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• WGS of high grade serous ovarian tumours and matched blood normals

  FASTQ reads for 34 matched tumour-normal WGS pairs for high grade serous ovarian cancer patients. Scottish HGSOC samples were collected via local Bioresource facilities at Edinburgh, Glasgow, Dundee and Aberdeen and stored in liquid Nitrogen until required. HGSOC patients were determined from pathology records and were included in the study where there was matched tumour and whole blood samples. Tumour samples were divided into two for DNA and RNA extraction and slivers of tissue were taken, fixed in formalin and embedded in paraffin wax (FFPE). Samples were only included if they were confirmed as HGSOC and there was greater than 40% tumour cellularity throughout the tumour, determined using H&sE staining of the FFPE sections and pathology review. Somatic DNA was extracted from the tumour and germline DNA was extracted from whole blood. Somatic DNA was extracted using the Qiagen DNeasy Blood and tissue kit (cat no 69504). The tissue was initially homogenised using a Qiagen Bioruptor, followed by the manufacturers recommended protocol (including RNase digestion step). Germline DNA was extracted from 1-3ml whole blood using the Qiagen FlexiGene kit (cat no 51206) following the manufacturers recommended protocol. The resulting DNA underwent quality control as follows: firstly, A260 and A280nm were measured on a Denovix DS-11 Fx to qualitatively illustrate A260/280nm and A260/230nm ratios as surrogate measures of DNA purity. A260/280 had to be 1.8 or greater and A260/230 had to be 2.0 or greater. Then, DNA was quantified using LifeTechnologies Qubit dsDNA BR kit (cat no Q32850) and we required a minimum of 50ul at 25ng/ul for WGS. Thirdly, DNA was diluted to 25ng/ul and a representative sample was loaded onto a 0.8% TAE gel, ran at 100v for 60mins and then imaged using a BioRad ChemiDoc imaging system to visualise the DNA quality.

  Dataset EGAD00001010135

• Microinjection_of_hIPSC_derived_intestinal_organoids_with_Salmonella_Typhimurium

  To generate an RNA-Seq dataset for organoids apically stimulated with Salmonella Typhimurium.These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001001253

• Optimizing Primary Stroke Prevention in Children with Sickle Cell Anemia (STOP II)

  The STOP II trial evaluated whether prophylactic transfusion in patients with sickle cell disease and high risk of stroke can be safely halted after 30 months of treatment during which patients became low risk for stroke.Stroke causes substantial morbidity in children with sickle cell disease. To prevent first strokes, the Stroke Prevention Trial in Sickle Cell Anemia (STOP) used prophylactic transfusions in children who were identified by transcranial Doppler (TCD) ultrasonography as being at high risk for stroke. This strategy reduced the incidence of stroke among such children from 10% per year to less than 1% per year, leading to recommendations for TCD screening and prophylactic transfusion for children with abnormal velocities on ultrasonography. Despite the reduced risk of stroke, long-term use of transfusions can cause adverse side effects, such as iron overload or alloimmunization. However, cessation of transfusions is associated with recurrence of stroke, and at the time of the STOP II trial, there were no clinical or laboratory indicators to guide the duration of prophylaxis. Therefore the STOP II trial was initiated to determine whether transfusions could be limited by monitoring patients with TCD examinations after transfusions were halted and resuming transfusions if the examination indicated a high risk of stroke.The trial was halted for safety concerns after 79 of a planned 100 children were randomized. Discontinuation of transfusion for the prevention of stroke in children with sickle cell disease resulted in a high rate of reversion to abnormal blood-flow velocities on Doppler studies and stroke incidence.Instructions for requesting individual-level data are available on BioData Catalyst at https://biodatacatalyst.nhlbi.nih.gov/resources/data/. Apply for data access in dbGaP. Upon approval, users may begin accessing requested data in BioData Catalyst. For questions about availability, you may contact the BioData Catalyst team at https://biodatacatalyst.nhlbi.nih.gov/contact.

  Study phs002386

• Single-cell omics data for COVID-19 patients

  Single-cell RNA-seq, single-cell ATAC-seq, and genotypes used in the analysis for the study "Altered and allele-specific open chromatin landscape reveal epigenetic and genetic regulators of innate immunity in COVID-19". The RNA-seq and ATAC-seq are raw data in FASTQ format while the genotypes are in the VCF format which was filtered and imputed (more details are available in the main text of the study).

  Dataset EGAD00001009331

• Clinical Sequencing Exploratory Research Consortium: Incorporation of Genomic Sequencing into Pediatric Cancer Care

  This project includes data derived from subjects enrolled in the BASIC3 (Baylor College of Medicine Advancing Sequencing in Childhood Cancer Care) study. BASIC3 is a National Genome Human Research Institute (NHGRI) and National Cancer Institute-funded Clinical Sequencing Exploratory Research (CSER) consortium project that focused on prospective implementation of clinical whole exome sequencing in the pediatric oncology clinic. The primary study objective were to integrate information from CLIA-certified germline and tumor exome sequencing into the care of newly diagnosed solid tumor patients at Texas Children's Cancer Center, and to perform parallel evaluation of the impact of tumor and germline exomes on families and physicians. Blood and frozen tumor (if available) samples were collected from children undergoing surgery or biopsy of newly diagnosed solid tumors and subjected to exome sequencing in a CLIA-certified laboratory. Germline and tumor (if applicable) exome sequencing reports were generated and submitted into the electronic health record and returned to each patient/family by their primary oncologist. In addition to the clinical exome sequencing, specific (optional) consent was requested for research sequencing studies. If this consent was obtained then research studies of some of the children and parents participating in the BASIC3 study (including tumor transcriptome and whole genome sequencing of blood and/or tumor) are performed. The Clinical Sequencing Exploratory Research Consortium Cohort is utilized in the following dbGaP sub-study. To view molecular data, and derived variables collected in this sub-study, please click on the following sub-studies below or in the "Sub-study" section of this top-level study page phs001383 Clinical Sequencing Exploratory Research Consortium Cohort. phs001026 BASIC3 phs001878 GMKF BASIC3

  Study phs001683

• Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET)

