15041 results for "cancer studies using rna-seq"

in 168.80 milliseconds.

• Genome and transcriptome sequence data from a leiomyosarcoma patient

  Genome and transcriptome sequence data from a leiomyosarcoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010957

• Genome and transcriptome sequence data from a liposarcoma patient

  Genome and transcriptome sequence data from a liposarcoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001011032

• Genome and transcriptome sequence data from a cholangiocarcinoma patient

  Genome and transcriptome sequence data from a cholangiocarcinoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001002623

• Genome and transcriptome sequence data from a leiomyosarcoma patient

  Genome and transcriptome sequence data from a leiomyosarcoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001004922

• Whole genome sequencing

  The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC) is not well understood. We performed whole genome sequencing on primary and metastatic sites from highly clinically annotated HGSC samples. Samples were obtained pre-treatment based on a laparoscopic triage algorithm from patients who underwent R0 tumor debulking, or received neoadjuvant chemotherapy (NACT) with excellent or poor response.

  Dataset EGAD00001005240

• Predictor_ChemoNEAR_TNBC (2019-08-14)

  In this study a collection of core biopsies from breast cancer patients receiving neoadjuvant chemotherapy as part of the ChemoNEAR trial will be investigated. The study is intended to detect early acquired resistance in women with diagnosed breast carcinoma. Samples will undergo whole genome sequencing and analysis, including use of HR Predict. . This dataset contains all the data available for this study on 2019-08-14.

  Dataset EGAD00001005255

• Genome and transcriptome sequence data from a hemangioma patient

  Genome and transcriptome sequence data from a hemangioma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001005900

• Whole exome sequencing of long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer

  The dataset contains Whole Exome Sequencing data (BAM files) of 22 samples from HER2+ metastatic breast patients. For 9 of the 13 tumours samples there are paired controls available from normal tissue. There are 8 tumours samples that are from treatment-responder patients and 5 tumours samples from non responder patients.

  Dataset EGAD00001006217

• Genomic and transcriptomic data of glioma specimens

  Dataset consists of 207 glioma samples of WHO grades II, III and IV. Dataset consists 182 tumor derived genomic data of ~700 cancer-related and epigenetic-related genes with matched blood samples for 48 specimens. Dataset also consists transcriptomic data for 105 specimens. In total 335 bam files were deposited.

  Dataset EGAD00001006299

• The mutation burden of narrowband ultraviolet B phototherapy in human skin - Nanoseq

  Background: Ultraviolet radiation (UV) is used as a treatment for psoriasis, but UV can also induce mutations which may lead to development of skin cancer. Information on the mutagenicity of narrowband UVB (NBUVB) would help inform clinicians and patients who are concerned about the potential risks of this treatment.

  Dataset EGAD00001015249

• The mutation burden of narrowband ultraviolet B phototherapy in human skin - WGS

  Background: Ultraviolet radiation (UV) is used as a treatment for psoriasis, but UV can also induce mutations which may lead to development of skin cancer. Information on the mutagenicity of narrowband UVB (NBUVB) would help inform clinicians and patients who are concerned about the potential risks of this treatment.

  Dataset EGAD00001015250

• Genome and transcriptome sequence data from a myoepithelioma patient

  Genome and transcriptome sequence data from a myoepithelioma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010938

• Genome and transcriptome sequence data from a leiomyosarcoma patient

  Genome and transcriptome sequence data from a leiomyosarcoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010939

• Genome sequence data from a metastatic rectal carcinoma patient

  Genome sequence data from a metastatic rectal carcinoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010972

• Genome sequence data from a metastatic paraganglioma patient

  Genome sequence data from a metastatic paraganglioma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010985

• Genome and transcriptome sequence data from a thymoma patient

  Genome and transcriptome sequence data from a thymoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001011039

• ChIP-seq of GOF p53 mutants

  Gain-of-function TP53 mutations were detected in 41.3% of cases, in which co-occurring del(17p) underscored a dominant effect in >25%. Missense mutations of TP53 clustered within the core DNA-binding domain, where R249S was most common. To explore the transcriptional effect of mutant p53(R249S), we performed chromatin immunoprecipitation-sequencing in the HCC cell line HKCI-11, which has a p53(R249S) mutation, and the human hepatocyte line MIHA, which is p53(WT). The results revealed distinct binding profiles between wildtype p53 and p53 mutant.

  Study EGAS00001002463

• Tagged-amplicon deep sequencing

  This dataset contains a collection of tumour samples from high grade serous ovarian carcinoma patients with recurrent disease collected near the point of diagnosis as well as tumour samples collected after patient relapse upon or some time after study entry. Whole blood samples were also collected from patients at study entry for the purpose of germline variant detection. The majority of diagnosis samples were preserved in neutral buffered formalin whereas the majority of post-relapse samples were preserved in universal molecular fixative (UMFIX, Sakura Finetek USA, Inc). DNA was extracted and the tagged-amplicon deep sequencing assay was applied (TAm-Seq, Forshew et al. 2002, Sci Transl Med) with the aid of fluidigm access array technology. Targeted loci were sequenced at very high depths (typically >100X) for the detection of both somatic and germline variants. Sequenced reads were aligned to the GRCh37 reference genome (release hs37d5).

