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• 10x Genomics Single Cell Gene Expression for SA1051DX1XB01482

  10x Genomics Single Cell Gene Expression for High grade serous ovarian carcinoma patient-derived xenograft SA1051 passage 1

  Dataset EGAD00001009133

• 10x Genomics Single Cell Gene Expression for SA1052JX1XB01535

  10x Genomics Single Cell Gene Expression for High grade serous ovarian carcinoma patient-derived xenograft SA1052 passage 1

  Dataset EGAD00001009134

• 10x Genomics Single Cell Gene Expression for SA1181AX1XB02700

  10x Genomics Single Cell Gene Expression for High grade serous ovarian carcinoma patient-derived xenograft SA1181 passage 1

  Dataset EGAD00001009135

• 10x Genomics Single Cell Gene Expression for SA1096CX1XB02039

  10x Genomics Single Cell Gene Expression for High grade serous ovarian carcinoma patient-derived xenograft SA1096 passage 1

  Dataset EGAD00001009136

• 10x Genomics Single Cell Gene Expression for SA1096BX1XB02037

  10x Genomics Single Cell Gene Expression for High grade serous ovarian carcinoma patient-derived xenograft SA1096 passage 1

  Dataset EGAD00001009137

• 10x Genomics Single Cell Gene Expression for SA1162BX1XB03004

  10x Genomics Single Cell Gene Expression for High grade serous ovarian carcinoma patient-derived xenograft SA1162 passage 1

  Dataset EGAD00001009138

• 10x Genomics Single Cell Gene Expression for SA1049CX1XB01422

  10x Genomics Single Cell Gene Expression for High grade serous ovarian carcinoma patient-derived xenograft SA1049 passage 1

  Dataset EGAD00001009140

• 10x Genomics Single Cell Gene Expression for SA1050EX1XB01442

  10x Genomics Single Cell Gene Expression for High grade serous ovarian carcinoma patient-derived xenograft SA1050 passage 1

  Dataset EGAD00001009141

• 10x Genomics Single Cell Gene Expression for SA1047BX1XB01022

  10x Genomics Single Cell Gene Expression for High grade serous ovarian carcinoma patient-derived xenograft SA1047 passage 1

  Dataset EGAD00001009146

• Scalable ultra-high-throughput multiplexed single-cell chromatin and RNA profiling reveals gene regulatory dynamics during stimulation time courses and CRISPR perturbation screens

  Data for 1) hiPSC-derived macrophages across a polarization time course from the naive M0-state to the M1- and M2-states, 2) Primary T-cells differentiated to helper subtypes, and 3) spontaneous differentiation of hiPSCs upon perturbation of GATA2, NR4A2 or SOX17

  Dac EGAC50000000485

• WES for CNV-verified CTCs from 2 patients with metastatic prostate cancer

  This dataset contains 4 paired fastq files sequenced by illumina Novoseq 6000. WES analysis (illumina platform, PE150, 100x coverage) was performed on a pool of CNV-verified CTCs that were enriched using high-throughout microfluidic device from entire leukopak from patients with metastatic prostate cancer (GU-1 and GU-2).

  Dataset EGAD50000001005

• SF11979 scRNA-Seq Primary GBM IDHR132H Wild-type Female

  Single Cell-RNA Seq IDHR132H Wild-type Primary GBM Female, 76. Single Cell RNA seq from high grade primary glioma sample. NovaSeq6000 was used for RNA seq. The files uploaded are bam files created with grch38 reference through cellranger count (10xGenomics.)

  Dataset EGAD00001005390

• Single cell characterization of arrested B-lymphoid differentiation and leukemic cell states in ETV6-RUNX1-positive pediatric leukemia

  Leukemic bone marrow in primary ETV6-RUNX1 positive acute lymphoblastic leukemia samples (Six diagnostic and two 15 days after treatment) using Chromium 3' single cell RNA-seq. Samples sequenced on 1-3 lanes and raw fastq files provided for each sample.

  Dataset EGAD00001006074

• Sequencing data for oesophageal and related samples - Katz-Summercorn, Jammula et al (RNA)

  Data supporting: “Multi-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals structural variation and retrotransposon activity occur early in cancer evolution.” Katz-Summercorn, Jammula et al. RNAseq (BAM files)

  Dataset EGAD00001006353

• RNA-seq on neuroblastoma PDX model COG-N-519 treated with control miR-1283 and test miR-99b-5p mimics

  RNA-sequencing on neuroblastoma PDX model COG-N-519 treated with control miR-1283 and test miR-99b-5p mimics. Three samples from each of the treatment condition were analysed. Next-Seq platform was used for sequencing.

  Dataset EGAD00001007754

• Whole genome sequencing of GM09237 cells with and without folate depletion

  Two DNA samples extracted from GM09237 cell line cultured with either normal medium or medium with no folic acid for 5 days were sequenced using the BGISEQ500 platform (BGI whole genome 100 bp paired-end sequencing 60x) as well as PacBio Sequel long read sequencing.

  Dataset EGAD00001007732

• Spatial transcriptomics of 1 untreated prostate cancer.

  Two sections of cryopreserved prostate cancer tissue from one untreated prostate cancer patient were profiled for spatial transcriptomics using the Visium Spatial library preparation protocol from 10x Genomics. The GRCh38 aligned sequencing reads from the two prostate cancer tissue sections are provided as BAM files.

  Dataset EGAD00001007921

• Human Hi-C

  This dataset contains 2 human tumor-derived cell lines and 1 human tumor Hi-C samples. The raw fastq files and the processed .hic file is provided for each sample.

  Dataset EGAD00001009050

• PacBio HiFi sequencing of telobait-captured DNA from 68 patients

  PacBio HiFi sequencing was performed on 68 barcoded patients' genomic DNA after a telobait-capture protocol to enrich for telomeric regions. The sequencing reads of each patient were de-multiplexed and presented as patient-specific PacBio CCS BAM files. There are 56 new samples and 12 repeated samples from run 1.

  Dataset EGAD00001009397

• RNA-seq dataset of Ewing and Ewing-like-sarcoma tumoroid biobank reveals distinct drug sensitivities: translocation makes the difference

  Creation of living organoid biobank for ewing and ewing-like sarcomas

  Dataset EGAD00001015419

• Low-coverage whole-genome sequencing (lcWGS) data of Genome in a Bottle (GIAB) reference samples

  This dataset contains low-coverage whole-genome sequencing (lcWGS) data generated from three GIAB reference samples (HG001–HG003) for method benchmarking and concordance analysis in FFPE-GWAS workflows. The data were generated using Illumina NovaSeq with paired-end 150bp reads and downsampled to 2x coverage.

  Dataset EGAD00001015533

• NHLBI TOPMed: My Life Our Future (MLOF) Research Repository of Patients with Hemophilia A (Factor VIII Deficiency) or Hemophilia B (Factor IX Deficiency)

  Hemophilia A and B are X-linked bleeding disorders resulting from a deficiency in coagulation factor VIII (FVIII) or factor IX (FIX), respectively. Hemophilia affects approximately 1/5000 male births worldwide, and results in premature death and disability due to bleeding if coagulation factor replacement therapy is not used effectively. Hemophilia is clinically categorized by coagulation factor activity levels and ranges in severity from mild (6% to 30%) to moderate (1-5%) to severe (<1%). Many female "carriers" of hemophilia also have decreased factor activity and morbidity from bleeding. Hemophilia A and B are almost always caused by identifiable mutations in the F8 and F9 genes, respectively, and these mutations are found throughout the structural genes. Although the hemophilias are monogenic disorders, there are wide variations in disease severity and therapeutic outcomes which are not readily explained by the disease causing mutations alone. The My Life Our Future (MLOF) project (www.mylifeourfuture.org) is a national resource developed by a partnership of BloodworksNW (BWNW, formerly the Puget Sound Blood Center), the American Thrombosis and Hemostasis Network (ATHN), the National Hemophilia Foundation (NHF) and Bioverativ, to provide free F8 and F9 gene variant analysis to patients with hemophilia A or B, and to establish a research repository of DNA sequence, DNA, RNA, buffy coat, serum and plasma. The sequence analysis and serum samples are linked to a phenotypic database hosted by ATHN, with samples submitted and clinical data entered at ~100 hemophilia treatment centers (HTCs) nationwide. (See ATHN Research Report Brief in the resource center at www.athn.org). MLOF has become the largest hemophilia genetic project worldwide. The roles of the MLOF partners are: BWNW, to serve as the central laboratory for the project and house the research repository; ATHN, to support and provide the administrative link with HTCs, to facilitate the collection of accurate phenotypic data, to conduct research review and approval for use of the repository and with BWNW to provide samples and data for research projects; NHF, to provide consumer education and facilitate consumer input into the project; and Bioverativ, to provide financial support and scientific input. The project is governed by a Steering Committee consisting of one representative from each organization. Subject samples chosen from the MLOF parent study for TOPMed and WGS were drawn from those who gave (or parents gave) informed consent for the Research Repository and included patients of all severities and type, but with an emphasis on those with severe hemophilia and others at increased risk of neutralizing antibody (inhibitor) formation and who had samples in the Research Repository (plasma, serum, RNA) for potential additional -omic studies. Also included were samples from subjects where a likely causative variant for hemophilia was not found in the F8 or F9 coding region, intron-exon boundaries or immediate upstream and downstream regions. Since hemophilia is an X-linked disorder, the majority of subjects are male. Racial distribution is similar to the overall population distribution.