  STARNET is a genetics of RNA expression study of multiple disease-relevant tissues obtained from living patients with cardiovascular disease. Tissue samples are obtained from blood, atherosclerotic-lesion-free internal mammary artery (MAM) and atherosclerotic aortic root (AOR), subcutaneous fat (SF), visceral abdominal fat (VAF), skeletal muscle (SKLM), and liver (LIV) during open thorax surgery of 600 coronary artery disease (CAD) patients. All patients gave written informed consent. The inclusion criterion was eligibility for coronary artery by-pass graft (CABG) surgery. Patients with other severe systemic diseases, such as active systemic inflammatory disease or cancer, were excluded. The primary clinical end points were the SYNTAX score based on the extent of coronary atherosclerosis assessed from preoperative angiograms. The STARNET patients are Caucasians (31% females); 32% had diabetes, 75% had hypertension, and 67% had hyperlipidemia; and 33% had an MI before age 60. By New York Heart Association criteria, 45% were class I, 42% class II, 9% class III, and 1% class IV. TYPES AND RNA SEQUENCING: 566 DNA genotype and 3577 RNA-seq profiles from seven tissues from 600 STARNET CABG patients passed quality control (on average 511 RNA-seq profiles/tissue). DNA was genotyped with the OmniExpress Exome array (Illumina, ~900k SNPs) and imputed to a total of 14,098,063 DNA variant calls (6,245,505 with minor allele frequency >5%). The STARNET subjects mainly overlap with Caucasian of Northern European (Finnish) descent. RNA sequencing was performed using the HighSeq2000 platform, poly-A (LIV, SKLM, VAF, SF and blood) and ribo-zero (AOR, MAM) protocols with 50-100 bp read lengths, single end to 15-30 million read depth.

  Study phs001203

• Multi-Ethnic Study of Atherosclerosis (Electrocardiogram Tracing Repository)

  The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. MESA researchers study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Thirty-eight percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent. Electrocardiogram Tracing Repository includes ECG tracings performed during MESA Exam 1 conducted between 2000 and 2002 and during MESA Exam 5 conducted between 2010 and 2012.

  Study phs003703

• A Collaborative Search for New Genes for Non-Syndromic Deafness

  We seek to identify the DNA variants underlying sensorineural hearing loss. We obtain the DNA sequence of affected individuals and their family members. DNA variants are filtered to determine their segregation in affected families.

  Study phs003701

• Tubulointerstitial fibrosis is the histological hallmark of chronic kidney disease (CKD). Hypoxia and inflammation (i.e., interleukin (IL)-1β signalling) are independent mediators of tubulointerstitial fibrosis. However, the physiological response of human kidney tubular cells to IL-1β/IL-1RI signalling under the hypoxic conditions of CKD is poorly understood and remains a clinical imperative for therapeutic targeting. This study reports that hypoxia and IL-1β act in synergy to trigger cell cycle arrest/cellular senescence of ex vivo patient-derived primary proximal tubular epithelial cells (PTECs).

  Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patient-derived PTECs were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions in the absence or presence of IL-1β and examined for maladaptive repair signatures. Hypoxic PTECs incubated with IL-1β displayed a discrete transcriptomic profile distinct from PTECs cultured under hypoxia alone, IL-1β alone or under normoxia. Hypoxia+IL-1β-treated PTECs had 692 ‘unique’ differentially expressed genes (DEGs) compared to normoxic PTECs, with ‘cell cycle’ the most significantly enriched KEGG pathway based on ‘unique’ down-regulated DEGs (including CCNA2, CCNB1 and CCNB2). Hypoxia+IL-1β-treated PTECs displayed signatures of cellular senescence, with reduced proliferation, G2/M cell cycle arrest, elevated senescence-associated β-galactosidase (SA-β-gal) activity and increased production of pro-inflammatory/fibrotic senescence-associated secretory phenotype (SASP) factors compared to normoxic conditions. Treatment of Hypoxia+IL-1β-treated PTECs with either a senolytic drug combination, quercetin+dasatinib, or a type I IL-1 receptor (IL-1RI) neutralizing antibody attenuated senescent cell burden. Our data identify a mechanism whereby hypoxia in combination with IL-1β/IL-1RI signalling trigger PTEC senescence, providing novel therapeutic and diagnostic check-points for restoring tubular regeneration in human CKD.

  Study EGAS00001007904

• Link to the Finnish FEGA Node's service provider

  We would like to direct you to the service provider for the Finnish FEGA Node, which is CSC – IT Center for Science (https://research.csc.fi/-/fega). It's important to note that this is not a genuine DAC and does not serve as the data controller. To obtain access to data stored in FI-FEGA, it is essential to utilize the local access management system SD Apply. Please be aware that applications submitted through the EGA DAC portal will not be processed. For a seamless experience, we kindly request you to refer to the policy of your selected dataset and submit your access application through SD Apply (https://sd-apply.csc.fi/). Your cooperation is highly appreciated.

  Dac EGAC50000000022

• Treatment stratification and biomarker validation using patient-derived head and neck cancer organoids

  Background Organoids are three-dimensional structures that can be grown from patient-derived material including carcinomas. These in vitro models can be cryopreserved to generate “living” biobanks that reflect patient heterogeneity. Head and neck cancer (HNC) is a collective term used for tumors arising in the head and neck area, including squamous cell carcinomas (HNSCC) and adenocarcinoma of the salivary gland. Methods to culture patient-derived HNC organoids have previously been described. Methods Organoids were derived from resection or biopsy material of patients included between 2016 and 2022. Organoids were characterised with immunohistochemistry and whole exome sequencing (WES) and exposed to chemo-, radio- and targeted-therapies. CRISPR/Cas9-based gene editing was applied to validate proposed biomarkers. Results We have extended our previously published organoid biobank to a total of 110 organoid models, some of which were characterised by histology and WES. Organoids recapitulated both single nucleotide variants and copy number alterations as found in patient HNSCC samples. Organoid and patient response to radiotherapy (RT; primary (n=6) and adjuvant (n=15)) could be compared in 21 HNC cases. In the adjuvant RT group, organoids derived from patients that relapsed were more resistant to RT in vitro, showing potential for guiding treatment options in this subset of patients. Conclusion Taken together, these results indicate illustrate the potential of organoids as a diagnostic tool in personalised medicine for HNC and indicate the potential of this technology for biomarker discovery and validation within the context of relevant patient heterogeneity.

