19074 results for "Buy fc coins Buyfc26coins.com is EA Sports official for FC 26 coins They are the best FC seller..nEoY"

in 67.48 milliseconds.

• Whole genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes

  The dataset comprises of an aggregate level VCF (version 4.1), containing the somatic point and indel mutations found across the glioblastoma cohort (SweGBM-1, n=38 samples). The VCF file is in accordance with the HTS format specifications (https://samtools.github.io/hts-specs/).

  Dataset EGAD00001006084

• Methylation Profiles of Cell-Free DNA Using Nanopore Sequencing

  Epigenetic characterization of cell-free DNA (cfDNA) is an emerging approach for detecting and characterizing diseases such as cancer. We developed a strategy using nanopore-based single-molecule sequencing to measure cfDNA methylomes. This approach generated up to hundreds of millions of reads for a single cfDNA sample from cancer patients, an order of magnitude improvement over existing nanopore sequencing methods. We developed a single-molecule classifier to determine whether individual reads originated from a tumor or immune cells. Leveraging methylomes of matched tumors and immune cells, we characterized cfDNA methylomes of cancer patients for longitudinal monitoring during treatment.Control subjects consist of healthy individuals without a positive diagnosis of cancer. cfDNA was obtained through purification of plasma from blood draws. Genomic DNA (gDNA) was derived from extraction of primary tumor tissue or from leukocytes from blood draws.

  Study phs002950

• WGS of human colorectal cancer organoid exposed to genotoxic pks+ E. coli

  Organoid cultures were exposed to different E.Coli strains and a dye control. In total 25 organoid cultures were whole-genome sequenced using the Novaseq6000 platforms. The data is deposited as .bam format.

  Dataset EGAD50000000304

• DIAMOND PCR : plasma DNA LINE-1 targeted bisulfite sequencing, a new non-invasive multi-cancer detection marker

  The detection of circulating tumor DNA, which allows non-invasive tumor molecular profiling and disease follow-up, promises optimal and individualized management of patients with cancer. However, detecting small fractions of tumor DNA released when the tumor burden is reduced remains a challenge. We developed a PCR-based targeted bisulfite method coupled to deep sequencing to detect methylation patterns of L1PA elements,which we named DIAMOND (for Detection of Long Interspersed Nuclear Element Altered Methylation ON plasma DNA). We used sodium bisulfite chemical conversion to achieve base-pair resolution analysis and designed a multiplexed PCR based on 8 amplicons covering L1PAs .

  Dataset EGAD50000000646

• PacBio Revio WGS on 10 carriers of ring and marker chromosomes

  Bam files containing PacBio HiFi reads from carriers of ring and marker chromosomes. The reads where genereated using the PacBio Revio platform. Each individual was sequenced to roughly 30X coverage on one flow cell per individual. The chromosome of interest is indicated in the file name.

  Dataset EGAD50000002111

• whole exome sequencing (WES) data of the HIPO head and neck cancer (HNC, n=83)

  Paired whole exome sequencing data of the HIPO head and neck cancer (HNC) (n=83), using Agilent SureSelect V4+UTRs and V6+UTRs with the sequencing platforms HiSeq2000 and HiSeq2500. The reads were aligned to hg19. This is part of project H019.

  Dataset EGAD00001006336

• Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high risk disease

  Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are poorly understood. We performed whole exome sequencing, copy number variation and/or RNA-Seq for 65 patients to discover mutations at diagnosis and blast crisis (BC). Forty-six chronic phase patients with the extremes of outcome were studied at diagnosis. Cancer gene variants were detected in 15/27 patients (56%) with subsequent BC or poor outcome and in 3/19 optimal responders (16%), P=.007. Frequently mutated genes at diagnosis were ASXL1, IKZF1 and RUNX1. The methyltransferase SETD1B was a novel recurrently mutated gene. A novel class of variant associated with the Philadelphia translocation was detected at diagnosis in 11/46 patients (24%) comprising fusions and/or rearrangement of genes on the translocated chromosomes, with evidence of fragmentation, inversion and imperfect sequence reassembly. These were more frequent at diagnosis in patients with poor outcome: 9/27 (33%) versus 2/19 optimal responders (11%), P=.07. Thirty-nine patients were tested at BC and all had cancer gene variants, including ABL1 kinase domain mutations in 58%. However, ABL1 mutations co-occurred with other mutated cancer genes in 89% of cases, and these predated ABL1 mutations in 62% of evaluable patients. Gene fusions not associated with the Philadelphia translocation occurred in 42% of patients at BC and commonly involved fusion partners that were known cancer genes (78%). Genomic analysis revealed numerous relevant variants at diagnosis in patients with poor outcome and all patients at BC. Future refined biomarker testing of specific variants will likely provide prognostic information to facilitate a risk-adapted therapeutic approach.

  Study EGAS00001003071

• Integrative Analysis of Tumor Biopsies on Sequential CTLA-4 and PD-1 Blockade Reveals Markers of Response and Resistance

  Blockade of T cell coinhibitory molecules such as CTLA-4 and PD-1, can activate T cell antitumor response. Although these immune checkpoint blockades (CTLA-4 blockade and PD-1 blockade) have shown durable response, response rate is modest. Therefore, there is a need to find stable biomarkers predictive of response to immune checkpoint blockades and to understand underlying resistance mechanisms. We collected longitudinal tumor biopsies from a cohort of metastatic melanoma patients treated with sequential immune checkpoint blockades and performed whole exome sequencing of this cohort. The comprehensive genomic characterization of tumors enabled identification of higher copy number loss burden as a resistance mechanism and clonal T cell repertoire as a predictive biomarker.

  Study phs001425

• Moroccan Genome Project: Sequencing Data from 109 Whole Genomes of Moroccan Individuals

  This study is the first phase of the Moroccan Genome Project, which included the complete sequencing of 109 genomes from the Kingdom of Morocco. The sequencing was performing using the Illumina NovaSeq6000 platform, with a mean coverage of 30X.

  Dataset EGAD50000000750

• Characterization of mutational signatures in human cancer cell lines reveals episodic APOBEC mutagenesis

  Multiple signatures of somatic mutations have been identified in human cancer genomes. To investigate whether mutational signatures continue to be generated, and if so their temporal patterns of activity, subsets of cell lines were cultured in vitro for extended periods and subjected to single cell cloning and whole genome or exome sequencing or directly to single cell whole genome sequencing. As expected, signatures of past exogenous exposures, such as tobacco smoke and ultraviolet light, were not generated in vitro. In contrast, signatures of normal and defective DNA repair and replication continued to be generated at essentially constant mutation rates. Signatures of APOBEC cytidine deaminase DNA-editing activity exhibited a distinctive pattern with substantial fluctuations in mutation rate over time and episodic bursts of mutations. The initiating factors for these bursts are unclear although retrotransposon mobilisation may play a role. This cell line set now constitutes a comprehensive resource of live experimental models of mutational processes of both known and unknown aetiologies potentially retaining the patterns of activity and regulatory influences operative in human cells in vivo.

  Dataset EGAD00001004201

• The cellular state space of AML unveils novel NPM1 subtypes with distinct clinical outcomes and immune evasion properties

  Acute myeloid leukemia (AML) is a genetically and cellularly heterogeneous disease. We characterized 120 AMLs using bulk genomic and transcriptomic analyses (WES, MP-WGS, RNA-seq), and single-cell RNA sequencing (scRNA-seq). Our results reveal an extensive cellular heterogeneity that distorts the bulk transcriptomic profiles. Notably, NPM1 mutated AML could be stratified into two novel, clinically relevant classes (NPM1class I and NPM1class II).

