11750 results for "cancer rna-seq"

in 32.64 milliseconds.

• The University of Hong Kong Gastric Cancer XClone Study Single Cell CNV Data

  Single cell encapsulation and DNA libraries were prepared by Chromium™ Single Cell DNA Reagent Kits and Chromium™ Single Cell C and D Chip Kits.

  Dataset EGAD00001015383

• Genome and transcriptome sequence data from a diffuse aarge B-cell lymphoma (relapse) tumor patient

  Genome and transcriptome sequence data from a diffuse large B-cell lymphoma (relapse) patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015308

• Genome and transcriptome sequence data from a relapsed blastic plasmacytoid dendritic cell neoplasm tumor patient

  Genome and transcriptome sequence data from a relapsed blastic plasmacytoid dendritic cell neoplasm patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015312

• Genome and transcriptome sequence data from a metastatic malignant peripheral nerve sheath tumor tumor patient

  Genome and transcriptome sequence data from a metastatic malignant peripheral nerve sheath tumor patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015322

• Genome and transcriptome sequence data from a CNS non-germinoma germ cell tumour tumor patient

  Genome and transcriptome sequence data from a CNS non-germinoma germ cell tumour patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015327

• sWGS for genome-wide copy number profiling

  Shallow whole-genome sequencing (sWGS) data for the identification of somatic copy number alterations (SCNA) and the estimation of tumor fractions in plasma DNA of metastatic colorectal cancer patients (mCRC).

  Dataset EGAD00001006384

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 9 part 1)

  Whole genome sequencing data of 6 high-grade serous carcinoma (HGSC) patients (11 samples) sequenced with MGISEQ-2000

  Dataset EGAD00001011353

• Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway

  Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. We address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP+ CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8+ T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment. Single cell analysis, spatial transcriptomics and immunohistochemistry reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) is the most affected by chemotherapy. Moreover, functional assays demonstrate that ECM-myCAF isolated from HGSOC reduce CD8+ T-cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, efficient inhibition after treatment of YAP1-signaling pathway in the ECM-myCAF cluster is required to enhance CD8+ T-cell cytotoxicity. Altogether, these data pave the way for novel therapy targeting YAP1 in ECM-myCAF in HGSOC.

  Study EGAS50000000136

• Stability of gut microbiome after COVID-19 vaccination in healthy and immuno-compromised individuals

  Bidirectional interactions between the immune system and the gut microbiota are key contributors to various physiological functions. Immune-associated diseases such as cancer and auto- immunity, and efficacy of immunomodulatory therapies, have been linked to microbiome variation. Although COVID-19 infection has been shown to cause microbial dysbiosis, it remains understudied whether the inflammatory response associated with vaccination also impacts the microbiota. Here, we investigate the temporal impact of COVID-19 vaccination on the gut microbiome in healthy and immuno-compromised individuals; the latter included patients with primary immunodeficiency and cancer patients on immuno- modulating therapies. We find that the gut microbiome remained remarkably stable postvaccination irrespective of diverse immune status, vaccine response, and microbial composition spanned by the cohort. The stability is evident at all evaluated levels including diversity, phylum, species, and functional capacity. Our results in- dicate the resilience of the gut microbiome to host immune changes triggered by COVID-19 vaccination and suggest minimal, if any, impact on microbiome-mediated processes. These findings en- courage vaccine acceptance, particularly when contrasted with the significant microbiome shifts observed during COVID-19 infection.

  Study EGAS50000000179

• Primary Prostate Tumor Tissue DNA Methylation Profiles

  The study cohort includes 525 Caucasian and African American prostate cancer (PCa) patients who underwent radical prostatectomy (RP) as primary therapy for clinically localized adenocarcinoma of the prostate. These patients were previously enrolled in one of two population-based studies: 1) men 40-64 years of age, diagnosed between January 1993 and December 1996; and, 2) men 35-74 years of age, diagnosed between January 2002 and December 2005. Gleason grade and sum, diagnostic PSA, and pathological tumor stage were obtained from the SEER cancer registry. Formalin-fixed paraffin-embedded prostate tumor tissue blocks were obtained from RP specimens and used to make hematoxalin and eosin stained slides, which were reviewed by pathologists to confirm the presence/location of adenocarcinoma. For each patient two 1-mm tumor tissue cores from the dominant lesion that were enriched with >=75% tumor cells were taken for DNA purification. The RecoverAll Total Nucleic Acid Isolation Kit (Ambion/Applied Biosciences, Austin, TX) was used to extract DNA, which was then quantified (PicoGreen), aliquoted onto 96-well plates and shipped to Illumina for DNA methylation profiling using the Infinium® HumanMethylation450 BeadChip.

  Study phs001921

• Genome-Wide Association Studies in Upper Gastrointestinal Cancers (Asian)

  This project aims to conduct genome-wide association studies (GWAS) in two anatomically different upper gastrointestinal (UGI) cancer sites in two populations with distinctly different disease rates and genetic profiles. One population has very high rates for both esophageal squamous cell carcinomas (ESCCs) and gastric cancers (GCs) and is comprised of Asians (the "Asian UGI GWAS"), while the other population has low rates of ESCC and GC and includes non-Asians from the Americas, Europe, and Australia (the "Non-Asian UGI GWAS"). Study participants for the Asian UGI GWAS reported here (Illumina 660W Quad chip) were drawn from 2 studies, the Shanxi Upper Gastrointestinal Cancer Genetics Project (Shanxi) and the Linxian Nutrition Intervention Trial (NIT), a prospective cohort, and included a total of 1898 ESCCs, 1625 GCs, and 2100 controls. For the 2nd phase (8 TaqMan SNPs), additional subjects from Shanxi and NIT as well as subjects from the Shanghai Men's Health Study (SMHS), the Shanghai Women's Health Study (SWHS), and the Singapore Chinese Health Study (SCHS) were also included (217 ESCCs, 615 GCs, 1202 controls). Altogether 2115 ESCCs, 2240 GCs, and 3302 controls were genotyped in this study.

