborative approach to the translation of promising research leads deriving from the initial wave of cancer GWAS. Specific goals included replication of previous GWAS findings and identification of new susceptibility loci through meta analyses of existing GWAS data and fine mapping of identified loci to better pinpoint causal variants; and identify germline variants that are associated with risk of multiple cancers. The other four funded GAME-ON projects were: the ColoRectal TransdisciplinaryStudy (CORECT), Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), Follow-up of Ovarian Cancer Genetic Association and Interaction Study (FOCI), and Transdisciplinary Research in Cancer of the Lung (TRICL). To identify additional cancer risk loci, improve the precision of fine-mapping, and facilitate cross-cancer analyses, the GAME-ON projects and other consortia formed the OncoArray network (http://epi.grants.cancer.gov/oncoarray/), which developed and genotyped a new custom genotyping array (the "OncoArray") in large numbers of cancer cases and controls (over 400,000 samples). The OncoArray is a custom array manufactured by Illumina. The array includes a backbone of approximately 260,000 SNPs that provide genome-wide coverage of most common variants, together with markers of interest for each of the five GAME-ON cancers identified through genome-wide association studies (GWAS), fine-mapping of known susceptibility regions, sequencing studies, and other approaches. The array also includes loci of interest identified through studies of other cancer types, and other loci of interest to multiple cancer types (including loci associated with cancer related phenotypes, drug metabolism and radiation response). Additionally, SNPs relating to quantitative phenotypes such as body mass index (BMI), height, and breast density that correlate with common cancer risks are also included. The DRIVE data included under this dbGAP submission include OncoArray data from 60,015 breast cancer cases and controls genotyped at the Center for Inherited Disease Research (CIDR), University of Cambridge, National Cancer Institute, University of Copenhagen, University of Southern California and Mayo Clinic. Details on an additional approx. 80,000 breast cancer cases and controls genotyped at other centers can be found at http://bcac.ccge.medschl.cam.ac.uk/bcacdata/oncoarray/.

  Study phs001265

• UW TAN Study of Metastatic Urothelial Carcinoma

  Patients with metastatic urothelial carcinoma treated at our institution, who elected to undergo rapid autopsy at the time of death, are included in this study. These patients agreed to submit their tissue (normal samples for germline analysis [kidney or liver] as well as primary and metastatic tumor sites [urothelial carcinoma]) and the time of autopsy. Each patient signed consent to allow study of these tissues including histologic, sequencing (DNA/RNA), and implantation in to animals as able for future study.

  Study phs001797

• 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

• CATHeterization GENetics (CATHGEN)

  The CATHGEN biorepository consists of biological samples collected on 9334 sequential consenting individuals undergoing cardiac catheterization at Duke University Medical Center between 2001 and 2010 inclusive. The Institutional Review Board informed consent allowed for 50 mL of blood to be collected from fasting patients through the femoral arterial sheath during the catheterization procedure. Three 7.5 mL EDTA tubes for DNA extraction are stored at -80°C. The Duke Database for Cardiovascular Disease (DDCD) provides the bulk of the clinical data used for analysis. Follow-up includes mortality information gleaned from the National Death Index and Social Security Death Index plus follow-up phone calls and written questionnaires regarding MI, stroke, re-hospitalization, coronary re-vascularization procedures, smoking, exercise, and medication use.

