16770 results for "sec+and+unspecified+malignant+neoplasm"

in 41.28 milliseconds.

• High Resolution Analysis of Spatial Interactions of Hundreds of Promoters in HeLa Cells

  In this study we developed a new hybridisation-based promoter Capture-C protocol that makes use of biotinylated dsDNA probes and allows high-resolution promoter interactome description. Experiments aimed to describe spatial interactions of set of 861 promoters were performed in HeLa cells. We have found that enrichment efficiency and quality of final libraries in our study is on a par with established promoter Capture-C protocols. Meanwhile, our version of the probe preparation protocol is reasonably simple and makes Capture-C experiments more affordable and flexible.

  Study phs002014

• Spatial Transcriptomic Analysis (Xenium in situ) of Large Cell Neuroendocrine Carcinoma

  Lung LCNEC (Large Cell Neuroendocrine Carcinoma) has a poor prognosis, and no effective treatment has yet been established. We have discovered that LCNEC exhibits highly heterogeneous distribution of proteins such as neuroendocrine markers and YAP1 within the tumor. We hypothesize that this heterogeneity may be responsible for the variability in chemotherapy effectiveness and treatment resistance among LCNEC patients. Therefore, by using Xenium to analyze gene expression in greater detail along with tumor morphology, we aim to identify new characteristics of LCNEC and explore potential treatment strategies.

  Study JGAS000733

• NHLBI TOPMed: African American Sarcoidosis Genetics Resource

  This study aims to comprehensively interrogate the genomes of African American sarcoidosis families. Sarcoidosis is characterized by a hyperimmune response resulting in granuloma formation in multiple organs. It affects African Americans (AAs) more frequently and more severely than whites. While previous linkage, admixture, candidate gene and genome-wide association (GWA) studies show statistically compelling effects, causal variants are still unknown and much of sarcoidosis heritability is yet to be explained. This "missing" heritability likely includes effects of both common (minor allele frequency (MAF)>5%) and rare variants (MAF

  Study phs001207

• Androgen activity in the normal male embryonic hindbrain drives lethal PFA ependymoma

  PFA ependymoma is an unusual infantile brain tumor with few somatic mutations, thought to be driven by epigenetic mechanisms. PFA ependymomas have a markedly higher incidence, and a worse prognosis in males as compared to female infants. Here we show that the cellular hierarchy of male PFA is less differentiated than female PFA. Androgen supplementation promotes the growth of PFA ependymoma. We conclude that androgen signaling in both the normal developing hindbrain, and PFA ependymoma are both necessary and sufficient to promote growth and delay differentiation.

  Study EGAS50000000507

• ARID1A Mutations in Endometriosis-Associated Ovarian Carcinomas

  We have sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas

  Study EGAS00000000075

• Single cell transcriptome sequencing of the developing human embryonic meninges

  There are no effective medical therapies for meningiomas, partly due to our limited understanding of their cellular origin and composition For this purpose, we generated data to make a comprehensive reference single cell and spatial transcriptomic atlas of human fetal meninges. Samples of meninges from human embryos of post-conceptional week (PCW) 5.0-13.0 were dissected and subject to 10Xgenomics chromium single cell RNA sequencing with the purpose of identifying cell types and gene expression programs for normal meninges development, Furthermore, this dataset should help discover cells of origin for meningiomas.

  Study EGAS50000000980

• A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome

  Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) tumors leads to a significant proportion of unresolved cases classified as suspected Lynch syndrome (SLS). A tumor-focused testing approach reclassified 86.9% of SLS into Lynch syndrome, sporadic dMMR or MMR-proficient cases. These findings support the incorporation of tumor sequencing and alternate MLH1 methylation assays into clinical diagnostics to reduce the number of SLS patients and provide more appropriate surveillance and screening recommendations.

  Study EGAS50000000021

• PARK7/DJ-1 deficiency modulates microglial activation in response to LPS-induced inflammation

  Specific microglia responses are thought to contribute to the development and progression of various neurodegenerative diseases, including Parkinson’s disease (PD). However, the phenotypic acquisition of microglial cells and their role during the underlying neuroinflammatory processes remain largely obscure. Here, according to the multiple-hit hypothesis, which stipulates that PD etiology is determined by a combination of genetics and various environmental risk factors, we investigate microglial transcriptional programs and morphological adaptations under PARK7/DJ-1 deficiency, a genetic cause of PD, during lipopolysaccharide (LPS)-induced inflammation.