  Dataset EGAD00001011058

• Exome-seq data of two non-obstructive azoospermia patients

  Azoospermia, characterized by the absence of spermatozoa in the ejaculate is a common cause of male infertility with a poorly characterized etiology. Exome sequencing analysis of two azoospermic brothers allowed the identification of a homozygous splice mutation in SPINK2, encoding a serine protease inhibitor believed to target acrosin, the main sperm acrosomal protease. In accord with these findings we observed that homozygous Spink2 KO male mice had azoospermia. Moreover, despite normal fertility, heterozygous male mice had a high rate of morphologically abnormal spermatozoa and a reduced sperm motility. Further analysis demonstrated that in the absence of Spink2, protease-induced stress initiates Golgi fragmentation and prevents acrosome biogenesis leading to spermatid differentiation arrest. We also observed a deleterious effect of acrosin overexpression in HEK cells, effect that was alleviated by SPINK2 coexpression confirming its role as acrosin inhibitor. These results demonstrate that SPINK2 is necessary to neutralize proteases during their cellular transit towards the acrosome and that its deficiency induces a pathological continuum ranging from oligoasthenoteratozoospermia in heterozygotes to azoospermia in homozygotes.

  Dataset EGAD00001003326

• Ischemia Reperfusion Responses in Human Lung Transplants at the Single Cell Resolution

  Ischemia reperfusion is an unavoidable step of organ transplantation. Development of therapeutics for lung injury during transplantation has proved challenging; understanding lung injury from human data at the single cell resolution is required to accelerate the development of therapeutics. Donor lung biopsies from six human lung transplant cases were collected at the end of cold preservation and 2-hour reperfusion and underwent single cell RNA sequencing. Donor and recipient origin of cells from the reperfusion timepoint were deconvolved. Gene expression profiles were (1) compared between each donor cell type between timepoints and (2) compared between donor and recipient cells. Inflammatory responses from donor lung macrophages were found after reperfusion with upregulation of multiple cytokines and chemokines, especially IL-1 and IL-1. Significant inflammatory responses were found in alveolar epithelial cells (featured by CXCL8) and lung endothelial cells (featured by IL-6 upregulation). Different inflammatory responses were noted between donor and recipient monocytes and CD8+ T cells. The inflammatory signals and differences between donor and recipient cells observed provide insight into the cellular and molecular mechanisms of ischemia reperfusion induced lung injury. Further investigations may lead to the development of novel targeted therapeutics.

  Study EGAS50000000490

• Harnessing Epigenetic Regulators to improve HSC-based lentiviral gene therapy

  Curative benefits of autologous and allogeneic transplantation of hematopoietic stem cells (HSCs) have been proven for various diseases. However, the low number of true HSCs that can be collected from patients and subsequently in vitro maintenance and expansion of true HSCs for genetic correction remain challenging. Addressing this issue, we here focused on optimizing culture conditions to improve the ex vivo expansion of true HSCs for gene therapy purposes. In particular, we explore the use of epigenetic regulators to enhance the effectiveness of HSC-based lentiviral (LV) gene therapy. The HDAC inhibitor Quisinostat and the bromodomain inhibitor CPI203 each promote ex vivo expansion of functional HSCs, as validated by xenotransplantation assays and single cell RNA-sequencing analysis. We confirmed the stealth effect of LV transduction on the loss of HSC numbers in commonly used culture protocols, while addition of Quisinostat or CPI203 improved expansion of HSCs in transduction protocols. Of note, we demonstrated that addition of Quisinostat improved LV transduction efficiency of HSCs and early progenitors. Our suggested culture conditions highlight the potential therapeutic effect of epigenetic regulators in hematopoietic stem cell biology and their clinical applications to advance HSC-based gene correction.

  Study EGAS50000000175

• Biallelic loss of function PAX4 variants are a Novel Cause of Transient Neonatal Diabetes

  The identification of genes in which loss of function (LoF) variants cause neonatal diabetes mellitus (NDM) can provide unique insights into the development and function of human pancreatic beta cells. We describe the identification of biallelic PAX4 LoF variants in 2 unrelated individuals with transient NDM: one due to a homozygous p.(Arg126*) PAX4 stop gain variant and a second due to a homozygous c.-352_104del 2.65kb deletion affecting the first 4 exons and promoter of the PAX4 Matched Annotation from NCBI and EMBL-EBI select transcript. We confirmed reduced transcript expression due to nonsense mediated decay for the e p.(Arg126*) variant in CRISPR-edited iPSC-derived pancreatic endoderm cells. Analysis of PAX4 binding through integration of CUT&RUN and RNA-sequencing in PAX4 depleted endocrine cells identified genes directly regulated by PAX4 involved in both pancreatic islet development and glucose-sensitive insulin secretion. The remitting and relapsing diabetes in both probands demonstrates that in contrast to mice PAX4 is not essential for the development of pancreatic beta-cells and supports differences in the requirements of functional beta-cell mass across the life-course.