  Study phs001515

• Mechanism of Action of Vitamin E in NAFLD

  We conducted a single-center prospective mechanistic randomized trial (clinicaltrials.gov NCT01792115). Adult patients with NAFLD were enrolled between May 2013 and November 2016. All patients underwent a 12 weeks run-in period of lifestyle intervention. Following the run-in phase, patients underwent a baseline evaluation including blood tests, glucose tolerance testing, measurement of liver fat content by 1H-magnetic resonance spectroscopy (MRS) and a percutaneous liver biopsy. Patients with no evidence of NAFLD on the entry liver biopsy ended their participation in the study at that point. Patients with histological confirmation of NAFLD (either NAFL or NASH) on the baseline biopsy were randomized at a 1:1:1 ratio to receive one of 3 doses of natural vitamin E (RRR-alpha-tocopherol, Pharmavite), 200, 400 or 800 IU/d, for 24 weeks, and were followed at a 1-8 week intervals in a parallel assigned design. While on vitamin E treatment, patients were encouraged to continue and adhere to the lifestyle and dietary guidelines of the run-in phase. On week 4 of vitamin E treatment, a repeat MRS and liver biopsy were performed. On week 24, a final MRS was performed to assess treatment response. The primary endpoint was the reduction of liver fat content by MRS from baseline (immediately prior to starting vitamin E) to week 24 of treatment, and a response was defined as a relative reduction of ≥25% in liver fat content by MRS between baseline and week 24. Early changes in the hepatic transcriptome were investigated at week 4 comparing non-responders to responder in a nested design.

  Study phs001930

• Population Genetic Testing and SERPINA1 Sequencing Identifies Unidentified Alpha-1 Antitrypsin Deficiency Alleles and Gene-Environment Interaction with Hepatitis C Infection

  Design and aims: Data were available through an institutional effort to combine de-identified electronic health records (EHR) data with genomic information from a DNA biobank. The design of this work was a retrospective cohort study in which we investigated the rates of liver transplantation and hepatitis C infection as it relates to genotype risk for alpha-1 antitrypsin deficiency (AATD). We used regression analysis to look for relationships between these risks and outcomes. This led to further investigation of environmental exposures and phenotypes as it related to the underlying genotypic risk. Population information: The cohort consisted of 72,027 individuals of European ancestry for whom genotype and EHR data were available. Molecular technologies employed: Genome-wide genotyping was previously performed using the Illumina Infinium Expanded Multi-Ethnic Genotyping Array plus custom content (referred to as the Vanderbilt University Medical Center BioVU MEGAEX). Individuals' AATD-related alleles were inferred from the genotyping data. Principal findings of the study: Liver transplantation was associated with presence of the Z AATD allele and with hepatitis C infection. There was a significant interaction between AATD genotype groups and hepatitis C infection as it related to liver transplantation. Data available through dbGaP: Inferred AATD genotype status, sex, age, length of EHR in years, presence/absence of AATD clinical diagnosis, liver transplant status, and hepatitis C infection status.

  Study phs003297

• HTAN MCL Pre-Cancer Atlas Pilot Project - Targeted Sequencing Development Study

