20309 results for "Fc coins Buyfc26coins.com is EA Sports official for FC 26 coins They are efficient and quick always..Z2Xg"

in 61.66 milliseconds.

• The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer

  Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, fundamental steps in the initiation of human cancer. Multiple cancer types, including up to 83% of glioblastomas (GBM), harbor highly recurrent TERT promoter mutations of unknown function but specific to two nucleotide positions. We identify the functional consequence of these mutations in GBM to be recruitment of the multimeric GABP transcription factor specifically to the mutant promoter. Allelic recruitment of GABP is consistently observed across four cancer types, highlighting a shared mechanism underlying TERT reactivation. Tandem flanking native ETS motifs critically cooperate with these mutations to activate TERT, likely by facilitating GABP heterotetramer binding. GABP thus directly links TERT promoter mutations to aberrant expression in multiple cancers.

  Study EGAS00001001242

• Efficacy and safety of entrectinib in patients with ROS1-positive advanced/metastatic non-small cell lung cancer (NSCLC) from the Blood First Assay Screening Trial (BFAST)

  BFAST is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations, identified by blood-based molecular testing. We present data from Cohort D (ROS1-positive). Patients ≥18 years old with stage IIIB/IV, ROS1-positive NSCLC detected by blood-based testing, received entrectinib 600 mg daily. At data cut-off (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint; the confirmed objective response rate (ORR) by investigator was 81.5% which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR: 73.4%, data cut-off May 2019, ≥12 months follow-up). The safety profile of entrectinib was consistent with prior reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing and support the clinical value of blood-based testing to inform clinical decision-making.

  Study EGAS50000000105

• Analysis of DNA methylation in normal B cells and chronic lymphocytic leukemia

  Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes.As second study using these samples focued on evolution and resulting intra-tumor heterogeneity in CLL. We used 450k bead-chip arrays to study DNA methylomes in 68 chronic lymphocytic leukemia (CLL) cases, including 28 serial cases. The result establishs linked evolution of epigenetic and genetic alterations in progressive disease, revealing an important aspect of the biology of epigenetics in cancer.

  Study EGAS00001000534

• The impact of BNT162b2 mRNA vaccine against SARS-CoV-2 on adaptive and innate immune responses

  The mRNA-based BNT162b2 protects against severe disease and mortality caused by SARS-CoV-2 through induction of specific antibody and T-cell responses. Much less is known about its broad effects on immune responses against other pathogens. In the present study, we investigated the specific adaptive immune responses induced by BNT162b2 vaccination against various SARS-CoV-2 variants, as well as its effects on the responsiveness of human immune cells upon stimulation with heterologous viral, bacterial, and fungal pathogens. BNT162b2 vaccination induced effective humoral and cellular immunity against SARS-CoV-2 that started to wane after six months. We also observed long-term transcriptional changes in immune cells after vaccination, as assessed by RNA sequencing. Additionally, vaccination with BNT162b2 modulated innate immune responses as measured by the production of inflammatory cytokines when stimulated with various microbial stimuli other than SARS-CoV-2, including higher IL-1/IL-6 release and decreased production of IFN-α. Altogether, these data expand our knowledge regarding the overall immunological effects of this new class of vaccines and underline the need of additional studies to elucidate their effects on both innate and adaptive immune responses.

  Study EGAS00001006818

• Childhood Cancer Data Initiative (CCDI): Texas Pediatric Patient Derived Xenograft 

  The DNA/RNA samples of patients for which PDX models were developed were from a population of children, adolescents, and young adults from South Texas. Consent was obtained for collection of malignant and non-malignant tissue samples for genetic analysis and for the development of models to study new ways to treat cancer. For additional details, please refer to these publications: PMID: 37915590; PMID: 37990009.

  Study phs003215

• Comprehensive cancer predisposition gene testing in an adult multiple primary tumor series shows a broad range of deleterious variants and atypical tumor phenotypes

  Multiple primary tumors (MPT) affect a substantial proportion of cancer survivors and may result from various causes including inherited predisposition. Currently, germline genetic testing of MPT cases for cancer predisposition gene (CPG) variants is mostly targeted by tumor type. We ascertained pre-assessed MPT cases from genetics centers (defined as ≥2 primaries by age 60 years or ≥3 by 70) and performed whole genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment/molecular investigations, pathogenic variants in moderate and high-risk CPGs were detected in 67/440 (15.2%) of probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies including structural variants at low frequency (6/440 (1.4%) of probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant) the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice site CPG variants and at least one discordant tumor type was significantly higher than a control population (χ2=43.642 P=<0.0001). 2/67 (3%) of probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Summing together variant detection rates from a similarly ascertained previous MPT case series, the present results suggest that first-line comprehensive CPG analysis in a clinical genetics referral-based MPT cohort would detect a deleterious variant in about a third of cases.

  Dataset EGAD00001004088

• Lung cancer, healthy control and non-cancerous plasma cfDNA samples

  The dataset contains 106 lung cancer, 12 healthy control and 11 non-cancerous lesion plasma cfDNA sample. Shallow WGS was performed on an Illumina Novaseq S4 PE150bp. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001008321

• Genomic characterisation of SDH deficient renal cell carcinoma - WGS

  SDH deficient renal cell carcinomas are a rare and recently defined subtype of kidney cancer, often associated with an inherited mutation in one of the SDH gene subunits. This dataset sought to understand the genomic events that underpin tumour formation, from putative cell of origin, characterisation of the tumour microenvironment, to the genomic evolution of these rare tumours. We performed whole genome and RNA sequencing of 4 patients with SDH deficient renal cell carcinomas, including one patient who had an additional paraganglioma. An addition patient in this cohort had the initial diagnosis revised to a clear cell renal cell carcinoma.

  Dataset EGAD00001008469

• Blood Transcriptome Profiling Links Immunity to Disease Severity in Myotonic Dystrophy Type 1 (DM1)

  Here, we explore the molecular signatures in RNA sequencing data from blood associated with disease severity as measured in Myotonic dystrophy type 1 (DM1) patients with less than 400 CTG-repeat length size in the DMPK gene in blood. These DM1 patients participated in the OPTIMISTIC study. This approach involved stratifying those within the OPTIMISTIC study into different patient groups with different degrees of disease severity (as measured by the muscle-impairment rating scale (MIRS)) and assessed at baseline. Patients were divided into groups with mild (MIRS 1–2) and severe (MIRS 3–5) neuromuscular symptoms with different DMPK repeat length characteristics. Therefore these .Bam files are baseline samples from this study.

  Dataset EGAD00001010010

• Human inflammatory cardiomyopathies following SARS-CoV2 infection and COVID-19 vaccination

  Title: The cellular and molecular responses in human inflammatory cardiomyopathies following SARS-CoV2 infection and COVID-19 vaccination. Abstract: Abstract: Myocarditis is a cardiac disorder with multiple etiologies characterised by inflammatory cell infiltration and can occur after SARS-CoV-2 infection or rarely following mRNA-based COVID-19 vaccination. The underlying cellular and molecular mechanisms driving these pathologies remain poorly understood.Here we performed single-nucleus-RNA-sequencing in left ventricular endomyocardial biopsies from patients with Non-COVID-19 myocarditis, following SARS-CoV-2 infection (Post-COVID-19) and COVID-19 vaccination (Post-Vaccination). We detected specific cytokine expression patterns highlighting a particular role of interferon-γ in Post-COVID-19 and upregulated IL16 and IL18 expression as a Post-Vaccination hallmark. While the myeloid response was similar between groups, CD4+T-cell proportions were higher in Post-Vaccination and cytotoxic CD8+T and NK cells expanded in Post-COVID-19. Endothelial cells showed gene expression changes suggestive of vascular barrier function deficiency in Post-COVID-19 and angiogenesis response to cardiac inflammation in all groups. Together, our results illuminate shared and distinct cellular and molecular architectures of Non-COVID-19, Post-COVID-19 and Post-Vaccination associated myocardial inflammation in human hearts.