  Study EGAS50000000857

• Non-neuronal TGF-β–mediated extracellular matrix remodeling drives neurodegeneration in a PSP-Richardson syndrome model

  Progressive supranuclear palsy-Richardson syndrome (PSP-RS) is a devastating neurodegenerative disorder marked by rapid motor decline, cognitive impairment, and widespread accumulation of pathological tau. Yet, the molecular triggers of sporadic PSP-RS remain elusive. In this study, we combined patient-derived midbrain organoids with integrative multi-omics to uncover a previously unrecognized pathological cascade. At the core lies an early and aberrant activation of TGF-β signaling, which initiates profound extracellular matrix (ECM) remodeling and aberrant integrin-mediated focal adhesion. This cascade leads to persistent hyperactivation of PI3K/AKT and MAPK/ERK pathways, disrupting cytoskeletal integrity, impairing autophagy, promoting pathological tau phosphorylation and mislocalization, and ultimately driving synaptic degeneration. Single-cell RNA sequencing revealed an ectopic expansion of vascular leptomeningeal-like cells (VLMCs), a collagen-producing population, accompanied by a broad ECM gene dysregulation unique to PSP-RS. Remarkably, pharmacological blockade of TGF-β, AKT, ERK, or mTOR signaling reversed tau pathology and restored synaptic integrity. These findings position TGF-β-driven ECM remodeling as a master regulator of neurodegeneration in sporadic PSP-RS and unveil multiple actionable therapeutic targets for this currently untreatable disease.

  Study EGAS50000001236

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

  Endometriosis is a highly prevalent condition that remains underdiagnosed and poorly managed due to the lack of clinically validated biomarkers and limited understanding of its underlying pathophysiology. Although menstrual blood–derived stem cells (MenSCs) have been implicated in disease pathogenesis, their potential as a diagnostic source has not been systematically explored. We conducted a clinical study including 42 women (19 with endometriosis and 23 controls) to evaluate whether DNA methylation profiles from freshly isolated MenSCs could identify disease-specific biomarkers. Whole-genome DNA methylation sequencing identified differentially methylated regions (DMRs) enriched in genes associated with key features of endometriosis, including inflammation, tissue remodelling, and developmental processes. These DMRs robustly discriminated cases from controls, independently of technical and clinical confounders. Machine learning models trained and validated on these regions demonstrated strong diagnostic performance (specificity 83%, sensitivity 79%). Integration with an independent single-cell RNA sequencing dataset suggested that the identified DMRs may influence gene expression, supporting their biological relevance. Collectively, these findings highlight MenSC DNA methylation profiling as a promising, non-invasive strategy for early diagnosis and personalised management of endometriosis. (PubMed IDs will be provided once the manuscript is published.)

  Study EGAS50000001640

• SINGLE-CELL RNA SEQUENCING Single-cell RNA sequencing was performed on 13 ‘mild-moderate’ and 10 ‘critical’ COVID19 PBMC samples

  Summary Epidemiological and clinical reports have indicated that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we performed cytokine and multiplex immune profiling in mild-moderate and critically ill COVID-19 patients. Hypercytokinemia in COVID-19 differed from the IFN-γ-driven cytokine storm in macrophage activation syndrome, and was more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling showed that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Expression of antigen presenting machinery was also reduced in critical disease. Furthermore, we found that neutrophils contributed to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together these findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

  Study EGAS00001005039

• Germline biallelic mutation affecting the transcription factor Helios causes pleiotropic defects of immunity

  We studied a patient with recurrent respiratory infections and hypogammaglobulinemia and identified a germline homozygous missense mutation in IKZF2 encoding Helios (p.Ile325Val). We show that HeliosI325V retains DNA-binding and dimerization properties, but loses interaction with several partners, including epigenetic remodelers HDAC1, HDAC3 and the ATAC complex. Single-cell RNA-sequencing of peripheral blood mononuclear cells revealed gene expression signatures indicative of a shift towards pro-inflammatory, effector-like status in the patient’s T cells. We observed an upregulation of the anti-inflammatory gene, TSC22D3, encoding the glucocorticoid-induced leucine zipper (GILZ), whose expression was reported to increase upon IL-2 deprivation. We validated this finding in primary T cells, where we observed a pronounced reduction in IL-2 production upon their stimulation, together with a defect in their ability to proliferate, rendering them more anergic. Collectively, we identify a novel germline-encoded inborn error of immunity and define a role for Helios in conventional T cells, whereby interactions with specific binding partners is necessary to mediate the transcriptional programs that enable T-cell homeostasis in health and disease.

  Study EGAS00001005675

• Identification of Germline Monoallelic Mutations in IKZF2 in Patients with Immune Dysregulation.