  The HTAN-MCL Pre-Cancer Atlas Pilot Project (PCAPP) is the result of a collaboration between the seven members of the MCL consortium. Across four organ types, PCAPP's goal is to collect and profile pre-malignant lesions for gene expression, DNA mutations, single-cell gene expression and immune-environment. Most PML are small in size and only available come from formalin fixed paraffin embedded archived tissue. The primary goal of PCAPP is to 1) understand the logistical challenges of PML specimen collection, 2) document technical limitations of the assays that are specific to the PML and 3) overcome them to support the generation of a more comprehensive Pre-Cancer Atlas in the future. The current upload provides RNA and DNA sequencing from participants with DCIS who were studied at the University of San Diego and the University of Vermont. Description of the overall study: A. Background/Significance One of the critical barriers to developing new approaches for cancer detection and prevention is the lack of understanding of the key molecular and cellular changes that cause cancer initiation and progression. Unlike the extensive work that has been done profiling advanced stage tumors, few studies have comprehensively profiled the molecular alterations found in precancerous tissues. Premalignant lesions are currently characterized by histologic changes that precede the development of invasive carcinoma1,2.These lesions can often be identified in regions surrounding an invasive tumor or in biopsies taken from patients undergoing diagnostic evaluation for suspicion of cancer. Currently, limited metrics exist to identify lesions that will likely progress to carcinoma and require intervention from those that will naturally regress or remain stable3,4. Characterization of the molecular alterations in premalignant lesions and the corresponding changes in the microenvironment would hasten the development of biomarkers for early detection and risk stratification as well as suggest preventive interventions to reverse or delay the development of cancer. Our pilot study will establish the feasibility of transcriptomic, genomic and immune profiling of FFPE premalignant lesions from multiple organ sites, collected and profiled with uniform SOPs across multiple institutions within the MCL consortium. We will characterize the molecular alterations in precancerous lesions and the corresponding microenvironment in four major organ sites, in order to uncover the molecular and cellular determinants of premalignancy, and establish standardized sequencing and immunohistochemistry protocols on FFPE precancerous tissue. We will also evaluate the technical feasibility of single nuclei sequencing of small FFPE pre-cancer lesions. Successful completion of the proposed pilot study will set the stage for expansion and development of a comprehensive Pre-Cancer Atlas (PCA) as part of the NCI's moonshot.B. Specific Aims Aim 1: Collect premalignant lesions (PML) and their associated microenvironment via LCM from FFPE tissue across four organ sites (breast, lung, pancreas & prostate). Aim 2: Perform bulk RNA and DNA seq on premalignant FFPE samples (and flash frozen tissue where available) and compare the genomic/transcriptomic alterations within and across organ sites. C. ApproachAim 1: Collect premalignant lesions (PML) and their associated microenvironment via LCM from FFPE tissue across four organ sites (breast, lung, pancreas & prostate). MethodsI. Patient Population/Sample Collection: Overview of the sites collecting PML tissue from the respective organs is provided in Table 1 and a full description of the biospecimens to be obtained is described in detail for each organ type below. Table 1. Breakdown of cohort by tissue type and collection site.Organ siteBreastLungPancreasProstateType of PMLDCISAAH, Squamous Dysplasia/CISIPMNsPINCollection of PatientsUCSF/UCSDUVMBU*/UCLAVanderbilt/MoffittMDACC*JHUStanford*# of Patients201920 (10 of each type)20 (10 of each type)242020Total patients per Organ39402440Note: single nuclei/cell RNA-Seq will be performed on 4-5 FFPE samples from each of the organ types 1. DCIS lesions from breast tissue: DCIS lesions will be collected from 39 patients (20 from UCSF/UCSD & 19 from UVM) with primary low or high-grade DCIS diagnosed from a breast core biopsy. Subsequent resected lumpectomy or mastectomy tissues will be prospectively sampled in the vicinity of the prior biopsy site using multiple approaches: 1) Live cells (heterogeneous mix) will be obtained as a cell scrape slurry from the lesion surface or by fine needle aspirate (FNA); 2) For a subset of specimens where size is sufficient, a block of breast tissue with DCIS will be fresh-frozen; 3) The remainder of the specimen will be taken for routine formalin-fixation and paraffin-embedding (FFPE). The FFPE sample will be annotated to identify the matched FFPE tissue block adjacent to the fresh-frozen sample and will be sectioned for use in bulk and single nuclei sequencing . We will dissect DCIS, adjacent normal and when available, associated carcinoma. In addition, when possible, normal tissue will be collected from a tissue block lacking lesions as well as collection of blood. A subset of patients (n = 5 | FFPE, flash frozen and fresh) will be sent to the Broad Institute for single nuclei/cell sequencing.2. AAH and squamous dysplastic/CIS lesions from airway and lung tissue: For squamous cell lung cancer, we will collect endobronchial biopsies from abnormal airway regions identified on autofluroscence bronchoscopy or identify PMLs in the margins of resected lung tissue. We will study 20 patients (5 each from BU/UCLA/Vanderbilt/Moffitt) with pre-invasive squamous lesions (moderate-severe dysplasia or carcinoma in situ (CIS)) identified on pathologic examination. LCM of the premalignant region and adjacent normal epithelium will be performed as well as the invasive tumor for those collected from the resection margin (n=5 from UCLA). On a subset of lesions collected at bronchoscopy (n=5), we will collect additional biopsies that will be flash frozen and fresh for single nuclei and cell sequencing, respectively, performed at the Broad Institute. In parallel to the work at the Broad, BU will perform single cell RNA-seq on these freshly cell sorted tissues (n = 5). Blood will be collected on all patients for genomic studies. For lung adenocarcinoma, we will collect resected FFPE lung tissues from 20 patients (10 from UCLA and 10 from Vanderbilt/Moffitt) with early stage lung adenocarcinoma that harbor atypical adenomatous (AAH) premalignant lesions in the resection margin. We will LCM multiple AAH regions (3-5 per patient) as well as adjacent regions of normal epithelium and invasive adenocarcinoma. In addition, blood will be collected on all patients for genomic studies. 3. IPMNs from pancreatic tissue: For pancreatic cancer PML, we will collect low and high grade lesions from 24 patients representing macroscopic Intraductal Papillary Mucinous Neoplasms (IPMN) (n=24) from surgically resected specimens along with blood samples. Archival FFPE specimens of microscopic PanIN lesions, occurring multi-focally adjacent to invasive PDAC, and archival IPMN lesions (with or without associated invasive cancer), along with the adjacent normal tissue, will undergo LCM and utilized for bulk DNA and RNA sequencing. If matched frozen tissues are available for a subset of these FFPE samples, we will bank for comparison of profiles. Because IPMNs are macroscopic lesions, they provide an opportunity for obtaining the samples fresh and therefore can be used for single cell sequencing (in contrast to PanINs). Therefore, 5 freshly obtained IPMNs will be used for the single cell RNA sequencing studies performed at both the Broad Institute and MDACC, and the matched FFPE and/or frozen sections from these lesions (obtained from the adjacent PML) will be sent to Broad Institute as a pilot to assess "single nuclei" RNA sequencing.4. PINs from prostate tissue: For prostate cancer PML, there will be 40 samples of Prostatic Intraepithelial Neoplasia (PIN) collected between the Stanford and JHU sites (20 cases per site). At the Stanford site, 20 prostate specimens detected by PSA screening who have/will undergo surgery (radical prostatectomy) for clinically localized disease will make up the final cohort. The age range of the participants would be 40-75, and we anticipate that 18 will be Caucasian, 1 Asian and 1 Latino or African American based on the practice demographics practice at Stanford. Clinical and MRI data will also be collected for these samples. We will collect low grade (e.g. Gleason score of 6/Grade group 1; n=10) and high grade (Gleason score 4+3=7 or higher/Grade group 3 or higher; n=10) PINs from FFPE samples that have prostate carcinoma. In addition to obtaining LCM archival samples of low and high grade PIN, we will also obtain normal prostatic epithelial from the peripheral, central and transition zones as well as multiple samples of prostate carcinoma in order to obtain the spectrum of Gleason grades in the carcinoma as needed. LCM samples will be used for bulk DNA and RNA sequencing. In addition, single cells will be dissected from FFPE samples to prepare single cell RNA seq libraries using techniques developed at Stanford, and FFPE tissue will be sent to the Broad for single nuclei sequencing. When available, flash frozen and fresh samples from these prostates will be archived and prepared for single nuclei and cell sequencing, respectively, at the Broad Institute and at Stanford (single cell only). JHU will also capture 10 cases (5 grade group 1 and 5 grade group 2) of high grade PIN, normal and invasive adenocarcinoma using frozen sections from fresh frozen tissues. When possible these will be from the same patients as the FFPE samples. Since frozen sections can be quite challenging to morphologically determine high grade PIN from normal epithelium, for these samples we will perform a number of additional tissue-based characterizations. These will include a multicolor combined basal cells (p63 and CK903) and PIN/carcinoma markers (AMACR) referred to in the cocktail as "PIN4", c-MYC (referred to as MYC) protein5, by IHC and mRNA by in situ hybridization (AM De Marzo, Q Zheng unpublished observations), telomere length by in situ hybridization6 and the 5'ETS/45S rRNA7. For these slides, the whole slides will be scanned with a Hammamatsu Nanozoomer with a 40x objective and regions of interest will be annotated as a guide for LCM.II. Laser-capture microdissection (LCM): FFPE tissue blocks will be sectioned at 7μm thickness and serial sections will be stained with H&E. LCM will be performed utilizing standard LCM systems, such as Leica LMD7000 and ArcturusXT at each site. Regions of premalignancy will be dissected and RNA/DNA will be extracted from microdissected cells using the Qiagen All Prep DNA/RNA FFPE Kit. Aim 2: Perform bulk RNA and DNA seq on premalignant FFPE samples and compare the genomic/transcriptomic alterations within and across organ sites. Rationale: There have been limited studies characterizing the genomic and transcriptomic landscape of premalignant lesions associated with breast, pancreatic, lung or prostate cancers. Characterizing the molecular determinants of premalignant disease that are unique and shared across multiple organs will enable new candidate biomarkers for early detection and novel therapeutic strategies for early intervention. MethodsBulk RNA-seq of LCM FFPE tissue: All participating sites will perform bulk RNA-seq in accordance with SOPs developed at BU. In brief, total RNA will be isolated from LCM'd lesion and associated microenvironment tissue using the Qiagen All Prep DNA/RNA FFPE Kit and quality will be assessed with the Agilent Bioanalyzer. Libraries will be generated with the Illumina TruSeq Access kit (for FFPE samples). They will be sequenced on the Illumina HiSeq2500 with 75base-pair paired-end reads. Quality of FASTQ files will be assessed with FastQC. Reads will be aligned to the human genome with STAR and gene-level and isoform-level expression will be quantified with RSEM. Splice junction saturation, transcript integrity, and biotype distributions will be calculated for each sample with RSeQC. DESeq2 and EdgeR will be used to identify associations between gene expression profiles and clinical variables while controlling for confounding covariates. BU will serve as an RNA-seq Core to assess reproducibility of FFPE RNA-seq methods across sites. We will perform RNA-seq according to the SOP listed above on a subset of samples for each organ type (total n ~ 20). Bulk seq of DNA from FFPE tissue: All participating sites will perform targeted or whole exome-seq (WES) in accordance with SOPs. In brief, DNA from laser captured material will be isolated using the Qiagen All Prep DNA/RNA FFPE Kit and undergo stringent quality control to ensure high quality input material for genomic profiling. Purified DNA (ideally 100-200 ng) will be used for library preparation and amplification, followed by next generation sequencing using standard protocols distributed by CDMG. Exome-seq methods are considered standardized, thus we will not need a DNA-seq Core to assess reproducibility across sites. We anticipate local centers will use Illumina paired end reads, following the following general approach. 1) DNA library preparation: Paired-end libraries will be prepared following the manufacturer's protocols (Illumina and Agilent), fragmented to 150-200 bp 2) Capture of targeted exome: Whole exome capture will be carried out using the protocol for Agilent's SureSelect Human All Exon kit. Purified capture products will be amplified using the SureSelect GA PCR primers (Agilent) for 12 cycles. 3) Sequencing will be carried out for the captured libraries using at least 100 bp paired-end reads. To achieve high level sensitivity and accuracy for detecting all the mutations in the whole exome, each sample will be sequenced at 200X mean depth. 4) Read mapping and alignment and variant analysis: Sequence short reads will be aligned to a reference genome (NCBI human genome assembly build 38) using BWA-MEM. Local realignment of aligned reads will be performed using Genome Analysis Toolkit (GATK).Data QC: To ensure scientific rigor and consistency among sites in RNA and DNA processing we will include a preliminary analysis of steps in processing and analysis. Protocols for extraction of high quality RNA and DNA from formalin fixed paraffin embedded (FFPE) tissues, which will be used extensively in these studies continue to improve and may have variable implementation among the sites participating in this study. To evaluate consistency of preliminary steps in processing and downstream analyses, we will initially distribute slides from one large FFPE fixed cancer of origin from prostate, breast, lung and pancreatic cancer. Analysis of these samples will allow us to review the DNA and RNA characteristics (yield, purity and strand length) among sites. Downstream analysis of these same samples will also allow us to compare among sites the consistency of variant calls among centers. We will be able to identify if there are some times of calls (such as small insertion deletions) that are more variable among centers versus other types of calls (such as relative gene expression or single base pair substitutions) that we expect to be less variable and to characterize the reliability of findings across sites. We are also including a 5% blind duplicate analysis of RNA sequencing. Samples will be analysed by the participating genomics cores without knowledge of the phenotype. RNA seq and CNA analyses are normalized for batch effects. We will also compare the observed sex to the self-reported sex as based on RNA profiles and exome sequencing of X chromosome genes as another check for processing accuracy and sample management. D. References 1. Wacholder, S. Precursors in Cancer Epidemiology: Aligning Definition and Function. Cancer Epidemiol. Prev. Biomark. 22, 521-527 (2013). PMID: 23549395.2. Berman, J. J. Precancer: The Beginning and the End of Cancer. (Jones & Bartlett Learning, 2011).3. Nasiell, K., Nasiell, M. & Vaćlavinková, V. Behavior of moderate cervical dysplasia during long-term follow-up. Obstet. Gynecol. 61, 609-614 (1983). PMID: 6835614.4. Merrick, D. T. et al. Persistence of Bronchial Dysplasia Is Associated with Development of Invasive Squamous Cell Carcinoma. Cancer Prev. Res. (Phila. Pa.) 9, 96-104 (2016). PMID: 26542061.5. Gurel, B. et al. Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod. Pathol. Off. J. U. S. Can. Acad. Pathol. Inc 21, 1156-1167 (2008). PMID: 18567993.6. Meeker, A. K. et al. Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis. Cancer Res. 62, 6405-6409 (2002). PMID: 12438224.7. Guner, G. et al. Novel Assay to Detect RNA Polymerase I Activity In Vivo. Mol. Cancer Res. MCR 15, 577-584 (2017). PMID: 28119429.

