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• Etiology of congenital thyroid dysfunction in Down Syndrome: a multi-omics investigation

  The goal of this study was to investigate dfiferences in the thyroid DNA methylome and transcriptome between fetuses with Down syndrome and fetuses with no genetic/developmental abnormality.

  Study EGAS50000000264

• Microbial signatures and innate immune gene expression in lamina propria phagocytes of inflammatory bowel diseases patients

  The microbial populations associated with the lamina propria phagocyte population in CD and UC patients was examined. Specifically, the differences between phagocyte-associated microbiota (PAM) and mucosa-associated microbiota were determined.

  Study EGAS00001003105

• Whole-genome sequences of single-cell derived clonal samples and bulk blood samples from human

  Human single cells were clonally expanded by culture and whole-genome sequenced. This dataset includes 334 clonal samples and 7 blood bulks from seven individuals (DB2, DB3, DB5, DB6, DB8, DB9, DB10). We extracted genomic DNA materials from clonally expanded cells and matched peripheral blood using DNeasy Blood and Tissue kits (Qiagen) according to the protocol. DNA libraries for WGS were generated by an Accel-NGS 2S Plus DNA Library Kit (Swift Biosciences) from 1 µg of genomic DNA materials. WGS was performed on either the Illumina HiSeq X platform or the NovaSeq 6000 platform to generate mean coverage of 25.2X for 374 clonally expanded cells and 94.8X for 7 matched blood tissues.

  Dataset EGAD00001007032

• Dataset of 4 WGS and 35 WES tumor and control runs linked for the ImmuNEO publication out of EGAS00001004813

  Sequencing data of 39 tumor and control runs (different tumors and blood controls), which were uploaded to EGAS00001004813 and reused in this ImmuNEO publication. The sequencing was always paired.

  Dataset EGAD00001009671

• Whole genome sequencing of mature B-cell lymphomas to identify MYC, BCL2, and BCL6 rearrangements

  Whole genome sequencing (WGS) data of 12 tumours was generated on an Illumina NovaSeq or HiSeqX instrument. For frozen samples, libraries were constructed using a PCR-free library construction method. For tumours preserved by formalin fixation and paraffin embedding (FFPE), libraries were constructed with a method that included S1 nuclease treatment. Reads were aligned to the grch37 reference with bwa-mem 0.7.17.

  Dataset EGAD50000000474

• Exome sequencing of control DNA samples from patients with Waldenstrom macroglobulinemia

  DNA extracted from sorted CD3+ cells (16 patients) was used for exome capture with the SureSelect All Exon Kit following the standard protocols. Paired-end sequencing (2 x 100 bp) was performed using HiSeq2000 sequencing instruments.The files are in FASTQ format.

  Dataset EGAD00001005323

• Pediatric Patient-Derived-Xenograft development in MAPPYACTS – international pediatric cancer precision medicine trial in relapsed and refractory tumors

  Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Paediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This new PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and new treatments development in advanced pediatric malignancies.

  Dataset EGAD00001011048

• Induction of fetal meiotic oocytes from embryonic stem cells in cynomolgus monkeys

  Human in vitro oogenesis provides a framework for clarifying the mechanism of human oogenesis. To create its benchmark, it is vital to promote in vitro oogenesis using a model physiologically close to humans. Here, we establish a foundation for in vitro oogenesis in cynomolgus (cy) monkeys: cy female embryonic stem cells harboring one active and one inactive X chromosome (Xa and Xi, respectively) differentiate robustly into primordial germ cell-like cells, which in xenogeneic reconstituted ovaries develop efficiently into oogonia and, remarkably, further into meiotic oocytes at the zygotene stage. This differentiation entails a comprehensive epigenetic reprogramming, including Xi reprogramming, yet, as partly observed in vivo, Xa and Xi remain epigenetically asymmetric with incomplete Xi reactivation. In humans and monkeys, the Xi epigenome in pluripotent stem cells functions as an Xi-reprogramming determinant. We further show that developmental-pathway over-activations with suboptimal up-regulation of relevant meiotic genes impede in vitro meiotic progression. Cy in vitro oogenesis exhibits critical homology with the human system, including with respect to bottlenecks, providing a salient model for advancing human in vitro oogenesis.

  Study JGAS000573

• Melanoma_post_mortem_analysis

  This is a targeted pulldown validation in support of the existing whole-genome sequencing study of melanoma metastases (Canapps ID:1888). We are studying the genomic evolution of cutaneous melanoma metastases. In this pulldown analysis we are specifically sequencing the subclonal variants that we believe account for the variability between the metastases.