  Study EGAS50000001084

• Clinical outcomes and immune correlates of response to nivolumab plus chemoradiotherapy in women with locally-advanced cervical cancer – NiCOL study

  Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 trial was designed to determine safety, tolerance, and immune correlates of response to the PD-1 blocking antibody, nivolumab, with and following concurrent CRT in 16 women with locally advanced cervical cancer (LACC). Three patients experienced grade 3 dose-limiting toxicities. The overall response rate was 93.8% [95%CI: 69.8%-99.8%] with a 2-year PFS of 75% [95% CI: 56.5%-99.5%]. Compared to patients with progressive disease (PD), progression-free (PF) subjects showed a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3+ T cells to PD-L1+ tumor cells and of Foxp3+ T cells to proliferating CD11c+ myeloid cells. PF had higher baseline levels of PD-1 on EMRA CD4+ T cells and ICOS-L on tumor-associated macrophages (TAMs) vs PD, which instead displayed enhanced PD-L1 expression on TAMs and higher, circulating frequencies of proliferating Tregs at baseline. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of LACC displaying pre-existing, adaptive immune activation is warranted.

  Study EGAS00001007297

• Multiple system atrophy - bulk RNA seq of prefrontal cortex

  Dataset corresponding to the bulk RNA-seq dataset from prefrontal cortex for a total of N=35 samples. Tissue samples correspond to donors with pathologically confirmed multiple system atrophy. RNA-seq was carried out using ribosomal depletion. Dataset contains paired fastq files, sample metadata and downstream quantification files. Quantification was performed with salmon v1.3.0 with Gencode 35 (GRCh38.p13). N=6 samples are overlapping with EGAS50000000301.

  Dataset EGAD50000002624

• Parkinson's disease - bulk RNA seq of prefrontal cortex

  Dataset corresponding to the bulk RNA-seq dataset from prefrontal cortex for a total of N=448 samples. Tissue samples correspond to donors with pathologically confirmed Parkinson's disease. RNA-seq was carried out using ribosomal depletion. Dataset contains paired fastq files, sample metadata and downstream quantification files. Quantification was performed with salmon v1.3.0 with Gencode 35 (GRCh38.p13). N=81 samples are overlapping with EGAS50000000301.

  Dataset EGAD50000002627

• Controls - bulk RNA seq of prefrontal cortex

  Dataset corresponding to the bulk RNA-seq dataset from prefrontal cortex for a total of N=283 samples. Tissue samples correspond to health control donors. RNA-seq was carried out using ribosomal depletion. Dataset contains paired fastq files, sample metadata and downstream quantification files. Quantification was performed with salmon v1.3.0 with Gencode 35 (GRCh38.p13). N=21 samples are overlapping with EGAS50000000301.

  Dataset EGAD50000002628

• Smart-seq2 analysis of 11 ETMR patient samples (4,031 high-quality single cells/nuclei).

  We analyzed 11 ETMR patient samples using single-cell transcriptomics (6 from fresh and 5 from frozen material). Samples were profilied by paired-end scRNA-sequencing using the Smart-Seq2 protocol on a NextSeq 500 sequencer (Illumina). The dataset contains 8,062 fastq files of 4,031 high-quality single cells/nuclei. Raw fastq files of high-quality cells are shared.

  Dataset EGAD50000001379

• Targeted RNA-Seq

  This dataset contains targeted RNA-Seq generated with the Illumina RNA Pan-Cancer panel. It comprises 2200 cancers from children and adults. The cancers represent a wide range of CNS, solid and haematopoietic tumours. Samples are from pathology specimens including FFPE, fresh frozen, bone marrow aspirate and peripheral blood. Samples were tested in a clinical diagnostic lab to identify relevant SNVs, indels and gene fusions.

  Dataset EGAD50000000980

• Acute myeloid leukemia single cell RNA-seq (Diagnosis and Relapse)

  To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed single-cell RNA-seq (SORT-seq) to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases. All the samples are Bone marrow aspirates.

  Dataset EGAD00001008373

• He et al. WES data

  This dataset are the bam files of WES data from the paper by He et al.

  Dataset EGAD00001007134

• Whole genome sequencing data of lung adenocarcinomas

  This dataset includes the whole-genome sequencing data from a study entitled "Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma". Whole-genome sequencing libraries were generated by PCR-free methods, and sequencing run was made in HiSeq X Ten machines. PCR duplicates-marked, indel-realigned, and base-recalibrarted BAM files are provided in our dataset.

  Dataset EGAD00001004793

• Whole exome and transcriptome sequencing of BPDCN

  This data set contains whole exome and transcriptome data from 47 case with BPDCN. For exome data, bam files are provided (mapped against GRCh38), for transcriptome raw fastq-files (paired-end data).

  Dataset EGAD00001008692

• RNAseq of primary mesothelioma cell lines

  Mesothelioma is an aggressive cancer associated with previous exposure to asbestos and dismal prognosis. Since a pemetrexed/cisplatin combination was introduced for treatment of mesothelioma, no new first- or second-line therapies have been discovered. Thus, to better understand what drives mesothelioma carcinogenesis and to identify potential targets for therapy, in this project we aim at performing RNAseq analysis of a panel of mesothelioma cells lines.

  Dataset EGAD00001009642

• RNA-seq from time-course experiment treating cells for 72h

  RNA sequencing from MSTO-211H cell line cultures treated for 72h with vehicle solution, palbociclib 250nM, or abemaciclib 250nM (N = 3, each). RNA-seq prepared using TruSeq Stranded mRNA libraries and sequenced with Illumina HiSeq 4000. Data is in raw fastq format, paired end. Some samples have been split in two lanes, with a final count of 24 fastq files.

  Dataset EGAD00001007737

• 503 genotypes from Inner Asia used in 'Close inbreeding and low genetic diversity in Inner Asian human populations despite geographical exogamy' publication

  Inner Asia is particularly interesting to understand human history and evolution, as two groups presenting contrasting cultural traits (notably their language, their social organisation and matrimonial system) cohabit. We sampled 503 individuals from these two groups, belonging to 17 populations from 11 distinct ethnic groups (AltaiKizhi, Kazakh, Khakas, Kyrgyz, Mongolian, Shore, Tajik, Telengit, Tubalar, Turkmen and Uzbek). The samples were then genotyped with 5 different DNA-arrays and, after quality-control, the 253,532 autosomal SNPs present in all the arrays were merged together in the present dataset.

  Study EGAS00001002951

• Transcriptional characterization of human innate lymphoid cells (ILCs) and natural killer (NK) cells from fresh umbilical cord blood

  The heterogenicity of cord blood ILCs (ILC1, ILC2, ILC3) and NK cells in humans has so far not been assessed. In this study, we sorted from fresh cord blood the respective cell types from 3 donors and performed single-cell transcriptome analysis. To achieve high resoluation, each sorted population was labelled individually via multiplexing antibodies and subsequent Abseq staining before pooling. To determine single-cell transcriptomes the BD Rhapsody pipeline was performed. This is the first data set to characterize human ILCs and NK cells at such depth.

  Study EGAS50000001204

• 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.

  Study EGAS00001001035

• Human Vaccines Project: scRNAseq Characterization of HepB Vaccine Response

  In adult systems vaccinology studies, baseline immune status (i.e. pre-vaccine) of vaccine recipients was highly predictive of vaccine immunogenicity. The aim of this study is to characterize pre-vaccine immune signatures that predict immunogenicity of HBV in humans using single cell transcriptomics. To investigate the pre-vaccine status of these patients, we characterized transcriptomic responses in 5 FACS sorted populations of circulating immune cells, mDCs, monocytes, pDCs, natural killer cells and neutrophils, sample at baseline, 3, 7 and 14 days after vaccination.

  Study phs002508

• APOLLO1: Proteogenomic Analysis of Lung Adenocarcinoma

  APOLLO is a proteogenomic study seeking to describe the major genome, transcriptome, proteome and phosphoproteome alterations, subtypes, and molecular predictors of patient outcomes. This study includes 87 lung adenocarcinomas and matched normal tissues from the Lung Cancer Biospecimen Resource Network (https://lungbio.sites.virginia.edu/). Tumor tissues were profiled by whole genome sequencing, transcriptome sequencing, MS-based proteomics and phosphoproteomics, and reverse phase protein arrays. Matched normal tissues were profiled by whole genome sequencing. Clinical and sample data include survival times, patient features, and tumor characteristics.