  Study phs002225

• Resequencing candidate genes for male spermatogenic impairment

  This study aims to identify novel candidate variants from human Y-chromosomal genes DAZ, BPY2 and CDY1/2 by resequencing the coding regions of these genes from male patients with spermatogenic impairment. The coding regions of the genes plus a selection of phylogenetically informative Y-chromosomal markers have been amplified by standard PCR, amplicon lengths range from 178 to 486 bp. Amplicons were quantified by gel electrophoresis and pooled in approx. equimolar concentrations per patient. For each of the 480 submitted samples, approx. 1 microgram of amplified DNA pool was provided in a total volume of 120 microlitres. The samples were indexed and libraries prepared for PE250bp Illumina MiSeq runs. 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/ .

  Dataset EGAD00001006784

• Acral Melanoma PDXs from the admixed Brazilian Population- Tumour RNA expression data - htseq count files

  Files containing the read counts obtained with obtained with HTSeq for all the genes in Ensembl v103 annotation for GRCh38 human reference genome. This dataset contains the files for all Tumour samples. Acral melanoma (AM) is an aggressive melanoma subtype with limited therapeutic options and poor outcomes. In non-European descent and admixed populations, like in Latin America, it can account for a significant proportion of cutaneous melanoma cases. Here, we performed comprehensive genomic and functional profiling of AM from a uniquely diverse Brazilian cohort. Whole-exome and transcriptome sequencing was performed on both tumours and patient-derived xenograft (PDX) samples. The PDX were obtained from a comprehensive collection of patient-derived xenograft (AM-PDX) models that we established which faithfully retained the histopathological and genomic features of the original tumours.

  Dataset EGAD00001015745

• Genetics and Functional Studies of Autosomal Recessive Neurological Disorders

  Neurological conditions account for over 6% of the global disease burden. There are more than 600 neurological disorders, and cognitive dysfunction, also referred to as intellectual disability (ID), occupies a prominent position in this list. Cognitive dysfunction arises from the failure of neuronal cells to organize into a complex network and remodel this network in response to learning and experience. It is manifested by deficits in adaptive behaviors in everyday social and practical skills. Due to its high prevalence and the lifetime cost of care per individual, in the range of $1-2 million in United Sates (CDC), it presents a significant health burden. Genetic and functional studies of the genes and protein determinants of ID have helped to elucidate the molecular pathways of human brain development in health and disease. However, the identity of a large number of essential molecular and cellular components still remain elusive. The objectives of our study are to expand the genetic repertoire of causal ID genes and characterize their role in neuronal structure and cognitive function. The rationale is that identification and functional elucidation of causative gene variants that lead to cognitive dysfunction will be essential for understanding brain function and for developing improved diagnostic tools and efficacious preventive and therapeutic agents for neurological disorders, including ID. There are 3 aims of our comprehensive research program: 1) Ascertain and clinically phenotype members of extended families segregating autosomal recessive intellectual disability (ARID); 2) identify new ARID genes and gene products; and 3) determine the functions of prioritized novel ARID genes using multifaceted approaches, including analysis of spatiotemporal expression patterns in mouse brain, targeting in cultured rat hippocampal neurons, effects on cell morphology and synapse abundance, synaptic transmission and plasticity in neuronal cells by electrophysiology and live-cell imaging assays. The project will advantageously combine human clinical assessment, genetic and functional analyses relevant to brain development and function. Impact: Execution of the proposed studies will generate new knowledge that is clinically relevant, with high potential to impact ID molecular diagnosis, prognoses, and identify novel therapeutic targets to slow progression, delay onset, and possibly devising precision medicine approaches for ID.

  Study phs003298

• Epi4K: Gene Discovery in 4,000 Epilepsy Genomes

  The Epi4K project began in 2011 as an international, multi-center study that seeks to identify and characterize the genetic bases of complex epilepsies. The Center without Walls Epi4K project includes three cores and four scientific projects, as well as a steering committee comprised of the primary study investigators and representatives from the National Institute of Neurological Disorders and Stroke (NINDS). The three cores include: (1) The Administrative Core which handles the overall coordination of Epi4K activities; (2) The Sequencing, Biostatistics and Bioinformatics Core which is responsible for generating the next-generation sequence data, inferring the genetic variation in each of the study participants, and performing the primary analyses to identify epilepsy genes; and (3) The Phenotyping and Clinical Informatics Core which verifies and archives all the phenotypic data from each study participant. The proposed number of patients to be sequenced and analyzed in the scientific projects is a minimum of 4,000; thus the Center was named "Epi4K: Gene Discovery in 4,000 Genomes". Project 1 addresses the genetics of rare and severe childhood epilepsies, including epileptic encephalopathies (infantile spasms and Lennox-Gastaut syndrome), and malformations of cortical development (periventricular nodular heterotopia and polymicrogyria). Exome and genome sequence data generated from DNA collected from patients will be screened for mutations (single nucleotide substitutions, small insertion-deletions, and copy number variations) that cause or contribute to the diseases. Project 2 is focused on genetic discovery in multiplex families. This study will use next-generation sequencing to identify genomic variation that influences risk for common subtypes of epilepsy including idiopathic generalized epilepsy and nonlesional focal epilepsy. Project 3 seeks to identify genetic determinants of prognosis in patients with a range of epilepsy disorders. This study will study established epilepsy cohorts with well-characterized data on seizure outcome to look for relationships between genetic variation and pharmacological control of seizures. Project 4 will use next-generation sequencing data (exome and genome) to screen for epilepsy-associated copy number variation across all Epi4K projects using novel computational algorithms.

  Study phs000653

• Genomic Data Archive From the Network for Pancreatic Organ Donors With Diabetes

  The Network for Pancreatic Organ Donors with Diabetes (nPOD) is the largest biorepository of human pancreata from organ donors with type 1 diabetes (T1D), maturity-onset diabetes of the young (MODY), cystic fibrosis-related diabetes (CFRD), type 2 diabetes (T2D), gestational diabetes, and islet autoantibody positive (AAb+)/pre-T1D. The mission of the nPOD is to distribute biospecimens and associated de-identified data/metadata to an international researcher network, and to promote the development of new treatments for these diabetes conditions. Here, we describe the release of high-parameter genotyping data for the nPOD cohort. Specifically, 372 subjects were genotyped using a customized precision medicine single nucleotide polymorphism (SNP) microarray (UFDIchip). These data were technically validated using published algorithms to evaluate donor relatedness, ancestry, imputed HLA, and T1D genetic risk score. Additionally, 207 subjects were queried for rare known and novel coding region variants via whole exome sequencing (WES). These data are now publicly available, enabling genotype-selected sample requests and the study of novel genotype : phenotype associations, ultimately to explain diabetes heterogeneity and inform precision medicine strategies to interrupt diabetes pathogenesis.

  Study phs002861

• Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression

  Immunotherapy with chimeric antigen receptor T cells for pediatric solid and brain tumors is constrained by available targetable antigens. Cancer-specific exons present a promising reservoir of targets; however, these have not been explored and validated systematically in a pan-cancer fashion. To identify cancer specific exon targets, we analyze 1,532 RNA-seq datasets from 16 types of pediatric solid and brain tumors for comparison with normal tissues using a newly developed workflow. We find 2,933 exons in 157 genes encoding proteins of the surfaceome or matrisome with high cancer specificity either at the gene (n=148) or the alternatively spliced isoform (n=9) level. Expression of selected alternatively spliced targets, including the EDB domain of fibronectin 1, and gene targets, such as COL11A1, are validated in pediatric patient derived xenograft tumors. We generate T cells expressing chimeric antigen receptors specific for the EDB domain or COL11A1 and demonstrate that these have antitumor activity. The full target list, explorable via an interactive web portal (https://cseminer.stjude.org/), provides a rich resource for developing immunotherapy of pediatric solid and brain tumors using gene or AS targets with high expression specificity in cancer.