  Study EGAS50000000769

• bam files Targeted BS

  Data from the paper Context-specific Effects of TGFβ/SMAD3 in Cancer Are Modulated by the Epigenome. Tufegdzic et al, Cell Reports 2015

  Dataset EGAD00001001667

• BAM Files MBD-SEQ

  Data from the paper Context-specific Effects of TGFβ/SMAD3 in Cancer Are Modulated by the Epigenome. Tufegdzic et al, Cell Reports 2015

  Dataset EGAD00001001668

• shallow whole genome sequencing dataset

  shallow whole genome sequencing dataset contains 44 samples. all the samples are early stage high ovarian high grade serous carcinoma.

  Dataset EGAD00001008588

• Characterization of Autosomal CNV Among the Negrito from Peninsular Malaysia

  Copy number variation (CNV) has been recognized as a major contributor to human genome diversity. It plays an important role in determining phenotypes and has been associated with a number of common and complex diseases. However the CNV data from diverse populations is rather limited. Here we report the first investigation of copy number variation (CNV) in the indigenous populations from Peninsular Malaysia. We genotyped 34 Negrito genomes from Peninsular Malaysia using the Affymetrix SNP 6.0 microarray and identified 62 putative novel CNVs, consisting of 25 gains and 37 losses. These CNVs appear unique to the Negrito population and were absent in the DGV, HapMap3 and Singapore Genome Variation Project (SGVP) datasets. Analysis of gene ontology revealed that genes within these CNVs were enriched in the immune system (GO:0002376), response to stimulus mechanisms (GO:0050896), as well as the metabolic pathways (GO:0001852). Copy number gains in CNVRs enriched with genes were significantly higher than the losses (P value <0.001). Therefore, in view of the small population size, relative isolation and semi-normadic lifestyles of this community, we speculate that these CNVs may be attributed to recent local adaptation of Negritos from Peninsular Malaysia.

  Study phs000664

• Temporal Evolution Reveals Bifurcated Lineages in Aggressive Neuroendocrine Small Cell Prostate Cancer Trans-Differentiation

  Trans-differentiation from adenocarcinoma to small cell neuroendocrine (SCN) cancer is an adverse consequence of treatment escape in various cancers, including prostate, lung, and bladder cancers (Balanis and Sheu et al., PMID 31287989). Expression of dominant negative p53 (TP53DN), myrAkt1, RB1-shRNA, c-Myc, and Bcl2(PARCB forward transformation) using human naïve prostate basal epithelial cells recapitulated both transcriptional and histological characteristics of small cell neuroendocrine prostate cancer (NEPC) (Park et al., PMID 30287662). To study the temporal transcriptional landscape during this trans-differentiation process, we conducted a time course study using a PARCB model by integrating multi-omics sequencing, including bulk RNA-sequencing and ATAC-sequencing on samples taken at different time point, as well as single cell RNA sequencing on serial xenograft tumors. We found a common SCN pathway that resulted in two distinct end states defined by mutually exclusive expression of ASCL1 and ASCL2. Further investigation using CUT&RUN sequencing identified TFAP4 as a potential epigenetic regulator of both proteins. Our study reveals temporal and transcriptional changes from prostate adenocarcinoma to NEPC trans-differentiation.

  Study phs003230

• Systematic dissection of tumor-normal single-cell ecosystems across a thousand tumors of 30 cancer types

  The complexity of the tumor microenvironment poses significant challenges in cancer therapy. Here, to comprehensively investigate the tumor-normal ecosystems, we perform an integrative analysis of 4.9 million single-cell transcriptomes from 1,070 tumor and 493 normal samples in combination with pan-cancer 137 spatial transcriptomics, 8,887 TCGA, and 1,261 checkpoint inhibitor-treated bulk tumors. We define a myriad of cell states constituting the tumor-normal ecosystems and also identify hallmark gene signatures across different cell types and organs. Our atlas characterizes distinctions between inflammatory fibroblasts marked by AKR1C1 or WNT5A in terms of cellular interactions and spatial co-localization patterns. Co-occurrence analysis reveals interferon-enriched community states including tertiary lymphoid structure (TLS) components, which exhibit differential rewiring between tumor, adjacent normal, and healthy normal tissues. The favorable response of interferon-enriched community states to immunotherapy is validated using immunotherapy-treated cancers (n=1,261) including our lung cancer cohort (n=497). Deconvolution of spatial transcriptomes discriminates TLS-enriched from non-enriched cell types among immunotherapy-favorable components. Our systematic dissection of tumor-normal ecosystems provides a deeper understanding of inter- and intra-tumoral heterogeneity.

  Study EGAS50000000324

• Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T-cell lymphomas with hemophagocytic lymphohistiocytic syndrome

  Sub-cutaneous panniculitis-like T-cell lymphomas (SPTCL), a non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation which adversely impacts survival1,2. T-cell-immunoglobulin mucin-3 (TIM-3) is a modulator of immune responses expressed on subgroups of T- and innate immune cells. We identify in ~60% of SPTCL cases germline, loss-of-function, missense variants in highly conserved residues of TIM-3, c.245A>G(p.Y82C) and c.291A>G(p.I97M), each with specific geographic distribution. Y82C-TIM-3 occurs on a potential founder chromosome in patients with East Asian and Polynesian ancestry, while I97M-TIM-3 occurs in Caucasians. Both variants induce protein misfolding and abrogate TIM-3’s plasma-membrane expression leading to persistent immune activation, increased production of inflammatory cytokines, including TNF-α and IL-1β, promoting HLH and SPTCL. Our findings highlight HLH/SPTCL as a new genetic entity and showcase TIM-3 mutations as the first causative genetic defect in SPTCL. While TIM-3-mutant HLH/SPTCL benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint may have adverse consequences.

  Study EGAS00001002765

• The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients

  Telomere fusions (TFs) can trigger the accumulation of oncogenic alterations leading to malignant transformation and drug resistance. Despite their relevance in tumour evolution, our understanding of the patterns and consequences of TFs in human cancers remains limited. Here, we characterize the rates and spectrum of somatic TFs across >30 cancer types using whole-genome sequencing data. TFs are pervasive in human tumours with rates varying markedly across and within cancer types. In addition to end-to-end fusions, we find novel patterns of TFs that we mechanistically link to the activity of the alternative lengthening of telomeres (ALT) pathway. We show that TFs can be detected in the blood of cancer patients, which enables cancer detection with high specificity and sensitivity even for early-stage tumours and cancers of high unmet clinical need. Overall, we report a novel genomic footprint that enables characterization of the telomere maintenance mechanism of tumours and liquid biopsy analysis.