  Study phs000361

• E5103 Correlative Studies

  ECOG-ACRIN E5103 (E5103) was a phase III adjuvant breast cancer trial that randomized 4994 patients with node-positive or high-risk node-negative breast cancer to intravenous doxorubicin and cyclophosphamide every 2 or 3 weeks (at the discretion of treating physician), for four cycles of adriamycin and cyclophosphamide (AC) followed by 12 weeks of weekly paclitaxel (80 mg/m2) alone (Arm A), or to the same chemotherapy with either concurrent bevacizumab (Arm B), or concurrent plus sequential bevacizumab (Arm C). To develop predictive genetic biomarkers for chemotherapy efficacy and toxicities, we have successfully performed genome-wide genotyping and whole exome sequencing in the germline (blood) DNA of 3215 and 672 patients, respectively, from the E5103 trial to investigate the association of genetic variants with chemotherapy efficacy and toxicities. Case and control studies were performed with genome-wide analyses (GWAS) and whole exome analyses (WES) across all arms of E5103 to identify genotypes at single-nucleotide polymorphisms (SNPs) and deleterious gene mutations that were associated with paclitaxel-induced peripheral neuropathy (TIPN). Through GWAS, we have identified a SNP, rs3125923, and through WES, Cytochrome P450 oxidoreductase (POR), that was significantly associated with grade 3-4 TIPN.

  Study phs003201

• Rapid brain tumor classification from sparse epigenomic data

  Although the intraoperative, molecular differential diagnosis of the approximately one hundred different brain tumor entities described to date has been a goal of neuropathology in the last decade, this has not yet been achieved in a clinically relevant time frame of less than one hour after biopsy collection. Recent advances in third-generation sequencing technologies have brought this once-elusive goal within reach. However, established machine learning techniques rely on concepts and methods, impractical for live diagnostic workflows in clinical applications. Here, we present MethyLYZR, a Naïve Bayesian framework enabling fully tractable live classification of cancer epigenomes. MethyLYZR can be run in parallel with an ongoing Nanopore experiment with negligible computational cost and provides clinically relevant and accurate cancer classification results within 15 minutes of sequencing. Therefore, only the time required for DNA extraction and the Nanopore sequencer's maximum parallel throughput remain limiting factors for even faster time-to-results. We demonstrate the potential utility of the MethyLYZR framework not only for the neurosurgical intraoperative use case but also for other oncologic indications and cell-free DNA from liquid biopsies.

  Study EGAS50000000559

• Final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial evaluating peri-operative atezolizumab for early-stage triple-negative breast cancer

  In IMpassion031, adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate (primary endpoint) for stage II/III triple-negative breast cancer (TNBC). Patients with stage II/III TNBC were randomized 1:1 to neoadjuvant chemotherapy plus peri-operative atezolizumab or pre-operative placebo. Descriptive secondary endpoints included event-free, disease-free, and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival HR 0.76, 95% CI: 0.47–1.21). Among patients without pCR, 14/70 (20%) atezolizumab-treated and 33/99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory analyses, pCR was prognostic for long-term outcome. Patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. Adding atezolizumab to chemotherapy for stage II/III TNBC is associated with more favorable long-term outcomes. ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935

  Study EGAS50000000974

• Error-corrected flow-based sequencing at whole genome scale and its application to circulating cell-free DNA profiling

  Differentiating sequencing errors from true variants is a central genomics challenge calling for error suppression strategies that balance costs when sparse material or ultra-rare variants require high-accuracy methods. For example, circulating cell-free DNA (ccfDNA) sequencing for cancer monitoring is limited by sparsity of circulating tumor DNA (ctDNA), abundance of genomic material in samples, library preparation error rates and sequencing errors. Whole-genome sequencing (WGS) can overcome the low abundance of ccfDNA by integrating signal across the mutation landscape, but higher cost limits adoption compared with targeted panels, where ccfDNA abundance limits maximal coverage depths. Here we applied deep (~120x) lower-cost WGS (Ultima Genomics) with analytic error correction for tumor-informed ctDNA detection within the part-per-million range. We further developed high-coverage duplex error-corrected WGS of ccfDNA, achieving 7.7x10-8 error rates, to assess disease burden in melanoma and urothelial cancer patients without matched tumor sequencing. Together, we show that deeply sequenced error-corrected WGS accurately calls somatic variants, demonstrating the feasibility of WGS for tumor-informed and tumor-agnostic ctDNA detection.

  Study EGAS50000000844

• Gut microbiome modulates response to anti PD1 immunotherapy in metastatic melanoma patients

  There is a growing appreciation of the role of the microbiome in cancer, and evidence in pre-clinical models that the gut microbiome may modulate responses to immune checkpoint blockade though this has not been well-characterized in patients. We analyzed the oral (n=86)and gut (n=43) 16S microbiome in melanoma patients on PD-1 blockade. Significant differences were noted in the diversity and composition of the gut microbiome between responders and non-responders in patients with a fecal microbiome sample, with significantly higher alpha diversity and relative abundance of Ruminococcaceae bacteria) in R. Metagenomic studies (n=25) revealed functional differences in gut bacteria in R including enrichment of anabolic pathways. Immune profiling demonstrated enhanced systemic and anti-tumor immunity in patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplant from responding patients. Together, these data have important implications for treatment with immune checkpoint blockade in cancer. The fastq files associated with this dataset are stored at ENA under the following accession numbers: PRJEB22894 (Fecal 16S), PRJEB22874 (Oral 16S), PRJEB22895 (Murine 16S), PRJEB22893 (Fecal WGS).