  Study EGAS00001007766

• RNA Ligation Precedes U6 snRNA/LINE-1 Retrotransposition

  Long Interspersed Element-1 (L1) retrotransposons make up approximately 17% of the human genome. L1 moves throughout the genome via a copy-and-paste mechanism termed retrotransposition. L1 retrotransposition also mobilizes other cellular RNAs such as SINES, U6 snRNA and, mRNA, which for the latter results in the formation of processed pseudogenes. In this study we demonstrate that the RNA ligase RtcB can create chimeric RNAs by joining U6 snRNAs to 5'-truncated L1 or other cellular RNAs. We also show that the retrotransposition of U6/L1 chimeric RNA leads to U6/L1 pseudogene formation. In sum, our data suggests that U6 snRNA and RtcB may have biological roles in addition to their essential functions in mRNA and tRNA splicing, and that the retrotransposition of chimeric RNAs could be a mechanism to create novel genes.

  Study phs001671

• Selection of somatic escape variants in SERPINA1 in liver tissue of patients with alpha-1 anti-trypsin deficiency - WGS

  Somatic variants accumulate in non-malignant tissues with age. Functional variants leading to clonal advantage of hepatocytes accumulate in the liver from patients with acquired chronic liver disease (CLD). Whether somatic variants are common to CLD from differing aetiologies is unknown. We analysed liver somatic variants in patients with genetic CLD from alpha-1 anti-trypsin (A1AT) deficiency or haemochromatosis. We show that somatic variants in SERPINA1, the gene encoding A1AT, are strongly selected for in A1AT deficiency, with evidence of convergent evolution. Acquired SERPINA1 variants are clustered leading to truncation or coding change at the C-terminus of A1AT. In vitro and in vivo, C-terminal truncation variants reduce disease-associated Z-A1AT polymer accumulation and disruption of the endoplasmic reticulum, supporting the C-terminal domain swap mechanism. Therefore, somatic escape variants from a deleterious germline variant are selected for in A1AT deficiency, suggesting functional somatic variants are disease-specific in CLD and point to disease-associated mechanisms.

  Dataset EGAD00001015430

• A Multimodal Atlas of Human Brain Cell Types

  "A multimodal atlas of human brain cell types" includes sample data targeting two cell types that show species differences between mouse and human. First, it includes a detailed transcriptomic, morphological, and electrophysiological characterization of cell types in layer 1 of human middle temporal gyrus, focusing primarily on different inhibitory cell types. This project also includes gene expression data collected from nuclei in layer 5 of human fronto-insula, with a goal of identifying transcriptomic signatures of Von Economo neurons. Control samples collected as part of the same experiment are also included in the data set. This study was conducted as part of a collaboration between the Allen Institute for Brain Science, the University of Szeged, and the J. Craig Venter Institute. Collaborators request that publications resulting from these data cite their original publication: Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type (PMID: 30150662).

  Study phs001791

• The Ultrasound Study of Tamoxifen

  The Ultrasound Study of Tamoxifen is a 12-month longitudinal study to describe volumetric breast density change over time among women with and without tamoxifen exposure. Women were enrolled at the Karmanos Cancer Institute and Henry Ford Health Systems in Detroit, Michigan between 2011-2014. Enrollment included women prescribed tamoxifen for clinical indication (n=82) and a comparison group of women frequency matched on age, race, and menopausal status (n=165). Whole breast ultrasound tomography (UST) scans were used to measure volume averaged sound speed (m/s) as a surrogate of volumetric breast density. Ultrasound tomography (UST) scans were completed at baseline prior to tamoxifen initiation and were repeated at 1-3 months, 4-6 months, and 12 months after tamoxifen initiation. For the comparison group, UST scans were completed at baseline and 12 months. Questionnaires were completed at each scan.

  Study phs003183

• NHLBI TOPMed: Boston Early-Onset COPD Study

  Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States and the only leading cause of death that is steadily increasing in frequency. This project collected a set of extended pedigrees ascertained through subjects with severe, early-onset COPD. This study has enrolled subjects with severe COPD (forced expiratory volume in one second (FEV1) < 40% predicted) at an early age (< 53 years) without alpha-1 antitrypsin deficiency (a known Mendelian risk factor for COPD). Extended pedigrees are enrolled, primarily in New England, although some more geographically distant subjects have been included. This study has been used for epidemiological studies, familial aggregation analysis, linkage analysis, and candidate gene association analysis. Approximately 80 of the severe, early-onset COPD probands will undergo whole genome sequencing in this project with sequencing data available through dbGaP.

  Study phs000946

• The Contribution of De Novo Coding Mutations to Meningomyelocele

  Meningomyelocele (MM) is considered a genetically complex disease resulting from the failure of the neural tube to close; a neural tube defect (NTD). Patients display neuromotor disability and frequent hydrocephalus requiring ventricular shunting. A few genes have been proposed to contribute to disease susceptibility, but most risk remains unexplained. 851 MM trios were recruited and we found 187 likely gene disrupting or damaging missense de novo mutations (DNMs) that are estimated to contribute to disease risk. These DNMs collectively define networks including actin cytoskeleton and microtubule-based processes, axon guidance, and histone modification. Gene validation demonstrates partial or complete loss of function, impaired signaling and defective neural tube closure in Xenopus embryos. Our results suggest DNMs make key contributions to MM risk, and highlight critical pathways required for neural tube closure in human embryogenesis. Data for 245 WES trios and 1 quad are available through dbGaP.

  Study phs003746

• Immediate Postoperative Minimal Residual Disease Detection with MAESTRO Predicts Recurrence and Survival in Head and Neck Cancer Patients Treated with Surgery

  We selected 24 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who were surgically treated. MAESTRO, our ultrasensitive, tumor-informed, mutation enrichment sequencing assay, was applied in a pooled format (MAESTRO-Pool) to plasma samples collected from these patients at baseline (pre-op) and postoperatively. We show that detection of circulating tumor DNA (ctDNA) 1 to 9 days after surgery is associated with significantly worse survival. Many plasma samples also had tumor fractions detected below 100 parts-per-million, the detection limit for first-generation commercial assays, highlighting the need for more sensitive ctDNA assays. Here we provide whole genome sequencing of matched tumor biopsy and normal germline DNA from 24 patients that were used to identify somatic single nucleotide variants (SNVs) to be tracked using our MAESTRO-Pool assay.

  Study phs003981

• Recurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissue

  In this study, the genomic landscape of extracutaneous juvenile xanthogranuloma (JXG) was analyzed. By leveraging the Dutch Nationwide Pathology Databank (Palga), tumor samples were obtained from different academic medical centers in the Netherlands. The study was approved by the Palga Scientific Council and Privacy Committee (LZV-2016-183) and the Institutional Review Board of Leiden University Medical Center (B19.074). In addition, the study was approved by the Biobank and Data Access Committee of the Princess Máxima Center for Pediatric Oncology (PMCLAB2024.0512). Provided are whole transcriptome sequencing (WTS) data of 3 histiocytic tumors with CLTC::SYK fusions. WTS was performed in the routine workflow of the Princess Máxima Center for Pediatric Oncology (as described in Hehir-Kwa, et al. JCO Precis Oncol 2022). RNA was derived from formalin-fixed paraffin-embedded tumor tissue (n=1) or from frozen tumor tissue (n=2).

  Study EGAS50000000584

• Autozygosity_pilot___British_Pakistani_from_Birmingham_2

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.

  Study EGAS00001000567

• Autozygosity_pilot___Pakistani_from_Birmingham

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 50-80%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples.

  Study EGAS00001000511

• Autozygosity_pilot___QMUL

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.

  Study EGAS00001000717

• Whole Genome Sequencing to track subclonal heterogeneity in 18 samples from 3 Chronic Lymphocytic Leukemia patients subjected to repeated cycles of therapy.

  This study took 18 samples from three patients with Chronic Lymphocytic Leukemia. The 3 CLL patients received multiple different treatments sequentially for a period of up to 7 years. Peripheral blood samples were taken at 5 specific time points during disease progression together with 1 matched buccal swab per patient. All the selected patients had unmutated IgVH status reflecting poor prognosis. However, none of the patients had complex genomic aberrations associated with aggressive disease. Peripheral blood samples and buccal smears were obtained from patients, who had given informed consent for sequential sample collection and analysis. Tumour samples were obtained before treatment, after treatment and at relapse and subjected to Ficoll separation. Lymphocyte cell purity was assessed by full blood count enumeration. Buccal smears were obtained and processed using Isohelix.