  Dataset EGAD00001012101

• Multi-omics datasets (WES, RNA-seq) of mesothelioma NERO study, a phase II PARP inhibitor clinical trial

  Niraparib Efficacy in Patient With Unresectable Mesothelioma, NERO, this randomised phase II trial is designed to evaluating the efficacy of the PARP inhibitor Niraparib versus active symptom control.

  Study EGAS50000001825

• Sebaceous carcinoma tumor/normal exome sequencing and transcriptome sequencing. Transcriptome sequencing of

  Sebaceous carcinomas (SeC) are cutaneous malignancies that, in rare cases, metastasize and prove fatal. Here we report whole exome sequencing on 32 SeC, revealing distinct mutational classes that explain both cancer ontogeny and clinical course. A UV-damage signature predominated 10/32 samples, while 9 were instead defined by microsatellite instability (MSI) mutations. UV-damage SeC exhibited poorly differentiated, infiltrative histopathologycompared to MSI signature SeC (p = 0.003), features previously associated with dissemination. Strikingly, UV-damage SeC transcriptomes and anatomic distributionclosely resembling those of cutaneous squamous cell carcinomas (SCC), implicating sun-exposed keratinocytes as a cell of origin. Like SCC, this UV-damage subclass harbors a high somatic mutation burden with >50 mutations/Mb, predicting immunotherapeutic response. In contrast, ocular SeC acquire far fewer mutations without a dominant signature, but show frequent truncating mutations in the ZNF750 epidermal differentiation regulator. Our data exemplify how different mutational processes convergently drive histopathologically related but clinically distinct cancers.

  Dataset EGAD00001004016

• ScRNA sequencing and snp-array genotyping of peripheral immune cells in Type 1 diabetes mellitus (T1DM)

  Type 1 diabetes mellitus (T1DM) is a prototypic endocrine autoimmune disease resulting from an immune-mediated destruction of pancreatic insulin-secreting beta-cells. A comprehensive immune cell phenotype evaluation in T1DM has not been performed thus far at the single. In this cross-sectional analysis, we generated a single-cell transcriptomic dataset of peripheral blood mononuclear cells (PBMCs) from 46 manifest T1DM (Stage 3) cases and 31 matched controls.Our study reveals a surprisingly strong systemic dimension at the level of immune cell network in T1DM, defines disease-relevant molecular subtypes and has the potential to guide non-invasive test development and patient stratification.

  Dataset EGAD50000000345

• Whole Genome Sequencing of Liver Cancers

  Genomic alterations driving tumorigenesis result from the interaction of environmental exposures and endogeneous cellular processes. With a diversity of risk factors including viral infection, carcinogenic exposures and metabolic diseases, liver cancer is an ideal model to study these interactions. Whole genome sequencing of liver tumors identified 10 mutational signatures showing distinct relationships with environmental exposures, replication and transcription. Transcription-coupled damage was specifically associated with the liver-specific signature 16 and alcohol intake. Flood of indels were identified in very highly expressed hepato-specific genes, likely resulting from replication-transcription collisions. Reconstruction of sub-clonal architecture revealed mutational signature evolution during tumor development exemplified by the vanishing of aflatoxin-B1 signature in African migrants. These findings shed new light on the natural history of liver cancers.

  Dataset EGAD00001003281

• Identification of rare variants associated with cardiovascular traits in Cilento isolates

  The aim of this project is to identify rare genetic variants of large effect implicated in complex diseases by focusing on the study of cardiovascular diseases and related quantitative traits in a well characterized isolated population in Cilento area, Italy. The reference panel has been selected carefully in order to maximize the imputation coverage and quality on the all population samples. The selected individuals should meet three criteria: selected individuals should be chip-genotyped and closely related to the maximum number of chip-genotyped individuals so as to maximize imputation coverage; relatedness between selected individuals should be minimal, so as to minimize redundancy in genetic information of the reference panel. We perform exome sequencing on samples from 250 individuals from the Campora and Gioi-Cardile populations.

  Dataset EGAD00001002195

• Single-cell RNA-seq of peripheral blood mononuclear cells in classic Hodgkin lymphoma

  Abstract: Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (paired samples from cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors.

  Dataset EGAD00001011360

• Characterization of Leukemic Stem Cells in DNMT3Amut and NPM1mut AMLs

  Trascriptomic profile of FACS-sorted LSCs from diagnostic DNMT3Amut and NPM1mut AML patients using a novel sorting strategy. Briefly, positive selection for GPR56 and a negative selection for NKG2DLigands were used to enrich for LSCs in both CD34+ and CD34- subpopulations. Primary samples were retrospectively collected based on their mutational profile.

  Study EGAS00001006527

• Dataset of RNA-sequencing of childhood acute myeloid leukemia

  This dataset includes 139 bam files of mRNA sequencing. All subjects are tumor samples of pediatric acute myeloid leukemia.

  Dataset EGAD00001005078

• Melanoma microRNA profiling

  This dataset includes microRNA profiling of 61 early-passage metastatic melanoma cell lines. The data are provided as single-end small RNA seq fastq files.

  Dataset EGAD00001006269

• Melanoma transcriptome profiling

  This dataset includes transcriptome profiling of 68 early-passage metastatic melanoma cell lines. The data are provided as paired-end RNA seq fastq files.

  Dataset EGAD00001006270

• Paired-end Whole Exome-seq analysis of the 3D spatially mapped GBM samples.

  Dataset contains 50 paired-end Whole Exome sequencing samples from 3 patients. 3 normal blood samples are also included.

  Dataset EGAD00001010289

• Transcriptomic changes in amniotic fluid associated with the fetal inflammatory response

  The fetal inflammatory response (FIR) increases the risk of perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, < 28 weeks of gestation). Most FIR cases are subclinical, i.e., usually FIR does not trigger observable symptoms in the mother beyond those associated with premature birth. The study of transcriptomic changes asssociated with FIR in amniotic fluid could help finding new clinical actionable FIR biomarkers.

  Study EGAS50000000866

• Single cell and plasma RNA sequencing

  Single cell and plasma RNA sequencing for RNA liquid biopsy for hepatocellular carcinoma

  Study EGAS00001005194

• Molecular profiling of DLBCL patients treated in the HOVON84 trial

  Using a comprehensive NGS assay for simultaneous screening of mutations, copy number alterations, and translocations, 5 biology-based risk profiles could be reproduced in a Dutch DLBCL population and validated for outcome prediction. This approach will enable application as a diagnostic tool to select DLBCL patients for risk adapted treatment and help to develop biomarker-driven clinical trials for personalized medicine.

  Study EGAS00001003949

• Genomic-Enabled Medicine for Recurrent Glioblastoma

  In this prospective study, we performed genome-wide tumor/normal exome sequencing and tumor RNA-sequencing for recurrent glioblastoma patients. A subset of patients had both enhancing tumor and non-enhancing tissue sequenced to investigate spatial heterogeneity of this disease. Together, this information builds our understanding of the genomic underpinnings of glioblastoma, and contributes toward the knowledge base for identifying and developing more effective treatments for patients with glioblastoma.

  Study phs001460

• Germline mutations in the transcription factor IKZF5 cause thrombocytopenia.

