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• Suspected Lynch syndrome dataset

  This dataset comprises a genomic and a phenotypic excel sheet displaying 137 cases classified as suspected Lynch syndrome. Included are genotypic data such as tumour mutational burden, tumour mutational signatures and germline/somatic variant calls for each colorectal, endometrial or sebaceous skin tumour screened. Genomic data is derived from targeted multigene panel sequencing including ~300 hereditary cancer genes.

  Dataset EGAD50000000031

• SNP Array data for: Three-dimensional patient-derived models of glioblastoma retain intra-tumoral heterogeneity

  4 sets of matched patient-derived-organoids (PDOs),  -neurospheres (PDNs), and parent glioblastoma tissue (12 samples total) underwent SNP array analysis. 200ng of each sample DNA extracted via a commercial kit (Qiagen) and loaded onto the Global Screening Array v2.0 array. Data is provided as raw red and green .idat files.

  Dataset EGAD00010002744

• single-cell RNA-Seq samples of CRC patients

  The dataset contains samples of 11 CRC patients (2 samples for each patient, tumor and normal adjacent tissue site, 22 samples in total). Dataset is composed by fastq file (paired end) type from 10x single-cell RNA-Seq.

  Dataset EGAD00001009634

• 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

• Sequencing data for personalized therapy design and endotype identification

  Whole exome sequencing of 15 DNA samples, and whole genome sequencing of 2 matched DNA samples. Whole exome sequencing is of RMS samples (both alveolar and embryonal) and from cell lines as well as patient samples. Patient samples are of pediatric RMS patients.

  Dataset EGAD00001005458

• cfMeDIP-seq for 18 patients with pleural mesothelioma

  The dataset contains cfMeDIP-sequencing data (bam files) for 18 plasma samples from pleural mesothelioma patients. The libraries were prepared according to the published protocol (Shen, S. Y., Burgener, J. M., Bratman, S. V. & De Carvalho, D. D. Preparation of cfMeDIP- seq libraries for methylome profiling of plasma cell-free DNA. Nat. Protoc. 14, 2749–2780 (2019)). Whole genome sequencing (WGS) was performed for pre-made libraries on NovaSeq X Plus with a 150 paired-end strategy. Low-quality reads and adapters were removed with Trim Galore version 0.6.6 (https://www.bioinformatics.babraham.ac.uk/projects/trim_galore). The trimmed reads were aligned to hg38 with Bowtie2 version 2.3.4.3. SAMTools version 1.9 was used to convert the SAM alignment files to BAM files, sort and index reads, and remove duplicates.

  Dataset EGAD50000002126

• Epigenetic analyses of methylation and nucleosome occupancy in cell-free DNA (cfNOMe)

  Cell-free DNA (cfDNA) has become essential in cancer diagnostics and prenatal testing. We investigate enzymatic cytosine conversion for epigenetic analyses of cfDNA and find that it reliably measures cytosine methylation and nucleosome occupancy. Whereas previously, separate experiments had to be performed to study either epigenetic marking, this approach delivers reliable results for both, enabling more comprehensive and inexpensive epigenetic profiling of cfDNA.

  Study EGAS00001004370

• The Causes of Clonal Blood Cell Disorders Study - SCOR (2018-04-19)

  We will take a bone marrow aspirate and peripheral blood samples from a healthy patient aged around 60, and use flow cytometry to isolate 100 HSCs, 50 MEPs, and 50 GMPs. We will grow these up into colonies, then whole genome sequence each colony. Somatic mutations will act as a unique barcode for each clone. We will then design a panel for targeted resequencing of the mutations that we find. It will then be possible to look for these mutations in the peripheral blood over several years, to see the dynamics of how HSCs contribute to the peripheral blood in health. This dataset contains all the data available for this study on 2018-04-19.

  Dataset EGAD00001004086

• Integrated clinical, whole genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer

  We report the first combined analysis of whole genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole genome and transcriptome sequence was obtained from 9 anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 years prior to death. Transcriptome analysis revealed increased expression of AR-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only 1 of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today given this knowledge, use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations is critical for actionability, and can only be determined through analysis of multiple sites of metastasis. Our findings suggest that a large set of deeply analyzed cases could serve as powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials.

  Dataset EGAD00001001869

• Whole Exome Sequencing of Head and Neck Patients-Derived Tumor Organoids and Formalin Fixed Paraffin Embedded Tumor Tissue