  Study EGAS00001000885

• Germline MBD4 Mutations and Predisposition to Uveal Melanoma

  Uveal melanoma (UM) arises from malignant transformation of melanocytes from the uveal tract. This rare tumor has a poor outcome with frequent liver metastases and primary resistance to treatment1. The only strong predisposing condition for UM is the BAP1 tumor predisposition syndrome due to germline BAP1 deleterious mutations. UMs are generally characterized by a very low tumor mutation burden (TMB). However, some UMs display a high level of CpG to TpG mutations associated with MBD4 inactivation. Here, we explored the incidence of germline MBD4 variants in a consecutive series of 1, 099 primary UMs, and identified 8 deleterious MBD4 mutations, an aprox 10-fold increased incidence compared with the general population. These mutations were associated with a high TMB in tested UMs. We thus demonstrated that MBD4 is the second major predisposing gene for UM.

  Study EGAS00001003941

• The impact of mutational clonality in predicting the response to anti-PD-L1/PD-L1 in advanced urothelial cancer

  The advent of immune checkpoint inhibitors (ICI) has radically changed the management and therapeutic treatment landscape for patients with cancer. It has been shown that the use of these inhibitors can result in long-term complete remissions even in cases with advanced stages of the disease. However, only a small fraction of patients respond to the treatment. A better understanding of which factors could drive this clinical benefit is fundamental to building more accurate predictive biomarkers and developing alternative therapeutic options for patients who are unlikely to benefit. In order to address this issue, we have generated and analyzed whole exome sequencing (WES) and RNA sequencing (RNASeq) data from a cohort of metastatic urothelial carcinoma patients (N = 27) treated with ICI such as anti-PD-(L)1 monoclonal antibodies.

  Study EGAS00001007086

• Transcriptome Changes in ASD (NRXN1α+/-) iPSC-derived neurons

  NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/β/γ. Previous studies on cultured cells show that the short NRXN1β primarily exerts excitation effect, whereas the long NRXN1α which is more commonly deleted in patients involves in both excitation and inhibition. However, patient-derived models are essential for understanding functional consequences of NRXN1α deletions in human neurons Quantitative RNA sequencing was performed by BGI using 50bp single-end strategy with BGI-SEQ500 sequencing device on iPSC-derived cortical neurons from 6 control lines; (2VC1, 3VCX1, 3VC2, 4C3, 4CX1, NCRM-1) of 4 healthy donors, and 4 NRXN1α+/- lines; (ND1C1, ND2C11, ND2CX1, ND4-1C2) from 3 ASD patients.

  Study EGAS00001005536

• Whole genome sequence: cardiomyopathy, 1 HCM patient

  In this study, we analyzed the genomic information by whole genome sequencing using peripheral blood samples from patients with various cardiovascular diseases including severe heart failure to identify genetic variants related to the pathology of cardiovascular diseases. The purpose is to elucidate the underlying mechanism and develop new therapeutic interventions for cardiovascular disease.

  Study JGAS000704

• Whole genome sequence: cardiomyopathy, 1 ARVC patient

  In this study, we analyzed the genomic information by whole genome sequencing using peripheral blood samples from patients with various cardiovascular diseases including severe heart failure to identify genetic variants related to the pathology of cardiovascular diseases. The purpose is to elucidate the underlying mechanism and develop new therapeutic interventions for cardiovascular disease.

  Study JGAS000705

• Sequencing data for oesophageal and related samples - ICGC DCC release 28 (WGS)

  WGS sequencing for 409 cases (832 samples) from the ICGC ESAD-UK project Tumours 50x Normals 30x HiSeq X BAM files These samples are all available in ICGC release 28

  Dataset EGAD00001004137

• IBD Whole Genome Sequencing Phase 1 (2018-08-03)

  We will sequence at 15X coverage the genomes of 960 IBD patients. These samples are currently onsite at Sanger and made available for sequencing via our collaboration with the UK IBD Genetics consortium. During the next quinquennium we intend to sequence the genomes of many thousand IBD patients and these 960 represent the first stage of this effort. Ultimately we will perform association tests comparing these genomes to similar numbers of control genomes to identify rare and low-frequency variants underlying IBD. . This dataset contains all the data available for this study on 2018-08-03.

  Dataset EGAD00001004272

• Investigating the genetics of immunity against Salmonella in humans (2019-09-05)

  This study entails whole genome sequencing of an interleukin (IL)-12 b-1 receptor-deficient individual who presented with a chronic systemic Salmonella Enteritidis infection that did not resolve with standard IFNg and antibiotic treatment. Whole genome sequencing of the patient's parents are also included. 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/ . This dataset contains all the data available for this study on 2019-09-05.

  Dataset EGAD00001005311

• Longitudinal profiling of circulating tumour DNA for tracking tumour dynamics in pancreatic cancer

  Whole genome sequencing from two resectable patients with pancreatic cancer for both normal and tumour tissue samples; whole exome sequencing from the two resectable patients and five unresectable patients of peripheral blood mononuclear cells and blood plasma (1-5 time points per patient), and whole exome sequencing of plasma samples from three chronic pancreatitis patients.

  Dataset EGAD00001008593

• Normal sample for patient SA495

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA495

  Dataset EGAD00001009372

• Normal sample for patient SA425

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA425

  Dataset EGAD00001009371

• Normal sample for patient SA423

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA423

  Dataset EGAD00001009370

• Normal sample for patient SA300

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA300

  Dataset EGAD00001009369

• Normal sample for patient SA291

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA291

  Dataset EGAD00001009368

• Normal sample for patient SA289

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA289

  Dataset EGAD00001009367

• Normal sample for patient SA286

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA286

  Dataset EGAD00001009366

• Normal sample for patient SA280

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA280

  Dataset EGAD00001009365

• Normal sample for patient SA239

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA239

  Dataset EGAD00001009364

• Normal sample for patient SA679

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA679

  Dataset EGAD00001009379

• Normal sample for patient SA680

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA680

  Dataset EGAD00001009380

• Normal sample for patient SA681

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA681

  Dataset EGAD00001009381

• Normal sample for patient SA682

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA682

  Dataset EGAD00001009382

• Normal sample for patient SA683

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA683

  Dataset EGAD00001009383

• Normal sample for patient SA678

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA678

  Dataset EGAD00001009378

• Normal sample for patient SA677

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA677

  Dataset EGAD00001009377

• Normal sample for patient SA673

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA673

  Dataset EGAD00001009373

• Normal sample for patient SA676

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA676

  Dataset EGAD00001009376

• Normal sample for patient SA674

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA674

  Dataset EGAD00001009374

• Normal sample for patient SA675

  Whole genome sequencing of normal sample for triple negative breast cancer patient SA675

  Dataset EGAD00001009375

• National Heart, Lung, and Blood Institute (NHLBI) Heart Healthy Lenoir (HHL) Genomics Study

  The HHL genomics study uses a systems approach to develop models integrating clinical and genomic data. Previously we developed and tested an approach known as the SAMARA (Supporting A Multidisciplinary Approach to Research in Atherosclerosis) project that applied recent advances in biomedical and computational sciences at The University of North Carolina at Chapel Hill to develop a deeper understanding of human cardiovascular disease (CVD). The Heart-Healthy Lenoir Project expands these studies into the community, using this methodology to: 1) determine the prevalence of genomic risk signatures in high-risk community populations using genome-wide Single Nucleotide Polymorphism (SNP) analysis; 2) develop novel genomic models incorporating high-risk features in this population; and 3) determine whether genomic signatures can be used to predict responsiveness to interventions that underlie CVD disparities. DNA was obtained from participants enrolled in two of the HHL clinical trials, 1) Improving Care for Patients With High Blood Pressure (NCT01425515) or 2) Heart-Healthy Lenoir Lifestyle Study (NCT01433484). Participants could enroll in both trials concurrently.

  Study phs001471

• CD8-targeted IL-2 unleashes tumor-specific immunity in human cancer tissue by reviving the dysfunctional T cell pool

  Tumor-specific CD8+ T cells are key effectors of antitumor immunity but are often rendered dysfunctional in the tumor microenvironment. Immune checkpoint blockade can restore antitumor T cell function in some patients, however most do not respond to this therapy, often despite T cell infiltration in their tumors. We here explored a CD8-targeted IL-2 fusion molecule (CD8-IL2) to selectively reactivate intratumoral CD8+ T cells in patient-derived tumor fragments. Treatment with CD8-IL2 broadly armed intratumoral CD8+ T cells with enhanced effector capacity, thereby specifically enabling reinvigoration of the dysfunctional T cell pool to elicit potent immune activity. Notably, the revival of dysfunctional T cells to mediate effector activity by CD8-IL2 depended on simultaneous antigen recognition and was quantitatively and qualitatively superior to that achieved by PD-1 blockade. Finally, CD8-IL2 was able to functionally reinvigorate T cells in tumors resistant to anti-PD-1, underscoring its potential as a novel treatment strategy for cancer patients.