  To identify novel causes of hereditary thrombocytopenia, we performed a genetic association analysis of whole-genome sequencing data from 13,037 individuals enrolled in the NIHR BioResource, including 233 cases with isolated thrombocytopenia. We found an association between rare variants in the transcription factor encoding gene IKZF5 and thrombocytopenia. We report five causal missense variants in or near IKZF5 zinc fingers (Znfs), of which two occurred de novo and three co-segregated in three pedigrees. A canonical DNA-Znf binding model predicts that three of the variants alter DNA recognition. Expression studies showed that chromatin binding was disrupted in mutant compared to wild-type (WT) IKZF5 and electron microscopy revealed a reduced quantity of alpha granules in normally sized platelets. Proplatelet formation (PPF) was reduced in megakaryocytes (MKs) from seven cases relative to six controls. Comparison of RNA-seq data from platelets, monocytes, neutrophils and CD4 T-cells from three cases and 14 healthy controls showed 1,194 differentially expressed genes in platelets but only four DEGs in each of the other blood cell types. In conclusion, IKZF5 is a novel transcriptional regulator of megakaryopoiesis and the eighth transcription factor associated with dominant thrombocytopenia in humans.

  Study EGAS00001003736

• Whole genome sequence and RNA-seq data from paired tumour and germline samples from mesothelioma patients.

  Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with RNA sequencing (RNA-seq) analysis of the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials. We analysed somatic mutation and RNA-seq data from 229 MPM samples, including 58 MPM samples that had undergone WGS from our own institutions, together with other published data. This combined analysis identified somatic driver genes, including newly identified candidate genes. Whole genome doubling was a frequent event that correlated with shorter survival. Mutational signature analysis revealed dominant signatures and showed that defects in homologous recombination repair were infrequent in our cohort. Within the tumour immune environment we identified high M2 macrophage infiltrate linked with MMP2, MMP14, TGFB1 and CCL2 expression, representing an immunosuppressive environment. A small subset of samples had a higher proportion of CD8 T cells and a high cytolytic score, suggesting a ‘hot’ immune environment which is independent of the somatic mutations. We propose that our findings on genomic changes and subtypes of immune microenvironments may influence therapeutic planning in the future.

  Study EGAS00001005196

• A single-cell atlas of the early COPD lung

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

  Dataset EGAD50000001001

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

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

  Dataset EGAD00001002207

• IG-MYC ALL - DNA and RNA sequencing

  The dataset is composed by the raw RNA sequencing (n=6), targeted DNA sequencing (n=18) and whole exome sequencing (n=17) from 19 patients with IG-MYC-rearrangements.

  Dataset EGAD00001008705

• WGS and WES of 78 pairs Chinese gastric cancer

  Gastric Cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with 3 primary tumours and 2 matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC).

  Dataset EGAD00001001118

• RNA-seq of iPSC-derived oligodendrocytes of individuals with and without t(1;11) translocation

  This dataset contains high-throughput RNA-sequencing of 14 samples, each sample comprising oligodendrocytes derived from human induced pluripotent stem cells, from individuals with and without a balanced t(1;11) translocation which substantially increases risk of major mental illness. 5 samples derive from 2 control individuals, and 9 samples from 3 individuals carrying the translocation. Libraries were prepared from each total-RNA sample using the TruSeq Stranded Total RNA with Ribo-Zero kit. Libraries were then sequenced using the NextSeq 500/550 High-Output v2 (150 cycle) Kit on the NextSeq 550 platform. Raw paired-end sequencing data is stored in two FASTQ files per sample.

  Dataset EGAD00001006341

• Y_chromosome_mis_segregation_in_the_DLD_1_cell_line

  Study of the well-established DLD-1 colorectal cancer cell line, engineered with an inactivatable Y centromere that leads to mis-segregation. The goal is to gain insights into the mechanism of chromothripsis due to chromosome mis-segration.

  Study EGAS00001002551

• Heterogeneous endocrine cell composition defines human islet functional phenotypes

  Phenotyping and genotyping initiatives within the Integrated Islet Distribution Program (IIDP), the largest source of human islets for research in the U.S., provide standardized assessment of islet preparations distributed to researchers, enabling the integration of multiple data types. Data from islets of the first 299 organ donors without diabetes, analyzed using this pipeline, highlights substantial heterogeneity in islet cell composition associated with hormone secretory traits, sex, reported race and ethnicity, genetically predicted ancestry, and genetic risk for type 2 diabetes (T2D). While α and β cell composition influenced insulin and glucagon secretory traits, the abundance of δ cells showed the strongest association with insulin secretion and was also associated with the genetic risk score (GRS) for T2D. These findings have important implications for understanding mechanisms underlying diabetes heterogeneity and islet dysfunction and may provide insight into strategies for personalized medicine and β cell replacement therapy.

  Study EGAS50000000697

• Multi-omic dataset of neuroendocrine neoplasm organoids

  This dataset corresponds to one of the first biobanks for the understudied neuroendocrine neoplasms from multiple grades and body sites (lung, pancreas, small intestine). It contains whole-genome sequencing data for original tumors, patient-derived tumor organoids at multiple passages, and matched normal tissue, and RNA-seq data for the original tumor and patient-derived tumor organoids.

  Study EGAS00001005752

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

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

  Study EGAS00001007635

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

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

  Study EGAS00001005478

• Epigenetic characterization of patient-derived glioblastoma stem cell (GSC)

  ATAC-Seq data on 43 samples of glioblastoma stem cells mapped to hg19. Fastq files are available. PMID: 33427645

  Dataset EGAD50000002603

• Uncovering the potential of circulating tumor DNA for pediatric precision oncology

  Pediatric solid high-risk malignancies mostly lack molecular biomarkers for early tumor detection, assessment of minimal residual disease or therapy monitoring. Small patient numbers, limited sample volumes, low tumor mutational burden, and few recurrent alterations in pediatric tumors pose further challenges to liquid biopsy analyses for this patient population. Within the prospective, multinational molecular profiling program INFORM, we collected liquid biopsies from 130 children patients followed by optimized isolation of cell-free DNA (cfDNA). CfDNA was subjected to whole-genome, whole-exome, and targeted panel sequencing applying liquid biopsy-adapted protocols. Integration with tissue-derived molecular information and orthogonal comparison revealed low-coverage whole genome sequencing (lcWGS) as a reliable method for tumor detection. In silico integration of fragment length with differentially weighted genome segment alterations into a ctDNA estimation score (CES) significantly increased sensitivity and specificity to 95% and allowed for plasma-based tumor detection in 93% of patients. Performance of whole exome sequencing (WES) and panel sequencing for detection of molecular targets being predictive for matched treatment responses varied between groups of high-risk entities and cumulative evidence for presence of cancer by all three methods was found in 92% of patients. In-depth analyses for selected patients also demonstrated great the potential of liquid biopsies to decipher temporal and spatial tumor evolution. This study establishes improved methods for liquid biopsy analyses in pediatric oncology and provides the rationale for well-informed implementation of these approaches in future clinical trials to improve the clinical management of high-risk pediatric cancer patients.

  Study EGAS50000000393

• TSCA-LI amplicon sequencing of called variants in WXS data of DSALL.