  Study EGAS00001002698

• Study on the proliferation history of colorectal adenomas

  Mismatch repair (MMR) deficient colorectal adenomas are composed of transformed cells that descend from a common founder and progressively accumulate genomic alterations but their proliferation history is still largely unknown. Here we rebuilt the proliferation history of four MMR deficient colorectal adenomas from male individuals by deep sequencing the X chromosome and mapping the somatic mutations that were progressively acquired during tumor growth. We developed a novel method to call high and low frequency mutations, to cluster them according to their frequencies and rebuild the proliferation trees directly from these mutation clusters using a recursive algorithm. The trees of all four lesions were formed of a dominant subclone that coexisted with other genetically heterogeneous subpopulations of cells. Despite this similar hierarchical organization, however, the growth dynamics varied among and within tumors, likely depending on a combination of tumor-specific genetic and environmental factors. Our study provides insights into the biological properties of individual MMR deficient colorectal adenomas that may influence their growth and also the response to therapy. Extended to other solid tumors, our approach could inform on the mechanisms of cancer progression, thus providing insight into the best choice of cancer treatment methods.

  Study EGAS00001000883

• We performed whole-exome sequencing of 20 samples (10 actinic keratosis and 10 cutaneous squamous cell carcinoma) to investigate a potential relationship between DNA methylation-based subtypes and genetic mutation patterns (Rodriguez-Paredes et al., Nat Commun 2017)

  Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer type and arises from keratinocytes. Most cSCC progress from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain only partially understood. Here we have used Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status of about 850.000 CpGs in epidermal preparations from healthy skin, AK and cSCC. Importantly, we found that the premalignant AK samples displayed classical features of cancer methylomes and were highly similar to cSCC methylomes. Further analysis identified typical features of stem cell methylomes, such as a reduced DNA methylation age, non-CpG methylation and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature was detected only in one half of the AK and cSCC samples, while the other half showed keratin and enhancer methylation patterns that were more closely related to the control epidermis. These findings suggest the existence of two distinct subclasses of AK and cSCC that originate from distinct keratinocyte differentiation stages.

  Study EGAS00001002670

• Comprehensive molecular profiling identifies novel genetic drivers and subtypes underlying medulloblastoma

  Current therapies for medulloblastoma (MB), a highly malignant childhood brain tumor, impose debilitating effects on the developing child, warranting the development of molecularly targeted treatments with reduced toxicities. Prior studies have failed to disclose the full spectrum of driver genes and molecular processes operative in MB or adequately explain heterogeneity among molecular subgroups. Herein, we detail the somatic landscape across 491 sequenced MBs and molecular heterogeneity amongst 1,256 epigenetically analyzed cases, identifying subgroup-specific mutational signatures, driver genes, and pathway alterations including previously unappreciated actionable therapeutic targets. Integrative approaches for assigning driver genes to subgroups explained >65-70% of Group 3 and Group 4, doubling previous knowledge. Novel subtypes underlying Group 3 and Group 4 were differentially enriched for specific driver events, including hotspot in-frame indels targeting KBTBD4 and ‘enhancer hijacking’ driving activation of PRDM6. Thus, application of integrative genomics to an unprecedented cohort of clinical samples derived from a single childhood cancer entity has disclosed a series of new cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for treating MB.

  Study EGAS00001001953

• Longitudinal study of whole blood gene expression in Kenyan children exposed to malaria

  We have collected RNA samples from whole blood of Kenyan children exposed to malaria in the Kilifi region of Kenya. Collections were performed each year from 2015 until 2018. This is a follow-up study to that described in Bediako et al. (in preparation). The SIMS consortium is seeking to identifying the underlying reasons why some children are more susceptible to malaria than others. In this study we hope to track changes in children’s immune systems over time which relate to the number of malaria episodes they experience. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001015405

• Single-cell Transcriptomic and TCR Repertoire Profiling of DENV-specific CD8+ T Cells Across Dengue Disease Severities

  This dataset contains single-cell RNA sequencing (Smart-seq2) and paired TCR repertoire data of sorted dengue virus (DENV)-specific CD8⁺ T cells from individuals with differing clinical outcomes: asymptomatic dengue (AD), dengue fever (DF), and dengue hemorrhagic fever (DHF). Samples were obtained from HLA-A11⁺ and HLA-A24⁺ individuals during acute and convalescent phases, with antigen-specific CD8⁺ T cells isolated using HLA tetramers loaded with immunodominant DENV epitopes. The study identifies phenotypically distinct T cell subsets associated with disease severity, TCR avidity, and antigen reactivity to current or prior DENV serotypes. The dataset supports the understanding of CD8⁺ T cell heterogeneity, TCR features, and potential mechanisms of CD8⁺ T cell-mediated protection versus immunopathogenesis in dengue infection.

  Dataset EGAD00001015637

• COIN_CRC_GWAS

  Genotype data of 1,950 individuals from the COIN and COIN-B trials of advanced/metastatic colorectal cancer. Data provided in plink format, and has been quality controlled. Control data used was from the WTCCC2 project National Blood Donors (NBS) Cohort (EGAD00000000024).

  Dataset EGAD00010002186

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 10)

  Whole genome sequencing data of 56 high-grade serous carcinoma (HGSC) patients (208 samples) sequenced with Novoseq 6000

  Dataset EGAD50000000275

• Multiple Myeloma GWAS Meta-analysis

  Meta-analysis of Multiple Myeloma genome-wide association study datasets. Included are meta-analyses with and without the UK Biobank dataset.

  Study EGAS50000000292

• Nanopore whole-genome sequencing of human sarcomas

  We performed single and multi-region nanopore whole-genome sequencing on human sarcoma samples from adult and paediatric patients.

  Study EGAS50000000651

• Shallow dataset

  Associated with Molecular biomarkers in progression from refractory celiac disease to the lethal cancer variety enteropathy associated T cell lymphoma (EATL) Study. shallow Whole Genome Sequencing (sWGS) of 63 samples. sWGS was done to analyze copy number aberration.

  Dataset EGAD50000001165

• DNA sequencing of sgRNAs enriched from the CRISPR-Cas9 screened HCC organoids

  Project aims to find enriched or depleted sgRNAs to identify functional genes in HCC progression and lenvatinib resistance

  Study EGAS50000000848

• Single-cell Transcriptome Profiling of Treatment-naïve and Post-treatment Colorectal Cancer: Insights into Putative Mechanisms of Chemoresistance

  These terms and conditions govern access to the managed access datasets to which the User Institution has requested access. The User Institution agrees to be bound by these terms and conditions.