  Study phs003011

• APOLLO-OV: Applied Proteogenomics of High Grade Serous Ovarian Carcinoma

  APOLLO is a proteogenomic study seeking to describe the major genome, transcriptome, proteome and phosphoproteome alterations, subtypes, and molecular predictors of patient outcomes. This study includes 70 high grade serous ovarian carcinoma tissues from the Gynecologic Cancer Center of Excellence (https://medschool.usuhs.edu/gso/research/gyn-cancer-center-of-excellence). Bulk and laser microdissection enriched tumor tissues were profiled by whole genome sequencing, transcriptome sequencing, MS-based proteomics and reverse phase protein arrays. Clinical and sample data include survival times, patient features, and tumor characteristics.

  Study phs003488

• Filtered variants including SLC12A2 in patients with hearing loss

  Hereditary hearing loss is challenging to diagnose because of the heterogeneity of the causative genes. Further, some genes involved in hereditary hearing loss have yet to be identified. Using whole-exome analysis of three families with congenital, severe-to-profound hearing loss, we identified a missense variant of SLC12A2 in five affected members of one family showing a dominant inheritance mode, along with de novo splice-site and missense variants of SLC12A2 in two sporadic cases, as promising candidates associated with hearing loss.

  Study JGAS000379

• Comprehensive molecular profiling of pulmonary pleomorphic carcinoma

  Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. Whole exome sequencing (WES) of fresh-frozen tissue samples and target-capture sequencing of formalin-fixed-paraffin-embedded (FFPE) samples were performed. Fresh-frozen tissue samples and FFPE samples were subjected to WES and target-capture sequencing as normal control, respectively. Fresh-frozen tissue samples and 56 FFPE samples were subjected to RNA-seq.

  Study JGAS000297

• Whole exome sequencing identifies clinically relevant mutational signatures in resected hepatocellular carcinoma

  We conducted a multicentre pilot study on patients with localized HCC following complete radiological response to surgical resection. Patients received 250 mg oral gefitinib once daily as adjuvant therapy, up to a maximum of 6 months. The clinical endpoints included recurrence-free survival (RFS) and overall survival (OS), and correlative genetic analyses were conducted from whole exome sequencing data (n=33). All statistical analyses were carried out on an intention-to-treat basis. The study is registered with ClinicalTrials.gov (NCT00282100).

  Study EGAS00001004371

• North American Brain Expression Consortium (NABEC) Exome Sequencing

  A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on mRNA expression distinct human brain regions. We show that brain tissues may be readily distinguished based on expression profile. We find an abundance of genetic cis regulation mRNA expression. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation.

  Study EGAS00001002110

• The Finland-United States Investigation of NIDDM Genetics (FUSION) Study - Islet Expression and Regulation by RNAseq and ATACseq

  This study evaluates gene expression and its regulation in human pancreatic islets, a tissue relevant in the study of genetic risk factors contributing to diabetes. We obtained pancreatic tissue sections and purified pancreatic islets from deceased donors and processed these biological samples to generate various data types. We generated spatial transcriptomic data from pancreatic tissue samples using the 10X Genomics VISIUM technology with sequencing on the Illumina NovaSeq platform. We also generated multiple data types from the purified pancreatic islets using genome-wide SNP chips, bulk RNA-Seq, microRNA (miRNA)-Seq, whole genome sequence, DNA methylation (methyl)-Seq, cap analysis of gene expression (CAGE)-Seq, single cell RNA-seq, and single nuclei ATAC-seq approaches. These data include ATAC-seq of two islet subjects, RNA-seq of 31 additional subjects, genome-wide chip genotypes, and imputed genotypes of the 33 subjects released with phs001188.v1. For genotyping, 500-1000 islet equivalents (IEQ) were cultured as in Gershengorn (Science, 2004, PMID: 15564314); genomic DNA isolated from islet cultures. For RNA analyses, 2500-5000 IEQ from each islet source were used for bulk or single-cell RNA isolation. Messenger RNA was isolated with trizol extraction and 12-plex libraries were generated using the Illumina TruSeq directional mRNA-seq library protocol. Bulk RNA sequencing was performed on HiSeq2000/HiSeq2500/Hiseq4000/NovaSeq6000 sequencers using paired-end reads at the NIH Intramural Sequencing Center (NISC). miRNA libraries were prepared from total RNA from 68 samples, pooled and sequenced 50bp single-end reads on Illumina HiSeq2500. CAGE libraries were prepared from total RNA samples using the nAnT-iCAGE protocol at DNAFORM, Japan. CAGE libraries were sequenced at the NIH Intramural Sequencing Center (NISC) on the HiSeq2000 sequencer. Genotyping on the Illumina Omni2.5M array was performed at the NHGRI Genomics Core facility. Genotypes were imputed using the HRC.r1.1.2016 reference panel. To assess regions of open chromatin in islets, we performed bulk ATAC-seq on HiSeq2000 sequencers using paired-end reads at NISC. Single-nuclei ATAC-seq libraries were prepared using single-cell-combinatorial-indexing (sci-) ATAC-seq protocol and sequenced on Illumina NextSeq using paired-end reads. scRNA-seq libraries were generated using the 10X Genomics platform and sequenced on Illumina HiSeq3000 at the Genomics Technology Core of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Greater than 90% of the loci associated with T2D through genome-wide association studies occur in non-coding regions, suggesting a strong regulatory component to disease susceptibility. Therefore, there is a critical need to understand the full spectrum of genetic variation and regulatory element usage in T2D-relevant tissues. To that end, this study contains multiple genomic and transcriptomic data sets from pancreas tissue sections and pancreatic islets, a resource that will contribute to our efforts to investigate the genetic risk factors for type 2 diabetes.

  Study phs001188

• Whole Exome Sequencing of High grade T1 non-muscle invasive bladder cancer

  The dataset consists of a multisample VCF (version 4.1) and the corresponding annotated MAF file, containing the somatic point mutations found from exome sequencing across the high-grade T1 bladder cancer cohort (HGT1, n=61 samples). The VCF file is in accordance with the HTS format specifications (https://samtools.github.io/hts-specs/). The dataset comprises also a CSV file with clinical data.

  Dataset EGAD00001006346

• An aggregated vcf file

  Germline variants calls were defined using the sequenced reads derived from 230 patients with hepatocellular carcinoma. This dataset is comprised of one aggregated vcf file.

  Dataset EGAD00001009410

• Single Cell Genome Variation Induced by Mutational Processes in Cancer - HGSOC Trios Study

  Mutational signatures derived from whole genome sequencing have potential prognostic significance. Identification of high grade serous ovarian cancer patients with deficiency in homologous recombination repair pathways could identify a subset of patients that would benefit from homologous recombination deficiency-specific treatments independent of identification of a pathological BRCA1/2 gene mutation. Clinical protocols rely on a pathologist's assessment of formalin-fixed paraffin-embedded (FFPE) tissues, and thus FFPE tissue samples are readily available. However, the bulk of mutational signature analyses have been performed on fresh frozen tissues. In this study, we aimed to assess the reliability of whole genome sequencing, variant calling, and mutational signature analysis from FFPE tissue samples.

  Study phs003036

• Molecular Genetics of Heroin Dependence in China

  Our principal goal was to determine the chromosomal locations of genetic variations associated with increased vulnerability to heroin dependence. This goal was attained by identifying specific DNA markers that are genetically linked to heroin dependence. We collected blood and diagnostic information (using a structured diagnostic interview) from 1230 people (sib-pairs) having DSM-IV defined heroin dependence as well as from their parents and other affected and unaffected siblings, when possible. Genotype and clinical data was archived using database software. We conducted a multipoint linkage analysis using the guidelines of Lander and Kruglyak to assert statistical significance, and followed up on regions of interest with a dense set of markers to evaluate candidate genes.