  Targeted resequencing of samples was done with TruSeq custom amplicon low input kit (TSCA-LI, Illumina). The oligo capture probes were designed to include a prefix of 8 random nucleotides at the 5 end of each probe. The assay is designed such that each targeted locus is annealed with two probes, resulting in amplicons tagged with unique molecular identifiers (UMI) (22) of 16 bases. Raw FASTQ sequencing files were processed as following: (a) The first 8 bases were trimmed from each read and recorded with the corresponding base quality scores (BQ) in the attribute field. (b) Reads were aligned with BWA. (c) First round of PCR duplicate cleaning was performed with picard tools markDuplicates using the parameters BARCODE_TAG=BC TAGGING_POLICY=All REMOVE_DUPLICATES=true (d) Since in the previous step only duplicate reads with identical UMIs were removed, a second pass of filtering was done. Reads with identical mapping were considered unique only if their corresponding UMIs were different in at least 3 positions (i.e., UMI edit distance &gt; 2). (e) Paired-end read pairs overlapping genomic positions were clipped to avoid overestimation of the sequencing coverage using bamUtils clipOverlap.

  Dataset EGAD00001003275

• Transcriptomic analysis of metastatic colorectal cancer

  Metastatic colorectal cancer (mCRC) is the main cause of CRC mortality, with limited treatment options. Although immunotherapy has benefited some cancer patients, mCRC typically lacks the molecular features that respond to this treatment. However, recent studies indicate that the immune microenvironment of mCRC may be modified to enhance the effect of immune checkpoint inhibitors. This dataset was used to explore the metastatic immune microenvironment by comparing immune cell populations in colorectal liver (CLM), lung (mLu) and peritoneal (PM) metastases.

  Dataset EGAD50000000926

• snRNA-seq in white matter post-mortem tissue from MS and controls

  This Dataset is currently hosted by the European Nucleotide Archive. To access the data contained within the Dataset please follow the link below: https://www.ebi.ac.uk/ena/browser/view/PRJEB39323 Dataset consists of 20 snRNA-seq bam files from 10X v2. 5 samples from postmortem white matter tissue from non-neurological controls and15 samples from different MS lesions from the white matter tissue of 4 postmortem progressive MS patients.

  Dataset EGAD00001004544

• RNA-seq data from Follicular Lymphoma samples

  Dataset included RNA-seq data (Two Fastq files per sample as paired end sequencing was performed) from ribosomal-depleted total RNA in 28 Follicular Lymphoma (FL) criopreserved samples to analyze long non-coding RNA and coding transcript expression profiles. Sample metadata is referred to histological groups of FL tumors (FL1-3A versus FL3B/DLBCL) either in tumor purified cell samples (N=12) as in unpurified tumor samples including normal cells of the lymph node microenvironment (N=16).

  Dataset EGAD00001004109

• SAPCS Blood RNA-seq of prostate cancer patients

  The study aims to quantify the gene expression in blood samples in 20 prostate cancer patients under the Southern African Prostate Cancer Study (SAPCS). The objective is to identify a list of differentially expressed genes.

  Study EGAS50000000702

• Breast Cancer -Very young women with ER+ tumor

  Corresponding data set is composed of whole exome sequencing of Korean ER positive breast cancer under 35. This set provides 100 alignment files from normal-tumor paired whole exome sequencing of 50 patients. This is a part of total project data set.

  Dataset EGAD00001002256

• Long-read mRNA sequencing of retinal organoids

  Long-read (PacBio) sequencing of two retinal organoid samples. One sample was treated with cyclohexamide. Files are ccs BAM format files generated by a Sequel IIe machine.

  Dataset EGAD50000000100

• CMMRD tumors sequencing data

  Whole exome sequencing data from the tumors of individuals with constitutional mismatch repair deficiency. These are 16 tumors from the bigger study of 41 tumors in total (from 17 individuals in total).

  Dataset EGAD50000000113

• VIKING Health Study - Shetland 30X WGS

  30x whole genome sequencing of samples from the VIKING Health Study - Shetland. 500 DNA samples were sequenced using the Illumina HiSeq X system. FASTQ files are deposited

  Dataset EGAD00001005378

• Homologous recombination deficient breast cancers

  Exome sequencing data from homologous recombination deficient primary breast cancers as assessed by the functional RAD51 based HR test. There are 12 tumour samples, of which 10 also have matching normal.

  Dataset EGAD00001003929

• Human tumour bulk RNA-seq

  We profiled 18 high-grade gliomas patient tumor samples by bulk RNA-seq. The raw fastqs are provided.

  Dataset EGAD00001006098

• Epigenomic profile of diverse cancer

  The samples are from patients of multiple cancer types. The library preparation protocol was developed by the laboratory. The DNA libraries were then sequenced with 150bp paired-end reads.

  Dataset EGAD00001006124

• APL nanopore sequencing data

  APL nanopore sequencing data are deposited into 2 data formats: 1. CRAM files 2. h5 files

  Dataset EGAD00001008146

• Mutational_Signatures_of_relapse_in_rectal_cancer_FFPE_samples_in_the_CR07_clinical_trial

  The CRO7 clinical trial recruited patients with clinically operable rectal adenocarcinoma. Patients were randomized to either pre-operative short course surgery followed by chemo-radiotherapy only in those patients at high risk of local relapse. Patients in both arms the received standard %-FU based adjuvant chemotherapy as per local policy. We intend to use FFPE derived DNA from the primary tumours to identify patterns of mutations or copy number alterations that are predictive of local or distant relapse.

  Study EGAS00001000651

• Genomic Analyses of Germline and Somatic Variation in High-Grade Serous Ovarian Cancer

  The goal of this study was to identify and characterize germline and somatic genetic variation in women with high grade serous ovarian cancers treated at a single cancer center and their associations with relapse-free and overall survival. We conducted paired tumor/normal targeted next-generation sequencing of 577 genes in pathways of DNA repair, response to DNA damage, cell-cycle regulation, programmed cell death, MAPK, and P13K/AKT/MTOR signaling in 114 tumors from 71 women. In addition, we investigated single copy number alterations (SCNAs) and loss of heterozygosity in a subset of 61 tumors. We validated our results with data from ovarian tumors in TCGA. Our results were similar to other studies of high-grade serous carcinomas. As an example, we found that approximately one third of the tumors harbored loss of function variants in homologous recombination genes and that &gt;90% had TP53 somatic mutations. Through GISTIC analysis of the OncoScan data on tumor DNA from 61 cases, we identified several regions of high copy number alterations including including NOTCH3 and PIK3R2 that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. We identified few changes in mutation profiles where we had multiple tissues, either from multiple surgeries or from the primary site to metastatic sites within the same surgery. However, we did not investigate copy number alterations in multiple tissues from the same individuals, and so it may be that copy number alterations are more important. Data available through dbGAP will be the BAM files and the phenotypic data on the tumor samples, the age, race, ethnicity of the participants and their outcomes, and the Oncoscan OSCHP files.

  Study phs003198

• Amplicon-based sequencing of drug resistant organoids

  A BRAF V600E colorectal organoid which is sensitive to MAP kinase inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a combination of Trametinib, Dabrafenib and Cetuximab. Single cell derived organoids 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 from a screen in 2 2D BRAF V600E colorectal cell lines. Pools of resistant clones were also sequenced.