  Study EGAS00001007076

• Whole Exome Sequencing of Calcitonin Producing Pancreatic Neuroendocrine Neoplasms (CT-pNENs) Indicates a Unique Molecular Signature

  Calcitonin-producing pancreatic neuroendocrine neoplasms (CT-pNENs), which can mimic clinical and laboratory features of medullary thyroid carcinoma, are an extremely rare clinical entity with approximately 60 cases reported worldwide. The molecular profile of CT-pNENs is not yet known. Whole-exome sequencing (WES) was performed on tumor and corresponding serum samples of five patients with increased calcitonin serum levels and histologically proven calcitonin-positive CT-pNENs. cBioPortal analysis and gene enrichment analysis with DAVID were performed to validate candidate genes. Immunohistochemistry was used to detect protein expression of MUC4 and MUC16 in CT-pNEN specimens. Common somatic mutations of pNENs like MEN1, ATRX and PIK3CA were identified in cases of CT-pNENs. New somatic SNVs in ATP4A, HES4, and CAV3 have not yet been described in CT-pNENs. Pathogenic germline mutations in FGFR4 and DPYD were found in three of five cases. Mutations of CALCA (calcitonin) and the corresponding receptor CALCAR were found in all five tumor samples, but none of them resulted in clinical or protein sequelae. All five tumor cases showed single nucleotide variations (SNVs) in MUC4, and four cases showed SNVs in MUC16, both of which were membrane-bound mucins. Immunohistochemistry showed protein expression of MUC4 and MUC16 in one case each, and the liver metastasis of a third case was double positive for MUC4 and MUC16. The homologous recombination deficiency (HRD) score of all tumors was low.CT-pNENs have a unique molecular signature compared to other pNEN subtypes, specifically involving the FGFR4, DPYD, MUC4, MUC16 and the KRT family genes. However, these WES data from only five cases must be interpreted with caution because causal interpretation of the mutational landscape in CT-pNENs is difficult. Further research is needed to explain differences in pathogenesis compared with other pNENs. In particular, multi-omics data such as RNASeq, methylation, and whole genome sequencing could be informative.

  Study phs003060

• A spatial human thymus cell atlas mapped to a continuous tissue axis

  T cells develop from circulating precursor cells, which enter the thymus and migrate through specialised sub-compartments that support their maturation and selection. In humans, this process starts in early fetal development and is highly active until thymic involution in adolescence. To map the micro-anatomical underpinnings of this process in pre- and early postnatal stages, we established a novel quantitative morphological framework for the thymus, the Cortico-Medullary Axis, and used it to perform a spatially resolved analysis. By applying this framework to a curated multimodal single-cell atlas, spatial transcriptomics, and high-resolution multiplex imaging data, we demonstrate establishment of the lobular cytokine network, canonical thymocyte trajectories and thymic epithelial cell distributions within the first trimester of fetal development. We pinpoint tissue niches of thymic epithelial cell progenitors and distinct subtypes associated with Hassall’s corpuscles and uncover divergence in the timing of medullary entry between CD4 vs. CD8 T cell lineages. These findings provide a basis for a detailed understanding of T lymphocyte development and are complemented with a holistic toolkit for cross-platform imaging data analysis, annotation, and Organ Axis construction (TissueTag), which can be applied to any tissue.

  Dataset EGAD00001015384

• BCR Signaling in human BM PC

  The functions of bone marrow plasma cells (BMPC) beyond antibody production are not fully elucidated and distinct subsets of BMPC suggest potential different functions. Phenotypic differences were identified for human BMPC depending on CD19 expression. Since CD19 is a co-stimulatory molecule of the B-cell-receptor (BCR), and IgA+ and IgM+ BMPC express the BCR on their surface, we here studied whether CD19 expression affects cellular responses, such as BCR signaling and the expression of checkpoint molecules. We analyzed 132 BM samples from individuals undergoing routine total hip arthroplasty. We found that both CD19+ and CD19- BMPC expressed BCR signaling molecules. Notably, the BCR-associated kinase spleen tyrosine kinase (SYK) including pSYK was higher expressed in CD19+BMPC compared to CD19- BMPC. BCR stimulation also resulted in increased kinase phosphorylation downstream of the BCR while expression of CD19 remained stable afterwards. Interestingly, the BCR response was restricted to IgA+ BMPC independently of CD19 expression. With regard to the expression of checkpoint molecules, CD19- BMPC expressed higher levels of co-inhibitory molecule programmed cell death protein-1 (PD-1) than CD19+ BMPC. IgA+ BMPC characteristically upregulated PD-1 upon BCR stimulation in contrast to other PC subsets and inhibition of the kinase SYK abrogated PD-1 upregulation. In contrast, expression of PD-1 ligand, B and T lymphocyte attenuator (BTLA) and CD28 did not change upon BCR activation of IgA+ BMPC. Here, we identify a distinct functiotype of IgA+ BMPC that is independent of the phenotypic heterogeneity of the subsets according to their CD19 expression. The data suggest that IgA+ BMPC underlie different regulatory principles and/or exert distinct regulatory functions.

  Study EGAS00001004948

• Sequence Data from the phase 2 PrE0505 trial of Durvalumab with First Line Platinum-Pemetrexed for Unresectable Pleural Mesothelioma

  Dataset comprises of 84 bam files from exome sequencing data, including 40 tumor-normal pairs and 4 normal files. Each sample is numbered by the patient case ID such as 135, 156 and so on. The filenames are suffixed with "_tumor" and "_normal" to indicate tumor and normal bam files respectively.

  Dataset EGAD00001008016

• Whole Genome Sequencing to Discover Familial Myeloma Risk Genes

  We identified germline KDM1A truncating mutations in patients with multiple myeloma (MM), and loss of heterozygosity (LOH) in tumors. KDM1A mutation burden is higher in sporadic MM patients than in controls, and mRNA levels are lower in MM compared with normal plasma cells. KDM1A pharmacological inhibition in vitro promotes myeloma cell proliferation, and in mice promotes plasma cell expansion, enhanced secondary immune response to T cell dependent antigens, and upregulation of MYC oncogene transcriptional targets. Our findings provide important new insights into the role of KDM1A to suppress B cell malignancies.

  Study phs001819

• High-resolution lung adenocarcinoma expression subtypes identify tumors with dependencies on MET, CDK4, CDK6, and PD-L1

  Lung adenocarcinoma is one of the most common cancer types with various treatment modalities. However, better biomarkers to predict therapeutic response are still needed to improve precision medicine. We utilized a consensus hierarchical clustering approach on 509 LUAD cases from TCGA to identify five robust LUAD expression subtypes. We then integrated genomic (patient and cell line) and proteomic data to help define biomarkers of response to targeted therapies and immunotherapies. This approach defined subtypes with unique proteogenomic and dependency profiles.