  Study phs000703

• High Density SNP Association Analysis of Lung Cancer

  This research builds upon an extensive resource of a case-control study that has been ongoing at the UT MD Anderson Cancer Center since 1991. To identify risk variants for lung cancer, we conducted a genome-wide association study. Cases are newly diagnosed, histologically-confirmed patients presenting at MD Anderson Cancer and who had not previously received treatment other than surgery. Controls are healthy individuals seen for routine care at Kelsey-Seybold Clinics, the largest physician group-practice plan in the Houston Metropolitan area. This lung GWAS led to the identification of a susceptibility locus for lung cancer at 15q25.1. We used data from 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas in the discovery followed by the replication of the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, were significantly associated with risk of lung cancer with combined analysis yielded odds ratios of 1.32 (P < 1X10-17) for both SNPs. These two SNPs mapped to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5. (Nat Genet. 2008 May;40(5):616-22. PMID:18385676)

  Study phs000753

• Single-cell DNA sequencing on Pediatric MDS

  Single-cell DNA sequencing with antibody-oligonucleotide staining was performed using the Mission Bio Tapestri single-cell DNA sequencing platform, per the manufacturer’s instructions. All libraries were sized and quantified using an Agilent Bioanalyzer and pooled for sequencing on an Illumina NovaSeq6000 with 150 base-paired ending multiplexed runs. Fastq files generated by the sequencers were processed using the Tapestri Pipeline V2 and included adapter trimming, sequence alignment (BWA), barcode correction, cell finding, and variant calling (GATK v4/Haplotypecaller). FastQ files are provided for the 5 samples that were processed using the aforementioned pipeline.

  Study EGAS00001005433

• 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

• Leukemia Relapse via Genetic Immune Escape after Allogeneic Hematopoietic Cell Transplantation

  Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experience relapses because of the failure of the immunological responses to control leukemic outgrowth. Here we demonstrate, through a broad immunogenetic study, that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic defects in HLA alleles may lead to escape from GvL control. Both class I and II HLA genes are targeted by somatic mutations as clonal selection factors potentially impairing cellular immune responses and responses to immunomodulatory strategies. These findings define new molecular modes of post-transplant leukemia escape contributing to relapse.The present dataset provides HLA peripheral blood and bone marrow samples supporting the genotyping studies performed for this research. This sample set originates from patients with acute myeloid leukemia or myelodysplastic syndromes receiving allogeneic hematopoietic cell transplantation and relapsing after transplant.

  Study phs003235

• INCLUDE: Down Syndrome Early Post-Natal Brain Multiome

  Neurodevelopmental deficiencies and neuronal dysfunction contribute to cognitive impairment in individuals with Down syndrome, but what molecular pathways underlie the defects that lead to intellectual disability remain unclear. Human brain development is precisely choreographed through tightly regulated transcriptional programs. Proper regulation of these transcriptional programs is necessary for developing the numerous functionally distinct regions, cell types, and connections of the brain, and forming the basis for human-specific social, cognitive, and motor abilities. These data establish a reference of molecular features of the DS developing brain. Such foundational information will provide not only a reference for any existing and future models, but also a basis for understanding disrupted neural development and impaired cognition in DS.Dataset 1 contains single-nucleus RNAseq and ATACseq from frozen postmortem human basal forebrain tissue. Dataset 2 contains single-nucleus RNAseq and ATACseq from frozen postmortem human dorsolateral prefrontal tissue. Dataset 3 contains single-nucleus RNAseq and ATACseq from frozen postmortem human caudate nucleus tissue.

  Study phs004098

• Identification of gene mutations and fusion genes in patients with Sézary Syndrome

  Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma (CTCL) with an aggressive clinical course. The goal of our study is to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sezary cels, fourteen of them fulfilling the diagnostic criteria of SS. Peripheral blood samples were collected for each patient and CD4+ T-lymphocytes and Granulocytes were isolated. DNA and RNA was extracted for matched normal and tumor materials. Whole exome sequencing was performed on matched normal and tumor tissues of 12 patients and RNA sequencing was performed on 10 patients. For 7 of these patients, we have both exome as well as RNA sequencing data. In this study, we present a complex genomic landscape of Sezary syndrome with several point mutations, copy number variations and fusion events which could contribute to the pathogenesis of SS.