  Dataset EGAD00001003248

• Whole genome sequencing of core-binding factor leukemia

  Pediatric de novo acute myeloid leukemia (AML) is a heterogeneous disease that can be divided into clinically distinct subtypes based on the presence of specific chromosomal abnormalities or gene alterations. One of the best characterized subtypes of AML involves leukemias with alterations of the core-binding factor (CBF)-complex, which comprises the FAB subtypes M2 and M4Eo and associates with a favorable outcome. Patients with the AML M2 subtype harbor a translocation between chromosomes 8 and 21 [t(8;21)] that yields the chimeric fusion gene RUNX1(AML1)-RUNX1T1(ETO), while patients with AML M4Eo express the chimeric fusion gene CBF&#946;-SMMHC(MYH11) as a result of an inversion/translocation event of chromosome 16 [inv(16)/t(16;16)]. In an effort to define the total complement of genetic changes in CBF-leukemia, we performed paired-end whole genome sequencing (WGS) on diagnostic leukemia blasts and matched germ line samples from 17 pediatric CBF-leukemia patients using the Illumina platform. Somatic alterations, including single nucleotide variations (SNVs) and structural variations (SVs), including insertions, deletions, inversions, and inter- and intra-chromosomal rearrangements, were detected using complementary analysis pipelines (Bambino, CREST and CONSERTING). Recurrent screening of identified mutations will be performed in a cohort of approximately 94 cases of CBF-leukemias.

  Study phs000414

• The Genomic Landscape of Core-Binding Factor Acute Myeloid Leukemias

  Pediatric de novo acute myeloid leukemia (AML) is a heterogeneous disease that can be divided into clinically distinct subtypes based on the presence of specific chromosomal abnormalities or gene alterations. One of the best characterized subtypes of AML involves leukemias with alterations of the core-binding factor (CBF)-complex, which comprises the FAB subtypes M2 and M4Eo and associates with a favorable outcome. Patients with the AML M2 subtype harbor a translocation between chromosomes 8 and 21 [t(8;21)] that yields the chimeric fusion gene RUNX1(AML1)-RUNX1T1(ETO), while patients with AML M4Eo express the chimeric fusion gene CBFβ-SMMHC(MYH11) as a result of an inversion/translocation event of chromosome 16 [inv(16)/t(16;16)]. In an effort to define the total complement of genetic changes in CBF-leukemia, we performed paired-end whole genome sequencing (WGS) on diagnostic leukemia blasts and matched germ line samples from 17 pediatric CBF-leukemia patients using the Illumina platform. Somatic alterations, including single nucleotide variations (SNVs) and structural variations (SVs), including insertions, deletions, inversions, and inter- and intra-chromosomal rearrangements, were detected using complementary analysis pipelines (Bambino, CREST and CONSERTING). Recurrent screening of identified mutations will be performed in a cohort of approximately 94 cases of CBF-leukemias.

  Study EGAS00001000349

• Profiling Chromatin Accessibility in Humans Using Adenine Methylation and Long-Read Sequencing

  This dataset includes raw nanopore, base-called, and 6mA frequency data for EcoGII-treated NA12878 and MCF7 chromatin samples. It also includes raw nanopore data for the HG002 EcoGII-treated DNA.

  Study EGAS00001007852

• Stressors and Health Study

  ObjectivesThe objectives of the Stressors and Health Study were to: (1) examine the prevalence of stressors and health outcomes and (2) assess differences in the associations between multi-level stressors and health outcomes, and (3) explore the protective and adaptive factors in the associations between multi-level stressors and health outcomes. Background Stressors have been posited to explain disparities in health. However, no surveys to our knowledge have simultaneously collected multiple stressors at various levels and the coping strategies used to deal with these stressors. Measuring these factors can provide a better understanding of the stressors experienced by specific groups and the impact that these experiences have on their health and health practices. In addition, exploring the various resilience and coping strategies employed to deal with stressors can help design appropriate interventions to reduce health disparities. Participants Participants included 1000 White, 1000 Black or African American, 1000 Latino or Hispanic, 1000 Asian, 500 American Indian or Alaska Native, 500 Native Hawaiian or Pacific Islander, and 500 mixed or multi-race adults (&#8805;18 years) across the United States. Design The Stressors and Health Study is a cross-sectional online survey of adults across the US. A sampling frame (target population) of US residents based on the American Community Survey (ACS) was constructed using a rigorous two-step sampling matching approach to establish national representation.

  Study phs004019

• FFPE WGS for optimizing mutation signature extraction from archival HGSC samples

  HGSC cases were selected for which matched fresh frozen and FFPE samples were available from the same tissue specimens. Fresh frozen, FFPE and normal blood were subject to WGS for the purpose of assessing the possibility of using FFPE WGS in place of fresh frozen for somatic mutation calling

  Study EGAS00001007521

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

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

  Study EGAS00001005529

• Transcriptional and Epigenetic Profiles of Male Breast Cancer at Single-Cell Resolution Nominate Salient Cancer Specific Enhancers

  We performed matched single-cell RNA sequencing (scRNA-seq) and single-cell chromatin accessibility sequencing (scATAC-seq) for two fresh human tumors collected from male breast cancer patients. The integration of these datasets revealed the intratumoral heterogeneity in both transcription and chromatin accessibility for each male breast cancer patient and allowed for comparisons to be made between male and female breast cancer. We hope these data will be a useful reference in the field of breast oncology, specifically for the treatment of males, as few studies have explored male breast cancer genetics.

  Study phs003006

• RNA-seq of longitudinal human blood and nose swab samples from a controlled human infection experiment with SARS-CoV-2 virus

  Controlled human infection experiments enable longitudinal profiling of immune responses to a pathogen. 36 healthy volunteers aged 18-29 years, with no evidence of previous infection or vaccination, were inoculated with SARS-CoV-2 virus and quarantined for 14 days. Blood samples for RNA sequencing were collected into PAXgene tubes before virus challenge, 6 hours after challenge, daily thereafter for 14 days and on day 28. Mid-turbinate nose swabs for RNA sequencing were collected before virus challenge, and on days 1, 3, 5, 7, 10 and 14 after challenge, preserved in RNAprotect.

  Study EGAS50000000667

• Multiplexing cortical brain organoids for the longitudinal dissection of developmental traits at single cell resolution

  Dissecting human neurobiology at high resolution and with mechanistic precision requires a major leap in scalability, given the need for experimental designs to multiple individuals and, prospectively, population cohorts. To lay the foundation for this, we have implemented and benchmarked complementary strategies to multiplex brain organoids by pooling cells from different pluripotent stem cell lines (PSC) either during organoid generation (mosaic models) or before single cell-RNAseq library preparation (downstream multiplexing). We have also developed a new computational method, SCanSNP, and a consensus call to deconvolve cell identities, overcoming current criticalities in doublets prediction and low quality cells identification. We validated both multiplexing methods for charting neurodevelopmental trajectories at high resolution, thus linking specificity to genetic variation. Finally, we modelled their scalability across different multiplexing combinations and showed that mosaic organoids represent an enabling method for high-throughput settings. Together, this multiplexing suite of experimental and computational methods provides a highly scalable resource for disease modelling.

  Study EGAS50000000698

• Genomic Characterization of Brain Metastases from Lung Cancer

  Metastatic disease to the brain is associated with a poor prognosis. Our understanding of the genetic drivers of metastasis remain limited. Whole-exome sequencing was performed from brain metastases from lung adenocarcinoma to identify putative drivers of metastatic progression.

  Study phs001920

• Comprehensive analyses of genetic aberrations in gastroenterological tumors

  Intestinal metaplasia (IM) is a risk factor of gastric cancer in gastric mucosa with Helicobacter pylori infection. To explore the susceptibility to the cancer development in pure gastric IM, we investigated landscape of genetic alterations in gastric single-glands with IM.