  Study EGAS00001006461

• Genome-Wide Association Study of Anorexia Nervosa (Price Foundation, Klarman Family Foundation, Center for Applied Genomics at the Children's Hospital of Philadelphia, Scripps Translational Sciences Institute Clinical Translational Science Award)

  Twin studies are consistent with substantial heritability in anorexia nervosa (AN), although detecting and confirming individual risk alleles has been difficult, due to small effects of single alleles and limited samples in prior studies. Methods: 1105 AN DNA samples obtained in a multisite study and 3733 pediatric patients of normal body weight were genotyped using the Illumina 610Q chip at The Center for Applied Genomics at The Children's Hospital of Philadelphia. Cases and controls were of European ancestry. Single nucleotide polymorphism (SNP) genotypes were subjected to quality control procedures, including elimination of SNPs with: call rates < 95%, minor allele frequency < 5%, and if Hardy-Weinberg equilibrium testing yielded p < 0.0001. Samples were removed if not of European ancestry or if showing cryptic relatedness. Eight AN DNA samples were deleted for low call rate, and 51 AN samples were deleted for cryptic relatedness. The statistical program, PLINK, was used to calculate a P value for each SNP passing quality control using the Cochran-Armitage trend test. The PennCNV program was used to define copy number variation (CNV). Results: We performed a genome-wide association study (GWAS) using with 1033 AN cases and 3733 controls (genomic inflation factor = 1.08). There were 11 SNPs with P<1X10-5 [(rsID, chromosome location, nearest gene, distance to nearest gene (base-pair), P value) rs6959888, 7q21.13, ZNF804B, 0, 1.63E-06; rs17725255, 20p11.23, CSRP2BP, 39396, 1.72E-06; rs10494067, 1p13.3, NTNG1, 0, 5.83E-06; rs2383378, 14q12, AKAP6, 0, 6.41E-06; rs410644, 5q14.1, SSBP2, 40462, 6.74E-06; rs4479806, 5p14.1, CDH9, 156926, 7.79E-06; rs957788, 13q33.3, FAM155A, 0, 8.11E-06; rs830998, 2q31.1, LRP2, 0, 8.68E-06; rs6782029, 3p25.3, VGLL4, 0, 9.04E-06; rs512089, 9p21.3, ELAVL2, 47984, 9.85E-06; rs3808986, 11q24.3, APLP2, 29217, 9.92E-6]. CNV analyses were performed on 1015 AN cases and 3532 controls. Overall frequencies of common or rare CNVs were similar between cases and controls. Specific rare and large (>500 kb, <1%) CNVs of interest included deletion of a large (~1.4Mbp) region of chr13q12 found in 2 AN samples and at a 10 fold lower frequency in a large sample (72,918) of subjects containing the genes SGCG, SACS, TNFRSF19, MIPEP, PCOTH, C1QTNF9B, SPATA13, MIR2276, and C1QTNF9, and an overlapping deletion and a duplication observed in 3 AN samples overlapping the CNTN6 and CNTN4 genes. Partially overlapping ~ 30 kb duplications were seen in 12 AN cases and in 1 control at the CDC5L gene on chromosome 6. Partially overlapping deletion of the 3' half of the PSTPIP1 gene was seen in 5 AN cases and no controls. Finally, a ~ 60 kb deletion of the PLEC1 gene was observed in 5 AN cases and in none of 3532 controls. Discussion: This is the first GWAS of AN. These preliminary results are consistent with absence of a major gene effect in AN. These results are consistent with genetic risk conveyed by multiple common alleles of small effect, as well as some uncommon CNVs of potentially larger effect. None of the implicated genes has a clear role in eating behavior. It must be emphasized that these results are preliminary and an additional ~ 400 AN cases will be analyzed as time and resources permit. These results require confirmation through study of independent populations of AN women.

  Study phs000679

• Biased allelic expression in human primary fibroblast single cells.

  The study of gene expression in mammalian single cells using genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We have used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblast cells over 133,633 unique heterozygous single nucleotide variants (hetSNVs). We have observed that at the snapshot of analyses each cell contains mostly transcripts from one allele from the majority of genes; indeed 76.4% of the hetSNVs display stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibit haplotype consistent allelic ratio; in contrast distant sites located in two different genes are independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in majority of the single cells at a given time point are rare and enriched in highly expressed genes. The relative abundance of each allele in a cell is controlled by some regulatory mechanisms since we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability.

  Study EGAS00001001009

• A non-canonical lymphoblast in refractory childhood T cell leukaemia

  Refractory cancers may arise either through the acquisition of resistance mechanisms by cancer cells or represent distinct diseases. The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown. Refractory T-ALL carries a poor prognosis and cannot be predicted at diagnosis. Here, we performed single cell mRNA sequencing of T-ALL from children who did or did not respond to initial treatment. We identified a transcriptionally distinctive blast population, exhibiting features of innate-like lymphocytes, as the major source of refractory disease. Evidence of such blasts at diagnosis heralded refractory disease across independent datasets and was associated with survival in a large, contemporary trial cohort. Our findings portray refractory T-ALL as a distinct disease. They may have immediate clinical utility.

  Dataset EGAD00001015381

• Foetal_phylogeny_8pcw___WGS_of_LCM_tissues

  This study relates to the overall project of constructing the phylogeny of foetal haematopoiesis. This is an additional project relating to pre-existing work in projects 2043, 2169, 2243 and 2244. This project is to perform WGS (to around 40X) of polyclonal LCM tissues from the 8pcw foetus that have previously undergone library prep and targeted sequencing only. This work is to address reviewers comments for the publication of this work.