  Helios, encoded by IKZF2, is a member of the Ikaros family of transcription factors with pivotal roles in T-follicular helper, NK- and T-regulatory cell physiology. Somatic IKZF2 mutations are frequently found in lymphoid malignancies. Although germline mutations in IKZF1 and IKZF3, encoding Ikaros and Aiolos, have recently been identified in patients with phenotypically similar immunodeficiency syndromes, the effect of germline mutations in IKZF2 on human hematopoiesis and immunity remains enigmatic. We identified germline IKZF2 mutations (one nonsense (p.R291X)- and 4 distinct missense variants) in six patients with systemic lupus erythematosus, immune thrombocytopenia or EBV-associated hemophagocytic lymphohistiocytosis. Patients exhibited hypogammaglobulinemia, decreased number of T-follicular helper and NKcells. Single-cell RNA sequencing of PBMCs from the patient carrying the R291X variant revealed upregulation of pro-inflammatory genes associated with T-cell receptor activation and T-cell exhaustion. Functional assays revealed the inability of HeliosR291X to homodimerize and bind target DNA as dimers. Moreover, proteomic analysis by proximity-dependent Biotin Identification revealed aberrant interaction of 3/5 Helios mutants with core components of the NuRD complex conveying HELIOS mediated epigenetic and transcriptional dysregulation.

  Study EGAS00001005874

• Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling (hipo_021)

  Parathyroid carcinoma (PC) is an orphan malignancy with a high risk of recurrence after surgery. Tumor-directed systemic treatments for PC are not established. We used whole-genome and RNA sequencing in four patients with advanced PC to identify molecular alterations that could guide clinical management. In two cases, the genomic and transcriptomic profiles provided targets for experimental therapies that resulted in biochemical response and prolonged disease stabilization: (i) immune checkpoint inhibition with pembrolizumab based on high tumor mutational burden and a single-base substitution signature associated with APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) overactivation; (ii) multi-receptor tyrosine kinase inhibition with lenvatinib due to overexpression of FGFR1 and RET and, later in the course of disease, PARP inhibition with olaparib prompted by signs of defective homologous recombination DNA repair. In addition, our data provided new insights into the molecular landscape of PC with respect to the genome-wide footprints of specific mutational processes and pathogenic germline alterations. These data underscore the potential of comprehensive molecular analyses to improve care for patients with ultra-rare cancers based on insight into disease biology.

  Study EGAS00001006747

• Identification of ALS Associated Genes Using Whole Genome Sequencing

  The overall aim of this study is to discover of novel genetic elements associated with amyotrophic lateral sclerosis (ALS). Towards this goal, we have performed exome and whole genome sequencing for over 2000 samples. This data will be process and harmonized to yield high quality variant calling. These variants will be combined with control cohorts to identify novel genetic elements associated with ALS through case: control analyses.

  Study phs001585

• Whole-genome sequencing data of human hematopoietic stem and progenitor cells in post-transplant clonal hematopoiesis

  This dataset contains BAM files of whole-genome sequencing data of single human HSPCs after colony expansion, for three individuals who harbor a DNMT3A mutant clonal hematopoiesis clone in their blood system after hematopoietic cell transplantation. 29 samples are present in this dataset; 10 samples for LTHIT005, 10 samples for LTHIT131, and 9 samples for LTHIT069. In the sample name, samples are annotated for being DNMT3A wildtype (wt) or mutant (mut), except for LTHIT069 (wt samples: F13, H4, K2, L16, N12, mut samples: C8, E10, L9, N5). Whole-genome sequencing was performed after standard Illumina WGS library preparation and sequenced on a Novaseq 6000 using 150 bp paired-end sequencing. The sequencing depth is 15x genome coverage, or 50Gbases per sample.

  Dataset EGAD50000001347

• Analysis of Large Cell Neuroendocrine Carcinoma Expressing HNF4alpha Using WGS

  Lung LCNEC (Large Cell Neuroendocrine Carcinoma) has a poor prognosis, and no effective treatment has yet been established. We have found that the gastrointestinal marker HNF4alpha is specifically expressed in some LCNEC cases. By performing Whole Genome Sequencing (WGS) on samples from 10 LCNEC patients, we aim to identify changes characteristic of LCNEC expressing HNF4alpha and explore new classifications and treatment options for LCNEC.

  Study JGAS000732

• Survival and safety of laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial

  This dataset is the immune profiling of the trial patients. Cryopreserved PBMCs obtained from the patients at different time points were processed to single-cell transcriptomic or TCR libraries using 10x next GEM single Cell 5' v2 kit. We also performed whole exome sequencing (WES) of the tumor to identify the mutation burden. The WES data was generated by sequencing company Novogene. There are total of 69 of single cell libraires, 69 of single cell TCR libraries, and 13 of tumor WES data being generated from 18 trial patients recruited at University of Florida.

  Dataset EGAD50000001639

• ISCAPE V(D)J libraries from HA-specific single memory B cells of four Influenza A exposed individuals

  Peripheral blood mononuclear cells were used to produce paired, full-length IGM, IGK and IGL V(D)J libraries from HA-binding single memory B cells using the ISCAPE (Individualized Single Cell Analysis of Paired Expressed antigen receptors) technique. Locus-specific multiplexed nested PCR with primer sets targeting the 5’ UTR/leader and 3’ constant region was performed before well and plate indexing and paired chain sequencing with an Illumina MiSeq instrument. Expressed total IGM, IGK and IGL V(D)J libraries from each donor were acquired and analyzed to define personalized IG allele content. The fastq file names include the donor and a numerical plate index for the HA-specific ISCAPE BCR HC and LC V(D)J libraries.

