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• Integrative Somatic and Germline Computational Biology to Redefine Clinical Actionability in Solid Tumors

  Neuroendocrine tumors (NETs) are rare cancers that arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic NETs (GEP-NETs) growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we performed single-cell RNA-sequencing (scRNA-seq) of fresh resections of GEP-NETs, including four pancreatic NETs, three small intestinal NETs, and one perigastric NET. We used single-cell sequencing to investigate the tumor and immune cellular landscapes of GEP-NET patients. Malignant GEP-NET gene and regulon expression was compared with normal, gastrointestinal endocrine cell differentiation and fate determination stages. We further characterized immune-immune and immune-tumor interaction networks within GEP-NETs, identifying novel therapeutic opportunities in the myeloid compartment of the microenvironment. Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

  Study phs003141

• Single Cell RNA-Sequencing of BCG Naive and Recurrent Non-Muscle Invasive Bladder Cancer Reveals a CD6/ALCAM-Mediated Immune-Suppressive Pathway

  Non-muscle invasive bladder cancer (NMIBC) represents 70–80% patients with newly diagnosed bladder cancer, and Bacillus Calmette-Guerin (BCG) remains a cornerstone treatment for intermediate- and high-risk NMIBC to prevent disease recurrence and progression. However, a significant number of patients experience recurrence after their first course of BCG, posing significant challenges in the management of the disease. We conducted single cell RNA sequencing (scRNA-Seq) on freshly collected NMIBC samples, distinguishing between those naive to BCG treatment and those that recurred post-BCG treatment. We observed a clear activation of inflammatory pathways across cell types during recurrence, but these were not associated with canonical immune checkpoint or T cell exhaustion phenotypes. Analysis of cell-to-cell communication revealed enhanced interactions between T cells and urothelial cells in BCG-recurrence, predominantly modulated by CD6 and activated leukocyte cell adhesion molecule (ALCAM). Furthermore, we found CD6hi T cells to be immunosuppressed and enriched in recurrent samples, suggesting a potential role for CD6 as an immune evasion signal in NMIBC.

  Study phs003742

• 419 Japanese healthy control

  Genotypes of 419 Japanese healthy individuals genotyped by using of SNP arrays (Genome-Wide Human SNP Array 6.0 and Axiom Genome-Wide ASI 1 Array). CEL files and CHP files are included in this data set.

  Study JGAS000120

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 15)

  The dataset contains whole genome sequencing data of 8 high-grade serous carcinoma (HGSC) patients sequenced with Novoseq 6000. The 16 samples are either fresh frozen tumour samples or blood samples. The files provided are paired fastq files.

  Dataset EGAD50000000526

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 16)

  The dataset contains whole genome sequencing data of 58 high-grade serous carcinoma (HGSC) patients sequenced with Novoseq 6000. The 144 samples are either fresh frozen tumour samples or blood samples. The files provided are paired fastq files.

  Dataset EGAD50000000777

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 14)

  The dataset contains whole genome sequencing data of 42 high-grade serous carcinoma (HGSC) patients sequenced with Novoseq 6000. The 100 samples are either fresh frozen tumour samples or blood samples. The files provided are paired fastq files.

  Dataset EGAD50000000507

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 11)

  The dataset contains whole genome sequencing data of 23 high-grade serous carcinoma (HGSC) patients sequenced with Novoseq 6000. The 89 samples are either fresh frozen tumour samples or blood samples. The files provided are paired fastq files.

  Dataset EGAD50000000313

• Recurrent loss of heterozygosity correlates with clinical outcome in pancreatic neuroendocrine cancer

  Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report analysis of gene mutation, copy number and RNA expression of 57 sporadic well-differentiated pNETs.

  Study EGAS00001003038

• CAF-S3 subset in human breast and ovarian cancers

  Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. By combining 6 well-known stromal markers, we identify four CAF subsets (CAF-S1 to CAF-S4) in human breast and ovarian cancers.

  Study EGAS00001003344

• Whole-genome sequencing of paired tumor and blood samples from 65 bladder cancer patients

  65 paired tumor and normal whole-genome sequencing samples from urothelial bladder carcinomas (UBC, the most common type of bladder cancer) are used to uncover the whole-genome mutational landscape of UBC. Recurrent mutations in noncoding regions affecting gene regulatory elements and structural variations leading to gene disruptions are prevalent in this type of cancer.

  Dataset EGAD00001004545

• ECCO-GEN Valve Methylation Dataset (non-diseased)

  The valve methylation dataset consists of 12 bam files of human non-diseased valve tissue samples that are free from calcification (6 aortic and 6 mitral valves - matched; 10 males: 2 females; age range 42 – 64 years, mean age 52.2 years, SD 9.9682). Donor hearts are free from cardiovascular and valvular complications.

  Dataset EGAD00001006303

• Impact of Mobile Element Insertions on Human Transcriptome Variation

  Mobile DNA elements are ubiquitous in nearly all species and mobile element insertions can affect nearby gene expression through many mechanisms, from disrupting coding regions to initiating DNA methylation to altering RNA splicing patterns. Thousands of mobile element insertions are still polymorphic in human populations, and these polymorphic mobile element insertions (pMEIs) can contribute to transcriptome and phenotypic variation in humans. We identified and genotyped pMEIs using the whole genome sequencing (WGS) data from the Genotype-Tissue Expression (GTEx) project. We then used the extensive multi-tissue transcriptome data from the GTEx project to systematically assess the effects of pMEIs on human transcriptome variation.

  Study phs002030

• Longitudinal copy number variation analysis from plasma DNA of head and neck cancer patients under re-radiotherapy

  Recurrent locally advanced head and neck cancer (HNC) patients, receiving re-radiotherapy (re-RT), are presented with short progression-free (PFS) and overall survival. Hence, biomarkers predicting therapy failure are urgently needed. We analyzed copy number variations (CNVs) in blood plasma of HNC patients collected before, during and after re-RT. Detectable CNVs after five and ten fractions of re-irradiation as well as at the end of re-RT were associated with short PFS. Furthermore, we found that CNV kinetics in longitudinally collected plasma reflected therapy response and could detect disease progression in advance of radiographic tumor assessments.

  Study EGAS50000000163

• A single-cell atlas of the early COPD lung

  Single cell atlas of the human airways from 10 patients suffering of early stage Chronic Obstructive Pulmonary Disease and 12 healthy age matched volunteers. This dataset was sequenced by 10X Genomics 3’ RNA-seq profiling. It is composed of more than 400 000 cells coming from 119 samples total. Sampling was performed by brushings and biopsies from the nose to the 6 th division of the airways.

  Dataset EGAD50000001001

• Whole-exome sequencing of 20 samples of actinic keratosis (10s) and cutaneous squamous cell carcinoma (10s)

  Whole-exome sequencing of 20 samples of actinic keratosis (10) and cutaneous squamous cell carcinoma (10) was performed to investigate a potential relationship between DNA methylation-based subtypes and genetic mutation patterns. 7 samples were shown to belong to the stem cell-like subclass (4 AK and 2 SCC), 12 - to the keratinocyte-like subtype (6 AK and 6 SCC) and one SCC sample is unclassified (was not included in the methylation analysis). Exome regions were captured using Agilent Low Input Exome-Seq Human v5 kit and sequenced on Illumina Hiseq4000 with paired-end 100-nucleotide reads.