  Study EGAS00001007712

• ovarian cancer sample RNA-seq

  Tissue samples were collected from 18 ovarian cancer patients. After mechanical and enzymatic dissociation, a part of these tissues underwent growth factoromics analysis. For four cases, single-cell sequencing analysis was conducted under conditions with or without estradiol. Additionally, the remains of the tissues were frozen and subsequently subjected to bulk RNA-sequencing on 17 of these samples. Sixteen cases were diagnosed as HGSOC, while two samples were clear cell or mucinous type (Extended Data Table 1). All cases were grade 3, and none had received neoadjuvant chemotherapy. - Group C1, Epithelial Ovarian Cancer(EOC) patients with estrogen responsiveness : 6 samples - Group C2, Epithelial Ovarian Cancer(EOC) patients with estrogen non-responsiveness : 10 samples - non-classified 1-sample

  Dataset EGAD50000000613

• Illumina GSA-MD v3 genotyping arrays for 183 samples

  Genotyping arrays for 183 samples from patients with a neuroendocrine tumor of the small intestine. All samples have been hybridized on Illumina GSA-MD v3 arrays with standard automated protocols. Reading of the chips was performed on Illumina iScan+ scanners and this file is the result of primary analysis done using Illumina GenomeStudio software. It contains data for 147 tumors, 2 adenomas, 1 lymph node, 19 mesenteric nodules, 6 liver metastasis and 8 normal ileum samples.

  Dataset EGAD50000000905

• Targeted long-read snIso-Seq of the human brain in neurodegenerative diseases

  Nuclei were extracted from postmortem human brain, and cDNA libraries were generated using the 10X Genomics 3' v3.1 kit. Prior to fragmentation, 75% of the library was reserved for long-read sequencing. This unfragmented library was used for target enrichment with a custom 50 gene probe panel from Twist Biosciences. The resulting amplified cDNA libraries were sequenced on a Sequel II. The files provided have undergone CCS generation, and we recommend following the guidelines in https://isoseq.how/ for further analysis starting with removal of primers using lima. The primer sequences that should be supplied are the Read 1 and TSO primers from the 10X Genomics kit.

  Dataset EGAD50000000179

• Detection of cancer cell transcriptomes

  Single cell transcriptomes, generated using chromium 10X 3' sequencing, for two tumour types (AT/RT, and Ewing's sarcoma). For each individual, tumour and normal whole genome sequencing was also obtained using Illumina short read sequencing to an average depth of 30X. These data were used to validate the accuracy of a method for identifying cancer cell transcriptomes based on the allelic shift produced by copy number changes.

  Dataset EGAD00001009005

• BM xenograft TARGET-seq+ single-cell transcriptome sequencing

  Single-cell whole transcriptome sequencing data for 5 xenografted bone marrow samples (4 cases with clonal haematopoiesis and 1 without clonal haematopoiesis). For each sample, mice were treated with two doses of PBS or hTNFa. CD34+ HSPCs and CD34-CD33+ myeloid cells were isolated from xenografted mice, sorted into plates, and TARGET-seq+ was performed to generate plate-based 3' transcriptome data. Additionally, cells from a control primary bone marrow sample (NOC153) were included on each plate. Each library consist of 192 cells sorted into a single plate. FASTQ files are provided; R1 contains cell barcodes and R2 contains the cDNA read. For demultiplexing and pre-processing instructions see: https://github.com/asgerjakobsen/TARGET-seq-plus-RNA.

  Dataset EGAD50000002382

• Insights into non-crossover recombination from long-read sperm sequencing

  Meiotic recombination is a fundamental process that generates genetic diversity by creating new combinations of existing alleles. While crossovers in humans are well characterized, the more frequent non-crossovers that lead to gene conversion remain challenging to study. Here we show that single high-fidelity long sequencing reads from sperm can capture both crossovers and non-crossovers, allowing effectively arbitrary sample sizes for analysis from one male. Using fifteen sperm samples from thirteen donors we demonstrate variation between donors for the different types of recombination, even when they share the same PRDM9 genotype. Non-crossovers are less consistent with the genetic map and exhibit reduced association with meiotic double-strand break (DSB) sites identified by DMC1 binding. Where non-crossover gene conversions are close to PRDM9 sites they tend to occur upstream. We further provide evidence for two distinct non-crossover processes. One gives rise to the vast majority of non-crossovers with mean conversion tract length under 50bp, while ~1% of non-crossovers have much longer mean tract length. Applying the same analysis pipeline to public data from twelve blood samples, we also see non-crossover gene conversions, but very few crossover events. These non-meiotic events, not correlated with the genetic map, increase with age, consistent with double-strand break repair throughout life. We suggest that many of the non-crossover events seen in sperm also derive from non-meiotic repair prior to spermatogenesis.

  Dataset EGAD00001015736

• WGSPD Project 1: Whole Genome Sequencing for Schizophrenia and Bipolar Disorder

  The Center for Genomic Psychiatry at the University of Southern California (USC) and an extensive network of academic medical centers have created the Genomic Psychiatry Cohort (GPC). The GPC consists of a large clinical cohort of patients with schizophrenia, bipolar disorder, and healthy controls. The pilot phase of whole genome sequencing of the GPC has been done in collaboration with the USC and the Broad Institute of MIT and Harvard. Whole genome sequencing (20X) and analysis of 9,033 well-phenotyped individuals from the Genomic Psychiatry Cohort (GPC), divided among schizophrenia cases, bipolar disorder cases, and psychiatrically normal controls, and comprised of European-Ancestry (EA), African-Ancestry (AA), and Latino individuals. The combination of clinically well-characterized GPC participants and whole genome sequencing with rich functional annotation aims to identify functional variants associated with schizophrenia and bipolar disorder risk. Over half of the sequenced samples are patients with a diagnosis of either schizophrenia or bipolar disorder. The majority of the study participants are of African American ancestry, increasing the diversity of sampling for these important diseases in traditionally understudied populations. This data set also contains 545 samples that have undergone 10x Genomics Linked-Read Sequencing (169 participants overlapping with the 9,033 participant WGS 20X dataset). In addition to the benefits due to disease phenotyping and ancestry selection that apply to all of the WGSPD Project 1 samples, the 10x Genomics Linked-Read samples, through the use of barcodes that can identify the long input DNA fragment that each sequencing read was generated from, can be used to 1) identify structural variants that are difficult to call with standard short read data, 2) map short reads to repetitive regions of the genome that cannot be assayed with standard short reads, and provide highly accurate phasing information about genetic variants, including rare variants that are more difficult to phase using statistical phasing techniques.

  Study phs002041

• Annotated VCF Files for WGS of ASD Cohort with 68 Individuals from 22 families, enriched for recent shared ancestry

  We performed whole genome sequencing (WGS) in an ASD cohort of 68 individuals from 22 families enriched for recent shared ancestry. Samples were sequenced using Illumina HiSeq X platform, and Variants (single nucleotide variants (SNVs) and insertions or deletions (indels)) were detected using GATK with HaplotypeCaller. Quality control checks for (i) duplicate samples, (ii) samples per platform, (iii) genome call rate, (iv) missingness rate, (v) singleton rate, (vi) heterozygosity rate, (vii) homozygosity rate, (viii) Ti/Tv ratio, (ix) inbreeding coefficient, and (x) sex inference were performed as previously described. Variant call format (VCF) files for SNVs and indels were annotated with ANNOVAR using allele frequencies from the 1000 Genomes project (2015; 1000G), the Genome Aggregation Database (gnomAD), and the Greater Middle East Variome Project (GME).

  Dataset EGAD00001008634

• Single-cell RNA sequencing of sorted regulatory T cells

  Single-cell RNA sequencing of flow cytometry enriched CD4+ CD127- CD25+ regulatory T cells from 8 systemic lupus erythematosus patients (SLE_001 to SLE_007, and SLE_009) collected at baseline (day 0, before interleukin-2 immunotherpay) and day 5 (after 1 treatment cycle of interleukin-2 immunotherapy). Sorted immune cells were hash tagged and then stained with TotalSeq Human Universal Cocktail (Biolegend) before further processing for single-cell RNA sequencing using the 10X-Genomics platform (incl. generation of TCR libraries). Samples from patients SLE_001, SLE_002, SLE_004, SLE_006 were collected and processed on the first day of experiment (Day 1), and samples from patients SLE_003, SLE_005, SLE_007, SLE_009 on the second day of experiment (Day 2). On each day, samples were pooled and distributed to four lanes on the chromium controller. Run ID 245269 and ID 245270 identify samples sequenced on separate flow cells. Provided are raw sequencing files.