  Study EGAS00001004674

• NHLBI TOPMed - NHGRI CCDG: Pakistan Risk of Myocardial Infarction Study (PROMIS)

  The Pakistan Risk of Myocardial Infarction (PROMIS) study is a retrospective multicenter case-control cohort study of individuals with and without coronary heart disease from Pakistan. Multiple biological samples have been collected from the participants including DNA, plasma, serum, and whole blood. The goal of the study is to recruit 20,000 cases and 20,000 controls of Pakistani descent. Eligible cases were individuals aged 30-80 who presented to the emergency department of a participating recruitment center in Pakistan with clinical symptoms consistent with a myocardial infarction (MI), ECG changes consistent with MI, elevated troponin levels consistent with MI, and no prior history of cardiovascular disease. Controls were individuals of Pakistani descent who did not have a self-reported history of cardiovascular disease. This site hosts data generated via NHLBI's TOPMed program and NHGRI's Common Disease Genomics (CCDG) program. Both whole exome and whole genome data are presented here, namely 4,211 whole genomes from TOPMed, 3,859 whole genomes from NHLBI supplemental funds, 1,136 whole genomes and 16,855 whole exomes from CCDG. Please note that there is additional legacy whole exome data (7,298 subjects) also generated via NHGRI funds as part of the MIGen Exome Sequencing project that can be found in dbGaP at phs000917.

  Study phs001569

• Natural History and Structural Functional Relationships in Fabry Renal Disease

  Fabry disease is a rare genetic disease with deficient activity of an enzyme, which leads to accumulation of inclusions in different organs including kidney, heart and vessels. The purpose of the study is to conduct a cross-sectional investigation of the natural history of Fabry renal disease and measure renal function and renal structure in male and female Fabry's patients. The study will utilize the resultant cross-sectional information to determine the renal structural parameters or composite of parameters that most closely relates to the onset and progression of clinical renal disease in Fabry patients. This is an observational, cross-sectional study of 60 individuals with Fabry disease. Those participating in the study will be evaluated during a one day visit and on a PRN basis. The primary study objectives are as follows: To study the natural history of Fabry renal disease and measure renal function and renal structure in male and female Fabry's patients. These patients would encompass the broad age range from childhood to adulthood and from normal renal function to moderate renal insufficiency [serum creatinine (SCr) ≤ 2.5mg/dl (chronic kidney disease or CKD3)]. To utilize the resultant cross-sectional information to determine the renal structural parameters or composite of parameters that most closely relates to the onset and progression of clinical renal disease in Fabry patients.

  Study phs001333

• National Institute of General Medical Sciences (NIGMS) Human Genetic Cell Repository Human Variation Panels including 100 African-Americans (HD100AA), 100 Caucasians (HD100CAU), 100 Han People of Los Angeles (HD100CHI) and 100 Mexican American Community of Los Angeles (HD100MEX)

  The Human Genetic Cell Repository is sponsored by the National Institute of General Medical Sciences (NIGMS) with the mission of supplying scientists with the materials for accelerating disease gene discovery and functional studies. The resources available include highly-characterized, contaminant-free cell cultures and high quality, well-characterized DNA samples derived from these cultures, both subjected to rigorous quality control. The Repository was established in 1972 at Coriell and contains more than 9,500 cell lines, primarily fibroblasts and transformed lymphoblasts. The Repository has a major emphasis on inherited diseases and chromosomally aberrant cell lines. In addition, it contains a large collection dedicated to understanding human variation that includes samples from populations around the world, the CEPH collection, the Polymorphism Discovery Resource, Human Variation and many apparently healthy controls. The Human Variation collection provides cell lines and DNA samples from a variety of populations. The panels of African-Americans (HD100AA) and Caucasians (100CAU) used for this study are comprised of samples present in the Repository that were originally collected over the years from apparently healthy people to be used as "controls", for example, unaffected family members of persons with identified mono-genetic diseases. The samples for the Han people of Los Angeles (HD100CHI) and the Mexican American Community of Los Angeles (HD100MEX), however, were collected relatively recently from volunteers, identified as member of these communities, specifically for use in these panels. The Coriell Genotyping and Microarray Center in conjunction with the NIGMS repository used the Affymetrix Genome-Wide Human SNP 6.0 platform to genotype 400 samples from the NIGMS human variation panels. The populations genotyped included Americans of African, Caucasian, Mexican, and Han Chinese ancestry. The Affymetrix SNP 6.0 array detects approximately 940,000 SNPs and provides copy number information for more than 900,000 additional locations across the genome.

  Study phs000211

• Open_Targets_020_Epigenomes_of_Cell_Lines

  There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. The CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. Multiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001003138

• Transcriptomic classes of BCR-ABL1 lymphoblastic leukemia

  In BCR-ABL1 lymphoblastic leukemia, treatment heterogeneity to tyrosine kinase inhibitors (TKIs), especially in the absence of kinase domain mutations in BCR-ABL1, is poorly understood. Through deep molecular profiling, we uncovered three transcriptomic subtypes of BCR-ABL1 lymphoblastic leukemia, each representing a maturation arrest at a stage of B-cell progenitor differentiation. An earlier arrest was associated with lineage promiscuity, treatment refractoriness, and poor patient outcomes. A later arrest was associated with lineage fidelity, deep and durable leukemia remissions, and improved patient outcomes. Each maturation arrest was marked by specific genomic events that control different transition points in B-cell development. Interestingly, these events were absent in BCR-ABL1+ pre-leukemic stem cells isolated from patients regardless of subtype, which supports that transcriptomic phenotypes are determined downstream of the leukemia-initialing event. Overall, our data indicate that treatment response and TKI-efficacy is an unexpected outcome of the differentiation stage at which this leukemia transforms.

  Study EGAS00001007167

• SCANDARE HNSCC DNA targeted panel sequencing

  SCANDARE (NCT03017573) is a multicentric biobanking study, enrolling adult patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), ovarian and cervical cancer. Tumor tissue and blood samples are collected at several time points during patient's journey, including at diagnosis, post-neoadjuvant chemotherapy in case of neoadjuvant treatment, at surgery, at recurrence and at disease progression following treatment initiated at recurrence. Since its launch in 2017 at Institut Curie, SCANDARE has enabled the longitudinal collection and preservation of samples for in-depth analyses. Here, we describe molecular alterations in 232 FFPE samples at baseline from 83 HNSCC patients using DNA targeted panel sequencing, with FASTQ files deposited in the dataset.

  Dataset EGAD50000001654

• SCANDARE ovarian WES data

  SCANDARE (NCT03017573) is a multicentric biobanking study, enrolling adult patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), ovarian and cervical cancer. Tumor tissue and blood samples are collected at several time points during patient's journey, including at diagnosis, post-neoadjuvant chemotherapy in case of neoadjuvant treatment, at surgery, at recurrence and at disease progression following treatment initiated at recurrence. Since its launch in 2017 at Institut Curie, SCANDARE has enabled the longitudinal collection and preservation of samples for in-depth analyses. Here, we describe molecular alterations in 91 frozen samples (n = 53 at baseline, n = 31 Post-NAC, n= 7 Recurrence, and n = 62 germline DNA) from 64 ovarian cancer patients using WES technology, with FASTQ files deposited in the dataset.