  Study EGAS00001001706

• Multiregional sequencing of IDH-WT glioblastoma reveals high genetic heterogeneity and a dynamic evolutionary history

  Glioblastoma is the most common and aggressive primary brain malignancy in adults. In addi-tion to extensive inter-patient heterogeneity, glioblastoma shows intra-tumor extensive cellular and molecular heterogeneity, both spatially and temporally. This heterogeneity is one of the main reasons for the poor prognosis and overall survival. Moreover, it raises the important question of whether the molecular characterization of a single bioptic sample, as performed in standard di-agnostics, actually represents the entire lesion. In this study, we sequenced the whole-exome of nine spatially different cancer regions of three primary glioblastomas. We characterized their mutational profiles and copy number alterations, with implications for our understanding of tu-mor biology in relation to clonal architecture and evolutionary dynamics, as well as therapeuti-cally relevant alterations.

  Study EGAS00001005128

• Integrated multi-omics analysis of pediatric hepatoblastoma

  Hepatoblastoma (HBL) is the most common malignant liver tumor in childhood and is clinically heterogeneous. In spite of its heterogeneity, the molecular basis responsible for the difference between low-risk and high-risk HBL has not been fully clarified. To address this issue, we carried out multi-omics analysis on 59 HBL samples to generate comprehensive profiles of gene mutation, copy-number alteration, DNA methylation and gene expression. By integrating these data, we aimed to unravel the heterogeneity of HBL and identify genetic determinants and therapy targets of high-risk HBL.

  Study JGAS000188

• The Normal Human Tissue Sequencing Project: Non-Diseased, Non-Malignant Tissues

  The Normal Human Tissue Sequencing Project provides RNA expression and DNA methylation data from normal (non-diseased) human tissues. This data set from a variety of source tissue is a valuable resource for human disease studies.

  Study phs000819

• DETECT-A NGS Data Batch 4

  This batch is a subset of the full DETECT-A dataset, containing 25210 fastq files generated from 3040 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001015360

• DETECT-A NGS Data Batch 6

  This batch is a subset of the full DETECT-A dataset, containing 9 fastq files generated from 8 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001015458

• DETECT-A NGS Data Batch 5

  This batch is a subset of the full DETECT-A dataset, containing 12740 fastq files generated from 3211 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001015426

• DETECT-A NGS Data Batch 3

  This batch is a subset of the full DETECT-A dataset, containing 29294 fastq files generated from 3653 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001008597

• DETECT-A NGS Data Batch 2

  This batch is a subset of the full DETECT-A dataset, containing 498 fastq files generated from 71 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001008591

• DETECT-A NGS Data Batch 1

  This batch is a subset of the full DETECT-A dataset, containing 43963 fastq files generated from 3024 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001008415

• RNA Transcriptomic and DNA Methylation Landscape in FTLD-TDP and Controls

  Frontotemporal lobar degeneration (FTLD) is one of the leading causes of dementia in individuals younger than 65 years, with the aggregation of TDP-43 as one of the most common forms of FTLD. FTLD-TDP is clinically, genetically and pathologically heterogeneous, with GRN and C9orf72 as the most common genetic forms (although more than 50% of the cases are genetically unexplained), and A, B and C as the most common pathological subtypes. To investigate the molecular differences between the different forms of FTLD-TDP, we performed bulk RNA sequencing (RNAseq) and reduced representation bisulfite sequencing (RRBS) from different brain regions of FTLD-TDP patients and controls. The RNAseq dataset includes samples from the frontal cortex of 149 individuals, comprising 127 FTLD-TDP cases (genetically unexplained types A (27), B (20) and C (22), 24 GRN mutation carriers, and 34 C9orf72 expansion carriers) and 22 controls. The RRBS dataset includes samples from the frontal cortex of 158 individuals —119 FTLD-TDP cases (genetically unexplained types A (25), B (24), and C (25), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 39 controls; and from the cerebellum of 151 individuals —113 FTLD-TDP cases (genetically unexplained types A (24), B (21), and C (23), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 38 controls. In total, the study consists of data from 183 unique individuals, with some overlap across the different datasets.