  Dataset EGAD50000002019

• High hyperdiploid ALL single cell whole genome sequencing

  This dataset was collected from viable bone marrow cells obtained at diagnosis from nine patients with high hyperdiploid ALL and one normal bone marrow sample. All samples were subjected to low pass single cell whole genome sequencing with the median sequencing coverage of 0.02x. Single nuclei in G0/G1 phase were isolated using a fluorescence-activated cell sorting (FACS) cytometer. DNA libraries were constructed and associated next-generation sequencing was carried out by European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Further details regarding the DNA libraries construction are available by Bos et. al., 2019 (https://link.springer.com/protocol/10.1007/978-1-4939-8931-7_15).

  Dataset EGAD00001008988

• Bone marrow microenvironment of 6 newly diagnosed myeloma patients using 10X Genomics scRNA- and TCR-sequencing

  10X Genomics scRNA- and TCR-sequencing (Chromium Next GEM Single Cell 5’ Reagent Kit v1.1) was performed on the plasma cell depleted mononuclear fraction of bone marrow aspirates from 6 patients with newly diagnosed multiple myeloma. Generated gene expression libraries were paired-end sequenced on the NovaSeq 6000 S2. Generated V(D)J libraries were paired-end sequenced on the NextSeq 550.

  Dataset EGAD00001009270

• Whole exome sequencing of sequential samples from a CLL patient over the course of venetoclax treatment, BCR inhibitor treatment, and venetoclax re-treatment

  The dataset contains whole exome sequencing data (libraries prepared using the Agilent SureSelect Human All Exon V6 kit, and paired-end sequenced on Illumina HiSeq4000 (2 x 150bp)) of 6 samples taken from peripheral blood mononuclear cells (PBMCs) (Samples 1-5) and bone marrow (BM). Data are provided as fastq files. Sample 1 was taken prior to initial venetoclax treatment. Sample 2 was taken as disease progression on venetoclax. Sample 3 was taken during response to BTK and PI3K inhibitor therapy. Sample 4 and the BM sample were taken at disease progression/prior to venetoclax re-treatment. And Sample 5 was taken during venetoclax re-treatment response.

  Dataset EGAD00001008685

• sWGS of OV04 patient samples for ACN rascal study

  This dataset contains 142 .bam files of shallow WGS data (~0.1X) from OV04 patient samples. Sequencing reads were aligned to the 1000 Genomes Project GRCh37-derived reference genome using the BWA aligner (v.0.07.17; CRUK-CI alignment pipeline).

  Dataset EGAD00001008121

• Warm_autopsy__mutational_signatures_and_clonal_units

  Aims and objectives 1. To produce a ‘first generation map’ of mutational burdens and mutational processes that operate in normal human tissues. 2. To examine clonal units and their distribution across normal human tissues with the emphasis on these particular areas: a) Tissues with an architecturally defined unit: Are architectural structures populated by a progeny derived from a single stem cell? Are clonal units confined to a given architectural structure? Examples of tissues where such approach will be used include prostate gland (acini and ducts), small bowel (crypts), thyroid gland (follicles) and others. b) Tissues without an architecturally defined unit: What is the average size of clonal populations? This group includes stratified/pseudostratified epithelia with a basal layer within which there are stem cells that give rise to a progeny of cells showing upwards migration and lateral expansion (e.g. urothelium, cervical squamous epithelium, respiratory epithelium). This approach can also be used in tissues with a sheet-like cell arrangement, for example brain and adrenal gland. Methods To answer these questions, we will use a range of normal human tissue samples which have already been collected from a single deceased individual. The samples are currently stored in a -80C freezer. Ethanol fixed frozen sections will be prepared from these biopsies. Putative clonal units will be identified and dissected out using laser capture microscopy. DNA extraction will be performed using the in-house (CGP) protease based method. In terms of sequencing methods, the project will be split into 2 phases (2 different approaches): - Phase 1: This part of the project will utilise a combination of low input library preparation (developed by Peter Ellis) and standard whole genome sequencing (HiSeqX). The phase has already started (December 2016). This approach will be particularly useful in investigation of mitotically active tissues. - Phase 2: This part of the project will utilise a combination of low input library method (Peter Ellis) and Bottle-neck sequencing (BotSeqS). BotSeqS is a type of duplex sequencing method that offers a more accurate variant calling and allows genome interrogation at a single cell level. This method is currently being developed and is expected to be implemented in 3-6 months (March-April 2017). This approach will be particularly useful for post-mitotic tissues and tissues without pre-defined architectural units.