  Dac EGAC50000000482

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

  Targeted panel sequencing of 188 formalin-fixed paraffin-embedded p53abn endometrial cancer samples.

  Dataset EGAD00001015349

• Whole genome sequencing of osteosarcoma from patients seen at UT MD Anderson Cancer Center.

  Whole genome sequencing of 35 osteosarcoma patients (primary, relapsed, and metastatic) with matched normals. Tumors were sequenced at target 60X and matched normals at target 30X.

  Dataset EGAD00001005389

• Clinical data

  Clinical data from this cohort of patients, including hormone sensitive or castration resistant prostate cancer, overall survival, NMF subtypes, tumor TMB, prior treatment status, PD-L1 IC and TC scores from SP142 and SP263 as well as percentage of CD8 IHC at tumor center.

  Dataset EGAD00001008761

• 10x Genomics Single Cell Gene Expression for SA604X6XB01979

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA604 passage 6

  Dataset EGAD00001009117

• Dataset for cancer_of_unknown_primary-WHOLE_GENOME

  Rare cancer sequencing data of 46 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008869

• 10x Genomics Single Cell Gene Expression for SA535X6XB03099

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA535 passage 6

  Dataset EGAD00001009116

• 10x Genomics Single Cell Gene Expression for SA535X4XB05462

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA535 passage 4

  Dataset EGAD00001009115

• 10x Genomics Single Cell Gene Expression for SA604X7XB02089

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA604 passage 7

  Dataset EGAD00001009119

• 10x Genomics Single Cell Gene Expression for SA609X6XB01899

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA609 passage 6

  Dataset EGAD00001009120

• 10x Genomics Single Cell Gene Expression for SA605X3XB01966

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA605 passage 3

  Dataset EGAD00001009142

• 10x Genomics Single Cell Gene Expression for SA535X6XB03101

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA535 passage 6

  Dataset EGAD00001009149

• 10x Genomics Single Cell Gene Expression for SA1035X7XB03502

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA1035 passage 7

  Dataset EGAD00001009151

• 10x Genomics Single Cell Gene Expression for SA535X4XB02498

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA535 passage 4

  Dataset EGAD00001009152

• 10x Genomics Single Cell Gene Expression for SA1035X6XB03216

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA1035 passage 6

  Dataset EGAD00001009154

• 10x Genomics Single Cell Gene Expression for SA535X5XB02891

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA535 passage 5

  Dataset EGAD00001009155

• 10x Genomics Single Cell Gene Expression for SA535X5XB02895

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA535 passage 5

  Dataset EGAD00001009156

• 10x Genomics Single Cell Gene Expression for SA604X9XB02425

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA604 passage 9

  Dataset EGAD00001009159

• 10x Genomics Single Cell Gene Expression for SA610X3XB03802

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA610 passage 3

  Dataset EGAD00001009160

• Lowpass whole genome sequencing of single circulating tumor cells (CTCs) in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors

  Lowpass whole genome sequencing of 43 single CTCs and one tumor biopsy

  Dataset EGAD00001007700

• Single Cell Genome Sequence for DLP+ library A95670B

  Single Cell Genome Sequence for triple negative breast cancer patient-derived xenograft SA501 passage 6 on DLP+ library A95670B

  Dataset EGAD00001009449

• Single Cell Genome Sequence for DLP+ library A95722A

  Single Cell Genome Sequence for triple negative breast cancer patient-derived xenograft SA604 passage 6 on DLP+ library A95722A

  Dataset EGAD00001009451

• Single Cell Genome Sequence for DLP+ library A98247A

  Single Cell Genome Sequence for triple negative breast cancer patient-derived xenograft SA530 passage 3 on DLP+ library A98247A

  Dataset EGAD00001009646

• Target pilot trial

  In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer

  Dataset EGAD00001008358

• Single Cell Genome Sequence for DLP+ library A96212B

  Single Cell Genome Sequence for triple negative breast cancer patient-derived xenograft SA604 passage 7 on DLP+ library A96212B

  Dataset EGAD00001009476

• RNAseq - Colorectal organoids and tumoroids (2015-08-05)

  Transcriptome sequencing of tumour tissue, adjacent normal tissue and derived organoids/tumoroids from colorectal cancer. This dataset contains all the data available for this study on 2015-08-05.

  Dataset EGAD00001001459

• EPITREAT extended cohort

  Data set of 22 tumor/normal pairs of non-small cell lung cancer (NSCLC) patients. All tissue pairs were screened with MeDIP methylation enrichment sequencing and validations were performed with targeted bisulfite re-sequencing.

  Dataset EGAD00001003944

• WGS of a Li-Fraumeni patient's HSPCs

  WGS data of clonally expanded HSPCs from a Li-Fraumeni patient at the time of second cancer (Burkitt lymphoma and <5% t-MN) after primary osteosarcoma diagnosis and a reference MSC bulk.

  Dataset EGAD00001011257

• Genome and transcriptome sequence data from a pre-B all (2nd relapse in CNS) tumor patient

  Genome and transcriptome sequence data from a pre-B all (2nd relapse in CNS) patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015291

• 10x Genomics Single Cell Gene Expression for SA535X9XB03617

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA535 passage 9

  Dataset EGAD00001009157

• MutWP1: CRUK Grand Challenge Mutographs of Cancer: pancreas_LCM (2020-01-15)

  Samples prepared by LCM - 5 cases for pilot study. Bulk DNA not available. . This dataset contains all the data available for this study on 2020-01-15.

  Dataset EGAD00001005789

• Bulk RNAseq fastq files

  RNAseq FASTq files from 15 samples from patients with ovarian cancer, 5 samples for each of the 3 tumor immune phenotypes (Infiltrated, Excluded and Desert).