  Study phs001213

• Single Cell Analysis of Psoriasis Resolution following IL-23 Blockade

  Full-thickness skin biopsies were obtained from five individuals with severe psoriasis who were receiving risankizumab treatment. Skin biopsies were taken from lesional and non-lesional sites at baseline, and from lesional sites at day 3 and day 14 of therapy. All biopsies were taken from site-matched areas on the lower back/buttocks. Single-cell RNA sequencing was performed using a 10x Genomics platform. Myeloid and fibroblast populations showed the strongest change in gene expression after 3 days. An inflammatory, transient WNT5A+/IL24+ fibroblast state was identified, which was elevated in abundance in lesional skin versus non lesional skin, and decreased after 14 days of treatment. R1 and R2 FASTQs files are available.

  Study phs003351

• Pathologically Expanded Peripheral B Cell-Helper T Cells in Rheumatoid Arthritis

  PROSET-HD aims to identify and study immune cell populations altered in patients with autoimmune and inflammatory diseases. We have identified a population of PD-1hi CXCR5- 'peripheral helper' T (Tph) cells that are expanded in the joints and circulation of patients with seropositive rheumatoid arthritis. This T cell population uniquely combines potent B cell-helper function with a migratory program that directs homing to inflamed tissues. RNA sequencing was performed on sorted memory CD4+ T cell subpopulations to compare the global gene expression profiles of PD-1hi CXCR5- CD4+ T cells, PD-1hi CXCR5+ follicular helper T cells, and other T cell populations obtained from blood of rheumatoid arthritis patients.

  Study phs001262

• Multimodal Genomic Features Predict Outcome of Immune Checkpoint Blockade in Non-small Cell Lung Cancer

  Despite progress in immunotherapy, identifying patients that respond has remained a challenge. Through analysis of whole-exome and targeted sequence data from 5,449 tumors, we found a significant correlation between tumor mutation burden (TMB) and tumor purity, suggesting that low tumor purity tumors are likely to have inaccurate TMB estimates. We developed a new method to estimate a corrected TMB (cTMB) that was adjusted for tumor purity and more accurately predicted outcome to immune checkpoint blockade (ICB). To identify improved predictive markers together with cTMB, we performed whole-exome sequencing for 104 lung tumors treated with ICB. Through comprehensive analyses of sequence and structural alterations, we discovered a significant enrichment in activating mutations in receptor tyrosine kinase (RTK) genes in non-responding tumors in three immunotherapy-treated cohorts. An integrated multivariable model incorporating cTMB, RTK mutations, smoking-related mutational signature, and HLA status provided an improved predictor of response to immunotherapy that was independently validated.

  Study EGAS00001003892

• Segmental Cherry Angioma case

  Cherry angiomas are common benign blood vessel growths on the skin. In this study we characterise mutational profile of a cherry angioma and adjacent skin biopsied from a patient with multiple lesions with segmental presentation.

  Dataset EGAD00001015641

• 4C-seq in endometrial healthy and tumor tissues

  4C-seq performed on 10 slices (30um thick) of fresh frozen endometrial tissues. These tissue include 2 healthy tissues and 4 tumor tisseus (post-menopausal patients) in replicate. The library has been performed using DpnII (primary) and NlaIII (secondary) restriction enzymes. Raw single-end fastq.gz files are provided.

  Dataset EGAD00001010897

• Human tumor bulk RNA-seq

  We profiled 186 patient tumor samples by bulk RNA-seq. These includes 38 embryonal brain tumors, 101 high-grade gliomas, 24 low-grade gliomas, 10 medulloblastoma and 13 matched normals. The raw fastqs are provided.

  Dataset EGAD00001005131

• R compatible Seurat's objetc .rds files with count data and metadata from single cell RNA seq analysis to characterize the prostate cancer tumoral microenviroment of 31 fusion biopses.

  Pre-processed Seurat objects with cellular and functional annotation information from the scRNAseq study on PC fusion biopsy samples. The data consists of rds files composed of normalised counts matrices, normalised and scaled counts, functional enrichment counts at the cellular level and metadata with patient grouping and cellular annotation variables. There are 3 .rds files, one with the total cells (SCP_data_analysis), with the selection of cells annotated as cancerous (selected_cancer_analysis) and cancer-associated fibroblasts (selected_caf_analysis).

  Dataset EGAD50000001298

• Transcriptomic profiles of chronic lymphocytic leukemia before and after frontline therapy: 5-year results from the randomized CLL14 study

  CLL14 (NCT02242942) is a multinational, open-label Phase III study designed to compare venetoclax-obinutuzumab (Ven-Obi) versus chlorambucil-obinutuzumab (Clb-Obi) in previously untreated patients with CLL and co-existing conditions. Between Aug 7, 2015, and Aug 4, 2016, 432 patients were enrolled and randomly assigned to receive either venetoclax plus obinutuzumab (Ven-Obi, n=216) or chlorambucil plus obinutuzumab (Clb-Obi, n=216). In both study arms, patients received fixed-duration treatment of overall 12 cycles, each cycle 28 days long, and entered subsequent post-treatment surveillance. Peripheral blood samples were collected before the start of therapy, as well as every 3-6 months during and after therapy, including at the time of disease progression. The primary endpoint of the study was progression-free survival, secondary endpoints included overall response rate, minimal residual disease response, and overall survival. The primary read-out was conducted after a median follow-up of 28.1 months, when the primary endpoint was met with 30 primary end-point events (disease progression or death) in the Ven-Obi arm and 77 in the Clb-Obi arm (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53;P<0.001). Follow-up is ongoing until 9 years after the last patient enrollment. In an exploratory analysis, bulk RNAseq was conducted with CD19-enriched blood from patients before start of therapy (418 patients) and at first relapse (44 patients).

  Study EGAS00001006596

• UK_immunochip

  This dataset includes data from UK Multiple Sclerosis (MS) cases that were recruited through the University of Cambridge and included in the IMSGC immunochip experiment. Data from UK controls and additional UK cases that were recruited through other UK centres is available by direct application to those respective centres, as described in the original paper.

  Dataset EGAD00010002049

• Whole Exome Sequencing of a Chinese Cataract Girl

  Whole exome sequencing of a Chinese girl with congenital cataract. The dataset contains one sample with two fastq files. The novel PAX6 mutation (c.221G>A) is associated with congenital cataract, and the WFS1 mutation (c.2070_2079del) interactively aggravates this process.

  Dataset EGAD00001008267

• Lipomatous tumors with 12q amplification

  The project concerns whole genome sequencing (short-read and long-read) and RNA-sequencing of lipomatous tumors with 12q-amplification. A subset of lipomatous tumors is driven by amplification of genes mapping to chromosome arm 12q, including the MDM2 gene. The goals of the study were to compare expression levels of genes mapping to 12q in tumors with amplification in rod-shaped or circularized chromosomes as well as to assess and compare the structural variants in those tumors. In total, 20 samples were analyzed, and the data were correlated with genomic data on bulk and single cell DNA from the same tumors. The fastq files from the tumors were uploaded to EGA.

  Study EGAS50000000062

• Application of Hi-C sequencing to detect structural variants in B-cell acute lymphoblastic leukemia

  Large structural variants are easily detected by Hi-C sequencing as strong, distant signals on a Hi-C contact map. Translocations are frequently evident in B-ALL and accurate identification of these translocations can guide clinical treatment options. Here were apply shallow Hi-C sequencing as an unbiased, cost-effective approach to identify translocations among B-ALL patients.

  Study EGAS00001005605

• Whole Exome Sequencing of Colorectal Cancer Patients from the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS)

  Colorectal cancer is a molecularly heterogeneous disease. Whole Exome Sequencing from patients diagnosed with colorectal cancer in the NHS and HPFS cohorts will extend our understanding of the genetic changes occurring in specific clinical contexts in the disease. This effort has the potential to discover novel recurrently mutated genes and pathways in colorectal cancer that can be functionally validated and give further insights to colorectal cancer pathogenesis. All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Agilent SureSelect Human All Exon Kit v2 and sequencing was performed on an Illumina HiSeq 2000.