  Study EGAS00001002216

• Mayo-Perlegen LEAPS (Linked Efforts to Accelerate Parkinson's Solutions) Collaboration

  We performed a two-tiered, whole-genome association study of Parkinson disease (PD). For tier 1, we individually genotyped 198,345 uniformly spaced and informative single-nucleotide polymorphisms (SNPs) in 443 sibling pairs discordant for PD. For tier 2a, we individually genotyped 1,793 PD-associated SNPs (P<.01 in tier 1) and 300 genomic control SNPs in 332 matched case-unrelated control pairs. We identified 11 SNPs that were associated with PD (P<.01) in both tier 1 and tier 2 samples and had the same direction of effect. For these SNPs, we combined data from the case-unaffected sibling pair (tier 1) and case-unrelated control pair (tier 2) samples and employed a liberalization of the sibling transmission/disequilibrium test to calculate odds ratios, 95% confidence intervals, and P values. A SNP within the semaphorin 5A gene (SEMA5A) had the lowest combined P value (P=7.62E-6). The protein encoded by this gene plays an important role in neurogenesis and in neuronal apoptosis, which is consistent with existing hypotheses regarding PD pathogenesis. A second SNP tagged the PARK11 late-onset PD susceptibility locus (P=1.70E-5). In tier 2b, we also selected for genotyping additional SNPs that were borderline significant (P<.05) in tier 1 but that tested a priori biological and genetic hypotheses regarding susceptibility to PD (n=941 SNPs). In analysis of the combined tier 1 and tier 2b data, the two SNPs with the lowest P values (P=9.07E-6; P=2.96E-5) tagged the PARK10 late-onset PD susceptibility locus. Independent replication across populations will clarify the role of the genomic loci tagged by these SNPs in conferring PD susceptibility. Note: The following instruments were used: 1)clinical assessments form and manual; 2) sibling screening form and manual; 3) unrelated control screening and manual; and 4) risk factors questionnaire and manual. All cases underwent #1, as did sibling controls screening positive (see below). Unrelated controls were not examined. All siblings underwent #2. All unrelated controls underwent #3. All subjects (cases, sibling controls, and unrelated controls) underwent #4. Any publications using the data are to cite the original American Journal of Human Genetics article (Maraganore et al., 2005). Investigators using the data collection instruments are to acknowledge Drs. Maraganore and Rocca, and cite grants ES-10751 and NS-33978.

  Study phs000048

• Type 1 Diabetes Genetics Consortium (T1DGC): Multi-Ethnic ImmunoChip Study

  Type 1 diabetes (T1D) is characterized by an autoimmune attack that destroys the insulin-producing pancreatic beta cells and is driven by diverse genetic and environmental factors. Between 8-100 chromosome regions are known to contain variants that alter T1D risk, substantially fewer than many other common diseases. Less is known about the contribution of T1D risk alleles in non-European populations, despite recent increases in T1D diagnoses in multiple non-European ancestry groups. To address these gaps in T1D genetics, we doubled the sample size from the previous largest T1D association study, genotyped ancestrally diverse T1D cases, controls, and affected families with the Illumina ImmunoChip array, and imputed additional variants using a large haplotype reference panel. After quality filtering, a total of 61,427 participants and 140,333 genotyped ImmunoChip variants were included in analysis, providing dense coverage in 188 autosomal regions ("ImmunoChip regions") and sparse genotyping in other regions of the genome. Each participant was assigned to one of five ancestry groups using k-means clustering of ImmunoChip genotype principal components: European (EUR, N = 47,319), African Admixed (AFR, N = 4,290), Finnish (FIN, N = 6,991), East Asian (EAS, N = 588) and Other Admixed (AMR, N = 2,239). In total, 16,159 T1D cases, 25,386 controls (unrelated) and 6,143 trio families (i.e., an affected child and both parents) were genotyped and included in association analyses. Imputation with the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) multi-ethnic reference panel was used to improve discovery power and fine-mapping resolution. After imputation, the number of variants in ImmunoChip regions with imputation R-squared > 0.8 and MAF > 0.005 in each ancestry group was 322,084 (AFR), 166,274 (EUR), 163,612 (FIN), 137,730 (EAS) and 188,550 (AMR). Imputed genotypes were compared in the same participants who have whole genome sequencing data, resulting in high concordance. Unrelated cases and controls (N = 41,545) were analyzed initially, assuming an additive inheritance model. T1D trio families (N = 6,143 trios, some trio families were multiplex and analyzed as multiple trios) were analyzed separately, with meta-analysis of case-control and trio results used for discovery of regions associated with T1D (p < 5×10-8). Summary-level data at each SNP (genotype and imputed) for type 1 diabetes (outcome) are provided in dbGaP.