  Study JGAS000269

• Genetics of Microcephalic Osteodysplatics Primordial Dwarfism

  This project aims to find causal variants in 50 patients diagnosed with Microcephalic Osteodysplastic Primordial Dwarfism (MOPD), of presumed recessive inheritance performing whole exome sequencing to ~50x mean depth. This is a collaboration with Prof A. Jackson, MRC Human Genetics Unit, Edinburgh

  Study EGAS00001000064

• RNAseq_of_Human_Organoid_Lines

  The study will use RNAseq to aid in benchmarking different culture conditions in a set of genetically annotated human organoid lines. The data will be used to assess whether there is any clonal differences introduced when culturing these lines in different conditions.

  Study EGAS00001003888

• Whole_Genome_Sequencing_of_Human_Organoid_Lines

  The study will use WGS to aid in benchmarking different culture conditions in a set of genetically annotated human organoid lines. The data will be used to assess whether there is any clonal differences introduced when culturing these lines in different conditions.

  Study EGAS00001003538

• Bulk 3' mRNA-Seq of dome and suspension tubuloids

  Bulk 3' mRNA-sequencing of human kidney tubuloids grown in dome and suspension culture for the identification of transcriptional differences associated with culture method, passage, and donor. Tubuloids were generated from 4 separate donors and collected for sequencing at day 7 of passage 3, 4, and 5 in dome and suspension culture.

  Study EGAS50000001629

• cfRRBS on cfDNA from pediatric cancer patients

  This dataset contains cell-free reduced representation bisulfite sequencing data from 60 pediatric cancer samples. Files are provided in fastq format. Samples were sequenced on a NextSeq 500.

  Dataset EGAD00001005928

• Deep whole genome ctDNA chronology of treatment-resistant prostate cancer

  Circulating tumor DNA (ctDNA) in blood plasma is an emerging tool for clinical cancer genotyping and longitudinal disease monitoring. We performed deep whole-genome sequencing of serial plasma and synchronous metastases in patients with aggressive prostate cancer. We comprehensively assess all classes of genomic alterations and demonstrate that ctDNA harbors multiple dominant populations whose evolutionary histories frequently indicate whole-genome doubling and shifts in mutational processes. Although tissue and ctDNA showed concordant clonally-expanded cancer driver alterations, each individual metastasis contributed only a minor share of total ctDNA. By comparing serial ctDNA before and after clinical progression on potent androgen receptor (AR) pathway inhibitors, we reveal population restructuring converging solely on AR augmentation as the dominant genomic driver of acquired treatment-resistance. Finally we leverage nucleosome footprints in ctDNA to infer mRNA abundance in synchronously biopsied metastases, including treatment-induced changes in AR pathway transcriptional activity.

  Dataset EGAD00001008460

• Table of gene-level RNA counts from newborn screening dried blood spot samples

  Table of gene-level RNA counts from 21 newborn screening dried blood spot (DBS) samples. These DBS samples were obtained from extremely low gestional age newborns, where 10 of them were affected by a fetal inflammatory response (FIR) before birth, and 11 were unaffected. Total RNA was sequenced using an Illumina NextSeq-500 instrument. The sample preparation protocol included the depletion of rRNA and globin mRNA using the Globin Zero Gold rRNA Removal Kit from Illumina. Libraries were prepared using the NebNext Ultra TM II Directionl RNA LIbrary Prep Kit (New England Biolabs). Rows correspond to genes and columns to samples, where there is an additional column (BS13sub), corresponding to sample BS13, which was downsampled to 1/4 of its original depth.

  Dataset EGAD00010001707

• Single-nuclei gene-expression analysis of pheochromocytoma and paraganglioma links tumor subtypes with tumor microenvironment

  This dataset contains raw sequencing reads in FASTQ format from single-nuclei (30 samples) and bulk tissue (40 samples) transcriptome sequencing of pheochromocytoma and paraganglioma tissue specimens. Additionally, data from single-nuclei sequencing of two normal adrenal medulla specimens is included.

  Dataset EGAD00001008403

• Mutational signature in colorectal cancer induced by genotoxic pks+ E. coli

  Various species of the intestinal microbiota have been associated with the development of colorectal cancer (CRC), yet a direct role of bacteria in the occurrence of oncogenic mutations has not been established. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin. This compound alkylates DNA on adenine residues and induces double strand breaks in cultured cells. Here, we exposed human intestinal organoids to genotoxic pks+ Escherichia coli by repeated luminal injection over a period of 5 months. Whole genome sequencing (WGS) of clonal organoids before and after this exposure reveals a distinct mutational signature, absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature is detected in a subset of 3668 human metastatic cancer genomes, predominantly in a subset of CRC cases. Our study describes a distinct mutational signature in CRC and implies that the underlying mutational process directly results from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.

  Study EGAS00001003934

• Genomic sequencing data for PNG15 and PNG16

  This study includes both long- and short-read sequencing data for PNG15 and PNG16 as well as their phased haplotype assemblies.

  Study EGAS50000001105

• Activation-Induced Marker (AIM) Sequencing of Healthy Human T Cells

  T cells from five healthy human donors were stimulated with a peptide pool (CEFX, JPT) and anti-CD28/CD49d co-stimulation. Cells were then sorted based on activation (OX40 and PD-L1 for CD4s, CD137 for CD8s) and labeled with corresponding hashing antibodies prior to sequencing. In total, this dataset encompasses 42,370 cells (12,743 activation-induced marker (AIM)-positive, 15,369 AIM-negative, 14,258 Mock) for CITE-sequencing and TCR-sequencing of sorted activated, unactivated, and mock T cells derived from blood.

  Study phs004043

• 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.

  Dataset EGAD50000000373

• RNASeq of bone marrow endothelial cells upon regeneration, (fetal) niche formation, and steady-state.

  Comprehensive transcriptional characterization of bone marrow endothelial cells by RNA sequencing was performed to determine the molecular properties/signatures of endothelium during bone marrow recovery and niche formation. Regenerative bone marrow endothelium was FACS-isolated from bone marrow aspirates of Acute Myeloid Leukemia patients 17 days after receiving chemotherapy (n=3). Niche-forming endothelial cells were FACS-isolated from fetal bones (gestational age 15-20 weeks) (n=3). Healthy adult bone marrow endothelial cells (n=7) were used as steady-state controls. cDNA was prepared using the SMARTer procedure (SMARTer Ultra Low RNA Kit, Clonetech). The provided file type is FASTQ.

  Dataset EGAD00001003904

• A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer (D-Beyond)

  This is a prospective, single arm phase IIa trial in which patients with early breast cancer will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart (maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be collected at baseline and at surgery. Post-operative treatment will be at the discretion of the investigator.Primary objective: to determine if a short course of RANKL inhibition with denosumab can induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry (IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.