  In this study, tissue specimens were procured from head and neck squamous cell carcinoma (HNSCC) patients undergoing routine diagnostic procedures as part of their standard of care. For surgical cases, only excess tissue remaining after allocation for essential pathological diagnosis was utilized for research purposes. We aimed to validate the genomic fidelity of patient-derived organoids (PDOs) compared to their originating tumors. Whole exome sequencing was performed on four paired sets of PDOs and matched surgical specimens preserved as formalin-fixed paraffin-embedded (FFPE) samples. The objective was to demonstrate that the in vitro PDO models maintain the genomic profile of the patient-specific tumors, thus supporting their potential application in identifying efficacious personalized treatment regimens. Comparative analyses of single nucleotide variants (SNVs) and copy number variants (CNVs) between matched PDO and FFPE pairs were conducted to assess global genomic similarity and shared HNSCC-relevant variants. The results indicated that the PDOs closely recapitulated the mutational landscape of the resected tumors from which they were derived. This finding supports the validity of the employed in vitro culture conditions for potential use in precision medicine approaches for HNSCC. The data submitted to dbGaP comprise eight whole exome sequencing profiles of matched pairs of HNSCC FFPE and PDO samples from four subjects. Novogene (Novogene Co., Ltd, CA, USA) generated these profiles from 1.0μg genomic DNA per sample, using the Agilent SureSelect Human All Exon kit (Agilent Technologies, CA, USA). Deposited files include raw BAM files of reads aligned to human genome Hg19 using BWA (v.0.7.8-r455), sorted with Samtools (v1.0), and filtered for duplicate reads using Picard (v1.111). Additionally, we've deposited VCF files of SNV variant calls from GATK (v3.8).

  Study phs003755

• Reconstitution of Human Brain Cell Diversity in Organoids via Four Protocols [time-course bulkRNAseq]

  Time-course bulk-RNA sequencing of brain organoids grown in four distinct growth protocols designed to generate dorsal (D) and ventral (V) forebrain, midbrain (M) and striatum (S) tissue at days 13 (for dorsal and ventral)/16 (for midbrain and striatum), 25, 40, 80 and 120. Per per cell line-protocol-timepoint combination three organoids (biological replicates) were grown. For reference, also three samples of the pluripotent stem cells across cell lines, not yet exposed to any protocol, were sequenced (day 0, pluripotent).

  Study EGAS50000000663

• ARGO_GWAS

  Osteoarthritis (OA) is the most common form of arthritis affecting ~40% of people over the age of 70. OA is characterised by cartilage degeneration in the synovial joints and presents one of the leading causes of chronic disability and impaired quality of life in the developed world.The ARGO study is an ongoing collection of well-phenotyped OA patients undergoing total joint replacement and is based in Greece.

  Study EGAS00001000917

• Association studies using the Metabochip array - Samples analysed by the WTCCC (1958 British Birth Cohort (58BC), Hypertension cohort (HT), Type 2 Diabetes Cohort (T2D) and Coronary Artery Disease (CAD) cohort)

  Genomewide association studies (GWAS) have proven a powerful hypothesis-free method to identify common disease-associated variants. Even quite large GWAS, however, have only at best identified moderate proportions of the genetic variants contributing to disease heritability. To provide cost-effective genotyping of common and rare variants to map the remaining heritability and to fine-map established loci, the Metabochip Consortium has developed a 200,000 SNP chip that has been produced in very large numbers for a fraction of the cost of GWAS chips. This chip provides a powerful tool for genetic studies of metabolic, cardiovascular and anthropometric traits (Voight et al., in press PLoS Genetics).

  Study EGAS00000000115

• Systemic mutagen exposures reported by normal kidney cell genomes - peripheral blood samples (NanoSeq)

  Lifestyle, environmental and other exposures to exogenous mutagens generate somatic mutations in normal human cells in vivo and increase cancer risk. However, the global repertoire of exogenous mutagen exposures is uncertain. Using single-molecule duplex sequencing of normal kidney (n=319) and blood (n=272) samples from 10 countries, we show that kidney proximal tubule cells exhibit higher mutation rates than most normal cell types despite low cell division rates. Compared to cells from kidney glomeruli, medulla, distal tubules, or peripheral blood, proximal tubule cells show marked enrichment of mutational signatures due to the exogenous carcinogenic mutagens, aristolochic acids, and of several signatures of unknown causes. The results suggest the existence of multiple, common, systemically circulated mutagens affecting human populations and indicate that the genomes of kidney proximal tubule cells report such exposures with high sensitivity.

  Dataset EGAD00001015824

• Systemic mutagen exposures reported by normal kidney cell genomes - microdissected kidney samples (NanoSeq)

  Lifestyle, environmental and other exposures to exogenous mutagens generate somatic mutations in normal human cells in vivo and increase cancer risk. However, the global repertoire of exogenous mutagen exposures is uncertain. Using single-molecule duplex sequencing of normal kidney (n=319) and blood (n=272) samples from 10 countries, we show that kidney proximal tubule cells exhibit higher mutation rates than most normal cell types despite low cell division rates. Compared to cells from kidney glomeruli, medulla, distal tubules, or peripheral blood, proximal tubule cells show marked enrichment of mutational signatures due to the exogenous carcinogenic mutagens, aristolochic acids, and of several signatures of unknown causes. The results suggest the existence of multiple, common, systemically circulated mutagens affecting human populations and indicate that the genomes of kidney proximal tubule cells report such exposures with high sensitivity.