  Study EGAS00001003531

• Divergence between high metastatic tumor burden and low circulating tumor DNA concentration in metastasized breast cancer

  Circulating tumor DNA (ctDNA) was reported to represent a highly sensitive biomarker of metastatic cancer disease directly reflecting tumor burden and dynamics. Here we investigated the role of ctDNA in patients with metastatic breast cancer. In an index patient with more than 100,000 circulating tumor cells (CTCs) in serial blood analyses, whole genome, exome, or targeted deep sequencing of the primary tumor, metastases, and 551 CTCs were consistent with a genetically homogeneous cancer. However, the allele fractions (AFs) of ctDNA were only 2-3% in each analysis, which did neither reflect the tumor burden nor the dynamics of this progressive disease by far. Indeed, plasma analyses of 71 further patients demonstrated highly variable AFs of mutant fragments, which frequently did not correspond to the tumor burden. These results provide insights into mechanisms involved in CTC and ctDNA release into the circulation and have important implications for diagnostic tests based on liquid biopsies.

  Study EGAS00001000625

• Copy number analysis by SNP array

  Hybridization-based genomic profiling arrays were performed using Genome-Wide Human SNP Array 6.0 or the CytoScan HD array, according to the manufacturer’s instructions (Affymetrix, Santa Clara, CA, USA) now part of Thermo Fisher Scientific (Thermo Fisher Scientific, Inc.) Following the procedures of sample preparation, hybridization, and scanning, the CEL file of Genome-Wide Human SNP Array 6.0 was analyzed as previously described (Magrangeas et al. 2012) and the CEL file of CytoScan HD array was analyzed using the Chromosome Analysis Suite (ChAS) software (Thermo Fisher Scientific, Inc).

  Study EGAS00001005125

• Targeted DNA sequencing and mRNA sequencing data from patients with peritoneal metastasis from colorectal cancer

  Patients with peritoneal metastasis from colorectal cancer (PM-CRC) have inferior prognosis and respond particularly poorly to chemotherapy. This study aims to identify the molecular explanation for the observed clinical behavior and suggest novel treatment strategies in PM-CRC. Tumor samples (230) from a Norwegian national cohort undergoing surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (MMC) for PM-CRC were subjected to targeted DNA sequencing, and associations with clinical data were analyzed. mRNA sequencing was conducted on a subset of 30 samples to compare gene expression in tumors harboring BRAF or KRAS mutations and wild-type tumors.

  Dataset EGAD50000000593

• 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

• Repeated_clinical_malaria_episodes_are_associated_with_modification_of_the_immune_system_in_children_

  Repeated clinical malaria episodes are associated with modification of the immune system in children.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 EGAS00001003167

• 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

• Paired exome analysis in urothelial carcinoma

  In this study we characterized genomic alterations in two to five metachronous tumors from 29 patients initially diagnosed with early stage disease. Fourteen patients (32 tumors) had non progressive disease (NPD) and 15 patients (34 tumors) had progressive disease (PD). Whole exome sequencing (WES, ~50x mean read depth), Ultra deep targeted sequencing (~6,809x mean read depth) and whole transcriptome RNA-seq was performed for all samples. In addition multiregional WES was performed on 8 adjacent regions from a single tumor.

  Study EGAS00001001686

• Single nuclei RNA-Seq from 5 regions of the human fetal brain

  Data generated through single nuclei RNA sequencing on 5 regions of the brain (frontal cortex, ganglionic eminence, hippocampus, thalamus and cerebellum) from 3 fetuses (two of 14 and one of 15 post-conception weeks, all female). Tissue was acquired from the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) with ethical approval. snRNA-seq libraries were prepared from ∼10,000 nuclei from each sample using Chromium Single Cell 3ʹ (v3) reagents (10X Genomics). Quality control of libraries was performed using the Agilent 5200 Fragment Analyzer before sequencing on an Illumina NovaSeq 6000 to a depth of at least 865 million (median = 1.01 billion) read pairs per library. Raw sequencing data were converted into FASTQ files. For a full description of data generation, please see Cameron et al, Biological Psychiatry 2022, https://doi.org/10.1016/j.biopsych.2022.06.033.