  Study phs000722

• Comprehensive Analysis of the Immunogenomics of Triple Negative Breast Cancer Brain Metastases from LCCC1419

  Triple negative breast cancer (TNBC) is an aggressive subset of breast cancer that lacks expression of the estrogen and progesterone receptors (ER and PR) and HER2. Nearly 50% of patients with advanced TNBC will develop brain metastases (BrM), commonly with progressive extracranial disease. Immunotherapy has shown promise in the treatment of advanced TNBC; however, the immunogenomics of BrM remains largely unknown. Thus, we conducted a comprehensive analysis of TNBC BrM and matched primary tumors to characterize the genomic and immune landscape of TNBC BrM to foster the development of immunotherapy strategies in this aggressive and clinically unmet disease.  

  Study phs002457

• Genetic mutation profiling of lymphomas arising in the uterine cervix and vagina

  Follicle center lymphoma (FCL) of the lower female genital tract (LFGT) is a rare lymphoma, with fewer than 20 cases reported to date. Since the genetic features of FCL of the LFGT have not been well characterized, we aimed to identify genetic alterations in this tumor through whole-exome sequencing or targeted gene panel analysis. Genomic DNA was extracted from a frozen tissue sample obtained from a surgically resected uterine cervical tumor. Whole-exome sequencing was performed using the Illumina NovaSeq X Plus platform. Library preparation was conducted with the SureSelect Human All Exon V6 kit, and sequencing was carried out with 150 bp paired-end reads.

  Study JGAS000823

• Multi-omics analysis of cocaine use disorder in postmortem brain tissue of the ventral striatum [Proteomics data to study EGAS50000000623]

  We performed a multi-omics analysis of cocaine use disorder in postmortem human brain tissue of the ventral striatum in N=41 individuals (N=20 CUD cases, N=21 non-affected individuals). From the postmortem brain tissue samples, we generated miRNA-seq, RNA-seq, proteomics, and snRNA-seq data. The miRNA-seq, RNA-seq and snRNA-seq datasets can be found in the EGA under study ID EGAS50000000623. Proteomics data is deposited under study ID EGAS00001007945 (this study). The proteomic dataset was obtained using TMT-labeling. Measurement was performed on an Orbitrap Fusion Lumos device.

  Study EGAS00001007945

• IκBε deficiency accelerates disease development in chronic lymphocytic leukemia

  The NFKBIE gene, which encodes the NF-κB inhibitor IκBε, is mutated in 3-7% of patients with chronic lymphocytic leukemia (CLL). The most recurrent alteration is a 4-bp frameshift deletion associated with NF-κB activation in leukemic B cells and poor clinical outcome. To study the functional consequences of NFKBIE gene inactivation, both in vitro and in vivo, we engineered CLL B cells and CLL-prone mice to stably down-regulate NFKBIE expression and investigated its role in controlling NF-κB activity and disease expansion. We found that IκBε loss leads to NF-κB pathway activation and promotes both migration and proliferation of CLL cells in a dose-dependent manner. Importantly, NFKBIE inactivation was sufficient to induce a more rapid expansion of the CLL clone in lymphoid organs and contributed to the development of an aggressive disease with a shortened survival in both xenografts and genetically modified mice. IκBε deficiency was associated with an alteration of the MAPK pathway, also confirmed by RNA-sequencing in NFKBIE-mutated patient samples, and resistance to the BTK inhibitor ibrutinib. In summary, our work underscores the multimodal relevance of the NF-κB pathway in CLL and paves the way to translate these findings into novel therapeutic options.

  Dataset EGAD50000000754

• Identification of the Global miR-130a Targetome Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML

  In this study, we identified miR-130a as a regulator of HSC self-renewal and differentiation. To characterize gene expression changes following enforced expression of miR-130a OE, we performed RNA-seq in CD34+ cord blood (CB) cells transduced with control and miR-130a OE lentiviruses. To capture miRNA targets in an unbiased, transcriptome-wide manner, we perfomed enhanced CLIPseq procol in 2 replicates of CD34+ CB cells and Kasumi-1 cell line, which represent a model system for t(8;21) AML. We chose this cell line, as we found miR-130a to be highly expressed in this AML subtype where it is critical for maintaining the oncogenic molecular program mediated by AML1-ETO. Chimeric Ago2 eCLIPseq in CD34+ CB cells combined with Mass Spectrometry data analysis identified TBL1XR1 as a principal target of miR-130a. To elucidate gene expression changes associated with TBL1XR1 loss of function, we performed RNA-seq in CD34+CD38- CB cells transduced with control and shRNA targeted against TBL1XR1. To determine the functional significance of high miR-130a expression levels in Kasumi-1 cells on the molecular network controlled by AML1-ETO, we performed CUT&RUN assay and RNA-seq in Kasumi-1 cells following miR-130a knock-down (KD). Collectively, our findings reveal a unique role of miR-130a in regulating normal hematopoietic stem cell self-renewal and how elevated levels of miR-130a in t(8;21) AML contribute to the leukemogenesis of this AML subtype.

  Dataset EGAD00001008412

• Single cell and whole tissue transcriptomes investigating Barrett's oesophagus

  Data consists of 4,640 RNA-sequencing sample libraries. These libraries were sequenced from four sites of the upper gastro-intestinal tract (Barrett’s oesophagus, proximal normal oesophagus, proximal normal stomach, and duodenum) in two experiments. 4,587 libraries were produced in the first experiment in which whole transcriptomes were isolated single cells dissociated from endoscopic biopsy tissue obtained from the four previously mentioned tissues. The other 53 libraries were produced in the second experiment in which whole transcriptomes were isolated from whole tissue from endoscopic biopsies of the four previously mentioned tissues. The data found here are stored in the raw fastq file format from paired end sequencing.

  Dataset EGAD00001004344

• Targeted deep sequencing data of 386 T-ALL patients

  Targeted deep sequencing data of 386 T-ALL patients in several high-risk T-ALL genes. Samples were prepared according to Agilent's HaloPlex HS Target Enrichment Protocol and sequenced as 75bp paired-end reads. Data is available as paired-end FASTQ files for each sample.

  Dataset EGAD50000001168

• Single cell transcriptomics of adult human adrenal gland

  Single cell transcriptomics (10x 3') of human adrenal gland. The adrenal gland of this particular individual is characterized by the presence of mutant clone characterized by aneuploidy in chromosomes 8, 9, 13 and 22, occupying the zona glomerulosa and zona fasciculata. This dataset contains the primary sequencing data generated from the 10x genomics 3' library in fastq format.

  Dataset EGAD00001011288

• Whole-exome sequencing of extranodal NK/T cell lymphoma

  Extranodal NK/T cell lymphoma (ENKTCL) is an aggressive Epstein-Barr virus-associated T/NK neoplasm that predominantly affects Asians. To explore the causative somatic events, we conducted a comprehensive genetic analysis of 19 ENKTCL patients including whole-exome sequencing (N = 16). Commonly deregulated gene pathways in ENKTCL included epigenetic modifiers followed by human leukocyte antigen (HLA) and related genes and JAK-STAT pathway.

  Study EGAS00001004357

• Amplicon_based_sequencing_of_drug_resistant_lung_cancer_cell_lines

  A EGFR mutant NSCLC cell line which is sensitive to AZD9291 inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a AZD9291. Single cell derived colonies were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors hypothesised from currently available literature.

  Study EGAS00001001675

• Molecular landscape of blastic plasmacytoid dendritic cell neoplasm

  Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignancy assumed to originate from plasmacytoid dendritic cells (pDCs), which mostly affects the skin, bone marrow and lymph nodes and sequentially other organ systems. We applied paired WES/RNA-seq combined with genome-wide copy-number analysis to characterize 47 BPDCN patients regarding mutational drivers, cytogenetic aberrations and gene-expression profiles.