  Dataset EGAD00001003765

• Detection of clinically relevant genetic and transcriptomic landscape in DLBCL uniformly treated by R-CHOP

  Recent studies using next-generation sequencing strategies have described the landscape of genetic alterations in diffuse large B-cell lymphoma (DLBCL). However, little is known about the clinical relevance of recurrent mutations and copy number alterations and their transcriptional footprints. This study examines the frequency, interaction and clinical impact of recurrent genetic aberrations in DLBCL using high-resolution technologies in a large population-based cohort.

  Dataset EGAD00001003783

• Whole-genome plasma DNA sequencing in CRC patients under anti-EGFR therapy

  In this study we performed whole genome sequencing of plasma DNA (plasma-Seq) of 19 plasma-DNA samples from a total of 10 patients treated with anti-EGFR therapy. We demonstrated that development of resistance to anti-EGFR therapies is frequently associated with focal amplifications of KRAS, MET, and ERBB2. We also showed that focal KRAS amplifications can be acquired in tumor genomes of patients under cytotoxic chemotherapy. Furthermore, we provide evidence that specific chromosomal polysomies, such as overrepresentations of 12p and 7p, harboring KRAS and EGFR, respectively, determine responsiveness to anti-EGFR therapy.

  Dataset EGAD00001000748

• Identification of drug resistance genes in cancer cell lines by insertional mutagenesis

  Our aim is to identify genes involved in resistance to anti-cancer therapies. In order to do this we have taken advantage of a lentiviral vector (LV)-based insertional mutagen to mutagenize cancer cell lines. LV-transduced cell lines were then treated with anti-cancer therapies and the emergence of resistant clones scored. DNA from pools of resistant clones was collected, subjected to custom capture by baits designed against the LV sequence, and then sequenced to identify the LV-genomic junction. We hope that the identification of recurrently targeted genes in resistant cell population will allow us to identify genes that mediate drug resistance.

  Dataset EGAD00001002207

• Enabling sensitive and precise detection of ctDNA through somatic copy number aberrations in breast cancer

  Cell-free DNA (cfDNA) extracted from peripheral blood has emerged as a crucial biomarker source in oncology research. To enhance the detection of somatic copy number alterations (SCNAs) and circulating tumor DNA (ctDNA), we developed eSENSES, a 2Mb breast cancer-targeted NGS panel. It includes 15,000 genome-wide SNPs, 500 focal SNPs in breast cancer driver regions, and exons from 81 commonly altered genes, alongside a custom computational approach. eSENSES provides a reliable, powerful and cost-effective tool for monitoring disease progression and guiding therapeutic decisions in breast cancer patients.

  Study EGAS50000000793

• A standardised framework for robust fragmentomic feature extraction from cell-free DNA sequencing data

  Fragmentomic features of cell-free DNA represent promising non-invasive biomarkers for cancer diagnosis. However, a lack of systematic evaluation of biases in feature quantification has hindered the adoption of such applications. We compared features derived from whole-genome sequencing of ten healthy donors using nine library kits and ten data-processing routes, and validated them in 1,182 plasma samples from published studies. Our results clarify the variations resulting from library preparation and feature quantification methods. We designed the Trim Align Pipeline and the cfDNAPro R package as unified interfaces for data pre-processing, feature extraction, and visualisation, aiming to standardise multimodal feature engineering and integration for machine learning.

  Study EGAS00001008051

• Human Cancer-Targeted Immunity via Transgenic Hematopoietic Stem Cell Progeny

  Analysis of a patient biopsy from the clinical trial (NCT03240861), a first-in-human study of transgenic NY-ESO-1 TCR- T cells and NY-ESO-1 TCR+ sr39tk autologous hematopoietic stem cells tandem therapy for solid tumors after myeloablative conditioning chemotherapy with busulfan and fludarabine. Single-cell RNAseq and single-cell ATACseq analysis from peripheral blood mononuclear cells obtained from subject NYSCT-03.

  Study phs003898

• RNA-sequencing of platelets and immortalized megakaryocyte cell lines for inherited thrombocytopenia

  Total RNA-sequencing of platelets and immortalized megakaryocyte cell lines for inherited thrombocytopenia. Libraries were prepared using Illumina TruSeq Stranded Total RNA with Ribo-Zero Gold kits. The samples were paired-end sequenced using the NovaSeq 6000 platform at a depth of 60 million reads per sample with a read length of 100 base pairs.

  Dataset EGAD50000001818

• Comprehensive NGS Profiling to Enable Detection of ALK Gene Rearrangements and MET Amplifications in Non-Small Cell Lung Cancer

  We evaluate the analytical performance of the PGDx™ elio™ tissue complete assay, a 505 gene next-generation sequencing (NGS) tissue-based assay, that has now been FDA-cleared for use by physicians to help guide treatment decisions for cancer patients, using a NSCLC cohort of 38 patients.

  Dataset EGAD50000000016

• Genetic and expression landscape of Waldenstrom macroglobulinemia

  Exome analyses for the identification of somatic mutation in Waldenstrom macroglobulinemia by comparison of tumor and CD3+(germ line control) population in 16 patients. transcription profiling of a series of Waldenstrom macroglobulinemia samples

  Study EGAS00001003603

• SCLC study MGH - RNAseq dataset

  RNA-seq analyses were performed on cDNA libraries prepared from PolyA+ RNA using the Illumina TruSeq protocol for mRNA. The final libraries were sequenced with a paired-end 2×75 bp protocol aiming at 8.5 Gb per sample for a 30x mean coverage of the annotated transcriptome. All sequencing reactions were conducted on an Illumina HiSeq instrument (Illumina, San Diego, CA, USA).

  Dataset EGAD00001003969

• CRUK Accelerator: Pancreatic neuroendocrine tumours (panNETs) whole exome and RNAseq raw sequencing data

  Whole exome and RNASeq raw sequencing data for an individual with multiple pancreatic neuroendocrine tumours (panNETs). Age at diagnosis was 51. Tumour tissue and PBMCs were used for sequencing. This data was generated as part of a study funded by a Cancer Research UK Centres Network Accelerator Award Grant (A21998).

  Dataset EGAD00001009685

• Human data for chromatin accessibility (ATAC-Seq and scATAC-Seq) and transcriptome (RNA-Seq and scRNA-Seq) in eight B-cell precursors, from HSC to Naive B cells

  We generated paired transcriptomic (RNA-Seq) and chromatin accessibility (ATAC-Seq) profiles from 8 immune cell populations representing the early lymphoid hematopoietic differentiation stages along the B cell lineage: HSC, CLP, pro-B, pre-B, Immature B, Transitional B, Naive B CD5-, Naive B CD5+. Cell populations were isolated from healthy adult human bone marrow precursors and peripheral blood (n=13) following a predefined sorting strategy. For each donor, a subset of different cell type populations was obtained. Additionally, to explore the continuous dynamic of RNA and ATAC, we generated a single-cell sample of human CD34+ B cell precursors.

  Study EGAS00001007296

• The evolutionary history of human colitis-associated colorectal cancer

  Inflammatory bowel disease confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the evolutionary history of CA-CRC using multi-region sequencing. Exome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 CA-CRC patients (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using SNP arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD, n=30), high-grade dysplasia (HGD, n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC. 10/12 tumors were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNAs) per Mb, around 20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated aging-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighboring CA-CRC, indicating a pre-cancer mutational field. CA-CRCs were often near-triploid (42%) or near-tetraploid (21%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated catastrophic CNA increase.