  Study phs004075

• WGS and WES of Advance Prostate Cancer

  The dataset consists of BAM files of 2 pairs of matched tumor/normal samples of a men with advanced prostate cancer. One pair is whole genome sequencing: WGS_T/WGS_N for tumor and normal samples, respectively; and the other pair is whole exome sequencing: WES_T/WES_N for tumor and normal specimens, respectively. Details can be found at the publication titled: "Molecular Medicine Tumor Board: Whole Genome Sequencing to Inform on Personalized Medicine for a Man with Advanced Prostate Cancer"

  Dataset EGAD00001006487

• Cerebrospinal fluid circulating tumour DNA allows the characterisation and monitoring of medulloblastoma

  The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease. In this study we show that CSF ctDNA allows the molecular characterisation and monitoring of medulloblastoma. This can ultimately facilitate the clinical management of medulloblastoma patients.

  Study EGAS00001004651

• Molecular Tumor Board to Inform on Personalized Medicine for a Man with Advanced Prostate Cancer

  Purpose: Molecular profiling of cancer is increasingly common as part of routine care in oncology, and germline and somatic profiling may provide insights and actionable targets for men with metastatic prostate cancer. However, all reported cases are of deidentified individuals without full medical and genomic data available in the public domain. Patient and Methods: We present a case of whole genome tumor and germline sequencing in a patient with advanced prostate cancer, who has agreed to make his genomic and clinical data publicly available in an accompanying personal testimonial. Results: We describe an 84-year-old Caucasian male with a Gleason 10 oligometastastic hormone-sensitive prostate cancer. Whole-genome sequencing provided insights into his tumor’s underlying mutational processes and the development of an SPOP mutation. It also revealed an androgen-receptor dependency of his cancer which was reflected in his durable response to radiation and hormonal therapy. Potentially actionable genomic lesions in the tumor were identified through a personalized medicine approach for potential future therapy, but at the moment, he remains in remission, illustrating the hormonal sensitivity of his SPOP-driven prostate cancer. We also placed this patient in the context of a large prostate-cancer cohort from the PCAWG (Pan-cancer Analysis of Whole Genomes) group. In this comparison, the patient's cancer appears typical in terms of the number and type of somatic mutations, but it has a somewhat larger contribution from the mutational process associated with aging. Conclusion: We combined the expertise of medical oncology and genomics approaches to develop a molecular tumor board to integrate the care and study of this patient, who continues to have an outstanding response to his combined modality treatment. This identifiable case potentially helps overcome barriers to clinical and genomic data sharing.

  Study EGAS00001004648

• National Cancer Institute Genome-Wide Association Study of Renal Cell Carcinoma

  The National Cancer Institute (NCI) genome-wide association study (GWAS) of renal cell carcinoma (RCC) was conducted to investigate common genetic variants associated with RCC risk. The GWAS includes 1,453 RCC cases and 3,531 controls of European background from 4 studies (3 cohort, 1 case-control), scanned using the Illumina InfiniumHumanHap 550, 610 and 660W chips. This project was supported by the Intramural Research Program of the National Institutes of Health and NCI. Data from this GWAS were pooled with those from another GWAS of RCC (2,639 cases and 5,392 controls) conducted in Europe by the International Agency for Research on Cancer and the Centre National de Gènotypage. Findings from this collaboration are described in an upcoming report (Purdue et al. Nature Genetics 2011;43(1):60-65; PMID: 21131975). Only data from the NCI scan are included in this dbGaP submission.