  Study EGAS00001006166

• Whole-genome methylation profiling of menstrual stem cells identifies novel biomarkers for endometriosis

  Endometriosis, despite its high prevalence, is underdiagnosed and poorly managed due to lack of clinically validated biomarkers and pathophysiological insight. Menstrual bloodderived stem cells (MenSCs) have been implicated in disease pathogenesis, but their diagnostic potential remains unexplored. We conducted a clinical study (n=42; 19 endometriosis, 23 controls) to assess whether DNA methylation profiles of freshly isolated MenSCs can identify disease-specific biomarkers. Whole-genome methylation sequencing revealed differentially methylated regions (DMRs) enriched in genes linked to hallmarks of endometriosis (e.g., inflammation, tissue remodelling, development). These DMRs robustly distinguished cases from controls, independent of technical and clinical variables. Machine learning models trained and validated on these DMRs achieved high diagnostic performance (specificity 83%, sensitivity 79%). Integration with an independent single-cell RNA sequencing dataset showed that the DMRs may modulate gene expression, further supporting their biological relevance. These findings position MenSC DNA methylation profiling as a promising, non-invasive approach for early endometriosis diagnosis and personalised care.

  Dataset EGAD50000002353

• Long-term temporal stability of peripheral blood DNA methylation alterations in patients with inflammatory bowel disease.

  Introduction There is great current interest in the potential application of DNA methylation alterations in peripheral blood as biomarkers of susceptibility, progression, and treatment response in inflammatory bowel disease (IBD). To date, the intra-individual stability of peripheral blood leukocyte (PBL) methylation in IBD patients, a key consideration in biomarker development, has not been characterised. Here, we studied the long-term stability of all probes located on the Illumina HumanMethylation EPIC BeadChip array. Methods We followed a cohort of 46 adult IBD patients (36 Crohn’s disease (CD), 10 ulcerative colitis (UC), median age 44 (IQR: 27-56), 50% female) that received standard care without any intervention at the Amsterdam UMC. Paired PBL samples were collected at two time points with a median 7 (range: 2-9) years in between. Differential methylation and intra-class correlation (ICC) analyses were used to identify time-associated differences and temporally stable CpGs, respectively. Results Around 60% of all CpG loci on the EPIC array presented poor (ICC <0.50); 119,388 (≈14%) and 41,274 (≈5%) showed good (ICC ≥0.75) or excellent (ICC ≥0.90) intra-individual stability. Functional over-representation analyses of the stable methylated CpGs implicated genes involved in cell-cell signaling, adhesion and neurogenesis. Focusing on previously identified consistently differentially methylated positions indicated that 22 CD-, 11 UC-, and 24 IBD-associated loci demonstrated good stability (ICC ≥0.75) over time, where we observed a marked stability of CpG loci associated to the HLA genes. Conclusion Our data provide insight into the long-term stability of the PBL DNA methylome within an IBD context, facilitating the selection of biologically relevant and robust IBD-associated epigenetic biomarkers with increased potential for independent validation.

  Study EGAS00001006501

• The single plasma-cell transcriptional landscape in POEMS syndrome

  POEMS syndrome is a rare monoclonal plasma cell disorder that shows unique symptoms distinct from other plasma cell neoplasms, including high levels of serum VEGF; however, none of the previous studies have succeeded in direct identification of plasma cell clones in POEMS syndrome, leaving their real nature obscure.���We herein performed single-cell RNA sequencing (scRNA-Seq) of bone marrow (BM) plasma cells from patients with POEMS syndrome. These data unveil unique features of POEMS clones among plasma cell neoplasms and enhance our understanding of the pathogenesis of POEMS syndrome.

  Study JGAS000289

• Contribution of specific cell types to the development of Barrett’s esophagus and carcinoma via germline genetic risk

  This study was designed to elucidate how individual cell types in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) contribute to disease development via germline genetic risk. We performed single cell RNA-sequencing (scRNA-seq) of BE, EAC and paired normal esophagus and gastric fundus tissue samples. After analyzing individual cell types, we integrated the scRNA-seq data and data of a genome-wide association study (GWAS) on BE/EAC to determine cell type-specific genetic risk. Raw data from the RNA-sequencing is provided here.

  Study EGAS50000000530

• The effect of freezing delay of cell-type specific transcriptome responses in human brain via snRNA-seq

  In other analysis in the current manuscript, we find a similar gene signature (to dissociation based artifacts in mouse and human tissue) is present in post-mortem microglia and astrocytes, across all snRNA-seq datasets analyzed, although it is highly variable between subjects. ​ Using acutely-resected neurosurgical tissue, we performed single-nucleus RNA-seq and reveal that a similar signature can be detected in microglia following prolonged exposure to room temperature. Tissue handling and methods details, as well as sequencing and analysis details) can be found in the methods section of related manuscript (Marsh et al., 2022). Together, these results suggest that the presence of this signature in post-mortem brain samples may be the result of a combination of acute pre-mortem (agonal state, cause of death, comorbidities, etc.) and post-mortem (post-mortem interval (PMI), storage time, RNA quality, etc.) variables and may not represent normally present cell state.

  Dataset EGAD00001008541

• Colorectal cancer cells possess an equipotent capacity to enter a developmental pausing-like state to survive chemotherapy

  Cancer cells enter a reversible drug tolerant persister (DTP) state to evade death from both chemotherapies and targeted agents. It is increasingly appreciated that the DTP state is an important driver of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer xenograft models to identify and characterize the cancer cells capable of generating DTPs in response to standard-of-care chemotherapy. Barcode analysis revealed no loss in clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fits a mathematical model in which all cancer cells, and not a small subpopulation, possess an equipotent capacity to enter the DTP state. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides new insights into how cancer cells use a developmentally conserved mechanism to drive the DTP state pointing to novel therapeutic opportunities to target diapause-like DTPs.

  Dataset EGAD00001006849

• iRHOM2 Deficiency Causes Environmentally Directed Immunodysregulatory Disease

  We have conducted a study of two kindreds each with a unique mutation in the gene RHBDF2 that encodes the protein iRHOM2. Whole exome (kindred 1) and whole genome sequencing (kindred 2) have uncovered the first human loss-of-function mutations of RHBDF2 in 4 individuals. The affected patients are all children, 8 years old or younger, and were brought to our attention initially due to their suffering recurrent infections. Sequencing of their family members revealed parents with heterozygous RHBDF2 mutations, and heterozygous and wild type siblings – all of which were unaffected by this disease. A comprehensive investigation of this gene mutation through in vivo and in vitro experiments revealed that a loss of the protein iRHOM2 impairs the activity of the protease ADAM17 and subsequently compromises immune responses. This condition leads to the afflicted patients becoming vulnerable to different infections based on their unique environment and presenting with diverse clinical phenotypes. 

  Study phs002478

• Multiome_HB

  Hepatoblastoma (HB) cells display strong phenotypic heterogeneity with a major impact on drug response, but the underlying mechanisms are poorly understood. Here, we use a single-cell multi-omic strategy to unravel the molecular determinants of this plasticity. HB display a continuum of single-cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activation underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation poles. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.

  Study EGAS00001006932

• Peter Van Loo MPNST phase 1

  We comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment.

  Dac EGAC50000000904

• scRNA-seq data of Anti-Her2-CAR T cells treated with immunomodulatory metabolites

  Anti-Her2-CAR T cells produced from T cells derived from healthy human donors were treated with DMSO (control) or either of the immunomodulatory metabolites indole‐3‐carboxaldehyde (ICA), valeric acid (VA) and isovaleric acid (IVA) to assess effects on CAR T cell function. scRNA-seq libraries were generated on a 10X Chromium controller with On-Chip-Multiplexing. The individual samples in a library are distinguished during analysis on the single-cell level via the cell barcode class.

  Dataset EGAD50000002012

• Analysis of Cell-Free DNA to Predict Outcome to Bevacizumab Combination Therapy in Metastatic Colorectal Cancer Patients

  This dataset includes FASTQ files of low coverage whole genome sequencing of normal tissue (n = 8), tumor tissue (n = 55) and cell free DNA from plasma samples (n=101) from patients with metastatic colorectal cancer treated with bevacizumab. A total of 164 samples are present from two different cohorts. The first batch of samples (n = 139, sample names sAPD302T until sAPD502_P0) were collected from the AC-Angiopredict Phase 2 trial (NCT01822444), the second batch of samples (n = 25m, sample names sAPD503_P0 until sAPD527_P0) were collected from the UMM cohort.