  Study EGAS00001003028

• Massachusetts General Hospital/Eisai National Institute of Mental Health (NIMH) Genetics Initiative Alzheimer's Disease GWAS - Affymetrix GeneChip Human Mapping 500K Array Set

  This study cohort was collected as part of the National Institute of Mental Health (NIMH) Alzheimer's disease Genetics Initiative Study. Recruitment of families, predominantly sibling, for the cohort was focused on local memory disorder clinics, nursing homes, and the surrounding community. Clinical evaluation was performed at the University of Alabama at Birmingham, Johns Hopkins University, and Massachusetts General Hospital/Harvard Medical School. Informed consent was obtained from all study participants, for participants with extensive cognitive impairment, a legal guardian or caregiver with power of attorney provided consent. To determine age of onset, a creditable informer was interviewed and medical records were evaluated.

  Study phs000483

• RNA seq of intestinal biopsies and blood cells from patients with celiac disease and controls

  This study presents RNA sequenced from several intestinal phenotypes such as from patients with damaged intestinal mucosa as well as from those without a damaged intestine but still an autoantibody response to tissue transglutaminase (“potential celiac disease”) or those with treated celiac disease. By combining phenotypes in a much larger number of tissue samples from both peripheral blood and mucosal biopsies, we found highly differentially expressed genes, but also identify genes involved in controlling and triggering celiac disease associated changes. This study identifies molecular mechanisms involved in celiac disease and new possible targets for treatment and for identification of individuals at risk.

  Study EGAS50000001104

• 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.

  Study EGAS50000000404

• Population whole-genome bisulfite sequencing across two tissues highlights environment as principal source of human methylome variation

  The study includes whole-genome bisulfite sequencing (WGBS) on 34 adipose(7 MZ pairs, 6 DZ pairs and 8 singletons) and 27 blood (7 MZ pairs, 6 DZpairs and 1 singleton) DNA samples derived from a total of 43 female twinsbelonging to the MuTHER/TwinsUK cohort. We generated 11.5 billion 100bppaired-end reads covering 2.3 Tera-basepairs (Tbp) ofsequence using the Illumina HiSeq2000 or 2500 systems. Applying standardalignment methods and filters we obtain a mean genome coverage of 6.3-fold(range: 1.0- to 12.9-fold) for adipose and 8.7-fold (range: 0.7- to29.0-fold) for blood.

  Study EGAS00001001569

• LCCC 1108: Development of a Tumor Molecular Analyses Program and Its Use to Support Treatment Decisions (UNCseqTM)

  The primary objective of this specimen correlative study was two-fold: to provide a mechanism for the association of known molecular alterations with clinical outcomes, and to provide rapid genetic profiling of alterations with known clinical utility using tumor and germline specimens to support treatment decisions.

  Study phs001713

• Bulk TCRseq data from 149 patients with bladder cancer

  For this dataset we performed bulk TCRseq on tumor and serial blood samples from patients with muscle invasive bladder cancer (n patients = 119, n blood = 209, n tumor = 28) or non-muscle invasive bladder cancer (n patients = 30, n blood = 56, n tumor = 19) for a total of 149 patients and 312 samples. Each sample consists of a paired fastq file. Sequenced on the Ilumina NovaSeq6000 platform using SP and S1 flow cells (v1.5, 2x101 cycles), with a mean yield of 42 million reads covering the CDR3β region.

  Dataset EGAD50000001382

• Tumor detection by analysis of both symmetric- and hemi-methylation of plasma cell-free DNA

  Aberrant DNA methylation plays a critical role in tumorigenesis. While DNA methylation has been used for cancer detection and classification, DNA hemi-methylation, a novel epigenetic mark has not been analyzed extensively in cancer epigenomes. Here we report a strand-specific (ss) sequencing method (MeDIP-Seq) for plasma cell free (cf) DNA (sscf-MeDIP-Seq), which can analyze both symmetrically methylated DNA regions (DMRs) as well as hemi-methylated regions (DHMRs). Using the sscf-MeDIP-Seq method, we analyzed plasma cfDNA methylomes of 271 samples from subjects with liver cancer and brain cancer and from individuals without cancer (controls). Among them, 215 samples were chosen as the discovery cohort for the identification of DMRs and DHMRs specific in each subject group and for the training of machine learning models of multi-cancer detection (MCD) using DMRs, DHMRs and DMRs+DHMRs as inputs. These models were then used to predict the 56 samples in the validation cohort. We found that models trained with DMRs+DHMRs as inputs in general outperformed models trained with DMRs or DHMRs alone, with AUROC being 0.971, 0.981, and 0.99 in predicting control, liver and brain cancer samples in the validation cohort, respectively, by the DMR+DHMR-trained models.

  Study phs003462

• Whole-genome sequencing of BRCA-mutant breast cancer patient samples from tumour, germline tissue and plasma

  The use of circulating tumor DNA (ctDNA) to profile mutational signatures presents a non-invasive opportunity for understanding cancer mutational processes. In this study we developed MisMatchFinder, a liquid biopsy approach for mutational signature detection using low- coverage whole-genome sequencing of ctDNA. Through analysis of plasma samples across multiple different cancers, we demonstrated that MisMatchFinder accurately infers single-base and doublet-base substitutions as well as indels to enhance detection of ctDNA and clinically relevant mutational signatures. This study contains fastq files from whole-genome sequencing of temporally matched tumour (fresh frozen biopsies), blood germline and plasma samples collected from a BRCA1-mutant breast cancer patient to directly compare mutation signature analysis using gold-standard tumour-germline paired variant calling with our novel ctDNA-based method (MisMatchFinder).

  Study EGAS50000000569

• Single nucleus RNA sequencing of squamous cell carcinoma arising from mature teratoma of the ovary

  Squamous cell carcinoma arising from mature teratoma is one of the rare ovarian cancers. Therefore, the detailed molecular background of this disease has not been elucidated. The purpose of this study is to investigate the single-cell transcriptional landscape of this disease.

  Study JGAS000521

• Targeted capture sequencing for LySeqST

  Targeted capture sequencing of 445 lymphoma samples and 13 normal samples for LySeqST: A targeted sequencing assay for robust genomic classification of diffuse large B-cell lymphoma.

  Dataset EGAD50000002290

• BMI EWAS summary stats

  Summary statistics for a multi-cohort epigenome-wide association study. This includes summary statistics (effect-size, standard error, p-value) for 470,000 methylation markers.

  Dataset EGAD00010001029

• Multi-region sequencing of a RET fusion positive cancer patient

  Deep WGS sequencing (160x) of 2 different sites of disease of a patient with a RET fusion positive cancer. Amplicon sequencing of 19 other sites of the same patients for the RET fusion.

  Dataset EGAD00001005776

• Labcorp® Plasma Detect™ assay: whole genome sequencing analyses of plasma cfDNA, white blood cells and FFPE tumor tissue

  The dataset "Labcorp® Plasma Detect™ assay: whole genome sequencing analyses of plasma cfDNA, white blood cells and FFPE tumor tissue" includes CRAM and CRAI files derived from WGS of 555x plasma cfDNA, 209x white blood cells (normal DNA) and 209x FFPE tumor tissue (tumor DNA) samples for 209 stage III colorectal cancer patients. WGS (150bp PE) was performed on a NovaSeq 6000 with a target depth of coverage of 80x for tumor DNA, 40x for normal DNA and 30x for cfDNA. Reads were aligned to GRCh37 (plasma cfDNA) or GRCh38 (tumor/normal DNA).