  Study EGAS50000000202

• Mosaic structural variation sample

  Mosaic Normal-Tumor genomes are generated from real normal-tumor pairs with validated somatic variants. In this case, validated variants from the GRIDSS2 paper. Mosaic genomes were generated using GenomeMosaicMaker, an open-source software tool designed and implemented for this specific purpose. The variants provided in the VCF truth file for each mosaic tumor/normal pair were annotated using funnSV for SVs and VEP for SNVs and indels. All CRAM files are aligned to GRCh37. Please see https://github.com/EUCANCan/oncoliner and https://github.com/Computational-Genomics-BSC/GenomeMosaicMaker for more information.

  Study EGAS50000000460

• Manchester Eye Tissue Repository Genome-Transcriptome Project

  The Manchester Eye Tissue Repository Genome-Transcriptome (METR-GT) Project comprises whole genome sequencing data and paired short read, high-depth bulk-RNA sequencing data from the neurosensory retina (NSR) and the retinal pigment epithelium (RPE) from 201 unrelated individuals that donated eye-tissue post-mortem. None of the individuals included in the cohort had phenotypic presentation, assessed post-mortem, consistent with late-stage AMD or monogenic ophthalmic disorders. In this dataset we include WGS fastq files, WGS VCF files (at an individual level and an aggregate VCF that has undergone variant-level quality control), RNASeq BAM files of the NSR and RPE, gene expression quantification files of the NSR and RPE (including raw gene counts generated by RNASeQC and estimated TPM and FPKM values generated by RSEM). Additionally, we have included the output files from eQTL mapping in both tissues, generated by tensorQTL and instances of aberrant gene expression events generated by the OUTRIDER module of the DROP pipeline.

  Dataset EGAD50000002082

• Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling

  Pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT) are two distinct vascular diseases linked to impaired signaling through bone morphogenetic protein (BMP) receptor complexes in endothelial cells. Although BMP-9 plays a central role in activating this pathway by binding to ALK1 and BMPR-­II, its precise function in the pulmonary microvasculature has remained unclear. In this study, we uncover a previously unrecognized role for BMP-9 in regulating pulmonary vascular architecture and homeostasis. Our findings demonstrate that BMP-9 signaling intersects with VEGF pathways and contributes to the delicate balance between vascular growth and remodeling in the lungs. We also show that disruption of this pathway can shift vascular responses toward an HHT-­like state, potentially altering disease susceptibility. These insights offer a unique perspective on how BMP-9 and ALK1 shape pulmonary vascular biology and suggest that targeting this axis could inform future strategies for treating complex vascular diseases such as PAH.

  Dataset EGAD50000001496

• Whole genome sequencing of neuroendocrine tumors of the small intestine

  This dataset contains whole genome sequences for 13 patients with neuroendocrine (unique/multiple) tumor(s) of the small intestine. There are in total 25 tumor and 12 matched normal genomes. Libraries were prepared using a Illumina DNA PCR Free kit following the manufacturer’s recommendations and sequencing was performed on Illumina Novaseq6000 machine with a 2x151bp paired-end fashion. It contains data for : - 1 patient with 4 tumors and 1 matched normal - 1 patient with 3 tumors and 1 matched normal - 1 patient with 2 tumors, 1 liver metastasis and 1 matched normal - 2 patients with 1 tumor, 1 mesenteric nodule and 1 matched normal - 7 patients with 1 tumor and 1 matched normal - 1 patient with 3 tumors and 1 mesenteric nodule

  Dataset EGAD50000000907

• Elucidation of factors involved in the progression of diabetic kidney disease

  A new concept of diabetic kidney disease has been proposed as a more comprehensive disease concept for chronic kidney disease associated with diabetes.The factors and molecular mechanisms that determine the course of diabetic nephropathy, whether it is the classic diabetic nephropathy or the rapid decliner, are unknown.In order to develop effective diagnostic and therapeutic methods for individual cases and conditions of diabetic nephropathy patients, it is necessary to elucidate the molecular mechanisms.We performed single-cell RNA sequencing and analyzed the characteristics of 3 cases of rapid decline in diabetic kidney disease.