  Dataset EGAD50000001658

• SCANDARE TNBC transcriptomics data

  SCANDARE (NCT03017573) is a multicentric biobanking study, enrolling adult patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), ovarian and cervical cancer. Tumor tissue and blood samples are collected at several time points during patient's journey, including at diagnosis, post-neoadjuvant chemotherapy in case of neoadjuvant treatment, at surgery, at recurrence and at disease progression following treatment initiated at recurrence. Since its launch in 2017 at Institut Curie, SCANDARE has enabled the longitudinal collection and preservation of samples for in-depth analyses. Here, we describe molecular alterations in 124 frozen samples (n=84 at baseline and n=40 paired at post-NAC surgery) from 91 TNBC patients using total RNAseq technology, with FASTQ files deposited in the dataset.

  Dataset EGAD50000001416

• miRNA expression data from primary tumors, metastasis and matched normals.

  MicroRNAs (miRs) have been recognized as promising biomarkers. It is unknown to what extent tumor-derived miRs are differentially expressed between primary colorectal cancers (pCRCs) and metastatic lesions, and to what extent the expression profiles of tumor tissue differ from the surrounding normal tissue. Next-generation sequencing (NGS) of 220 fresh-frozen samples, including paired primary and metastatic tumor tissue and non-tumorous tissue from 38 patients, revealed expression of 2245 known unique mature miRs and 515 novel candidate miRs. Unsupervised clustering of miR expression profiles of pCRC tissue with paired metastases did not separate the two entities, whereas unsupervised clustering of miR expression profiles of pCRC with normal colorectal mucosa demonstrated complete separation of the tumor samples from their paired normal mucosa. Two hundred and twenty-two miRs differentiated both pCRC and metastases from normal tissue samples (false discovery rate (FDR) <0.05). The highest expressed tumor-specific miRs were miR-21 and miR-92a, both previously described to be involved in CRC with potential as circulating biomarker for early detection. Only eight miRs, 0.5% of the analysed miR transcriptome, were differentially expressed between pCRC and the corresponding metastases (FDR <0.1), consisting of five known miRs (miR-320b, miR-320d, miR-3117, miR-1246 and miR-663b) and three novel candidate miRs (chr 1-2552-5p, chr 8-20656-5p and chr 10-25333-3p). These results indicate that previously unrecognized candidate miRs expressed in advanced CRC were identified using NGS. In addition, miR expression profiles of pCRC and metastatic lesions are highly comparable and may be of similar predictive value for prognosis or response to treatment in patients with advanced CRC.

  Dataset EGAD00001001644

• Chromatin_Profiling_in_Twins

  50 lymphoblastoid cell lines of adult female Twins which are part of the MuTHER study, subjected to Chromatin Immunoprecipitation using an antibody for H3K4me1. H3K4me1 peaks mark distal regulatory elements.

  Study EGAS00001000098

• Characterizing the secretome of licensed hiPSC-derived MSCs

  Although mesenchymal stromal cells (MSCs) from primary tissues have been successfully applied in the clinic, their expansion capabilities are limited and results are variable. MSCs derived from human-induced pluripotent stem cells (hiMSCs) are expected to overcome these limitations and serve as a reproducible and sustainable cell source. We have explored characteristics and therapeutic potential of hiMSCs in comparison to hBMSCs. Our data qualify hiMSCs as a promising source for cell therapy and/or cell-based therapeutic products. Additionally, the herewith generated database will add to our understanding of the mode of action of regenerative cell-based therapies and could be used to identify relevant potency markers.

  Study EGAS50000000389

• HuBMAP: A Spatially Resolved Molecular Atlas of Human Endothelium

  The human circulatory system plays a vital role in the proper functioning of every organ in the human body. Because vascular related diseases, such as atherosclerosis, do not occur homogeneously throughout the vascular tree, differences in the endothelium of various organs must exist. There is even evidence of heterogeneity of adjacent endothelial cells. We are studying normal endothelium throughout the body and across individuals of different ages to characterize these differences. The first step will be to procure normal tissue samples from a wide range of organs. From disaggregated samples of these tissues, we will perform single cell combinatorial indexing (sci-) to generate chromatin accessibility (sci-ATAC-seq) and transcriptome (sci-RNA-seq) data from millions of single cells across hundreds of samples.  Molecular heterogeneity might correlate with multiple facets of the anatomical distribution of endothelium, including vascular vs. lymphatic, arteries vs. veins, capillaries vs. larger vessels, differences between organs, organ zonation, cell-to-cell differences, etc. Based on heterogeneous markers defined from deep profiling of disaggregated cells, we will employ seqFISH to spatially relate the distinct endothelial subpopulations arising from the single nuclei data to histologic preparations. For example, this will allow us to identify subpopulations with particular markers as arterial, capillary, venous, or lymphatic. The end product will include multiparameter images in which the complete gene expression and chromatin accessibility profile can be interactively visualized for every cell.

  Study phs002267

• MOSAIC Window Mesothelioma Data

  This dataset will include Spatial Transcriptomics from the 10x Genomics Visium SD technology, Single-Cell RNA-Seq from the 10x Genomics Chromium Flex protocol, Bulk RNA-Seq (sequenced on Illumina), WES (sequenced on Illumina), H&E, and Clinical data from 10 Mesothelioma patients. For Visium and Chromium data we are sharing the outputs of respectively Space Ranger and Cell Ranger. For Bulk RNA-Seq we are including processed files such as counts.tsv, FPKM.tsv, fusion_genes.tsv, TPM count matrix.tsv, DESeq2 count matrix.tsv, multiqc_report. For WES, we are sharing the presence or absence of single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variants (CNVs).* Researchers from private or public institutions outside the MOSAIC Consortium will be able to apply to access this data and, pending approval, use the data for their research.