  Dataset EGAD00001009303

• ISA Nutrition 2015

  Comprehensive data on lifestyle-related modifiable factors, sociodemographic, anthropometric, economic, biochemical, and genetic markers related to the occurrence of cardiometabolic diseases as part of the observational cross-sectional survey (2015 Health Survey of Sao Paulo with Focus on Nutrition (2015 ISA-Nutrition), a population-based study. Data of 805218 SNPs for 841 individuals was genotyped using the Axioma 2.0 Precision Medicine Research Array in the Thermo Fisher Scientific laboratory (Affymetrix Inc, Santa Clara, CA).

  Dataset EGAD00010002678

• University of Alabama at Birmingham (Xenotransplantation Project) - DAC

  This is a Data Access Committee (DAC) developed to govern access to sequence level data produced by the Porrett Lab, University of Alabama at Birmingham (Xenotransplantation Project), and headed by Dr. Jayme Locke, and Dr. Porrett M. Paige, Principal, and Co-Principal Investigators respectively. These data were largely used in the generation of the manuscript: “Spatiotemporal immune atlas of the first clinical-grade gene-edited pig-to-human kidney xenotransplant”. Access to these data will be granted to qualified investigators for appropriate use following data use approval from members of the DAC.

  Dac EGAC50000000188

• 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

• Egypt Genome Project - low coverage whole genome sequencing

  All humans outside Africa are descendants of the same single exit, usually dated at 50-70 thousand years ago. However, the route taken out of Africa is still debated. The two main candidates are a northern route via Egypt and the Levant, or a southern route via Ethiopia and the Arabian Peninsula. We are generating genetic data to evaluate these two possibilities. In this study we propose to generate low-coverage sequencing data for 100 Egyptian samples.

  Dataset EGAD00001001372

• Egypt Genome Project - high coverage whole genome sequencing

  All humans outside Africa are descendants of the same single exit, usually dated at 50-70 thousand years ago. However, the route taken out of Africa is still debated. The two main candidates are a northern route via Egypt and the Levant, or a southern route via Ethiopia and the Arabian Peninsula. We are generating genetic data to evaluate these two possibilities. In this study we propose to generate high-coverage sequencing data for 3 Egyptian samples.

  Dataset EGAD00001001380

• NHLBI TOPMed: Chicago Initiative to Raise Asthma Health Equity (CHIRAH)

  The CHIRAH project was a community-based study of the factors associated with asthma morbidity in the African American population. CHIRAH evaluated the role of various variables (biologic/environmental, psychologic/behavioral, and socioeconomic) on asthma morbidity and the function of changes in these variables on asthma morbidity in a longitudinal fashion. This involved collection of a cohort-based on school screening which was sampled to include similar numbers of underprivileged and non-underprivileged subjects which roughly equally represented self-reported African Americans and self-reported non-African Americans. Subjects were followed up every 3 months of this cohort over the course of 2 years.

  Study phs001605

• An analysis of humoral and cellular immune responses following COVID-19 vaccination.

  Two dose mRNA vaccination provides excellent protection against SARS-CoV-2. However, there are few data on vaccine efficacy in elderly individuals above the age of 801. Additionally, new variants of concern (VOC) with reduced sensitivity to neutralising antibodies have raised fears for vulnerable groups. Here we assessed humoral and cellular immune responses following vaccination with mRNA vaccine BNT162b22 in elderly participants prospectively recruited from the community and younger health care workers. Median age was 72 years and 51% were females amongst 140 participants. Neutralising antibody responses after the first vaccine dose diminished with increasing age, with a steep drop in participants over 80 years old. Sera from participants below and above 80 showed significantly lower neutralisation potency against B.1.1.7, B.1.351 and P.1. variants of concern as compared to wild type. Those over 80 were more likely to lack any neutralisation against VOC compared younger participants following first dose. Binding IgG and IgA antibodies were lower in the elderly, as was the frequency of SARS-CoV-2 Spike specific B- cells. We observed a trend towards lower somatic hypermutation in participants with suboptimal neutralisation, and elderly participants demonstrated clear reduction in class switched somatic hypermutation, driven by the IgA1/2 isotype. SARS-CoV-2 Spike specific T- cell IFN?? and IL-2 responses were secreted primarily by CD4 T cells, and impaired in the older age group. We conclude that the elderly are a high risk population that warrant specific measures in order to mitigate against vaccine failure, particularly where variants of concern are circulating. Specifically, the dosing interval should not be extended in this group.

  Study EGAS00001005380