  Dataset EGAD00001015827

• Massive parallel RNA sequencing of highly purified mesenchymal cells derived from bone marrow specimens of 10 healthy donors

  Highly purified mesenchymal cells (CD45-/7AAD-/CD235a-/CD31-/CD271+/CD105+) were prospectively FACS-isolated from bone marrow specimens of 10 healthy donors (HDs). This data set is used as a baseline control to observe the differences between gene expression profiles (GEPs) of pre-leukemia cases (45 low-risk myelodysplastic syndrome, 4 Shwachman-Diamond and 3 Diamond-Blackfan anemia patients) and gene expression patterns observed in a normal, healthy context. Through differential expression and gene set enrichment analysis we determined that inflammatory signaling pathways are significantly more active in mesenchymal cells of pre-leukemia cases compared to their healthy counterparts. Finally, we determined through statistical modelling of healthy donor's GEPs which pre-leukemia cases have significantly more active inflammatory signaling and demonstrated a strong relation to survival statistics.

  Dataset EGAD00001002659

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

  The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. We aim to characterise and track patient-specific somatic ctDNA variants, to assess longitudinal changes in disease burden and explore the landscape of actionable alterations.

  Study EGAS00001005981

• cfDNA in health

  This study investigates baseline methylome and fragmentomic profiles in circulating cell-free DNA (cfDNA) from healthy individuals. Two cohorts were assembled: a diurnal cohort to evaluate temporal variation in cfDNA features, and a cross-sectional cohort to assess inter-individual variability. The project’s goal was to generate a reference dataset for plasma cfDNA to support future studies in biomarker discovery and disease detection.

  Study EGAS50000001209

• Mutant_clone_mapping_in_oesohagus_restricted_bait

  We aim to assess the burden of mutant clones in normal human oesophagus from donors aged 65+. We will do this for a small number of genes which we know to be under positive dN/dS selection. This will allow us to assess the patient to patient variation in mutational burden as well as any changes in selection which may occur with age.

  Study EGAS00001005660

• Whole Exome Sequencing for Colorectal Cancer

  This project was designed to use next generation sequencing technology to screen the protein coding regions of the genome for low frequency variants in a panel of high-risk colorectal adenocarcinoma cases. Blood and cell-line DNA for colorectal cancer patients and a subset of quality control samples that had existing whole exome sequence data were analyzed using Illumina HiSeq sequencers. Samples from this project were from participants in the Women's Health Initiative (WHI) and the Diet, Activity, and Lifestyle Study (DALS).

  Study phs000410

• A Pharmcogenetic Study of Bipolar Disorder in a Taiwanese Han Chinese Population (TWBP)

  Objective: To identify genetic variants associated with response to lithium prophylaxis treatment. Materials: 294 bipolar I (BPI) patients receiving lithium treatment, a subset of 1761 bipolar I (BPI) patients recruited by the Taiwan Bipolar Consortium. Lithium response was assessed based on the Alda Scale. Methods: Responders to lithium treatment were defined if the patients' Alda Scale > 4, 5, 6, and 7. Genome-wide association (GWA) analysis was carried out on the 294 BPI patients for the 4 definitions of responders. The SNPs showing strongest association in the GWAS were then tested for association in a replication sample of 100 patients and further tested in a prospective follow-up series of 24 patients. Results: Two SNPs on GADL1 showed the strongest associations in the four GWA analyses and in the replication set of 100 patients. These two SNPs had a sensitivity of 0.93 for predicting lithium response and differentiated between the good and poor responders in the follow-up cohort. Summary: These genetic variants are associated with response to lithium prophylaxis treatment for BPI.

  Study phs000692

• Genotype and exome data for an Australian Aboriginal population: a reference panel for health-based research

  Genetic analyses, including genome-wide association studies and whole exome sequencing (WES), provide powerful tools for the analysis of complex and rare genetic diseases. To date there are no reference data for Aboriginal Australians to underpin the translation of health-based genomic research. Here we provide a catalog of variants called after sequencing the exomes of 72 Aboriginal individuals to a depth of 20X coverage in 80% of the sequenced nucleotides. We determined 320,976 single nucleotide variants (SNVs) and 47,313 insertions/deletions using the Genome Analysis Toolkit. We had previously genotyped a subset of the Aboriginal individuals (70/72) using the Illumina Omni2.5 BeadChip platform and found 99% concordance at overlapping sites, which suggests high quality genotyping. Finally, we compared our SNVs to six publicly available variant databases, such as dbSNP and the Exome Sequencing Project, and 70,115 of our SNVs did not overlap any of the single nucleotide polymorphic sites in all the databases. Our data set provides a useful reference point for genomic studies on Aboriginal Australians.

  Study EGAS00001001585

• ChIP-seq in colorectal cancer and paired adjacent normal mucosa

  Chip-seq samples for 20 colorectal patients with paired adjacent normal mucosa to characterize H3K27ac and H3K4me1.

  Study EGAS00001005303

• Melanoma Germlines subset for BAP1

  These samples comprise both melanoma cases and controls sequenced for a selection of loci linked to disease susceptibility. These bams are a subset of the sequencing restricted specifically to the GRCh37 coding areas of the BAP1 gene.

  Dataset EGAD00001002743

• Breast cancer topographs

  Whole genome sequencing to identify subclonal variants for subsequent mapping back to fixed tissue specimens. . This dataset contains all the data available for this study on 2023-03-09.

  Dataset EGAD00001010124