  Dataset EGAD00001006975

• HCA_Adrenal_Foetal_WSSS_RNA_SB

  The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). 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 EGAS00001004089

• Offspring Sex Impacts DNA Methylation and Gene Expression in Placentae from Women with Diabetes during Pregnancy

  Exposure to diabetes in utero is known to increase the offspring's likelihood of developing metabolic disease in adulthood, but the mechanisms involved are unknown. It has been proposed that early exposure to hyperglycemia and elevated insulin levels may lead to malprogramming of the fetus leading to the subsequent development of diabetes and obesity. Epigenetic modifications of the genome including DNA methylation, provide a plausible mechanism that allows for permanent propagation of gene activity states from one generation of cells to the next. The placenta, a fetal tissue easily accessible for study, is a complex organ that is essential in regulating fetal growth. The changes in placental nutrient transport associated with diabetes during pregnancy (DDP) have significant effects on the developing fetus, indicating that the placenta plays a critical role in fetal programming. The aim of our study was to investigate whether exposure to DDP alters genome-wide DNA methylation in the placenta obtained from term pregnancies resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression.

  Study phs001535

• Tissue and Fluid Analysis in Ocular Inflammatory Disease

  Granulomas are found in multiple infectious and non-infectious human diseases, yet the pathogenic drivers of granulomatous disease are still poorly understood. To enrich for pathologic inflammatory cells, we leveraged the intrinsic immunologic isolation of the eye by examining granulomatous uveitis, a form of ocular inflammation. We performed single-cell RNA-sequencing to obtain an unbiased gene expression survey of ocular immune cells in the anterior chamber of four live human donors with granulomatous uveitis. We paired this with antigen-receptor sequence analysis to identify clonally expanded lymphocytes. Each individual had robust clonal expansion arising from a single T or B cell lineage, suggesting distinct pathogenic processes in each patient. This variability in clonal expansion was mirrored by individualized combinations of TH1, TH1/TH17, and Tregs in ocular CD4 T cells. In contrast, ocular CD8 T cells were more transcriptionally similar across donors. Finally, clonally expanded, activated B cells displayed evidence of plasmablast differentiation and class-switching within the ocular microenvironment. Collectively, our study identified conserved and individualized features of granulomatous inflammation, illuminating parallel pathophysiologic mechanisms.

  Study phs002449

• The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR)

  The Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) Registry and Repository, supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), was established in 2000 to provide a resource for the scientific community to explore genetic and non-genetic factors affecting rheumatoid arthritis (RA) occurrence and outcomes in African Americans. The long term objective is a database and a repository of 1,100 RA and 550 matched healthy African-American subjects. This CLEAR Registry and Repository has two arms: a longitudinal arm for subjects with early RA (enrollment from 2000 to 2005) and a cross-sectional arm for subjects with any disease duration (enrollment from 2006 to 2012). CLEAR has two components: a database and a repository. The database contains extensive demographic, socioeconomic, clinical and radiographic (radiographs of hands and feet) information and bone mineral density data from DEXA scans. The repository contains genomic DNA, plasma and serum on most of the participants. Participants in CLEAR II had RNA isolated from peripheral blood cells.

  Study phs001360

• Transcriptomics sequencing analysis of pre-invasive lung adenocarcinoma in never-smokers

  The prevalence of lung adenocarcinoma (LUAD) has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. We performed whole exome-sequencing and RNA-sequencing for samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could categorize tumors into molecular subtypes within pathology-defined lesion types. These subtypes were linked with the advanced radiology-defined lesion type and coordinated with immune cell infiltration throughout the progression of LUAD. Characterization of these lesion types identified positively selected mutation patterns, and suggested that angiogenesis of the late-stage AIS type potentially contributes to tissue invasion of the MIA type. Our findings offer a novel resource that may help to improve early diagnosis and patient prognosis, and also suggest possible approaches for early disease interception.

  Study EGAS50000000439

• Whole exome sequencing of pre-invasive lung adenocarcinoma in non-smokers

  The prevalence of lung adenocarcinoma (LUAD) has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. We performed whole exome-sequencing and RNA-sequencing for samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could categorize tumors into molecular subtypes within pathology-defined lesion types. These subtypes were linked with the advanced radiology-defined lesion type and coordinated with immune cell infiltration throughout the progression of LUAD. Characterization of these lesion types identified positively selected mutation patterns, and suggested that angiogenesis of the late-stage AIS type potentially contributes to tissue invasion of the MIA type. Our findings offer a novel resource that may help to improve early diagnosis and patient prognosis, and also suggest possible approaches for early disease interception.

  Study EGAS50000000438

• 10x Multiome from Human Fetal Heart

  We hope to uncover the genetic basis of congenital heart disease by examining how genetic variants, especially those in non-coding regions, influence heart development. To achieve this goal, our research team created a single-cell atlas of human fetal heart development. The study population consists of 41 structurally normal fetal hearts spanning 6 to 22 weeks post-conception. We profiled close to 750,000 using single-cell RNA sequencing and ATAC sequencing technologies via the 10x Genomics Multiome platform.The molecular technologies employed allowed for simultaneous analysis of gene expression and chromatin accessibility at the single-cell level. This approach identified numerous distinct cell types and states within the developing heart, offering detailed insights into gene activity and enhancer usage during critical stages of heart development.Principal findings include the characterization of diverse cell populations and the identification of specific gene expression patterns and regulatory elements active during heart formation. This high-resolution atlas provides valuable insights into how genetic variants may disrupt normal heart development, particularly those in non-coding regions that affect gene regulation.

  Study phs003778

• Response​ to Tagraxofusp in Blastic Plasmacytoid Dendritic Cell Neoplasm

  Tagraxofusp is a CD123-targeted therapy comprised of a recombinant human interleukin-3 (IL-3) fused to a truncated diphtheria toxin (DT) payload. It is the first approved treatment specifically for patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). In order to identify biomarkers of response, bone marrow samples from 12 BPDCN patients who were treated with tagraxofusp in the pivotal phase II trial (NCT02113982) were profiled longitudinally using gene panel and/or single-cell RNA sequencing. Durable responders had either wildtype or missense TET2 mutations while transient and non-responders had at least one truncating TET2 mutation. Those who had progression at any one point during the treatment course (transient responders) and non-responders had enrichment of the chemokines CCL3, CCL4, and CCL5. Residual tumor cells following tagraxofusp treatment were identified in all patients, whose resistance may be due to their lower levels of TXNRD1 possibly preventing the potentiation of tagraxofusp. Thus, response to tagraxofusp may be related to culmination of intrinsic TET2 mutations, levels of TXNRD1, and extrinsic effects of chemokines within bone marrow.