  Dataset EGAD50000000663

• Transdisciplinary Studies of Genetic Variation in Colorectal Cancer(CORECT): Meta-analysis

  This study is part 2 of 2 for Schumacher et al, Nat Communication. 2015 Jul 7;6:7138. Part 2 is the pooled meta-analysis of 29 different studies of 37,955 European (18,299 Cases/19,656 Controls) participants using eight different genotyping platforms/variations. table, th, td { border: 1px solid black; border-collapse: collapse; } Study Name Participants Platform CFR-1 2976 Illumina 1M, 1M Duo, Omni1 CFR-2 3053 Affymetrix Axiom MECC 1 982 Illumina Omni 2.5 MECC2 1940 Affymetrix Axiom Kentucky 2172 Affymetrix Axiom ACS/CAPII 1086 Affymetrix Axiom Melbourne 1008 Affymetrix Axiom Newfoundland 672 Affymetrix Axiom ASTERKSI 1895 Illumina 300K COLO23 212 Illumina 300K DACHS1 3417 Illumina 300K DACHS2 1173 Illumina OmniExpress DALS1 1416 Illumina 550k/610K DALS2 874 Illumina 300K HPFS1 457 Illumina OmniExpress HPFS2 348 Illumina OmniExpress HPFS AA 658 Illumina OmniExpress MEC 674 Illumina 300K NHS1 1168 Illumina OmniExpress NHS2 340 Illumina OmniExpress NHSAA 1091 Illumina OmniExpress OFCCR 1172 Affymetrix 100k/500K PHS 771 Illumina OmniExpress PMH 402 Illumina 300K PLCO1 2509 Illumina 550k/610K PLCO2 901 Illumina 300K VITAL 573 Illumina 300K WHI1 1999 Illumina 550k/610K WHI2 573 Illumina 300K Since this study is a meta-analysis no corresponding phenotype, pedigree, sample, subjects, or primary molecular data are available. Each contributing study/platform will have fulfilled its own DBGAP submission commitment. This DBGAP entry is for European participants in the the pooled meta-analysis exclusively.

  Study phs001499

• National Cancer Institute Multi-Ancestry Genome-Wide Association Study of Kidney Cancer (NCI-3)

  The National Cancer Institute (NCI) multi-ancestral genome-wide association study (GWAS) of kidney cancer ("NCI-3") was performed by NCI to further investigate common genetic variants associated with risk of kidney cancer and its two major subtypes across individuals of different ancestries (European, African, East Asian, Latin American). The NCI-3 GWAS includes 12,315 cases and 73,091 controls from 25 centers in North America, South America and Europe, genotyped using the Illumina Global Screening Array v2.0. SNP-level results from this GWAS were combined by meta-analysis with results from two earlier NCI European-ancestry GWAS (RCC; phs000351: 1,311 cases and 3,424 controls and phs001736: 2,417 cases and 4,391 controls), a NCI GWAS of African Americans (phs000863; 255 cases and 375 controls), GWAS conducted at other institutions [International Agency for Research on Cancer (scan 1: 2,438 cases and 5,071 controls; scan 2: 2,781 cases and 2,940 controls), The University of Texas MD Anderson Cancer Center (scan 1: 893 cases and 556 controls, scan 2: 1,241 cases and 1,712 controls) and the Institute for Cancer Research, UK (944 cases and 4,024 controls)] and GWAS analyses of data from three large biobanks (Biobank Japan: 523 cases and 86,306 controls; FinnGen: 2,095 cases and 304,956 controls; UK Biobank: 1,807 cases and 348,824 controls). Only individual-level data from NCI-3 and the two MD Anderson Cancer Center scans are included in this dbGaP submission. All study-specific and meta-analysis summary statistics are included.

  Study phs003505

• Enhanced Adjuvanticity of a Personal Neoantigen Vaccine Generates Potent Neoantigen-Specific Immunity

  Personalized neoantigen-targeting vaccines can induce durable and diverse T cell responses and have been associated with improved outcomes. To augment immunogenicity, we tested a synthetic long peptide vaccine formulated with the adjuvants Montanide and poly-ICLC in 10 patients with melanoma. The vaccines, co-administered locally with ipilimumab and systemically with nivolumab, generated de novo ex vivo T cell responses against the majority of immunizing neoepitopes in all 9 fully vaccinated patients, and ex vivo CD8+ T cell responses in 6 of 9. Hundreds of circulating and intratumoral T cell receptor (TCR) clonotypes emerged following vaccination that were distinct from those arising after PD-1 inhibition. By linking vaccine-specificity and cellular phenotype of TCRs in post-treatment tumors at single cell resolution, we demonstrate remodeling of the intratumoral T cell repertoire following vaccination. These observations demonstrate the impact of multi-pronged immune adjuvanticity on the T cell repertoire in the context of neoantigen-targeting vaccines. We are submitting WES data from whole blood samples and tumor FFPE samples, and RNA-seq data from tumor FFPE samples. We are also submitting RNA-seq data from purified tumor samples. scRNA-seq data will also be submitted for skin samples (pre and post neoantigen vaccine dose #3), and tumor samples before starting treatment, before starting neoantigen vaccine Dose #1, and before neoantigen vaccine dose #4. Bulk TCR-seq data will be submitted for blood samples.

  Study phs003919

• EGAD00010000702

  SNP-chip genotyping data for one proband in the DDD study (Ref : Carvalho AJHG 2015)

  Dataset EGAD00010000702

• Sequencing data for ICGC Oesophageal Adenocarcinoma tissue samples - TLR_pathway_study

  upcoming publication

  Dataset EGAD00001001960

• Sequencing data for oesophageal and related samples - Mourikis et al (RNA)

  Data supporting: "Patient-specific detection of cancer genes reveals recurrently perturbed processes in esophageal adenocarcinoma." Mourikis et al. RNAseq (BAM files) 137 samples

  Dataset EGAD00001004776

• Sequencing data for oesophageal and related samples - Nowicki-Osuch, Zhuang et al (bulk RNA)

  Data supporting: “Deep molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition.” Nowicki-Osuch, Zhuang et al. RNAseq (BAM files) 241 tumour samples

  Dataset EGAD00001005388

• Long read sequencing of 5 Intellectual Disability (ID) trios with PacBio Sequel. Dataset of samples: T2P, T2F and T2M

  5 trios were whole genome sequenced with PacBio Sequel to a depth of 15X (Trios 1-4) or 40X (Trio 5). For each trio the child was affected with severe ID, and the parents were unaffected. Dataset consists of Trio 2 samples: T2P, T2F and T2M

  Dataset EGAD00001006050

• High coverage Whole exome DNA sequencing on pre-treatment tumor samples (n=3) matched with post-treatment metastasized lymph nodes isolated with laser microdissection (n=3)

  Data from NABUCCO cohort 1 (NCT03387761). This dataset includes High coverage Whole exome DNA sequencing on pre-treatment bladder tumor samples (n=3) matched with post-treatment metastasised adjacent lymph nodes isolated with laser microdissection (n=3) for 3 unique patients

  Dataset EGAD00001006852

• HV31 - Bionano DLS optical mapping

  Bionano DLS optical mapping data for individual HV31 generated using DNA from peripheral blood mononuclear cells, to a molecule depth of ~153×. Optical mapping was performed at the Weatherall Institute of Molecular Medicine using the Bionano Saphyr platform.

  Dataset EGAD00001007049

• HV31 - De novo assembly of eight immune system regions

  De novo assembly of eight immune system regions for individual HV31, generated using a multi-platform pipeline. A full description of the generation of these assemblies can be found at https://doi.org/10.1101/2021.02.03.429586.

  Dataset EGAD00001007050

• McGill EMC Community projects Release 7 for cell line "SaOS-2"

  Complete reference epigenome (as defined by IHEC) of a SaOS-2 cell line with osteosarcoma.

  Dataset EGAD00001007678

• RNA-seq on neuroblastoma PDX model COG-N-519 treated with control miR-1283 and test miR-99b-5p mimics

  RNA-sequencing on neuroblastoma PDX model COG-N-519 treated with control miR-1283 and test miR-99b-5p mimics. Three samples from each of the treatment condition were analysed. Next-Seq platform was used for sequencing.

  Dataset EGAD00001008035

• Sequencing data for oesophageal and related samples - Ng, Contino et al (RNA)

  Data supporting: "Interplay of processes shapes structural variations undergoing selection in oesophageal adenocarcinoma" Ng, Contino et al. RNAseq (BAM files) 214 oesophageal adenocarcinoma samples

  Dataset EGAD00001007809

• Paired healthy & tumor organoid Biobank _B16PON

  Organoid cultures derived from colorectal adenomas. RNA and DNA was isolated from these cultures for genome wide profiling.

  Dataset EGAD00001008949

• WXS dataset for Unraveling mutagenic processes influencing the tumor mutational patterns of individuals with Constitutional Mismatch Repair Deficiency

  Molecular characterization of 41 tumors from 17 individuals with CMMRD to gain a better understandig of mutational processes driving subsequent tumor development. The molecular characterization includes the investigation of tumor mutational load and mutational signatures.

  Dataset EGAD00001015158

• Profiling the Microbiome of Pediatric Gut with Metagenomic Short-Read Sequencing

  This dataset contains short-read metagenomic sequencing of stool, as well as intestinal tissue and tissue washes, from preterm infants. 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/

  Dataset EGAD00001016052