  Study JGAS000802

• Sequencing_probands_and_families_with_severe_insulin_resistance_syndromes

  This is an ongoing project and continuation to all the sequencing we have been doing over the last few years. We have some additional families and probands with syndromes of insulin resistance not previously sequenced within uk10k or other core funded projects. We would like to complete the sequencing in all of the good quality families and probands we have, this would require another ~50 samples to be WES sequenced. This cohort has already proven to be a rich source of interesting findings with papers in Science and Nature genetics.

  Study EGAS00001000488

• Myelodysplastic_syndrome_whole_genomes

  Wholegenome libraries will be prepared from at least two serial samples reflecting different stages of disease progression and matched constitutional DNA for 30 Myelodysplastic syndrome patient samples. Five lanes of Illumina HiSeq sequencing will be performed on each of the tumour samples and four lanes for each of the constitutional DNA. Sequencing data will mapped to build 37 of the human reference genome and analysis will be performed to characterize the spectrum of somatic variation present in these samples including single base pair mutations, insertions, deletions as well as larger structural variants and genomic rearrangements.

  Study EGAS00001000291

• Queensland Melanoma Genomic Biomarker Study

  There is a clinical need to identify melanoma patients not likely to benefit from current targeted and immuno-therapy and identify biomarkers that can predict patient outcome. Genomic biomarkers are not yet part of staging but show promising results. The aim of this study was to determine genomic and image-based biomarkers as adverse prognostic factors in stage III/IV melanoma patients with resected disease. We found combining genomic and PET/CT derived biomarkers with current clinical assessment may offer additional prognostic tools to stratify patients in the clinic.

  Study EGAS00001004619

• Myeloproliferative_Disease_Whole_Genomes

  Wholegenome libraries will be prepared from at least two serial samples reflecting different stages of disease progression and matched constitutional DNA for 30 Myeloproliferative Disease samples. Five lanes of Illumina HiSeq sequencing will be performed on each of the tumour samples and four lanes for each of the constitutional DNA. Sequencing data will mapped to build 37 of the human reference genome and analysis will be performed to characterize the spectrum of somatic variation present in these samples including single base pair mutations, insertions, deletions as well as larger structural variants and genomic rearrangements.

  Study EGAS00001000290

• Biological insights from the whole genome sequences of human embryonic stem cell lines

  Human embryonic stem cells (hESCs) are a powerful tool for the study of human development and can form the basis of cellular disease models or therapies. However, the genetic make-up and stability of hESCs has not been systematically studied at a genome-wide level with single nucleotide resolution. We therefore sequenced the whole genome and whole exomes of widely available hESC. This online resource will enable investigators to access raw sequencing data in order to interrogate cell lines for different disease- and trait-associated genetic variants.

  Study EGAS00001002400

• H3Africa - Collaborative African Genomics Network

  Genomic studies have become one of the potential tools that could aid in the understanding of disease. HIV disease progression and active TB infection have been studied using these genomic methods to interrogate host factors associated with these diseases and their progression. Prior work has focused on adult populations and limited African cohorts. The Collaborative African Genomics Network aims to fill this gap by conducting HIV and TB disease mapping studies in African children to understand how genetic variation impacts disease progression through the use of genomic technologies.

  Study EGAS00001002656

• Transcriptome analysis of samples derived from GBM tumors, and relevant cell lines established and maintained at 5% or 20% oxygen.

  The goal of the study was to compare the transcriptome of patient-derived serum-free GBM cell lines to that of parental GBM tumors. For each patient, three samples were analyzed: GBM tumor, cell line growing at 5% oxygen, and cell line growing at 20% oxygen. Analysis demonstrated the enrichement in cell cycle and DNA repair gene expression in cell lines when compared to parental tumor sample. Moreover, cells cultured at 5% oxygen maintained hypoxia, carbon metabolism and tumor progression transcriptional pattern characteristic for GBM.

  Study EGAS00001006267

• Whole genome sequencing based on short and long reads from GM09237 cell line with and without folate depletion

  To asess changes in the DNA-sequence occurring as a result of folate deprivation, DNA extracted from the GM09237 cell line grown with and without folate was sequenced using short read and long read sequencing. The DNA was extracted from cells cultured with either normal medium or medium with no folic acid for 5 days, and then sequenced by BGI PE100 platform (100 bp paired-end sequencing 60x coverage; performed by BGI), or PacBio Sequel system (SMARTbell; performed by BGI) respectively.