  Dataset EGAD50000001180

• Ultra-fast multiplex small DNA sequencing on the MinION nanopore sequencing platform

  Here, we developed an ultra-rapid multiplexed library preparation and sequencing method for the MinION and applied this method to accurately test euploid and aneuploid genomic DNA samples in under three hours, including library preparation and sequencing. This novel method shows great promise as a clinical diagnostic test for applications requiring rapid short-read DNA sequencing.

  Study EGAS00001002650

• Functional_characterisation_of_CpG_islands_in_human_and_mouse_tissues

  Tissue-specific methylation patterns suggest a role for CpG island (CGI) methylation in differentiation and cell-type-specific gene regulation. We have applied CXXC affinity purification (CAP), MBD affinity purification (MAP) and chromatin immunoprecipitation (ChIP) in combination with solexa sequencing to investigate the extent and functional significance of CGI methylation in sperm, blood, cerebellum and ES cells for both human and mouse.

  Study EGAS00001000075

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

  COG-N-519 primary neuroblastoma cells were innoculated by subcutaneous injection into NSG mice. When tumours reached a size of 100-200mm3 miRNAs conjugated to nanoparticles were injected intratumourally every 2 days for 1 week. 24 hr after the last injection, snap frozen tumour tissue was harvested for RNA extraction and RNA-seq analysis.

  Study EGAS00001005581

• Somatic mutation and selection at epidemiological scale - TwinsUK_TargetedEMSeq_Buccal

  Development of a targeted methylation assay to determine the cell-type composition of a sample. As we age, many tissues become colonised by microscopic clones carrying somatic driver mutations. Some of these clones represent a first step towards cancer whereas others may contribute to ageing and other diseases. However, our understanding of the clonal landscapes of human tissues, and their impact on cancer risk, ageing and disease, remains limited due to the challenge of detecting somatic mutations present in small numbers of cells. Here, we introduce a new version of nanorate sequencing (NanoSeq), a duplex sequencing method with error rates of less than 5 per billion base pairs, which is compatible with whole-exome and targeted gene sequencing. Deep sequencing of polyclonal samples with single-molecule sensitivity enables the simultaneous detection of mutations in large numbers of clones, yielding accurate somatic mutation rates, mutational signatures and driver mutation frequencies in any tissue. Applying targeted NanoSeq to 1,042 non-invasive samples of oral epithelium and 371 samples of blood from a twin cohort, we found an unprecedentedly rich landscape of selection, with 46 genes under positive selection driving clonal expansions in the oral epithelium, over 62,000 driver mutations, and evidence of negative selection in some genes. The high number of positively selected mutations in multiple genes provides high-resolution maps of selection across coding and non-coding sites, a form of in vivo saturation mutagenesis. Multivariate regression models enable mutational epidemiology studies on how carcinogenic exposures and cancer risk factors, such as age, tobacco or alcohol, alter the acquisition and selection of somatic mutations. Accurate single-molecule sequencing has the potential to unveil the polyclonal landscape of any tissue, providing a powerful tool to study early carcinogenesis, cancer prevention and the role of somatic mutations in ageing and disease.

  Dataset EGAD00001015622

• Somatic mutation and selection at epidemiological scale - TwinsUK_TargetedEMSeq_Blood

  Development of a targeted methylation assay to determine the cell-type composition of a sample. As we age, many tissues become colonised by microscopic clones carrying somatic driver mutations. Some of these clones represent a first step towards cancer whereas others may contribute to ageing and other diseases. However, our understanding of the clonal landscapes of human tissues, and their impact on cancer risk, ageing and disease, remains limited due to the challenge of detecting somatic mutations present in small numbers of cells. Here, we introduce a new version of nanorate sequencing (NanoSeq), a duplex sequencing method with error rates of less than 5 per billion base pairs, which is compatible with whole-exome and targeted gene sequencing. Deep sequencing of polyclonal samples with single-molecule sensitivity enables the simultaneous detection of mutations in large numbers of clones, yielding accurate somatic mutation rates, mutational signatures and driver mutation frequencies in any tissue. Applying targeted NanoSeq to 1,042 non-invasive samples of oral epithelium and 371 samples of blood from a twin cohort, we found an unprecedentedly rich landscape of selection, with 46 genes under positive selection driving clonal expansions in the oral epithelium, over 62,000 driver mutations, and evidence of negative selection in some genes. The high number of positively selected mutations in multiple genes provides high-resolution maps of selection across coding and non-coding sites, a form of in vivo saturation mutagenesis. Multivariate regression models enable mutational epidemiology studies on how carcinogenic exposures and cancer risk factors, such as age, tobacco or alcohol, alter the acquisition and selection of somatic mutations. Accurate single-molecule sequencing has the potential to unveil the polyclonal landscape of any tissue, providing a powerful tool to study early carcinogenesis, cancer prevention and the role of somatic mutations in ageing and disease.

  Dataset EGAD00001015623

• An Ultrasensitive Method for Detection of Cell-Free RNA

  Our study describes the development of a novel method for cell free RNA (cfRNA) analysis called RARE-Seq (Random priming & Affinity capture of cell-free RNA fragments for Enrichment analysis by Sequencing). We find RARE-Seq improves the limit of detection for tumor-naïve cancer detection while maintaining high specificity. We explore the potential utility of RARE-Seq in diverse clinical applications, including non-invasive ctRNA genotyping, treatment resistance monitoring, and molecular characterization of non-malignant conditions.

  Study phs004091

• Ultra-long sequencing for contiguous haplotype resolution of the human immunoglobulin heavy chain locus

  Genetic diversity within the human immunoglobulin heavy chain (IGH) locus influences the expressed antibody repertoire and susceptibility to infectious and autoimmune diseases. However, repetitive sequences and complex structural variation pose significant challenges for large-scale characterization. Here, we introduce a method that combines Oxford Nanopore ultra-long sequencing and adaptive sampling with a bioinformatic pipeline to produce haplotype-resolved, annotated IGH assemblies. Notably, our strategy overcomes prior limitations in phasing resolution, enabling single-contig haplotype assemblies that span the entire IGH locus. We applied this method to four individuals and validated the accuracy of the IGH assemblies using Pacific Biosciences HiFi reads, demonstrating near-complete sequence congruence, detecting only indels with a high degree of confidence. Moreover, when applied to the reference material HG002, our pipeline revealed no base differences and a limited number of indels compared with the Telomere-to-Telomere genome benchmark across the IGH region. Importantly, in the four individuals, our approach uncovered 30 novel alleles and previously uncharacterized large structural variants, including a 120 kb duplication spanning IGHE to IGHA1 and an expanded seven-copy IGHV3-23 gene haplotype. These findings underscore the power of our method to resolve the full complexity of the IGH locus and uncover previously unrecognized variants that may affect immune function and disease susceptibility. Thus, our method provides a strong basis for future immunological research and translational applications.

  Study EGAS50000001042

• Familial Melanoma Sequencing

  In this experiment we have sequenced the exome of 15 individuals from eight families who have familial melanoma. By sequencing the exome we hope to be able to identify new genes that are associated with this disease.

  Study EGAS00001000017

• Shared and distinct features of immune checkpoint therapy-induced myocarditis and myositis

  Immune checkpoint therapies (ICTs) can induce life-threatening immune-related adverse events including myocarditis and myositis, which are rare and often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood.

  Study EGAS00001007511

• Multiomics characterisation of Long Covid

  We generated 10X, droplet-based paired snRNAseq+snATACseq (Multiome) of patients suffering from Long Covid. In total, we included 31 patients. Single nuclei libraries are genetically multiplexed across donors, genotype files are available to enable demultiplexing. Phenotype sheets provide information of pools/donors as well as donor phenotype.