  Dataset EGAD50000000176

• RNA-seq analysis of CCO+/CCO- hepatocytes in normal human liver

  RNAseq data from Passman et al 2023. Clonal CCO-deficient hepatocyte patches and nearby CCO-proficient hepatocytes were identified in morphologically normal human livers and sampled at varying distances along the PT-CV axis. Samples are characterised according to their location within the liver lobule, with "PT" denoting samples abutting the portal triad, "CV" denoting samples abutting the central hepatic vein, and "Mid" sampled acquired midway between these structures. Analysis was performed on an Illumina Nextseq using a high output kit and 100 single-end cycles.

  Dataset EGAD00001010033

• RNA-seq Revision

  The dataset comprises bulk RNA‑seq libraries generated on the Illumina NextSeq 500 platform, including primary human hepatocytes (four donors), colon tissue (four masked replicates), and a comprehensive set of iPSC‑derived samples from the JHU106, ChiPSC18, ChiPSC22, and H9 lines. The collection covers multiple differentiation stages from iPSC to DE to HLC and cultivation protocols (CEL, HAY, SPH) with at least three replicates per condition. All sequencing data are provided as raw FASTQ files, with colon samples delivered as masked FASTQ in accordance with patient consent requirements.

  Dataset EGAD00001008951

• DNTR sequencing data of paediatric acute lymphoblastic leukemia

  This study used the DNTR-seq method in leukaemia samples to profile the whole-genome and mRNA jointly in single cells. Direct tagmentation is used in a collection of single-cell whole genome sequencing (scWGS) methods, including DNTR-seq, which provide high quality data at ultra-low to low coverage. The overall goal was to characterize the genetic and transcriptional heterogeneity of cancer samples. To infer clonal structure and evolutionary history, copy number analysis based workflows were implemented. Bone marrow mononuclear cells from pediatric acute lymphoblastic leukemia samples were FACS sorted into 384 plates to generate the DNA and RNA profiles.

  Study EGAS50000001247

• Mitochondrial DNA mosaicism in human somatic cells

  Genomic alterations accumulate in the somatic cells throughout an individual’s lifetime. Recent sequencing studies have documented widespread mutations in the nuclear genome and the frequent clonal competition of normal cells carrying mutations. However, the landscape of mitochondrial DNA (mtDNA) heteroplasmy in normal human tissues is poorly understood. This study investigated the whole genome sequences (WGSs) of 2,096 clones established from non-neoplastic healthy single cells obtained from 31 donors. In addition, we analyzed 31 WGSs of neoplastic cells, including 12 clones established from adenomatous polyps from one individual with MUTYH-associated polyposis and 19 matched colorectal carcinomas from individuals who donated normal colorectal clones.

  Study EGAS50000000254

• miRNA

  The purpose is to perform miRNA analysis on FACS sorted target immune cell populations to uncover novel potential miRNA diagnostic markers biomarkers predictive of therapy response but also possibly identify perturbed signaling pathways or miRNA targets of intervention with the use of agomirs/antagomirs.

  Dataset EGAD50000002025

• MESA colorectal cancer cfDNA EM-seq dataset

  This dataset contains the methylation sequencing data of 60 nonCancer and 70 colorectal cancer cfDNA samples. The methylation library is constructed by using NEBNext Enzymatic-seq Kit.

  Dataset EGAD00001009165

• IBDCA_Edinburgh

  In this experiment we have sequenced tumour normal pairs from patients presenting with CRC who have a prior history of inflammatory bowel disease. The idea is to identify driver mutations, new genes and novel pathways associated with the development of these malignancies.

  Dataset EGAD00001001330

• MM GWAS dataset

  This is a meta-analysis of myeloma datasets, both with and without the UK Biobank cohort included.

  Dataset EGAD50000000422

• danMAC5

  Three whole genome sequecing of three independent cohorts. The three cohorts derives from projects including samples of inviduals with Danish origin. Data is deviden into males and female and compiled.

  Dataset EGAD00001009756

• Transcriptomic profiling of human small intestine macrophage and DC subsets

  Using low input SMART-seq protocol, the whole transcriptome of human small intestine macrophage subtypes is characterized.

  Dataset EGAD00001003581

• Genome-wide evaluation of the maturation of the immune response to the tuberculin skin test from day 2 to day 7

  The tuberculin skin test (TST) is a standardised human challenge model to evaluate the immune response to Mycobacterium tuberculosis (Mtb) antigens in vivo. To study the temporal evolution of the TST, we recruited healthy volunteers with evidence of peripheral blood Mtb reactive T cells, to undergo a TST in each arm that was sampled on day 2 at one site and on day 7 at the contralateral site on day 7. Genome-wide TST transcriptomes at day 2 and day 7 were defined by differential gene expression compared to transcriptomes from the site of control saline injections performed in a separate subset of volunteers.

  Study EGAS50000000822

• Cerebrospinal Fluid Analysis of HIV-1 Viral Burden in HIV-1 Infected Subjects: Response to Antiretroviral Therapy

  The purpose of this study is to provide a reference profile of small extracellular RNAs in body fluids. These samples were originally obtained in a study that had a different purpose. The purpose of the original study was to collect information on the changes in cerebrospinal fluid (CSF) related to HIV infection, including the viral burden (amount of virus) and the body responses of the infected individual, such as the number and types of lymphocytes in the CSF. In addition to looking at the number and types of lymphocytes in the CSF, this original study also examined the presence of markers of inflammation and other chemical changes, and the relationship of those changes to nervous system dysfunction in AIDS.

  Study phs001694

• Evolutionary Analysis of Chronic Lymphocytic Leukemia Cells During Relapse After Allogeneic Hematopoietic Stem Cell Transplant

  We investigated the molecular dynamics driving relapse of chronic lymphocytic leukemia (CLL) following allogeneic hematopoietic stem cell transplant (allo-HSCT) through an integrated analysis of whole exome, bulk transcriptome, bulk methylome and single cell transcriptional data from paired leukemic samples representing 19 patients. We found that their clinical kinetics corresponded to distinct genetic and epigenetic evolutionary trajectories and suggest that the selection pressures of the post-transplant, immunologic bottleneck are distinct from those imposed by chemotherapy.In order to discover cancer antigens derived from annotated and unannotated protein-coding regions of the genome, we carried out ribosome profiling (Ribo-seq) and RNA-sequencing on CLL samples and isolated primary B cells from healthy donors. We discovered novel or unannotated open reading frames (nuORFs), their expression levels, as well as somatic mutations within them to predict potential neoantigens.

  Study phs001998

• Neutralizing Antibodies against West Nile Virus Identified Directly from Human B Cells by Single-Cell Analysis and Next Generation Sequencing

  West Nile virus (WNV) infection is a mosquito-borne disease that can cause severe neurological illness. We analyzed the humoral response to WNV of subjects infected with WNV at different stages of the infection and at different levels of detail, from single cells to the repertoire level. We integrated single-cell analysis by microengraving with next-generation sequencing and identified four novel WNV neutralizing antibodies with potential use as therapeutics against WNV infection. The results indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects and suggest that the antibody response itself does not predict the clinical severity of the disease.

  Study phs001200

• UQCCR/QCMG brain metastasis sequence analysis

  The present study, conducted by the UQCCR and QCMG at the University of Queensland, investigated the genomic landscape of brain metastases from 36 patients (with matched normal samples) that originated from a range of primary tumour sites (including breast (11), lung (18), melanoma (6) and oesophageal (1)) utilizing Illumina 2500 HiSeq Exome sequencing. Somatic substitutions were identified using a dual qSNP/GATK calling strategy. The Pindel tool was used to determined short insertions and deletions. Key biological pathways were investigated using pathway analysis tools. It is envisaged that the current work may provide important biological insights into the genomic characterization and evolution of brain metastasis and additionally identify druggable targets of clinical relevance.