  Study phs000351

• Defective Homologous Recombination DNA Repair as Therapeutic Target in Advanced-Stage Chordoma (HIPO_021)

  HIPO project: HIPO_021 Importance: Chordomas are rare tumors of the axial skeleton and skull base with few therapeutic options and no clinically validated molecular drug targets. The value of comprehensive genomic analyses for guiding medical therapy of patients with advanced-stage chordoma is unknown.Objective: To identify therapeutically tractable genetic lesions in a cohort of chordoma patients within a genomics-guided precision oncology program and to document the outcome of individualized, molecularly targeted chordoma therapy.Design, Setting, and Participants: We performed whole-exome sequencing of tumor and matched germline control samples from seven patients with locally advanced or metastatic chordoma who were enrolled in a cross-institutional molecular stratification registry trial for younger adults with advanced-stage cancer across all histologies and patients with rare tumors. All patients were heavily pretreated and had progressive disease prior to molecular analysis.Interventions: Individualized medical therapy was administered according to the patients’ molecular profiles.Main Outcomes and Measures: Candidate therapeutic targets identified by whole-exome sequencing and response to genotype-directed therapy.Results: All patients harbored alterations of two or more genes known to be involved in DNA repair via homologous recombination (HR), including heterozygous deletions of ERCC6, FANC family members, RAD51L (n = 6), BRCA2 (n = 5), ATR, CHEK2, RAD18, RAD51B, and XRCC3 (n = 4); inactivating PTEN mutations coupled with loss of heterozygosity (n = 2); and pathogenic germline variants in BRCA2 (n = 1), NBN (n = 1), and CHEK2 (n = 1) that were accompanied by somatic deletion of the corresponding wild-type alleles. Consistently, a mutational signature associated with defective HR was enriched in all samples and co-occurred with extensive genomic instability, as evidenced by HR deficiency scores and high numbers of large-scale state transitions. These results prompted off-label treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in a patient whose tumor was refractory to irradiation and systemic treatment with imatinib, which led to a prolonged response and substantial clinical improvement.Conclusions and Relevance: Advanced-stage chordomas are frequently characterized by genomic imprints of defective HR DNA repair. HR deficiency represents a new therapeutic opportunity in this intractable disease through repositioning of PARP inhibitors that warrants further exploration in clinical trials.

  Study EGAS00001002720

• Origins and functional consequence of somatic mitochondrial DNA mutations

  Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mitochondrial DNA (mtDNA) are unclear. Here, we analysed somatic alterations in mtDNA from 1,675 tumors across 31 histologies. We identified 1,907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C>T and A>G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. Numbers of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria, and is fundamentally linked to mtDNA replication.

  Study EGAS00001000968

• Reference epigenomes generated as part of the International Human Epigenomics Consortium (IHEC)

  The Centre for Epigenome Mapping Technologies (CEMT) is an epigenome sequencing platform funded by the Canadian Institutes of Health Research (CIHR) and Genome BC as part of the Canadian Epigenetics, Environment and Health Research Consortium (CEEHRC). CEMT aims to produce 100 human reference epigenomes, each comprising the following datasets: whole genome; whole genome bisulfite and oxidative bisulfite; transcriptome; microRNA; and chromatin immunoprecipitation (ChIP)-seq for the core chromatin marks (H3K4me1, H3K4me3, H3K9me3, H3K27me3, H3K36me3, and H3K27ac).CEEHRC is a full member of the International Human Epigenomics Consortium (IHEC), which aims to coordinate the production of 1,000 reference maps of human epigenomes for key cellular states relevant to health and diseases. As such, all datasets submitted by the CEMT platform conform to IHEC assay standards and metadata guidelines.

  Study EGAS00001000552

• Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

  No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

  Study EGAS50000000211

• HCA_Female_Reproductive_Adult_WSSS_RNA

  HCA Endometrium_LM The endometrium regenerates monthly and its transformation is executed through dynamic changes in states and interactions of multiple cell types. Using transcriptomics methods we seek to profile changes of the endometrium across the menstrual cycle. Our map will have implications in women’s health and cancer, by enabling the interpretation of GWAS analyses or the studying functional consequences of somatic mutations. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001004727

• LRS - episignature samples

  This dataset contains 22 long-read WGS fastq.gz files sequenced ONT PromethION. In total the dataset includes 20 individuals, for all of them sequencing starting from blood was performed, and for one of the samples sequencing from urine and from the buccal swab was also included. In all the samples methylation calls are included in the fastq file.