  Study phs003895

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000416

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000418

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000417

• Liverpool Preterm Birth Biomarker Study

  Preterm birth is a multifactorial condition defined as birth less than 37 weeks of gestation. This study aimed to identify early pregnancy biomarkers from maternal genome-wide and transcriptome-wide data of women experiencing two types of spontaneous PTB (sPTB): spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM). Whole blood samples were obtained from women with singleton pregnancies (N=567) recruited at the Liverpool Women’s Hospital at 16 and 20 weeks of gestation. Women with a previous history of sPTB pregnancies <34 weeks were categorised on their index pregnancy outcome as spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM) or high-risk term control (HTERM, ≥37 weeks). Women with no history of SPTB/PPROM and delivered at term were LTERM (≥39 weeks of gestation). DNA was genotyped on the UK Biobank Axiom™ array (Applied Biosystems™, Thermo Fisher Scientific) and RNA who processed using the Clariom™ D Human assay (Thermo Fisher Scientific). Genome-wide association analysis, differential expression analysis and expression quantitative trait loci (eQTL) were completed.

  Study EGAS00001005076

• Genomic Analyses Identify Recurrent MEF2D Fusions in Acute Lymphoblastic Leukemia

  Chromosomal rearrangements are initiating events in acute lymphoblastic leukemia (ALL). Here, using RNA-sequencing (RNAseq) of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1164 B-ALL cases identified 30 cases with MEF2D rearrangements which include an additional fusion partner, FOXJ2, thus MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age, and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitors treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukemia, for which new therapeutic approaches should be considered.

  Study EGAS00001001952

• Gene fusion and transcriptomic landscapes of sarcomas

  Sarcoma represents a highly heterogeneous group of tumors. We report here the first unbiased and systematic search for gene fusions and analysis of transcriptomic profiles in 100 monomorphic sarcomas cases using RNA-sequencing profiling. Fusion genes were detected in two thirds of samples. Similarly to fusion genes such as PAX3/7-FOXO1, EWSR1/FUS-ETS, SS18-SSX, BRD3/4-NUTM1 or EWSR1/FUS/TAF15-NR4A3 characterizing well-defined entities, we show that all sarcomas displaying CIC fusions- whatever their fusion partner (being DUX4, NUTM1 or FOXO4) - form a transcriptionally homogeneous group of tumors. Likewise, tumors with either a BCOR fusion (with CCNB3, MAML3 or ZC3H7B partners) or with a BCOR internal duplication form a single biological entity. We also found that EML4-ALK fusions also characterize a homogeneous infantile fibrosarcoma subgroup. In contrast, fusions like VGLL2-NCOA2/CITED2, TMP3/TRP-NTRK1 or ETV6-NTRK3 are observed in more heterogeneous tumors. Finally, we also describe a new group of bone sarcomas characterized by EWSR1- or FUS-TFCP2 fusions.

  Study EGAS00001002189

• CD36 defines CML cells less sensitive to imatinib

  Tyrosine kinase inhibitors (TKIs) are highly effective for treatment of chronic myeloid leukemia (CML), but very few patients are cured. Major drawbacks with TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon TKI cessation. Here, we performed RNA-sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase CML cells and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor (LEPR) by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting antibodies, we show that the CD36 positive cells can be targeted and killed by antibody dependent cellular cytotoxicity (ADCC). In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted by ADCC using an anti-CD36 antibody.

  Study EGAS00001002421

• Engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus

  Short hairpin RNA (shRNA) expression strategies that allow safe and persistent target mRNA knockdown are key to the success of many in vitro or in vivo RNAi applications. Here, we propose a novel solution which is expression of a promoterless miRNA-adapted shRNA (shmiRNA) from an engineered genomic miRNA locus. For proof-of-concept, we genetically “vaccinated” liver cells against a human pathogen, by using TALEns or CRISPR to integrate an anti-hepatitis C virus (HCV) shmiRNA into the liver-specific miR-122/hcr gene. Reporter assays and qRT-PCR confirmed anti-HCV shmiRNA expression as well as miR-122 integrity and functionality. Specificity and safety of shmiRNA integration were validated via PCR, cDNA and miRNA profiling, and whole genome sequencing. A subgenomic HCV replicon and a full-length reporter virus, but not a Dengue virus control, were significantly impaired in the modified cells. Our original combination of DNA engineering and RNAi expression technologies should benefit numerous applications, from basic miRNA research, to human cell and gene therapy.

  Study EGAS00001001252

• Using human induced pluripotent stem cells (iPSC) and iPSC-derived neurons to explore cellular phenotypes associated with schizophrenia.

  Schizophrenia and major mental illness are common devastating conditions. Whilst partially effective treatments are available, none are disease-modifying. Notwithstanding important insights provided by animal models there is a need for novel models of mental illness to develop more effective therapies. A study of sporadic schizophrenia-derived human induced pluripotent stem cells (hiPS) has demonstrated a neuronal phenotype representing a powerful proof of concept of in vitro disease modeling, even for diseases with complex causation such as schizophrenia. These techniques have been used here to examine the behaviour of neural stem cells and neurons derived from fibroblasts from subjects carrying NDE1 copy number variations (CNVs) associated with increased risk of major mental illness. Using hiPS from individuals with and without disease-associated CNVs we have investigated how disease risk is conferred at a cellular and molecular level through detailed comparative studies of neural progenitor proliferation, neuronal morphology, physiology, cytoskeletal organization, synaptic function, glutamate (NMDA) receptor expression and also RNA sequencing and proteomic studies of these patient-derived cells.