  Study EGAS00001000722

• OMRF SLEGEN GWAS Data from European-American Women with Lupus

  "Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10-7 < P(overall) < 1.6 x 10-23; odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10-5) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10-7). Our results show that numerous genes, some with known immune-related functions, predispose to SLE." Reprinted from Nature Genetics, 2008 Feb; 40(2):204-10, PMID:18204446, with permission from Nature Publishing Group. Data submitted to dbGaP includes 297 samples from Oklahoma. (Please see also Study Accession: phs000216.v1.p1)

  Study phs000202

• Dissecting Cell Composition and Drug Sensitivity in Human Adenoid Cystic Carcinomas (ACCs)

  The study reports the results of single-cell RNA sequencing (scRNA-seq), RNA sequencing (RNA-seq), and whole-exome sequencing (WES) experiments performed on malignant cells isolated by flow cytometry from seven patient-derived xenograft (PDX) lines established from human Adenoid Cystic Carcinomas (ACCs). Of these seven lines, five are characterized by well differentiated histology (ACCX5M1, ACCX6, ACCX14, ACCX22, SGTX6) and two by solid histology (ACCX9, ACCX11). Analysis by scRNA-seq of the well-differentiated PDX line ACCX22 led to identification of cell-surface markers (CD49f, KIT) that enabled the differential purification of the two major cellular components contained in well-differentiated ACCs: myoepithelial-like (CD49f-high/KIT-negative) and ductal-like (CD49f-low/KIT-positive) cells. The study reports the analysis by RNA-seq and WES of purified preparations of myoepithelial-like and ductal-like cells from well-differentiated PDX lines (ACCX5M1, ACCX6, ACCX14, ACCX22, SGTX6) and of ductal-like (CD49f-low/KIT-positive) cells from solid PDX lines (ACCX9, ACCX11).

  Study phs002764

• Whole-exome sequencing of intrahepatic cholangiocarcinoma tumors with matched normal tissue from the Medical Center – University of Freiburg

  This dataset contains raw whole-exome sequencing data from 40 samples of intrahepatic cholangiocarcinoma patients, including tumor and matched normal tissue. Samples were sequenced on the NovaSeq platform. The cohort is part of a proteogenomic profiling study integrating genomic and proteomic data.

  Dataset EGAD50000001926

• T cell responses of ALS patients

  In this project, we aimed to understand how T cell responses contribute to the disease progression of amyotrophic lateral sclerosis (ALS). The present data is on single-cell sequencing isolated from human cerebrospinal fluid (CSF) cells from both ALS patients (n=5) and controls (n=4). This analysis was conducted as part of a bigger project which is summarized in the section below. We used flow cytometry to define T cell subsets and phenotypes in blood and CSF samples collected at the time of diagnosis on a cohort of 89 newly diagnosed ALS patients in Stockholm, Sweden. High frequency of CD4+FOXP3- effector T cells in blood and CSF was associated with poor survival whereas high frequency of activated regulatory T (Treg) cells and high ratio between activated and resting Treg cells in blood was associated with better survival. T cell profiles also predicted disease progression rate. On an independent cohort of cases and controls, we used single cell transcriptomics data to demonstrate that ALS patients had altered T cell gene expression patterns and clonally expanded CD4+ and CD8+ T cells in CSF. In summary, T cell responses contribute to disease progression of ALS, supporting modulation of adaptive immunity as a viable therapeutic option.

  Study EGAS00001006675

• MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

  Despite the established role of the transcription factor MYC in cancer, little is known about the involvement of lncRNAs in mediating MYC’s function. Here we have intersected RNA-sequencing data from MYC-inducible cell lines, from a cohort of 91 mature B-cell lymphomas and from sorted germinal-center B-cells. By this approach, we identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated by MYC in the model cell lines. Among them we focused on a lncRNA that we named MINCR, showing a strong correlation with MYC expression in MYC-positive lymphomas and in pancreatic ductal adenocarcinomas. RNAi experiments showed that MINCR controls cellular viability by influencing the expression of MYC-regulated cell cycle genes. Finally we provide evidences that down-regulation of AURKA, AURKB and CTD1 may explain the reduction in cellular proliferation observed upon MINCR knock-down. We therefore suggest that MINCR acts as a modulator of MYC transcriptional control of cell cycle genes.

  Study EGAS00001001199

• MDS PacBio LRTS IsoSeq

  This dataset contains long read transcriptome sequencing of 25 myelodysplastic sndrome (MDS) patients with or without mutation in SF3B1. The BAM files are unaligned CCS reads.

  Dataset EGAD50000000077

• Human tumor single-cell RNAseq

  We profiled 7 high-grade gliomas patient brain tumor samples by single-cell RNA-seq and 18 single-nuclei RNA-seq using 10X Chromium 3' techonology. The raw fastq files are provided.

  Dataset EGAD00001008351

• Sequencing of Plasma DNA from breast cancer patients

  Dataset contains plasma DNA whole genome sequencing on 4 breast cancer patients. It also includes matched germline and tumour whole genome sequencing data. Two benign cancer patients were also sequenced and their plasma DNA and matched germline whole genome sequencing data are included in the dataset. Samples were sequenced on Illumina HiSeqX Ten.

  Dataset EGAD00001006869

• Influence of age on molecular changes and treatment stratification in multimodal glioblastoma therapy

  Background: The increasing life expectancy has led to a rise in high-grade gliomas, particularly in patients of older age. The impact of chronological age, associated molecular changes and contributing factors on therapy response, progression-free survival (PFS) and overall survival (OS) remain uncertain. Methods: Between January 1st, 2016, and December 31th, 2021, patients with glioblastoma IDH-wt (CNS WHO grade 4) were included. RNA- and T-cell receptor sequencing was performed in a subset of patients. Primary outcome parameters were extent of resection (EOR), progression free- and overall survival. Multivariate analysis was performed to identify independent predictors of survival. Results: A total of 286 patients were included. The mean age was 66.4 years. Chronological age did not correlate with overall survival (r=0.12). With age, tumor immune composition changed towards macrophages with M2 phenotype and decreased numbers of CD8+ and neutrophiles. Aging related genes were not enriched. Beyond 69.5 years of age, despite similar PFS (p=0.0783), OS (p<0.0001) was significantly shorter, compared to younger patients. Extent of resection and adjuvant radiochemotherapy were significant predictors of OS (p<0.0001). No difference in PFS and OS was found between younger and older patients treated with maximal safe resection, followed by concomitant RT and chemotherapy and adjuvant chemotherapy. Conclusions: This study suggests that age alone should not be the sole determinant in therapeutic decision-making for glioblastoma patients. Gross total resection and adjuvant therapy, tailored to individual clinical status, significantly impact survival outcomes. Patient-specific treatment strategies are important to minimize undertreatment and optimize therapeutic outcomes in older patients.

  Study EGAS00001008246

• Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers

  Purpose: Shallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities. Experimental Design: sWGS and targeted panel sequencing was performed on formalin-fixed paraffin-embedded p53abn ECs. CN alterations, mutational data and CN signatures were derived, and associations to clinicopathologic and outcomes data were assessed. Results: In 187 p53abn ECs, 5 distinct CN signatures were identified. Signature 5 was associated with BRCA1/2 CN loss with features similar to HGSOC HRD signature. 22% potential HRD cases were identified, 35 patients with signature 5, and 8 patients with BRCA1/2 somatic mutations. Signatures 3 and 4 were associated with whole genome duplication, and CCNE1, ERBB2 and MYC amplifications, with mutations in PIK3CA enriched in signature 3. We observed improved overall survival (OS) for patients with signature 2 and worse OS for signatures 1 and 3. 28% of patients had CCNE1 amplification and this subset was enriched with carcinosarcoma histotype. 34% of patients, across all histotypes, had ERBB2 amplification and/or HER2 overexpression on immunohistochemistry, which was associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the top 5 most common mutations. Conclusions: sWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.

  Study EGAS00001007661

• TenK10K project

  This DAC handles access to data from the TenK10K project, which is comprised of matched whole-genome sequencing (WGS), single cell RNA-sequencing (scRNA-seq), single nuclei ATAC-sequencing, and single cell Multiome datasets.

  Dac EGAC50000000931

• TCRab sequencing of CML patients

  This dataset contains 15 TCRab sequencing samples from 6 CML patients before and after TKI-cessation. The raw data is available as fastq files.

  Dataset EGAD00001012841