  Study phs002468

• Changes in Oral and Gut Microbiota and Incidence and Severity of Patient-Reported Symptoms in Pre- and Post-Kidney Transplant Patients

  This novel prospective cohort explores the relationships between oral and fecal microbiome features (alpha and beta diversity, differential relative abundances of bacterial taxa, and functional genes) and the incidence and severity of psychoneurological symptoms (e.g., pain, fatigue, depression, anxiety, and sleep disturbance) before and after patients receive a kidney transplant from a live donor. Thirty-five subjects provided fecal and saliva specimens for shotgun metagenomic sequencing of gut and oral microbiomes at 3 timepoints: 1) within 4 weeks prior to the transplant surgery (at end-stage kidney disease), 2) 1-3 weeks after the transplant surgery, and 3) at 3 months after the transplant (after restoration of kidney function). Subjects were enrolled between October, 2018, to November, 2021, and all study visits were completed by March, 2022. Data collected includes: Demographic (age, biological sex at birth, race/ethnicity, marital status); clinical data (body mass index, dialysis status, type of dialysis, high vs. low risk immune-suppression protocol, antibiotics during study period); laboratory data (serum creatinine; estimated glomerular filtration rate; serum blood urea nitrogen; immunosuppression trough levels), and outcome data (symptoms such as pain interference, pain intensity, fatigue, anxiety, depression, sleep disturbance, acute rejection, delayed graft failure, graft loss, post-transplant infections, and health-related quality of life). Incidence and severity of symptoms, including pain interference, pain intensity, fatigue, sleep dysfunction, and anxiety/depression-like symptoms, were measured using the Patient Reported Outcome Measurement Systems (PROMIS) 57 v2.1. Health related quality of life was assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF v1.3). The objective of this longitudinal study is to characterize changes in microbial features at baseline, before restoration of kidney function, and over time, after restoration of kidney function via kidney transplantation, and to identify relationships between microbiome features and transplant outcomes (rejection, infection, delayed graft function, graft failure), symptom burden, and health-related quality of life. Shotgun metagenomic sequencing of the oral and gut microbiomes will allow a higher-resolution examination of the gut microbiome compared to 16S rRNA gene amplicon sequencing, and will provide direct evidence of metabolic capabilities of the microbiota. This approach will allow us to explore the dynamic nature of symptom burden, and the effects of demographic and clinical variables on the oral and gut microbiomes before and after restoration of kidney function.

  Study phs002199

• Whole Genome Sequencing and Variant Calling for Autism Families

  We extracted DNA from whole blood or lymphoblast-derived cell lines and assessed the DNA quality with PicoGreenTM and gel electrophoresis. Whole genome sequencing was performed (Illumina HiSeq2000 and Illumina HiSeq X). WGS reads were mapped to the human reference genome assembly hg19 (GRCh37) using Burrows-Wheeler Aligner v.0.7.12 (TCAG) or Isaac v.2.0.13 (Macrogen). For each genome, we performed local realignment and quality recalibration and detected SNVs and small indels using GATK Haplotype Caller v.3.4.6 without genotype refinement. We detected CNVs using ERDS (estimation by read depth with single nucleotide variants) and CNVnator. We detected structural variants using Manta v.0.29.6. When available by the variant caller (i.e. GATK and Manta), trio-based joint variant calling was conducted for each family.

  Dataset EGAD00001008452

• DAC for Central African ancient demography processes NGS dataset

  Title DAC Ancient tree-topologies and gene-flow processes among human lineages in Africa Contacts: Paul Verdu +33144057317 paul.verdu@mnhn.fr CNRS-MNHN-Université de Paris UMR7206 Eco-anthropology Short description The Data Access Committee for acess to genotype and sample information used in the article "Ancient tree-topologies and gene-flow processes among human lineages in Africa" by Gwenna Breton et al. 2025 ensures that data-access requests comply with the Informed Consent provided by donors, and with ethical and deontological guidelines with respect to privacy. DNA samples from individuals were collected with the subjects’ informed consent following the Declaration of Helsinki guidelines and approved by the following Ethics committees: Institut de Recherche pour le Développement (IRD, France); Cameroon Ministry of Scientific Research and Technology; Central African Republic Ministère de l’Enseignement Supérieur et de la Recherche Scientifique; France Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation (Comité de Protection des Personnes DC-2016-2740); French Commission Nationale Informatique et Liberté CNIL (declaration n°1972648); Uganda National Council for Science and Technology; Institutional Review Board of the University of Chicago Biological Sciences Division and the Pritzker School of Medicine University of Chicago Hospitals (protocol number 16986A); Committee for the Protection of Human Subjects of the Trustees of Dartmouth College and the Dartmouth-Hitchcock Medical Center (protocol number 22410); Human Research Ethics Committee (Medical) at the University of the Witwatersrand, Johannesburg (Protocol Numbers: M980553, M050902, M090576, M10270, M180654); Working Group of Indigenous Minorities in Southern Africa (WIMSA); South African San Council (SASC); and the Swedish Ethical Review Authority (Dnr 2019-05174). Requests for accessing all or part of the Central African data used in the article "Ancient tree-topologies and gene-flow processes among human lineages in Africa", by Gwenna Breton et al. 2024 (doi - PENDING), should be addressed to the DAC providing: 1) Data can only be used to explore human genetic evolution, evolutionary ecology and population history 2) The research institution where data will be stored and were analyses will be conducted. 3) The detailed coordinates of the researcher responsible for data storage and analyses. 4) A description (max 20 sentences) of the scientific finality and context of the project and classes of methodological analyses that will be performed to achieve it using the requested data. 5) When applicable, mention also other previously published data sets that will be used jointly with the requested datas et For accessing any or all the Central African genetic data used in the article "Ancient tree-topologies and gene-flow processes among human lineages in Africa", by Gwenna Breton et al. 2024 (doi - PENDING), the requester hereby ensures that: 1) Individual donor privacy should be respected at all times. Data cannot be made publicly available under any circumstances. 2) Data cannot be shared nor transferred to a third party without re-applying for eGA access to the DAC. 3) No direct or indirect commercial use of the data can be made 4) No individual medical genetics or disease diagnostics can be performed with the data 5) No medical or legal forensic investigations can be conducted with the data 6) No genealogical research can be conducted with the data (e.g. no paternity nor maternity testing, no genetic identification, no search of relatives using other datasets) 7) Appropriate citation of the article and data set used for any scientific communication using the data 8) Data is destroyed after the completion of the project. Any further re-use of the data is subject to a novel application to the DAC.