  Study EGAS00001005345

• Genomic History of the Solomon Islands

  The aim of this study was to provide for a better understanding of the genetic relationships among and between populations of Near and Remote Oceania, with a focus on the initial settlement of the Solomon Islands and their role in the first dispersal of people from Near into Remote Oceania. Irina Pugach, Ana T Duggan, D Andrew Merriwether, Françoise R Friedlaender, Jonathan S Friedlaender, Mark Stoneking, "The Gateway from Near into Remote Oceania: New Insights from Genome-Wide Data", Molecular Biology and Evolution, Volume 35, Issue 4, April 2018, Pages 871–886

  Study EGAS00001006116

• RNA-seq analysis of metastatic prostate cancer solid tumor biopsies

  The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era of modern androgen receptor (AR)–targeting therapy. We sought to characterize the clinical and genomic features of t-SCNC in a multi-institutional prospective study. Patients with progressive, metastatic castration-resistant prostate cancer (mCRPC) underwent metastatic tumor biopsy and were followed for survival. t-SCNC is present in nearly one fifth of patients with mCRPC and is associated with shortened survival.

  Study EGAS00001006369

• Pediatric Patient-Derived-Xenograft development in MAPPYACTS – international pediatric cancer precision medicine trial in relapsed and refractory tumors

  Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Paediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This new PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and new treatments development in advanced pediatric malignancies.

  Dataset EGAD00001011048

• National Human Genome Research Institute (NHGRI) GENEVA Genome-Wide Association Study of Venous Thrombosis (GWAS of VTE)

  Overview: Our overall long-term goal is to determine risk factors for the complex (multifactorial) disease, venous thromboembolism (VTE), that will allow physicians to stratify individual patient risk and target VTE prophylaxis to those who would benefit most. In this genome-wide association case-control study (1300 cases and 1300 controls) we hope to identify susceptibility variants for VTE. Mutations within genes encoding for important components of the anticoagulant, procoagulant, fibrinolytic, and innate immunity pathways are risk factors for VTE. We hypothesize that other genes within these four pathways or within other pathways also are VTE disease-susceptibility genes. Therefore, we performed a genome wide association (GWA) screen and analysis using the Illumina 660W platform to identify SNPs within 1,300 clinic-based, non-cancer VTE cases primarily from Minnesota and the upper Midwest USA, and 1300 clinic-based, unrelated controls frequency-matched on patient age, gender, myocardial infarction/stroke status and state of residence. This is a subset of a slightly larger candidate gene study using 1500 case-control pairs to identify haplotype-tagging SNPs (ht-SNPs) in a large set of candidate genes (n~750) within the anticoagulant, procoagulant, fibrinolytic, and innate immunity pathways. Study Populations. Cases. VTE cases were consecutive Mayo Clinic outpatients with objectively-diagnosed deep vein thrombosis (DVT) and/or pulmonary embolism (PE) residing in the upper Midwest and referred by Mayo Clinic physician to the Mayo Clinic Special Coagulation Laboratory for clinical diagnostic testing to evaluate for an acquired or inherited thrombophilia, or to the Mayo Clinic Thrombophilia Center. Any person contacted to be a control but discovered to have had a VTE was evaluated for inclusion as a case. Cases were primarily residents from Minnesota, Wisconsin, Iowa, Michigan, Illinois, North or South Dakota, Nebraska, Kansas, Missouri and Indiana. A DVT or PE was categorized as objectively diagnosed when (a) confirmed by venography or pulmonary angiography, or pathology examination of thrombus removed at surgery, or (b) if at least one non-invasive test (compression duplex ultrasonography, lung scan, computed tomography scan, magnetic resonance imaging) was positive. A VTE was defined as: Proximal leg deep vein thrombosis (DVT), which includes the common iliac, internal iliac, external iliac, common femoral, superficial [now termed "femoral"] femoral, deep femoral [sometimes referred to as "profunda" femoral] and/or popliteal veins. (Note: greater and lesser saphenous veins, or other superficial or perforator veins, were not included as proximal or distal leg DVT). Distal leg DVT (or "isolated calf DVT"), which includes the anterior tibial, posterior tibial and/or peroneal veins. (Note: gastrocnemius, soleal and/or sural [e.g., "deep muscular veins" of the calf] vein thrombosis was not included as distal leg DVT). Arm DVT, which includes the axillary, subclavian and/or innominate (brachiocephalic) veins. (Note: jugular [internal or external], cephalic and brachial vein thrombosis was not included in "arm DVT"). Hepatic, portal, splenic, superior or inferior mesenteric, and/or renal vein thrombosis. (Note: ovarian, testicular, peri-prostatic and/or pelvic vein thrombosis was not included). Cerebral vein thrombosis (includes cerebral or dural sinus or vein, saggital sinus or vein, and/or transverse sinus or vein thrombosis). Inferior vena cava (IVC) thrombosis Superior vena cava (SVC) thrombosis Pulmonary embolism Patients with VTE related to active cancer, antiphospholipid syndrome, inflammatory bowel disease, vasculitis, a rheumatoid or other autoimmune disorder, a vascular anomaly (e.g., Klippel-Trénaunay syndrome, etc.), heparin-induced thrombocytopenia, or a mechanical cause for DVT (e.g., arm DVT or SVC thrombosis related to a central venous catheter or transvenous pacemaker, portal and/or splenic vein thrombosis related to liver cirrhosis, IVC thrombosis related to retroperitoneal fibrosis, etc.), with hemodialysis arteriovenous fistula thrombosis, or with prior liver or bone marrow transplantation were excluded. Controls. A Mayo Clinic outpatient control group was prospectively recruited for this study. Controls were frequency-matched on the age group (18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80+ years), sex, myocardial infarction/stroke status, and state of residence distribution of the cases. We selected clinic-based controls using a controls' database of persons undergoing general medical examinations in the Mayo Clinic Departments of General Internal Medicine or Primary Care Internal Medicine. Additionally persons undergoing evaluation at the Mayo Clinic Sports Medicine Center, and the Department of Family Medicine were screened for inclusion as controls. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to venous thrombosis through large-scale genome-wide association studies of 1,300 clinic-based, VTE cases and 1300 clinic-based, unrelated controls. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000289