  Dataset EGAD50000001706

• MOSAIC Window Ovarian Data

  This dataset will include Spatial Transcriptomics from the 10x Genomics Visium SD technology, Single-Cell RNA-Seq from the 10x Genomics Chromium Flex protocol, Bulk RNA-Seq (sequenced on Illumina), WES (sequenced on Illumina), H&E, and Clinical data from 15 Ovarian patients. For Visium and Chromium data we are sharing the outputs of respectively Space Ranger and Cell Ranger. For Bulk RNA-Seq we are including processed files such as counts.tsv, FPKM.tsv, fusion_genes.tsv, TPM count matrix.tsv, DESeq2 count matrix.tsv, multiqc_report. For WES, we are sharing the presence or absence of single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variants (CNVs).* Researchers from private or public institutions outside the MOSAIC Consortium will be able to apply to access this data and, pending approval, use the data for their research.

  Dataset EGAD50000001704

• MOSAIC Window DLBCL Data

  This dataset will include Spatial Transcriptomics from the 10x Genomics Visium SD technology, Single-Cell RNA-Seq from the 10x Genomics Chromium Flex protocol, Bulk RNA-Seq (sequenced on Illumina), WES (sequenced on Illumina), H&E, and Clinical data from 10 DLBCL patients. For Visium and Chromium data we are sharing the outputs of respectively Space Ranger and Cell Ranger. For Bulk RNA-Seq we are including processed files such as counts.tsv, FPKM.tsv, fusion_genes.tsv, TPM count matrix.tsv, DESeq2 count matrix.tsv, multiqc_report. For WES, we are sharing the presence or absence of single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variants (CNVs).* Researchers from private or public institutions outside the MOSAIC Consortium will be able to apply to access this data and, pending approval, use the data for their research.

  Dataset EGAD50000001702

• NHLBI TOPMed: HyperGEN - Genetics of Left Ventricular (LV) Hypertrophy

  The Hypertension Genetic Epidemiology Network Study (HyperGEN) - Genetics of Left Ventricular (LV) Hypertrophy is a familial study aimed to understand genetic risk factors for LV hypertrophy by conducting genetic studies of continuous traits from echocardiography exams. The originating HyperGEN study aimed to understand genetic risk factors for hypertension. Data from detailed clinical exams as well as genotyping data for linkage studies, candidate gene studies and GWAS have been collected and is shared between HyperGEN and the ancillary HyperGEN - Genetics of LV Hypertrophy study.

  Study phs001293

• Effects of interferon-gamma treatment on human small intestinal organoids generated from healthy donors

  The intestine is vulnerable to interferon-gamma as intestinal epithelial stem cells undergo cell death when exposed to interferon-gamma. Here, we developed a novel human intestinal organoid-based 3D model system to study the effects of interferon-gamma-induced intestinal epithelial damage at the RNA level. We treated organoids with 10 ng/mL for either 6 or 18h. Knowledge generated with this dataset is relevant for a variaty of intestinal pathologies with an immune component, for instance graft-versus-host disease.

  Study EGAS50000000083

• WGS analysis of Japanese liver cancer

  Liver cancer is prevalent worldwide, mainly associated with virus infection, and its underlying etiology and genomic structure are heterogeneous. Here we provide a whole-genome landscape of somatic alterations in 300 Japanese liver cancers. Our comprehensive analysis elucidated point mutations in non-coding regions, structural variants (SVs), and virus integrations, in addition to coding mutations, and demonstrated new mutational signatures related with liver carcinogenesis, novel recurrently mutated coding and non-coding regions such as lincRNA NEAT1/MALAT1, promoters, CTCF binding sites, and regulatory regions. SV analysis found a significant association with replication timing, and revealed that known cancer genes (CDKN2A, CCND1, APC, and TERT) and new cancer genes (ASH1L, NCOR1, MACROD2) were recurrently affected by SVs, leading to altered expression of nearby genes. These results emphasize the value of whole genome sequencing analysis to discover cancer driver mutations and to understand comprehensive molecular profiles of liver cancer, especially for SVs and non-coding mutations.

  Study JGAS000151

• A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies

  Pineoblastoma is a clinically aggressive childhood brain tumor composed of distinct molecular subgroups with divergent driver genes, demographics, and clinical outcomes. To identify developmental origins and mechanisms governing disease pathogenesis, we derive single-cell transcriptomes from pineal parenchymal tumors, aligning malignant cells with our atlas of pineal gland development to retrace cellular origins. Integrative computational analyses maps pineoblastoma origins to transient cycling pinealocyte progenitors during development. Lineage-specific perturbation of suspected drivers in the early pineal gland yields preclinical models representative of consensus molecular subgroups. Multi-omic characterization of patient tumors and these models uncovers a tumor-associated photoreceptor signature common to pineoblastoma, retinoblastoma, and Group 3 medulloblastoma. Transcriptional activity of this signature within respective cellular origins establishes a developmental basis for molecular similarities between entities. Photoreceptor signature constituents are selective dependencies across these anatomically distinct central nervous system malignancies, motivating future studies evaluating developmentally encoded programs of malignancy as potential therapeutic liabilities.

  Study EGAS50000001457

• RNAseq of 76 samples from Uveal Melanoma tumors

  Hotspot mutations in the spliceosome gene SF3B1 are reported in 20% of uveal melanomas. SF3B1 is involved in 3'-splice site (3'ss) recognition during RNA splicing; however, the molecular mechanisms of its mutation have remained unclear. Here we show, using RNA-Seq analyses of uveal melanoma, that the SF3B1 R625/K666 mutation results in deregulated splicing at a subset of junctions, mostly by the use of alternative 3'ss.

  Dataset EGAD00001004398

• Genetic Analysis of the Chiari I Malformation

  This study used whole exome sequencing (WES) on families affected with Chiari I Malformation (CM1). Individuals were recruited from the Republic of Tartarstan in the Russian Federation, where CM1 has a high prevalence (approximately 413 out of 100,000). At least one-third of these affected individuals have an affected relative. In collaboration with Dr. Enver Bogdanov of Kazan State Medical University, seven extended families affected with CM1 were identified. Eligible participants for this study were required to 1) have CM1 and a family member with syringomyelia or CM1, or 2) be a family member of a patient with CM1 and have at least two immediate family members diagnosed with CM1. Adults and minors were eligible for this study and recruitment was through self and physician referral. Patients were excluded if they had a contraindication to MRI scanning, were unable to understand the risks of testing, were under one year of age, or could not undergo MRI scanning without sedation. Study participants underwent SPGR (Spoiled Gradient Recalled) and T1-weighted MR-imaging of the brain and cervical spinal cord to assess the volume of the posterior fossa, as well as the presence of CM1. Individuals were defined as having CM1 if the inferior aspect of the cerebellar tonsils were lying ≥=2 mm caudal to the foramen magnum. Individuals were defined as having a small posterior fossa volume if the ratio of the posterior fossa volume to the supratentorial volume was < 0.15. Sixty-two patients (both cases and controls) from the seven extended families had DNA extracted from blood lymphocytes contained in 10 milliliters of stored blood. Whole exome sequencing (WES) was performed by the National Intramural Sequencing Center (NISC). These genotype data, as well as the case-control phenotype data on CM1 diagnosis and small posterior fossa diagnosis, were made available to dbGaP.