  Dataset EGAD50000000202

• Edinburgh_Naevi_Cohort

  In this project we have sequenced the exome of skin moles (melanocytic naevi) and also normal skin from young and old people. We are interested in looking at the clonality of these lesions and the burden of UV mutations

  Study EGAS00001002347

• ChIP-seq data of Hodgkin lymphoma cell line L-428

  ChIP-seq data (H3K4Me3, H3K27Ac histone modifications) of Hodgkin lymphoma cell line L-428. Samples were processed as previously described (Sud et al., 2018). The files are in bam format, aligned to build 37.

  Study EGAS00001003033

• Moles

  In this project we have sequenced the exome of skin moles (melanocytic naevi) and also normal skin from young and old people. We are interested in looking at the clonality of these lesions and the burden of UV mutations

  Study EGAS00001000789

• Monotherapy_Breast_Cancer

  These samples are from locally advanced breast cancers that have been treated with epirubicin monotherapy before surgery. We will sequence some samples from patients with good response to the therapy and some with poor response to the therapy.

  Study EGAS00001000165

• WGS bam

  We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Genome Sequencing (WGS) data from patient tumor, PDOX, and cell lines from our study.

  Study EGAS00001005159

• WES bam

  We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Exome Sequencing (WES) data from patient tumor, PDOX, and cell lines from our study.

  Study EGAS00001005160

• Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial

  The IMagyn050 trial (NCT03038100), which evaluated the efficacy of Atezo vs placebo (Pla) with carboplatin, paclitaxel and bevacizumab (CPB) in front line ovarian cancer patient (pts), did not meet its co-primary endpoints of PFS in ITT or PD-L1+ (Moore et al. JCO 2021). The aim of this exploratory study was to evaluate whether patients with BRCA1/2-mutated or homologous recombination-deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial. Methods: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. PD-L1 status of tumor-infiltrating immune cells was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan-Meier estimates. Results Among biomarker-evaluable samples, 22% (234/1050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1024) had TMB ≥10 mut/Mb and 0.3% (3/1022) were MSI-high. PFS was better in BRCA2-mutated versus BRCA2-non-mutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on immune cells) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab in BRCA1-mutated tumors. Conclusion Most ovarian tumors have low TMB despite BRCA1/2 mutations or HRD. Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors.

  Study EGAS00001006838

• A prospective trial comparing adaptive long-read sequencing and short-read genome sequencing for genetic diagnosis of cerebellar ataxia

  This study evaluated the effectiveness of long- and short-read sequencing as diagnostic tools for CA. We recruited 110 individuals (48 females, 62 males) with a clinical diagnosis of CA. Short-read genome sequencing (SR-GS) was performed to identify pathogenic RE and also non-RE variants in 356 genes associated with CA. Long-read adaptive sequencing (LR-AS) was performed to identify pathogenic RE in 67 genes.

  Study EGAS50000000573

• Variant calls for "Quality of Whole Genome Sequencing from Blood versus Saliva Derived DNA in Cardiac Patients"

  Paired blood and saliva samples from five unrelated individuals were directly compared for quality of whole genome sequencing. Two (Sample Pairs 1 and 2) were female probands diagnosed with tetralogy of Fallot, a type of congenital heart disease, and three (Sample Pairs 3, 4 and 5) were male probands diagnosed with hypertrophic cardiomyopathy. WGS was performed using Illumina HiSeq X to a target average coverage depth of 30x and a read length of 150 bp. The resulting reads were not filtered for minimum quality in order to avoid losing possible contaminant reads. Sequencing read alignment was done using Isaac Aligner to human genome build hg19. Short variant i.e. single-nucleotide variant (SNV) and small insertion-deletion (indel) calling was performed using Isaac Variant Caller with default parameters.

  Dataset EGAD00001005772

• Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers

  Background The encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy resistance cell states. Here, we deploy time series measurements of triple negative breast cancer (TNBC) single-cell transcriptomes, along with co-measured single-cell CN fitness, identifying genomic and transcriptomic mechanisms in drug associated transcriptional cell states. Results We present scRNA-seq data (53,641 filtered cells) from serial passaging TNBC patient-derived xenograft (PDX) experiments spanning 2.5 years, matched with genomic single-cell CN data from the same samples. Our findings reveal distinct clonal responses within TNBC tumors exposed to platinum. Clones with high drug fitness undergo clonal sweeps and show subtle transcriptional reversion, while those with weak fitness exhibit dynamic transcription upon drug withdrawal. Pathway analysis highlights convergence on epithelial-mesenchymal transition and cytokine signaling, associated with resistance. Furthermore, pseudotime analysis demonstrates hysteresis in transcriptional reversion, indicating generation of new intermediate transcriptional states upon platinum exposure. Conclusions Within a polyclonal tumor, clones with strong genotype-associated fitness under platinum remained fixed, minimizing transcriptional reversion upon drug withdrawal. Conversely, clones with weaker fitness display non-genomic transcriptional plasticity. This suggests CN-associated and CN-independent transcriptional states could both contribute to platinum resistance. The dominance of genomic or non-genomic mechanisms within polyclonal tumors has implications for drug sensitivity, restoration and re-treatment strategies.

  Study EGAS00001007242

• Single Cell Transcriptomics of peripheral immune cells pre- and post-Immune Checkpoint Blockade

  This is raw sequencing data, analysis of which is presented in the paper "Sensitivity to Immune Checkpoint Blockade and Progression-Free Survival is associated with baseline CD8+ T cell clone size and cytotoxicity", DOI: https://doi.org/10.1101/2020.11.15.383786

  Dataset EGAD00001007942

• Raw sequencing data from chromosome conformation capture, RNA sequencing and chromatin assays in human primary monocytes

  This dataset contains raw sequencing data from eQTL Capture Hi-C, ATAC-seq and RNA-seq experiments in monocytes isolated from 34 healthy male donors, as well as from Hi-C, 4C-seq and CTCF ChIP-seq in subsets of individuals. The data are released as paired-end Illumina FASTQ files. Hi-C and Capture Hi-C used DpnII digestion and Tn5-based low-input library preparation. In Capture Hi-C, this was followed by targeted capture with custom-designed biotinylated RNA probes targeting ~1100 eQTL regions. ATAC-seq was performed on PFA-fixed cells using a digitonin-based protocol. 4C-seq and CTCF ChIP-seq were performed using standard protocols.

  Dataset EGAD50000001116

• IYDP Indonesian Y chromosome Diversity Project

  The IYDP dataset includes BAM files of 126 Y chromosomes extracted from whole genome sequences. These are from individuals from a broad range of Indonesian islands - communities close to mainland Asia through to New Guinea. The original whole genome sequencing libraries were prepared using TruSeq DNA PCR-Free and TruSeq Nano DNA HT kits depending on DNA quantity. 150 bp paired-end sequencing was performed on the Illumina HiSeq X sequencer. Individuals were sequenced to expected mean depth of 30x, with an achieved median depth of raw reads across samples of 43x.

  Dataset EGAD00001008573

• WGS of peripheral blood leukocytes from patients with Li-Fraumeni syndrome

  We performed whole genome sequencing on 84 LFS family members from 47 families: 22 with wildtype TP53 and 62 with variant TP53. The variant TP53 cohort consists of 49 individuals who developed cancer and 13 individuals who remain cancer-free; 34 were from 13 families with 2-4 individuals sequenced within a given family and the remaining 28 had no family members sequenced. The wildtype cohort consists of 14 individuals who developed cancer and 8 individuals who are cancer-free, from 6 families.