• Asian Indian Diabetic Heart Study (AIDHS) /Sikh Diabetes Study (SDS)

  The Punjabi Sikh population is a well-defined, carefully collected homogeneous sample from northern India and the US. It has unique characteristics, which are ideal for genetic studies. Sikhs are strictly a non-smoking population and about 50% of participants are life-long vegetarians. All subjects included in the genome-wide association studies (GWAS) were recruited from one geographical location. Our population demonstrates a strong familial clustering of type 2 diabetes and related cardio-metabolic disorders that may be genetic and we believe that the contribution of alleles at specific loci are likely to be unique to Punjabi Asians compared to Europeans. Our group first showed that the association of a common variant at rs9939609 in the FTO (fat mass and obesity) gene in South Asians was independent of BMI (PMID:18598350) in contrast to Europeans where the association of same variant with T2D is mediated through obesity (PMID:17434869). These findings were later confirmed in an independent sample of South Indians (PMID:19005641), Pakistanis (PMID:21294771), and even East and South Asians in a large meta-analyses study comprising 96,551 individuals (PMID: 22109280). Earlier reported association of MTNR1B with fasting glucose concentrations and type 2 diabetes in European GWAS could not be confirmed in our Sikh cohort. On the other hand, our study revealed, for the first time, a significant protective association of another less common variant in MTNR1B with fasting glucose levels that was modulated by obesity. Ours was the first report that suggested that the low CETP activity was associated with higher CAD risk (PMID:22143414) in South Asians and that the genetic effects are significantly modulated by environmental factors (alcohol consumption). Our recent GWAS on type 2 diabetes has identified a novel locus at chromosome 13q12 in the SGCG gene (p=1.82x10-8) associated with type 2 diabetes (PMID:23300278) in Punjabi Sikhs. From these findings, we are optimistic that our resource will provide new insights to gene functions in the diabetic pathway and better help researchers to understand and translate these insights to novel therapeutic treatment and early prevention to T2D that may be important beyond Indians.