  Study EGAS00001002895

• HCA_Female_Reporductive_Adult_WSSS_RNA

  Cell atlas of the human placenta The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). 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 EGAS00001004210

• HCA_Placenta_Adult_Vento_RNA

  The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). 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 EGAS00001004069

• Tumour gene expression signature in primary melanoma predicts long-term outcomes: A prospective multicentre study

  Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We used differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR=1.63, p=5.24x10-5) and overall survival (HR=1.61, p=1.67x10-4), and validated in 177 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC=0.02), or published prognostic signatures. The signature score negatively correlated with measures of immune cell infiltration (ρ=-0.75, p<2.2x10-16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.

  Study EGAS00001004664

• Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups

  Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. In summary, Pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.

  Study EGAS00001006402

• GOSH_Childhood_Leukemia_Behjati_WellcomeCore_RNA

  Paediatric single-cell archival project This project is taking sequential samples of children with B-cell acute lymphoblastic leukaemia (B-ALL) treated at Great Ormond Street Hospital (GOSH) between 2011 and the present day. Patients selected, are those that have done badly (e.g. had to escalate treatment, relapsed or died) despite having apparently ""good"" or ""intermediate"" risk cytogenetics, and often also had immunotherapy (e.g., the bi-specific T-cell engager blinatumomab) because of this. Using samples from key treatment-points, we hope to better characterise their disease and treatment response, to re-define understandings of risk for patients who did unexpectedly poorly. Additionally, we hope to define the disease/immunological factors that determine response to increasingly used immunotherapies within the field of paediatric B-ALL. Each of the samples will be viably frozen bone marrow-derived mononuclear cells. They will come in Eppendorf's, frozen and de-anonymised, from GOSH. We plan to primarily do single cell analysis (GEX, BCR +/-TCR), and then tumour-only WGS and bulk-RNA expression on left-over

  Study EGAS00001007616

• Bone Microarchitecture

  Osteoporosis affects more than 28 million people in the United States and the lifetime risk for osteoporosis-related morbidity is higher than a woman's combined risk for breast cancer, endometrial cancer and ovarian cancer. Health care expenditures for osteoporotic patients in this country are currently nearly 13 billion dollars per annum and are predicted to increase markedly in the next decades due the aging of the population; therefore, it is important to understand the factors that contribute to bone strength and fracture risk. With the advent of skeletal imaging modalities such as high resolution peripheral quantitative computed tomography (HR-pQCT), it is now possible to study the genetics of more highly refined peripheral skeletal microarchitecture phenotypes. Because these refined phenotypes have not been measured in many cohort studies, this project was a collaborative effort to include almost all the existing data on HR-pQCT of the radius and tibia, and genetics from around the world. Cohorts involved in the discovery included: 1) Framingham Osteoporosis Study, 2) Mayo Clinic cohort; 3) Geneva Retirees cohort; 4) OFELY cohort from Lyon France; 5) STRAMBO cohort from Lyon France; 6) Swedish Male cohorts. Replication cohorts undergoing de novo genotyping include: 1) QUALYOR cohort from Lyon France; 2) CaMOS cohort from Canada. Other than the Framingham cohort and the Swedish male cohorts, all discovery cohorts underwent genome wide genotyping with the Affymetrix Axiom Biobank array that had common variants along with exome content based on the early findings from the Exome Sequencing Project. All genotype data from the discovery cohorts were then imputed using the Haplotype Reference Consortium reference panel. Variants for replication genotyping using the Kasp technology were selected based on novelty compared with previously identified loci using DXA phenotypes, minor allele frequency, underlying LD structure within a locus, and likelihood of a variant being functional as assessed using various algorithms for coding and non-coding variants.    

  Study phs002102

• Direct Transposition of Native DNA for Sensitive Multimodal Single-Molecule Sequencing

  STUDY GOALS: This study focuses on elucidating the epigenetic modulators of prostate cancer progression and metastasis at high resolution. This is achieved by applying a novel, high-sensitivity single molecule sequencing assay that measures chromatin state on single DNA molecules (SMRT-Tag) to matched primary and metastatic tumor samples from the same patient. Samples are obtained from patient derived xenograft (PDX) models. STUDY DESIGN: Individuals diagnosed with primary and metastatic prostate cancer in the course of routine care were consented and enrolled, and biopsies of primary and/or metastatic lesions performed to obtain sample material used for generating PDX models. Samples collected from these models were processed with a novel strategy developed for highly-sensitive multimodal profiling of single chromatin fibers using the third generation long-read sequencing. The resulting data indicates genetic variants, chromatin organization, and m5dCpG methylation status across the genome. PRINCIPLE FINDINGS: We determined characteristic single-molecule patterns of chromatin organization (spacing of nucleosomes, presence and absence of m5dCpG marks, etc.) that were altered in the transition from primary malignancy to metastasis. Broadly, global chromatin organization was severely disrupted in metastatic samples, resulting in increased accessibility at CTCF motifs, which may be relevant for disease progression. We further identified specific genomic domains including constitutive heterochromatin significantly enriched for irregular or hyper-accessible chromatin. Together, these findings suggest the involvement of ATP-dependent chromatin remodelers in evicting nucleosomes as a facet of metastatic prostate cancer. DATA AVAILABILITY: SAMOSA-Tag, the assay used in this study, is a sequencing assay that uses the third generation long read sequencing, specifically the SMRT sequencing platform from Pacific Biosciences. Demultiplexed raw SMRT sequencing BAM files generated in this study are deposited. Individual raw subread BAM files correspond to replicate sequencing assays performed on either primary or metastatic PDX prostate tumors.

  Study phs003511

• Single cell targeted DNA-sequencing (and antibody sequencing) of high hyperdiploid B-ALL

  This dataset contains all sequencing data of the publication "Single-cell DNA and Surface Protein Characterization of High Hyperdiploid Acute Lymphoblastic Leukemia at Diagnosis and During Treatment". We provide both the raw fastq-files as well as the processed data in the form of .h5 files. There are 13 patients: XJ176, XH135, XJ180, XI145, XI148, XI167, XI150, XJ175, XJ178, XI162, XF98, XG111 and XG115. Of 9 patients, also follow-up samples during/after treatment were sequenced: XJ180, XI145, XI148, XI167, XI150, XJ175, XJ178, XI162 and XG111. To identify the cell types and distinguish between normal and leukemic cells, cell surface proteins were also captured for 6 samples: XF98, XG111 (at diagnosis and during treatment), XG115, XI162 (after treatment) and XJ175 (after treatment). All samples were processed on the MissionBio platform with a custom amplicon panel, and DaB-seq for the combined targeted DNA and protein sequencing.