  Study phs001795

• scRNA transcriptome and TCR sequencing data modeling treatment responses in eight renal cell carcinoma patient

  Single cell RNA sequencing and coupled TCR sequencing data generated following immunological treatments in patient-derived ex vivo tumor models. Dataset consist of 46 sequencing samples originating from eight individual patient-derived ex vivo models. Single cell RNA and TCR sequencing data is generated using 10X Genomics platform with 5´ sequencing. The submission contains 46 Fastq files where each patient-derived ex vivo model and it's transcriptomic response to specified treatment is a unique sequencing run. TCR sequencing runs are submitted as one file per individual model, gathering all the treatment conditions.

  Dataset EGAD50000001934

• Orphan_Tumour_Study_NB

  The aim of this study is to investigate the transcriptional landscape of human cancer. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001003445

• Fixation effects on variant-calling in a clinical resequencing panel

  Formalin fixation is the standard method for preservation of tissue for diagnostic purposes, including pathological review and molecular assays. However, this method is known to cause artifacts that can affect the accuracy of molecular genetic tests. We assessed the applicability of alternative fixatives to determine whether these perform significantly better on next-generation sequencing assays, and whether adequate morphology is retained for primary diagnosis, in a prospective study using a clinical-grade laboratory-developed targeted resequencing assay. We examined and quantified several parameters relating to sequencing quality and variant-calling from tumor and normal colon epithelial tissues. We identify one alterative fixative, Sakura Universal Molecular Fixative that suppresses many formalin-related artifacts while retaining adequate morphology for pathological review.

  Study EGAS00001003507

• Gtag&T single-cell genome and transcriptome data

  This submission contains single-cell genome and transcriptome data that is used for the following manuscript: https://doi.org/10.1101/2023.01.13.521174. All Illumina data deposited here is retrieved from HCC38(BL) cell lines and a melanoma PDX model as described in the paper.

  Study EGAS00001007043

• WGS of T-cell and NK-cell lymphoma for ICGC (NKTL-SG)

  Lymphomas are malignancies originating from the lymphatic system and there is a worldwide significant increase in incidences of this cancer. Lymphomas can be further classified into 2 categories namely Hodgkin’s (HL), and Non-Hodgkin’s lymphoma (NHL). The latter can be divided further into B, T and NK cell NHL. Peripheral T-cell lymphoma (PTCL) and Natural Killer/ T-cell lymphoma (NKTL) arise from mature T lymphocytes and NK cells. The more common subtypes include NKTL, PTCL not-otherwise-specified (PTCL-NOS), systemic anaplastic large cell lymphoma (ALCL), follicular PTCL (F-PTCL), angioimmunoblastic T-cell lymphoma (AITL) and enteropathy-associated T-cell lymphoma (EATL). Whole genome analyses on T-cell and NK-cell lymphoma samples from various countries to gain a better understanding of the pathogenesis and biology of these tumors. The comprehensive profiling and comparison among patients from various countries with different etiopathogenesis will hopefully facilitate the elucidation of key pathways and underlying molecular mechanisms driving these cancers, opening up novel therapeutic strategies in the future.

  Study EGAS00001002398

• eccDNA in maternal plasma

  We developed a new bioinformatics method for detecting the eccDNA in plasma. We revealed that the biological properties between eccDNA and linear DNA are different. eccDNA could be potentially provided as a new class of circulating biomarker.

  Study EGAS00001003827

• Single-cell level characterization of B cell depletion and repopulation following rituximab in systemic lupus erythematosus

  Rituximab, a CD20+ B cell depletion therapy, is frequently used in the treatment of systemic lupus erythematosus (SLE). However, variability in patient response highlights the need for a deeper understanding of the underlying immune cell dynamics of B cell depletion and repopulation. In this study, we conducted longitudinal single-cell profiling of nine SLE patients treated with rituximab from pretreatment to up to 15 months post-treatment. These were compared to eight healthy controls. We profiled PBMCs via 10X Genomics single-cell RNA, surface protein (CITE-seq), B cell receptor (BCR), and T cell receptor (TCR) sequencing and sequenced bulk BCR repertoires in parallel. For single cell sequencing, 10 pools were created with an equal number of cells from 4 samples each. Samples collected at different timepoints from the same patient were distributed across different pools to allow demultiplexing of individuals using genotypes captured from the scRNA-seq data. Libraries were pooled using a ratio of GEX:CITE:TCR:BCR=9:2:1:1 and were sequenced across two lanes of the NovaSeq 6000. For bulk BCR sequencing, individual samples were demultiplexed using primer barcodes and paired-end BCR amplicon reads were merged prior to submission; data are provided as unmapped single-end reads.

  Dataset EGAD00001015817

• Sequencing data from a highly cost-effective cell-free DNA methylome test

  Plasma cell-free DNA (cfDNA), originating from multiple organs, holds significant potential for non-invasive diagnostics and prognostics. Current cfDNA methylation assays primarily focus on single clinical indications by targeting specific genomic loci. In contrast, comprehensive profiling of cfDNA methylome can enable simultaneous detection of multiple diseases by capturing organ-specific methylation signatures, thereby offering a holistic view of health, when disease etiology is unclear or when conventional biochemical diagnostics are unavailable. However, deep sequencing required for sensitive detection of methylation abnormalities remains prohibitively expensive, limiting widespread clinical use. To overcome this barrier, we developed MethylScan, a highly cost-effective approach for cfDNA methylome sequencing. We demonstrated its broad clinical utility in a cohort of 1,061 individuals across diverse applications, including multi-cancer detection in general population, liver cancer surveillance in high-risk individuals, liver disease classification, identification of organ abnormalities, and race prediction from cfDNA.

  Study EGAS00001008125