  Study phs000583

• HudsonAlpha Institute for Biotechnology Clinical Sequencing Exploratory Research (CSER): Genomic Diagnosis in Children with Developmental Delay

  The overarching goal of this project is to explore the ability for whole exome and genome sequencing technologies to identify the genetic causes of unexplained developmental delay, intellectual disability (DD/ID), and related congenital anomalies in children. Such information may be useful as an endpoint to the otherwise fruitless "diagnostic odyssey" that many DD/ID affected families undergo and in some cases, identification of these genetic variants may point to better therapeutic or educational options by precisely defining the root cause(s) of the child's condition. We seek to identify causal, diagnostically relevant, genetic variants in children with developmental delay and/or intellectual disability (DD/ID). In addition, because our analytical approach includes sequencing probands and their parents (parent-offspring trios and duos; parents are sequenced when available), secondary findings will be returned to adults (parents) at their request. The aims of this research project include: 1) Use exome and whole genome sequencing to identify genetic variation that results in DD/ID. 2) Return primary genetic results (DD/ID causative) as well as secondary findings to probands and their parents, respectively. 3) Understand how the return of genomic test results affects the health and well-being of study participants. The children participating in this study are patients at, or referrals to, North Alabama Children's Specialist (NACS) in Huntsville, Alabama. All blood samples from probands and their parents will be collected at NACS (project 1). Sequencing will be completed at the HudsonAlpha Institute for Biotechnology, with validation (via Sanger sequencing) conducted at Emory University for all returned variants (project 2). The University of Louisville will oversee questionnaires, surveys and interviews aimed at understanding study participants' perception of, and response to, genetic test results, in addition to assessment of secondary findings preferences (project 3).A subset of variants, largely those determined to be diagnostic or variants of uncertain significance for study participants at the time of disclosure, have been submitted to ClinVar. These variants are listed as part of the "CSER-HudsonAlpha" study within the database.

  Study phs001089

• DNA-Sequencing of Baseline Plasma From the Phase III Alliance A031201 Trial

  Liquid biopsy assays tailored for metastatic castration-resistant prostate cancer (mCRPC) patients are needed to identify molecular alterations and predict survival in the context of androgen receptor (AR) inhibitors. We developed a novel plasma cell-free DNA (cfDNA) sequencing assay to detect circulating tumor DNA (ctDNA) and alterations in key mCRPC driver genes, and tested associations with clinical features and survival outcomes in a phase III trial. cfDNA was isolated from evaluable baseline plasma specimens of untreated mCRPC patients (n=790) enrolled in the Alliance A031201 randomized phase III trial (NCT01949337) prior to enzalutamide therapy with or without abiraterone acetate and prednisone. A customized targeted cfDNA sequencing assay was used to detect AR and non-AR alterations in mCRPC. For this, DNA-seq libraries were constructed from cfDNA using Takara ThruPLEX Tag-Seq or Plasma-Seq kits, and subjected to hybridization enrichment using a custom-designed Agilent SureSelect bait panel. Post-capture DNA-seq libraries were pooled and sequenced on an Illumina HiSeq 2500 using 2x150 bp settings. ctDNA positivity was defined as >20% ctDNA using an aneuploidy-based estimate derived from ichorCNA (Group 1) or a novel definition of ≤20% ctDNA, but with detection of any alteration in AR, or gain of MYC and/or MYCN (Group 2). cfDNA sequencing data was obtained from 776 patients. There were 480/776 (62%) ctDNA-positive patients, with 324 (42%) in Group 1 and an additional 156 (20%) in Group 2 with AR or MYC/MYCN alterations detected. ctDNA-positive patients in Groups 1 and 2 had similarly poor median overall survival (OS) of 25.4 months (95% CI: 21.8-29.0) and 29.7 months (95% CI: 27.3-35.5), respectively, as compared to ctDNA-negative patients who had a median OS of 49.1 months (95% CI: 42.3-53.5). Relative to ctDNA-negative patients, OS was inferior in ctDNA-positive patients in Group 1 (HR 2.3, 95% CI: 1.9-2.9, P AR inhibitors in a contemporary phase III trial.