  Dataset EGAD50000001000

• EGA dataset for High Grade Serous Ovarian Carcinomas Originate in the Fallopian Tube

  The dataset for High Grade Serous Ovarian Carcinomas Originate in the Fallopian Tube includes 46 bam files from next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include multiple lesions from nine patients, five with high grade serous ovarian carcinoma and four who are BRCA-carriers.

  Dataset EGAD00001003792

• The University of Hong Kong Colon Cancer GCV Study

  Background: Ganciclovir (GCV) is widely used in solid organ and hematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown. Methods: This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCVsig) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs. Results: Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCVsig. A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCVsig¬¬ were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCV¬sig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCVsig in cell lines and organoids. Conclusions: In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.

  Study EGAS00001006707

• Adeno-associated virus in the liver: natural history and consequences in tumor development

  Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (40-80%). AAV infection has long been considered as non-pathogenic1, however few years ago we reported for the first time recurrent clonal AAV2 insertion in the pathogenesis of human hepatocellular carcinoma (HCC) developed on normal liver. These clonal viral insertions target cancer driver genes, including CCNA2, CCNE1, TERT, TNFSF10 and MLL4, leading to their overexpression. The viral inserted sequences involved in almost all the cases the 3’ inverse tandem repeat (ITR) of AAV2, which is important for virus integration in host DNA and exhibits a promoter/enhancer activity. Here, we used RNA sequencing (RNA-seq) to investigate their functional impact on the tissue, such as fusion transcript generation events.

  Study EGAS00001003310

• WGS of pre-T cell receptor-alpha immunodeficiency proband and family

  In this study, we describe the role of whole genome sequencing (WGS) in providing a definitive diagnosis for a child with T cell deficiency, where targeted panel sequencing of SCID genes and whole exome sequencing had failed. A novel homozygous 8kb deletion in PTCRA, encoding pTCR, was identified. WGS sequence data from the proband, proband’s mother, and proband’s father are deposited.

  Study EGAS50000000609

• Genetic regulation of gene expression in human brain cell types

  We leveraged single nuclei RNA-seq from 192 human brain samples to map cis-eQTLs in 8 brain cell types. We found extensive cell-type specific genetic effect on gene expression and integrated our results with GWAS to identify putative novel risk genes for brain disorders and the cell types in which the disease mechanisms are likely active.

  Study EGAS00001006345

• RNA Sequence-Based Analysis Used to Compare Breast Primary and Metastatic Tumor Pairs

  The goal of this study is to capture the transcriptome landscape of luminal and basal-like metastatic breast tumors. We will aim to show the importance of using the most up-to-date cancer biopsy for detecting cancer drivers that were often not present in the primary tumor.

  Study phs001866

• Biobank Japan WGS data of myocardial infarction and dementia

  The Biobank Japan (BBJ) Project started and has collected around 200,000 individuals with disease cases consisting of 51 diseases. The purpose of the BBJ is to realize personalized medicine. With the use of about 2200 samples in the BBJ, whole-genome sequnecing was conducted at RIKEN, Center for Integrative Medical Sciences.

  Study JGAS000381

• snRNA-seq schizophrenia control Prefrontal cortex

  In this study, we performed RNA sequencing of single nuclei from the prefrontal cortex of donors with and without schizophrenia using the 10x Genomics Chromium Single Cell protocol. The project rationale is to determine cell type specific transcriptomic changes between the two groups and linking them to the risk for schizophrenia.