  Dataset EGAD00001010200

• Single-Cell Analysis of Somatic Mutations in Human Bronchial Epithelial Cells in Relation to Aging and Smoking

  While lung cancer risk among smokers is dependent on smoking dose, it remains unknown if this increased risk reflects an increased rate of somatic mutation accumulation in normal lung cells. Here we applied single-cell whole genome sequencing of proximal bronchial basal cells from 33 subjects, aged between 11 and 86 years, with smoking histories varying from never smoking to 116 pack years. We found an increase in the frequency of single-nucleotide variants and small insertions and deletions with chronological age in never-smokers, with mutation frequencies significantly elevated among smokers. However, when plotted against smoking pack-years, mutations were found to follow the linear increase in cancer risk only until about 23 pack years, after which no further increase in mutation frequency was observed, pointing towards individual selection for mutation avoidance. Known lung cancer-defined global mutation signatures tracked with both age and smoking. Within study power limits, no significant enrichment for somatic mutations in lung cancer driver genes was observed.

  Study phs002758

• Dissecting intratumor heterogeneity of nodal B cell lymphoma on the transcriptional, genetic, and drug response level

  Tumor heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is well-known to affect the efficacy of anti-cancer, most personalized treatment approaches do not account for intratumor heterogeneity. We addressed this issue by studying the heterogeneity of lymph node-derived B cell non-Hodgkin lymphoma (B-NHL) by single cell RNA-sequencing (scRNA-seq) and transcriptome-informed flow cytometry. We identified transcriptionally distinct malignant subclones and compared their drug response and genomic profiles. Malignant subclones of the same patient responded strikingly different to anti-cancer drugs ex vivo, which recapitulated subclone-specific drug sensitivity during in vivo treatment. Tumor infiltrating T cells represented the majority of non-malignant cells, whose gene expression signatures were similar across all donors, whereas the frequencies of T cell subsets varied significantly between the donors. Our data provide new insights into the heterogeneity of B-NHL and highlight the relevance of intratumor heterogeneity for personalized cancer therapies.

  Study EGAS00001004335

• Whole exome and whole genome sequencing of juvenile myelomonocytic leukemia (JMML)

  To obtain a complete registry of gene mutations in JMML, whole-exome sequencing was performed for paired tumor-normal DNA from 13 JMML cases, of which 2 cases were also analyzed by whole genome sequencing.

  Study EGAS00001000521

• The Gut Microbiome in Parkinson's Disease

  The uploaded data come from a nested case-control study, with participants with Premotor Parkinson Disease (PPS) as cases. In addition to the PPS cases, the study has three control groups: 1) constipation only controls, defined as those who only reported constipation, but not probable REM sleep behavior disorder (pRBD) or hyposmia; 2) healthy controls  who did not report constipation, pRBD or hyposmia; and 3) patients with recently diagnosed confirmed PD (diagnosed after January 1, 2010).  Participants were contacted between 2016 and 2020 for a set of two stool samples. All participants provided a baseline stool sample and a subset (N = 120) will provide a second stool sample.

  Study phs002193

• Using human induced pluripotent stem cell-derived oligodendrocytes to explore cellular phenotypes associated with t(1;11) translocation.

  Although the underlying neurobiology of major mental illness (MMI) remains unknown, emerging evidence implicates a role for oligodendrocyte-myelin abnormalities. Here, we took advantage of a large family carrying a balanced t(1;11) translocation, which substantially increases risk of MMI, to undertake both diffusion tensor imaging (DTI) and cellular studies to evaluate the consequences of the t(1;11) translocation on white matter structural integrity and oligodendrocyte-myelin biology (this translocation disrupts among others the DISC1 gene which plays a crucial role in brain development). At a cellular level, we observe dysregulation of key pathways controlling oligodendrocyte development and morphogenesis in induced pluripotent stem cell (iPSC) case derived oligodendrocytes.

  Study EGAS00001004595

• snRNA-seq analysis in multinucleated myogenic FSHD cells identifies heterogeneous FSHD transcriptome signatures associated with embryonic-like program activation and oxidative stress-induced apoptosis

  The sporadic nature of DUX4 expression in FSHD muscle challenges comparative transcriptome analyses between FSHD and control samples. A variety of DUX4 and FSHD-associated transcriptional changes have been identified, but bulk RNA-seq strategies prohibit comprehensive analysis of their spatiotemporal relation, interdependence and role in the disease process. In this study, we used single-nucleus RNA-sequencing of nuclei isolated from patient- and control-derived multinucleated primary myotubes to investigate the cellular heterogeneity in FSHD. Taking advantage of the increased resolution in snRNA-sequencing of fully differentiated myotubes, two distinct populations of DUX4-affected nuclei could be defined by their transcriptional profiles. Our data provides insights into the differences between these two populations and suggests heterogeneity in two well-known FSHD-associated transcriptional aberrations: increased oxidative stress and inhibition of myogenic differentiation. Additionally, we provide evidence that DUX4-affected nuclei share transcriptome features with early embryonic cells beyond the well-described cleavage stage, progressing into the 8-cell and blastocyst stages. Altogether, our data suggests that the FSHD transcriptional profile is defined by a mixture of individual and sometimes mutually exclusive DUX4-induced responses and cellular state-dependent downstream effects.

  Study EGAS00001007635

• The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma

  Patients with metastatic uveal melanoma (UM) have an abysmal prognosis. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. Here we test if epigenetic therapy would enhance PD-1 immunotherapy in patients with metastatic UM. We report the results of the PEMDAC phase 2 clinical trial (n=29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic UM. The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Extensive genomics studies were performed using DNA/RNA and single cell sequencing and flow cytometry. Objective responses and prolonged survival were seen in three patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM. Further exploration of combined immunotherapy and epigenetic therapy in metastatic UM is warranted.

  Study EGAS00001005478

• Multi-omics integration reveals only minor long-term molecular and functional sequelae in immune cells of individuals recovered from COVID-19

  The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in convalescent COVID-19 and healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays moderate changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1RA and IFN?? was higher in convalescent individuals. In conclusion, despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals.

  Study EGAS00001005529

• Mutational landscape of normal epithelial cells in Lynch Syndrome patients

  Lynch Syndrome (LS) is an autosomal dominant disease conferring a high risk of colorectal cancer due to germline heterozygous mutations in a DNA mismatch repair (MMR) gene. Although cancers in LS patients show elevated somatic mutation burdens, information on mutation rates in normal tissues and understanding of the trajectory from normal to cancer cell is limited. Here we whole-genome sequenced 152 crypts from normal and neoplastic epithelial tissues from LS patients. In normal tissues the repertoire of mutational processes and mutation rates were similar to those found in wild type individuals. A morphologically normal colonic crypt with an increased mutation burden and mutational signatures consistent with MMR deficiency was identified, which may represent a very early stage of LS pathogenesis. Phylogenetic tress of tumour crypts indicated that the most recent ancestor cell of each tumour was already MMR deficient and had experienced multiple clonal evolution cycles. This study demonstrates the genomic stability of epithelial cells with heterozygous germline MMR gene mutations and highlights important differences in the pathogenesis of LS from other colorectal cancer predisposition syndromes.