  Dataset EGAD00001004391

• Genomic signatures define three subtypes of EGFR-mutant stage II-III non-small-cell lung cancer with distinct adjuvant therapy outcomes

  This dataset contains targeted sequencing data of 204 surgical samples from resected NSCLC. Genomic profiling identifies five predictive biomarkers, which is then integrated into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score. The MINERVA score categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy. This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

  Dataset EGAD00001008157

• MPM cell lines

  RNA-sequencing data for 12 MPM cell lines treated with 0.1% DMSO or 1 µM palbociclib for 9-10 days. Experiment was performed in duplicates for sensitive cells (MPM08, MPM21, MPM38, MPM57, MPM59, Meso11, Meso13, Meso34 and Meso56) and only once for resistant cells (MPM31, MPM34 and MPM36) except for Meso11 which was done in triplicates. For Meso11, Meso13, Meso34 and Meso56, a drug washout of 48 hours was also performed. 4 MPM cell lines (MPM31, MPM34, MPM59 and MPM66) were also analyzed in untreated condition. 2 FASTQ files for each sample (n=56) (paired)

  Dataset EGAD00001008741

• Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis

  Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 mutations. We performed whole-genome sequence (WGS) analysis of tumors from 22 TP53 mutation carriers. We observed somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy. We identified near-ubiquitous early loss of heterozygosity of TP53, with gain of the mutant allele. This occurred earlier in these tumors compared to tumors with somatic TP53 mutations, suggesting the timing of this mark may distinguish germline from somatic TP53 mutations. Phylogenetic trees of tumor evolution, reconstructed from bulk and multi-region WGS, revealed that LFS tumors exhibit comparatively limited heterogeneity. Overall, our study delineates early copy number gains of mutant TP53 as a characteristic mutational process in LFS tumorigenesis, likely arising very early in life or in utero.years prior to tumor diagnosis.

  Study EGAS00001005982

• Unraveling mutagenic processes influencing the tumor mutational patterns of individuals with Constitutional Mismatch Repair Deficiency

  Constitutional mismatch repair deficiency (CMMRD), caused by bi-allelic germline variants in one of the mismatch repair (MMR) genes, is a childhood cancer predisposition syndrome that often results in the development of multiple tumors early in life. A better understanding of mutational processes driving subsequent CMMRD tumors could advance optimal treatment. Therefore, we performed a genomic characterization of 41 tumors from 17 individuals with CMMRD. Mutational patterns in these tumors were found to be influenced by multiple factors, including the affected MMR genes, tumor types and somatic polymerase proofreading mutations. Temozolomide treatment left prominent mutational signatures in two second primary hematologic malignancies. Furthermore, a novel indel signature was found in 54% of the tumors, characterized by one base pair cytosine insertions in cytosine homopolymers. In conclusion, the analysis of sequential tumors in individuals with CMMRD reveals diverse mutational patterns influenced by the underlying mutated MMR gene, tumor type and treatment history.

  Study EGAS00001007660

• Transcriptomic data of a discordant monozygotic twin pair for ALS

  The dataset contains bulk RNAseq data of a discordant monozygotic twin pair for ALS; in particular the matrix with gene names and TPM counts for each sample. For both healthy and ALS twin, RNA sequencing was performed on RNA samples collected at two different time points (T1 and T2), for a total of seven samples. RNA extracted from PBMCs was used for library preparation according to Illumina TruSeq Stranded mRNA kit and processed on Illumina NextSeq 550 sequencer. Reads were aligned to the reference human genome GRCh38/hg38 and annotations were provided by the Ensembl v100 database.

  Dataset EGAD50000001330

• Genomic Translation for ALS Care (GTAC) - WGS

  To look for genetic correlates of disease progression, the GTAC study recruited patients with motor neuron disease from 13 academic medical center clinics and followed them longitudinally for up to 5 years. Participants were regularly assessed for changes in respiratory function, the ALS Functional Rating Scale, and the ALS Cognitive Behavioral Scale. Participants underwent PCR-free whole genome sequencing on the Illumina NovaSeq, as well as repeat-prime PCR assessment of the C9ORF72 repeat expansion. Participants had PBMCs and whole blood RNA banked for future correlative studies.

  Study phs002973

• DNA Methylation-based diagnostic biomarkers for ESCC in Han Chinese population

  DNA methylation-based biomarkers were suggested to be promising for early cancer diagnosis. However, DNA methylation-based biomarkers for esophageal squamous cell carcinoma (ESCC), especially in Chinese Han populations have not been identified and evaluated quantitatively. To identify the candidate DNA-methylation based biomarkers for ESCC diagnosis, we performed the targeted bisulfite sequencing analysis in this study. Based on these 94 pairs of ESCC tumors and adjacent normal tissues, we found out that ADHFE1, EOMES, SALL1 and TFPI2 could be an effective methylation-based assay for ESCC diagnosis.

  Study EGAS00001003158

• Whole Genome Sequence and RNASeq Samples for Lung Cancer

  Short Read Whole Genome Sequence and RNASeq Samples for Lung Cancer

  Study EGAS00001007832

• Mantle cell lymphoma exomes and genomes for finding driver mutations

  Tumor and normal exomes for 51 MCL patients and tumor and normal genomes for 34 MCL patients.

  Dataset EGAD00001006159

• The role of MALT1 in driving IBN resistance in MCL

  The bulk RNA-seq dataset was generated for the cell lines below and used for two major purposes: 1. DEG analysis and GSEA analysis comparing IBN-R and IBN-S cells 2. DEG analysis and GSEA analysis comparing MCL cells with/without MI-2 treatment.

  Study EGAS00001006832

• Whole genome sequencing of matched patient sample sets of normal and tumor DNA

  Sixteen matched, male and female patient sample sets, each comprising normal DNA, tumor DNA, and RNA, were processed for storage comparison studies. Upon receipt, 10 μl quality control aliquots were prepared from each sample. DNA samples were characterized using Qubit dsDNA High Sensitivity assay for quantification, Genomic DNA TapeStation for integrity assessment (DIN scores), and NanoDrop for purity evaluation. RNA samples were analyzed using Qubit RNA High Sensitivity assay, RNA TapeStation (RIN scores), and NanoDrop. Each sample was divided equally by volume for parallel processing.

  Dataset EGAD50000002441

• Sequence analysis of colorectal serrated lesions

  Recent studies have shown that colorectal serrated lesions, which include sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs), are precursors of colorectal cancer. However, the molecular mechanisms underlying the carcinogenesis, particularly in TSAs, remain largely uncharacterized. To clarify their molecular and clinicopathological characteristics, we performed mutation and methylation analyses of cancer-associated genes in 78 serrated lesions, including TSAs, SSAs and microvesicular hyperplastic polyps. Target exon sequence analysis was performed with 39 genes, including genes known to be frequently mutated in colorectal cancers and/or serrated lesions. We also used bisulfite pyrosequencing to assess the methylation status of various cancer-associated genes and marker genes of the CpG island methylator phenotype (CIMP). The prevalence of mutations in genes associated with Wnt signaling was significantly higher in TSAs than SSAs (65% vs. 28%, p < 0.01). Among those, RNF43 mutations were observed in 38% of TSAs and 17% of SSAs. In immunohistochemical studies of 39 serrated lesions, the prevalence of abnormal nuclear ?-catenin accumulation was significantly higher in TSAs (57%) than SSAs (8%) (P = 0.01). SMOC1 methylation was detected in 54% of TSAs but in no SSAs (p < 0.01). Additionally, SMOC1 methylation was more prevalent among TSAs with KRAS mutation (82%) than with BRAF mutation (38%, p = 0.03). Lesions with CIMP-high or RNF43 mutations were detected only in TSAs with BRAF mutation, suggesting two distinct carcinogenic pathways in TSAs. Mutations in genes associated with Wnt signaling play a greater role in the carcinogenesis of TSAs than SSAs.

  Study JGAS000217