  Dac EGAC50000000447

• Tracking the evolution of Therapy-Related Myeloid Neoplasms using chemotherapy signatures

  Patients treated with cytotoxic therapies, including autologous stem cell transplantation, are at risk for developing therapy-related myeloid neoplasms (tMN). Pre-leukemic clones (i.e., clonal hematopoiesis; CH) are detectable years before the development of these aggressive malignancies, though the genomic events leading to transformation and expansion are not well-defined. Here, leveraging distinctive chemotherapy-associated mutational signatures from whole-genome sequencing data and targeted sequencing of pre-chemotherapy samples, we reconstruct the evolutionary life-history of 39 therapy-related myeloid malignancies. A dichotomy is revealed, in which neoplasms with evidence of chemotherapy-induced mutagenesis from platinum and melphalan are hypermutated and enriched for complex structural variants (i.e., chromothripsis) while neoplasms with non-mutagenic chemotherapy exposures are genomically similar to de novo acute myeloid leukemia. Using chemotherapy-associated mutational signatures as temporal barcodes linked to a discrete clinical exposure in each patient’s life, we estimate that several complex events and genomic drivers are acquired after chemotherapy is administered. For patients with prior multiple myeloma who were treated with high-dose melphalan and autologous stem cell transplantation, we demonstrate that tMN can develop from either a reinfused CH clone that escapes chemotherapy exposure and is selected following reinfusion, or from TP53-mutant CH that survives direct myeloablative conditioning and acquires melphalan-induced DNA-damage. Overall, we reveal a novel mode of tMN progression that is not reliant on direct mutagenesis or even exposure to chemotherapy. Conversely, for tMN that evolve under the influence of chemotherapy-induced mutagenesis, distinct chemotherapies not only select pre-existing CH, but also promote the acquisition of recurrent genomic drivers.

  Study EGAS00001006903

• WGS of cell-free DNA derived from plasma of patients with pediatric sarcoma and healthy controls, and lcWGS/RRBS of matched tumor tissue

  This dataset contains: i) 241 deep (median 12x) whole-genome sequencing profiles of 95 patients with Ewing sarcoma, 31 patients with other pediatric sarcomas, and 22 additional profiles from healthy controls. Sequencing was performed on a NovaSeq 6000 instrument using the NovaSeq S4 2x100 bp configuration. In addition, pilot experiments for 18 cfDNA samples were performed using Illumina HiSeq 2000/2500 machines (2x75 bp configuration). Data is provided as .fastq.gz files (2 files, .R1 and .R2, per sample). i) Low coverage whole-genome-sequencing on 43 tumor biopsy samples from patients with Ewing sarcoma with matched cfDNA samples. The samples were sequenced using a NovaSeq 6000 instrument with the NovaSeq S4 1x100 bp configuration. Data are provided as unmapped (raw) .bam files. iii) Reduced-representation bisulfite sequencing data for 38 tumor biopsy samples from patients with Ewing sarcoma with matched cfDNA samples, and 2 control samples. RRBS libraries were sequenced on Illumina HiSeq 2000/2500 machines. Data are provided as unmapped (raw) .bam files.

  Dataset EGAD00001007080

• H021-Master Umbrella study2 (not to be released)

  Study EGAS00001005145

• APC-related multiple salivary gland lesions

  This study aims to investigate the genetic and molecular mechanisms underlying a novel phenotype of attenuated familial adenomatous polyposis (AFAP), where affected individuals develop multiple salivary gland tumours, including basal cell adenomas and adenocarcinomas.

  Study EGAS50000001159

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 17)

  The dataset contains whole genome sequencing data of 26 high-grade serous carcinoma (HGSC) patients sequenced with Novoseq 6000. The 86 samples are either fresh frozen tumour samples or blood samples. The files provided are paired fastq files.

  Dataset EGAD50000002409

• Molecular analysis of cancer genomes in children with Lynch syndrome: exploring causal associations

  Molecular characterization of 20 tumors of 18 children with Lynch syndrome to investigate causality. This characterization includes the investigation of second hits, tumor mutational load, mutational signatures and MMR protein expression.

  Study EGAS00001006992

• Single Cell RNAseq of blood and tumor from renal cancer patients

  Single-cell RNASeq (scRNAseq) showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and high IL8 expression was associated with the downregulation of the antigen presentation machinery in myeloid cells.

  Study EGAS00001004230