  Study EGAS50000001703

• Epigenomics Studies in Acute Myeloid Leukemia (AML)

  Acute Myeloid Leukemia (AML) remains a clinical challenge since most patients diagnosed with AML will die from the disease. Some patients harbor treatment-refractory disease and many others relapse with disease that in many cases is resistant to treatments. Our study was designed to understand the molecular basis of disease progression in AML through assessing genomics signatures in patient specimens collected through an international collaboration which assembled samples from 138 AML patients which experienced disease relapse and normal hematopoietic cells (n=15). It is hoped that this resource will help researchers understand mechanisms of disease relapse in AML and contribute to the general pool of data available for analyses for this disease and general research use.

  Study phs001027

• Detecting and tracking circulating tumour DNA copy number profiles during first line chemotherapy in oesophagogastric adenocarcinoma

  DNA somatic copy number aberrations (SCNAs) are key drivers in oesophago-gastric adenocarcinoma (OGA). Whether minimally invasive SCNA analysis of circulating tumour (ct)DNA can predict treatment outcomes and reveal how SCNAs evolve during chemotherapy is unknown. We investigated this by low-coverage whole genome sequencing (lcWGS) of ctDNA from 30 patients with advanced OGA prior to first-line chemotherapy and on progression.

  Study EGAS00001003695

• NHLBI TOPMed: Genetic Causes of Complex Pediatric Disorders - Asthma (GCPD-A)

  The Center for Applied Genomics (CAG) at the Children's Hospital of Philadelphia (CHOP) is focused on addressing the roles of both single nucleotide variants and structural copy number variants, and their functional impact, together with gene-environment interactions and their influence on asthma drug response.

  Study phs001661

• Whole_Genome_Sequencing_of_INTERVAL

  15x Whole Genome Sequencing of 15,000 individuals from the INTERVAL study cohort, phase II. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001002461

• Whole_Genome_Sequencing_of_INTERVAL

  15x Whole Genome Sequencing of 15,000 individuals from the INTERVAL study cohort, phase III. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001002787

• Post-zygotic germline mutations in sperm

  These data from sperm were generated to demonstrate detection of post-zygotic mutations in the male germline. 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 EGAS00001001700

• Genomic data from analysis of the human placenta, part of the Pregnancy Outcome Prediction study (POPs)

  The Pregnancy Outcome Prediction (POP) study is a prospective cohort study of nulliparous women attending the Rosie Hospital (Cambridge, UK) for their dating ultrasound scan. The study included 4512 women with a viable singleton pregnancy; study participants provided written informed consent and were recruited between January 2008 and July 2012. The POP study aimed both at evaluating performance of known biomarkers and serial ultrasonography in assessing maternal and fetal well-being, as well as identifying novel biomarkers. The study is sufficiently large to be powered for relatively uncommon adverse pregnancy outcomes. Women attended four study visits scheduled every 8 weeks, starting with the first trimester. Participants had blood taken during the dating/recruitment visit (at approximately 12 weeks gestation (wkGA)), as well as at three subsequent visits (at ∼20wkGA, ∼28wkGA and ∼36wkGA). For more detail, please visit: https://www.obgyn.cam.ac.uk/research/pops-2/.

  Study EGAS00001002205

• Whole exome data from PMID27216186

  This dataset comprises complete exome data from from the study PMID27216186 (Harbst & Lauss et al, Cancer Research 2016). These data are from 49 samples (tumor and matched normal) from 8 patients representing multi-region sequencing of human melanoma. Files are in the BAM format and contain aligned and processed data used for e.g. somatic variant calling. The sequencing libraries were constructed using SureSelect target enrichment with Clinical Research Exome Panel (Agilent) and sequenced on a HiSeq2500 (Illumina).