  Dataset EGAD00001008092

• Microsatellite data show recent demographic expansions in sedentary but not in nomadic human populations in Africa and Eurasia.

  The transition from hunting and gathering to plant and animal domestication was one of the most important cultural and technological revolutions in human history. According to archeologists and paleoanthropologists, this transition triggered major demographic expansions. However, few genetic studies have found traces of Neolithic expansions in the current repartition of genetic polymorphism, pointing rather toward Paleolithic expansions. Here, we used microsatellite autosomal data to investigate the past demographic history of 87 African and Eurasian human populations with contrasted lifestyles (nomadic hunter-gatherers, semi-nomadic herders and sedentary farmers). Likely due to the combination of a higher mutation rate and the possibility to analyze several loci as independent replicates of the coalescent process, the analysis of microsatellite data allowed us to infer more recent expansions than previous genetic studies, potentially resulting from the Neolithic transition. Despite the variability in their location and environment, we found consistent expansions for all sedentary farmers, while we inferred constant population sizes for all hunter-gatherers and most herders, which could result from constraints linked to a nomadic or semi-nomadic lifestyle and/or competition for land between herders and farmers. As an exception, we inferred expansions for Central Asian herders. This might be linked with the arid environment of this area, which may have been more favorable to nomadic herders than to sedentary farmers. Alternatively, current Central Asian herders may descent from populations who have first experienced a transition from hunter-gathering to sedentary agropastoralism, and then a second transition to nomadic herding.

  Study EGAS00001000652

• Multi-Modal Single-Cell, Spatial, and Genomic Analyses of Human Non-Small Cell Lung Cancer Brain Metastases

  We performed single nuclei RNA-sequencing (snRNA-seq) with matched T cell receptor sequencing (TCR-seq), and pool matched low pass whole genome sequencing (WGS) of 12 treatment-naive non-small cell lung cancer (NSCLC) primary tumors (PTs) and 31 treatment-naive NSCLC brain metastases (BMs). In total, we recovered 277,206 cell transcriptomes in 43 samples. Single-nuclei suspension from frozen NSCLC metastases were generated using methods published in Slyper et al. (Nature Medicine, 2020, PMID:32405060) with modifications. The tissue was first cut in 20 µm sections using a cryostat and stored on dry ice until the next step. Then the tissue was put on wet ice and washed once with 5 ml PBS to remove OCT. After this step nuclei were extracted by vigorous pipetting in salt-tris buffer with Tween-20 (TST) followed by a high-volume wash in salt-tris buffer (ST). Nuclei were counted and 10,000-14,000 and were loaded using a Chromium controller (10X genomics) and Chromium Single Cell 5' Reagents (V1.1 and V2). Complementary DNA libraries were generated according to manufacturer's instructions, with the modification of one additional cycle of amplification. Matched single nuclei T cell receptor (snTCR) sequencing libraries were prepared from amplified cDNA libraries using either Chromium Single Cell V(D)J Enrichment Kit for human T cells Reagent Kit, v1.1, or single cell human TCR amplification kit. Final snTCR sequencing libraries were prepared using Single Index Kit T Set A for V1.1 libraries or Library construction kit and Dual Index Kit TT set A for V2 libraries. Sequencing libraries were quantified using Tapestation D5000 reagents and a 2200 TapeStation and pooled for sequencing. Pool matched low pass whole-genome sequencing (lp-WGS) was performed in addition to snRNA-seq to improve the identification of the malignant and non-malignant cell compartments. Nuclei from snRNA-seq sample preparations were collected by centrifugation (500g, 5 min), snap frozen after removing excess ST buffer, and stored at -200C until further processing. If insufficient nuclei (0C for 9 minutes. Adapters were not diluted, and the optional PCR (5 cycles) and cleanup were performed. After library cleanup with AMPure beads (Beckman Coulter, Brea, CA), libraries were quantified with Tapestation D5000 HS tapes (Agilent) and stored at -200C until sequencing.Using multiplexed immunofluorescence in an independent cohort of treatment-naïve pairs of primary tumors and brain metastases from the same patients with NSCLC, we validated genomic and tumor-microenvironmental findings and identified a cancer cell population characterized by neural features that strongly enriched in brain metastases. This comprehensive analysis provides insights into human NSCLC brain metastasis biology and serves as an important resource for additional discovery.

  Study phs003865

• Development of a rapid and comprehensive genomic profiling test supporting diagnosis and research for gliomas

  Targeted sequencing dataset used for the paper entitled "Development of a rapid and comprehensive genomic profiling test supporting diagnosis and research for gliomas". The cohort includes 53 cases of targeted DNA squencing, 15 of them have matched control sequences. The capture panel was made by Agilent SureSelect and the sequence was performed using DNBSEQ or Illumina sequencer.

  Dataset EGAD50000000979

• BELLINI clinical trial bulk RNA-Seq data: cohorts A, B & С

  RNA-Seq data of 78 breast cancer primary tumors obtained from 45 unique patients from BELLINI clinical trial. The data includes pre- and post-treatment samples. Patients in cohort A (15 patients, 25 samples) received nivolumab for 4 weeks, patients in cohort B (15 patients, 28 samples) received nivolumab + ipilimumab for 4 weeks, and patients in cohort C (15 patients, 25 samples) received nivolumab + ipilimumab for 6 weeks. The included raw transcriptome sequencing data in fastq format was generated using Illumina NovaSeq 6000.

  Dataset EGAD50000000808

• Oxford Nanopore RNA sequencing for HLA typing

  A targeted RNA-based method for typing of 12 classical HLA genes using Oxford Nanopore sequencing. In the method, were enriched HLA genes from cDNA of 50 individuals using gene-specific reverse primers. The library molecules were then barcoded, pooled into 2 separate gene pools, and sequenced on MinION R9.4 SpotON flow cells.

  Study EGAS00001004918

• University of Washington Developmental Single Cell Atlas

  We set out to generate a human cell atlas of both gene expression and chromatin accessibility using tissues obtained during development. In this study, we applied an assay for single cell profiling of gene expression based on three-level combinatorial indexing (sci-RNA-seq3) to 121 fetal tissue samples representing 15 organs, altogether profiling transcription in over 4 million single cells. In parallel, we devised an improved assay for single cell profiling of chromatin accessibility also based on three-level combinatorial indexing (sci-ATAC-seq3). We applied this method to 53 fetal tissue samples representing 15 organs, altogether profiling on the order of one million single cells. From these data, we identify and characterize diverse human cell types and annotate them with respect to marker genes, expression and regulatory modules. These data comprise a rich resource for the exploration of human biology.

  Study phs002003

• Kidney_tumour_DNA_exome

  This is an exome DNA sequencing study of human renal tumours

  Study EGAS00001003616

• T cell repertorie analysis fom a Spanish cohort of mild and severe cases of COVID-19 recovered patients

  The cohort included 98 mild and 75 severe cases with a median age of 53 years. We amplified and sequenced the T Cell Receptor (TCR β) chain complementary determining region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, allelic usage, and epitope affinity CDR3b clustering. CDR3b sequences were amplified by multiplex PCR and sequenced by Illumina. The resulting raw files were processed for clonotype assembly, filtering for coding clonotypes, removal of non-TRB alleles, and downsampling.

  Study EGAS50000000331

• CPC-GENE primary prostate benign and tumour tissue Hi-C sequencing reads

  This dataset contains the raw sequencing data, in FASTQ format, for Hi-C assays from 17 primary prostate tissue samples. The sequencing data is paired-end, 150 bp sequencing data from an Illumina NovaSeq 6000 machine, and contains 5 benign tissue samples and 12 primary tumour samples from the Canadian Prostate Cancer Genome Network (CPC-GENE) project. Tumour samples have IDs starting with the "CPCG" prefix, and benign tissue samples have IDs starting with the "BP" suffix.