  Dataset EGAD50000000829

• Platelets contain a repertoire of DNA fragments that map over the human nuclear genome, including tumour-derived DNA in patients with active malignancy.

  This dataset consists of WGS from six patients with a recent diagnosis of gastrointestinal adenocarcinoma. DNA-Seq libraries were prepared from platelet DNA (pDNA) and plasma cfDNA obtained from the same peripheral blood sample. pDNA was size selected into 2 groups (small, s-pDNA: less than 600 bp and long, b-pDNA: greater than 600 bp). The short fragments were further cleaned to remove <100 bp fragments and large platelet fragments were fragmented via sonication. Libraries were then prepared using the NEBNext Ultra II DNA Sample Preparation Kit for Illumina according to the manufacturer’s protocol and sequenced on an Illumina NextSeq 500 (300 cycle PE) at low-pass (0.1X) for all samples, and 10X for the cfDNA and s-pDNA, using four lanes in each sample.

  Dataset EGAD00001009856

• Targeted bisulfite sequencing

  Raw reads from targeted bisulfite sequencing. The SureSelect Methyl-Seq target enrichment system (Agilent Technologies, Inc., CA, USA) was used to prepare bisulfite sequencing libraries from blood DNA samples of lymphoma patients (Ly1, Ly2), healthy family members (Ly8, Ly9, Ly10, Ly11, Ly12, Ly13 and Ly14), baseline controls (Control1-5), DNMT3A mutation carriers (Id5, Id7, Id9, Id11) and their age-matched controls (Id6, Id8, Id10, Id12). In addition, blood DNA sample of a patient (HLRCC_N7) with germline fumarate hydratase (FH) mutation is included. Illumina paired-end sequencing for targeted libraries from Ly1, Ly2, Ly8, Ly9, Ly10 and Ly11 was done at Karolinska Institutet using 100 base-pair read length and the HiSeq2000 platform. Illumina paired-end sequencing for targeted libraries from Ly12, Ly13, Ly14, and DNMT3A mutation carriers and their age-matched controls was done as a service at BGI (BGI Tech Solutions Co., Ltd., China) using 126 base-pair read length and the HiSeq2500 platform.

  Dataset EGAD00001004785

• COVID-19 Severity First Wave of Infection for Severe Patients in Madrid

  We recruited 98 hospitalised patients displaying severe COVID-19 symptoms from the first wave of infection. A stringent exclusion criteria based on non-genetic factors such as age, blood oxygen, radiologic findings and other typical COVID-19 signs was performed. Gingival or peripheral blood samples were taken for 98 individuals and whole exome sequencing performed using ExomeCapture-Seq capture KAPA HyperExome on Illumina machines.

  Dataset EGAD00001008464

• scDNA-seq for 'Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma'

  Neuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.

  Dataset EGAD00001015414

• Monotherapy Breast Cancer

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

  Dataset EGAD00001000349

• Signatures of mismatch repair deficiency in cancer genomes

  DNA replication errors occurring in mismatch repair (MMR) deficient cells persist as mismatch mutations and predispose to a range of tumors. Here, we sequenced the first whole-genomes from MMR-deficient endometrial tumors.

  Dataset EGAD00001000641

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 9 part 3)

  Whole genome sequencing data of 25 high-grade serous carcinoma (HGSC) patients (65 samples) sequenced with Illumina Novoseq 6000

  Dataset EGAD50000000211

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

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

  Dataset EGAD50000000304

• CRC cell line MPRA

  Massively Parallel Reporter Assays (MPRA) of colorectal cell lines HCEC-1CT (normal colon) and HT29 and SW403 (MSS cancer). Probes identified using the CRC GWAS.

  Dataset EGAD50000000596

• Chemotherapy induces myeloid-driven spatial T-cell exhaustion in ovarian cancer

  Gene expression profiles of single cells from 26 chemo-naïve and IDS tumor tissue and ascites samples from 17 HGSC patients

  Study EGAS50000000607

• Dataset for "HPV integration induces gene fusions" (pacBio)

  pacBio whole-genome sequencing data for "HPV integration induces gene fusions" We performed long read whole-genome sequencing on four HPV+ head and neck cancer samples using pacBio HiFi. The sequence reads were submitted in fastq format.

  Dataset EGAD50000001304

• Clonal hematopoiesis in metastatic urothelial and renal cell carcinoma

  This study aimed to determine the prevalence and clinical relevance of clonal hematopoiesis in metastatic urothelial and renal cell carcinoma.

  Study EGAS50000000870

• Microarray CDX or EDX from primary tumor and metastasis

  expression analysis of FACS sorted human cells from primary tumors and distant organs micrometastases in xenografts. Patient Derived xenografts were generated transplanting tumor cells from metastatic breast cancer patients into mammary fat pad of immunocompromised mice

  Dataset EGAD00010002711

• non-malignant plasma cfRNA

  Dataset contains mRNA capture sequencing data from plasma of 125 different human donors: 88 patients with a non-malignant disease and 37 cancer-free controls. Samples were sequenced on a NovaSeq X and sequencing data is provided in FASTQ format.

  Dataset EGAD50000001806

• Germline Pan-cancer Lynch syndrome sequencing dataset from India

  The dataset consists of germline whole exome sequencing data generated on the Illumina NovaSeq X Plus platform for 48 patients with MSI-high/ MMRd gastro-intestinal and genito-urinary cancers, in order to detect Lynch syndrome.

  Dataset EGAD50000002088

• Helleday_HRAS_Project

  This experiment is looking at the mutational signatures generated by engineered HRAS mutations by using whole genome sequence generated on massively parallel next generation sequencers.

  Study EGAS00001000332