  Dataset EGAD00001008149

• Significant and pervasive effects of RNA degradation on Nanopore direct RNA sequencing

  Abstract Oxford Nanopore direct RNA sequencing (DRS) is capable of sequencing complete RNA molecules and accurately measuring gene and isoform expression. However, as DRS is designed to profile intact RNA, expression quantification may be more heavily dependent upon RNA integrity than alternate RNA-seq methodologies. It is currently unclear how RNA degradation impacts DRS or if it can be corrected for. To assess the impact of RNA integrity on DRS we performed a degradation time-series using SH-SY5Y neuroblastoma cells. Our results demonstrate that degradation is a significant and pervasive factor that can bias DRS measurements, including a reduction in library complexity resulting in an overrepresentation of short genes and isoforms. Degradation also biases differential expression analyses; however, we find explicit correction can almost fully recover meaningful biological signal. In addition, DRS provided less biased profiling of partially degraded samples than nanopore cDNA-PCR sequencing. Overall, we find samples with RIN > 9.5 can be treated as undegraded and samples with RIN > 7 can be utilised for DRS with appropriate correction. These results establish the suitability of DRS for a wide range of samples, including partially degraded in-vivo clinical and post-mortem samples, whilst limiting the confounding effect of degradation on expression quantification.

  Study EGAS00001006542

• NHLBI TOPMed: Pulmonary Fibrosis Whole Genome Sequencing

  This is a set of cases diagnosed with idiopathic pulmonary fibrosis, a fatal interstitial lung disease. These cases were included in the TOPMed phase three studies. The planned study will compare these cases to within-TOPMed controls for genome-wide association studies.

  Study phs001607

• Whole-Genome and Exome Sequencing in clear-cell Renal Cell Carcinoma (ccRCC)

  Study to evaluate the molecular genetics of ccRCC through integrative analyses of tumors and tumorgrafts using multiple platforms in clinically annotated samples. Genome and exome data for patients giving consent to have the information available on a public, secure, database is being submitted.

  Study phs000491

• Yemen_and_Chad_Genotyping

  HumanOmni2.5-8 data from Chad and Yemen.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001001231

• Comprehensive genomic characterization of early stage bladder cancer - nanopore sequencing

  For this project about non-muscle invasive bladder cancer (NMIBC), we analysed long read sequencing data from 4 patients using the Nanopore platform. The dataset is composed of 8 BAM files: 4 tumor samples and 4 paired blood samples.

  Study EGAS50000000510

• Isotype_resolved_sequencing_of_B_cell_receptor__in_health_and_disease

  Sequencing of B-cell receptor repertoires in healthy individuals and patients with chronic lymphocytic leukemia. 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 EGAS00001002634

• Genomic stratification and liquid biopsy in a rare adrenocortical carcinoma (ACC) case, with dual lung metastases

  Adrenocortical carcinoma is a rare malignancy with a poor prognosis and few treatment options. Molecular characterization of this cancer remains limited. We present a case of an adrenocortical carcinoma (ACC) in a 37-yr-old female, with dual lung metastases identified 1 yr following commencement of adjuvant mitotane therapy. As standard therapeutic regimens are often unsuccessful in ACC, we undertook a comprehensive genomic study into this case to identify treatment options and monitor disease progress. We performed targeted and whole-genome sequencing of germline, primary tumor, and both metastatic tumors from this patient and monitored recurrence over 2 yr using liquid biopsy for ctDNA and steroid hormone measurements. Sequencing revealed the primary and metastatic tumors were hyperhaploid, with extensive loss of heterozygosity but few structural rearrangements. Loss-of-function mutations were identified in MSH2, TP53, RB1, and PTEN, resulting in tumors with mismatch repair signatures and microsatellite instability. At the cellular level, tumors were populated by mitochondria-rich oncocytes. Longitudinal ctDNA mutation and hormone profiles were unable to detect micrometastatic disease, consistent with clinical indicators of disease remission. The molecular signatures in our ACC case suggested immunotherapy in the event of disease progression; however, the patient remains free of cancer. The extensive molecular analysis presented here could be applied to other rare and/or poorly stratified cancers, to identify novel or repurpose existing therapeutic options, thereby broadly improving diagnoses, treatments, and prognoses.

  Study EGAS00001003497