  Dataset EGAD00001008024

• TenK10K Phase 1: Whole Genome Sequencing SNP + indels multi-sample VCFs

  SNP and indel variants were called for 1,925 samples from phase 1 of the TenK10K project. Variant calling from WGS alignments to the GRCh38 reference assembly was performed using GATK4 HaplotypeCaller in DRAGEN mode. These VCFs consist of common (>=1% minor allele frequency [MAF]) and rare (<1% MAF) variants . This dataset is comprised of autosomal variants provided as multisample compressed VCF format files. Principal component scores were derived by using gnomAD’s run_pca_with_relateds method.

  Dataset EGAD50000002377

• Clinical and serum metabolomics data for individuals with ACS

  Full clinical data for a cohort of 199 individuals with acute coronary syndrome. Untargeted serum metabolomics using the Metabolon platform for individuals with ACS (n=156). Serum metabolomics using the Nightingale Health (NMR) platform for individuals with ACS and controls (ACS, n=191; controls, n=961).

  Dataset EGAD00001007724

• RNASeq from PPGL-derived PC12 cell lines cultivated in normoxia and hypoxia conditions.

  PC12 cells derived from rat PPGL were then either continued cultivated in the same normoxia condition (37˚C, 5% CO2 and 21% O2 balanced with N2) or were placed in a hypoxic incubator, that maintained a constant hypoxic environment (37˚C, 5% CO2 and 1% O2 balanced with N2), for different short (12h, 24h, and 48h) or prolonged time (36 days, approximately 860h).

  Study EGAS50000000814

• QSEA – modelling of genome-wide DNA methylation from sequencing enrichment experiments

  We describe a new method, QSEA, for analyzing methylation enrichment data. We generated a benchmark experiment consisting of MeDIP-seq enrichment data, targeted BS-seq validation data, and RNA-seq data on five pairs of tumor and adjacent normal samples of non-small cell lung cancer patients. Details of the method and its performance on the data have been described in Lienhard et al. (2016).

  Study EGAS00001001822

• Prospective high-throughput genome profiling in advanced cancers:

  Genomics-based tumor profiling in advanced cancers (aC) was recently demonstrated as feasible in clinical practice. After the prospective pilot PANDORA study done on advanced breast cancers, we conducted a prospective monocenter clinical trial called PERMED01 to evaluate the number patients with locally advanced or metastatic cancer for whom identification of molecular alterations in tumor samples could lead to the delivery of a targeted therapy

  Study EGAS00001004554

• Somatic Genetics of lesions from a POT1 patient (2017-04-27)

  In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1). This dataset contains all the data available for this study on 2017-04-27.

  Dataset EGAD00001003307

• Somatic Genetics of lesions from a POT1 patient (2016-04-20)

  In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1). This dataset contains all the data available for this study on 2016-04-20.

  Dataset EGAD00001002050

• Multi-institutional collaboration to characterize 5hmC in prostate cancer, both tumor biopsies and cfDNA.

  This study used pull-down sequencing to measure 5-hydroxymethylcytosine (5hmC) levels in tissue biopsy specimens from patients with localized and metastatic castration-resistant (mCRPC) prostate cancer. For a subset of the cohort, the same technique was used to sequence cell-free DNA (cfDNA) isolated from patient plasma. To assess 5hmC levels in cfDNA from a larger number of specimens, plasma samples from another mCRPC cohort were also assayed with this method. The larger cohort of cfDNA samples was further anlayzed with a targeted sequencing gene panel.

  Study EGAS00001004942

• Splicing signature analysis of RNU4-2, RNU5A-1 and RNU5B-1

  Pathogenic variants in the snRNA RNU4-2 were recently described as a frequent cause of neurodevelopmental disorders. In our study we further delineate the phenotype associated with RNU4-2 and we also identify pathogenic variants in RNU5A-A and RNU5B-1. Capture-based RNA-Seq were performed to compare splicing pattern between affected and control individuals. A strong signature based on alternative 5' splice site usage was found for RNU4-2 patients, and we suggest an either 5' or 3' signature depending on the variant's localiztion in U5 genes.

  Study EGAS50000000889

• Multipolar zygotic divisions are characterized by parental genome segregation errors

  Study EGAS00001005543

• Whole exome sequencing of uterine cervical cancer

  We conducted whole-exome sequencing of cervical tissue samples to evaluate HLA loss of heterozygosity (LOH) and B2M gene mutations, which are key mechanisms of immune evasion that allow cancer cells to escape T-cell recognition and antigen presentation.

  Study JGAS000824

• exploration of biomarkers in colorectal cancer

  Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. To understand the molecular basis of colorectal cancer, we performed CAGE (Cap Analysis of Gene Expression) to quantify promoter activities on 45 colorectal cancers.

  Study JGAS000489

• Bulk RNA sequencing data of high-grade serous ovarian cancer samples (set 18-19)

  The dataset contains RNA sequencing data of 66 high-grade serous carcinoma (HGSC) patients sequenced with Novoseq 6000. The 155 samples are fresh frozen tissue samples that have been collected from different tissues and time points before and during treatment. The files provided are paired fastq files.

  Dataset EGAD50000002370

• RNA seq samples

  Dataset contains 12 RNA-Seq samples sequenced on the Illumina NextSeq500 sequencer. 6 samples are controls (D1-Tact-Plasma,D2-Tact-Plasma,D3-Tact-Plasma,D1-TUnstim-Plasma,D2-TUnstim-Plasma,D3-TUnstim-Plasma) 6 samples are case (D1-Tact-SF,D2-Tact-SF,D3-Tact-SF,D1-TUnstim-SF,D2-TUnstim-SF,D3-TUnstim-SF)

  Dataset EGAD50000001189

• ChIP seq samples

  Dataset contains 12 ChIP-Seq samples sequenced on the Illumina NextSeq500 sequencer. 3 samples are control samples (HcAct-Chip 1,HcAct-Chip 2,HcAct-Imput 2) 9 samples are case samples (HcAct2DG-Chip 1,HcAct2DG-Chip 2,HcAct2DG-Imput 1,JIAAct-Chip1,JIAAct-Chip2,JIAAct-Imput2,JIAAct2DG-Chip1,JIAAct2DG-Chip2,JIAAct2DG-Imput2)

  Dataset EGAD50000001188

• Clinical panel sequencing of cancer of unknown primary using Comprehensive cancer panel (CCP)

  This database includes comprehensive cancer panel (CCP) on paired tumour and germline DNA from cancer of unknown primary samples, all of which are matched to WGS data under this study. This data was used to compare biomarker yield against what was achieved with WGS. This dataset contains n=34 tumour-germline paired samples. All samples are in BAM format aligned with GRCh38 reference genome.

  Dataset EGAD50000000655

• Clinical panel sequencing of cancer of unknown primary using TruSight Oncology 500 (TSO500)

  TruSight Oncology 500 (TSO500) cancer panel sequencing data on paired tumour and germline DNA from cancer of unknown primary samples. All of the samples in this dataset are matched to WGS data. This data was used to compare biomarker yield against what was achieved with WGS and contains n=51 tumour-only samples. All samples are in BAM format aligned with GRCh38 reference genome.

  Dataset EGAD50000000657