  Study phs003325

• Columbia-Yale-Bilkent Study: Genetics Study of Essential Tremor

  This is a research development/planning grant application to initiate collaborative studies with investigators at Bilkent University in Turkey to study the genetics of Essential Tremor (ET). ET is one of the most common neurological diseases, with an estimated 7 million affected individuals in the United States. The most characteristic clinical feature of ET is a kinetic tremor in the hands or arms, which is mild early in the disease process. As the disease progresses, tremor becomes more severe and more anatomically widespread (e.g., head, trunk). Aside from tremor, patients with ET may also present with other motor features including gait ataxia. Non-motor features can include psychiatric manifestations, cognitive decline and dementia. Despite its extraordinarily high prevalence, the genetic causes of ET are largely unknown. We propose to develop a genetic study of ET focusing on consanguineous families in Turkey. Turkey with a population of about 70 million has a high rate of consanguineous marriages. The rate of consanguinity is estimated to be as much as 20-25% with approximately 70% of all consanguineous marriages involving first cousins. Studying the genetics of ET in the Turkish population, particularly in large consanguineous families, may identify novel genetic causes of ET that are also relevant to ET populations in the United States and worldwide. The proposed research has a high probability of success with our collaborators Drs Ozcelik and Tekinay's expertise in human genetics and functional studies together with an established resource of large consanguineous ET families. The specific aims of this planning grant are to: (1) further develop and solidify collaborations with the team in Bilkent and define the scope of the research that will be the focus of an R01 application, (2) assess the Bilkent team's resources and needs in order to successfully conduct the research, (3) implement cross-training between the United States and Turkish groups in the areas of human genetics, genetic epidemiology and risk factor assessment, genomics, clinical diagnosis, functional studies and personalized genomic medicine, and (4) conduct pilot studies to generate preliminary data necessary for an R01 application.

  Study phs001507

• UK10K NEURO GURLING

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set consists of DNA from multiply affected schizophrenia families. The families have been diagnosed using the SADS-L clinical instrument which gives diagnoses at the probable level of the research diagnostic criteria (RDC). In addition all diagnoses are available using DSMIIIR criteria. These criteria are widely accepted as being valid and reliable for the diagnosis of schizophrenia. All families have been collected to ensure that they are uni-lineal for transmission of schizophrenia, i.e. they have only one affected parent with schizophrenia, or a relative of only one transmitting or obligate carrier parent with schizophrenia. Families with bi-lineal transmission of schizophrenia (i.e. with both parents being affected) were not sampled for this study. All families have multiple cases of schizophrenia and related disorders. The families have been selected to ensure there are no cases of bipolar disorder within them and that they do not contain bipolar disorder in any relatives on either side of the family.For further information on this cohort please contact Hugh Gurling (h.gurling@ucl.ac.uk).

  Study EGAS00001000225

• Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets

  Untreated prostate cancers rely on androgen receptor (AR) signaling for growth and survival, forming the basis for the initial efficacy of androgen deprivation therapy (ADT). Yet, the disease can relapse and progress to a lethal stage termed castration-resistant prostate cancer (CRPC). Reactivation of AR signaling represents the most common driver of CRPC growth and next generation AR signaling inhibitors (ARSIs) are now used in combination with ADT as a first line therapy. However, ARSIs can result in selective pressure generating AR-independent tumors. The transition from AR-dependence frequently accompanies a change in phenotype resembling developmental trans-differentiation or ‘lineage plasticity’. Neuroendocrine prostate cancer, which lacks a defined pathologic classification, is the most studied type of lineage plasticity. However, most AR-null tumors do not exhibit neuroendocrine features and are classified as ‘double-negative prostate cancer’, the drivers of which are poorly defined. Lineage plasticity studies in CRPC are limited by the lack of genetically defined patient-derived models that recapitulate the disease spectrum. To address this, we developed a biobank of organoids generated from patient biopsies to study the landscape of metastatic CRPC and allow for functional validation assays. Proteins called transcription factors (TFs) are drivers of tumor lineage plasticity. To identify the key TFs that drive the growth of AR-independent tumors, we integrated epigenetic and transcriptomic data generated from CRPC models. By presenting a map of the chromatin accessibility and transcriptomic landscape of CRPC using a diverse biobank of organoids, PDXs and cell lines that recapitulate the heterogeneity of metastatic prostate cancer, we validate CRPC-AR and CRPC-NE subtypes and reveal two subtypes of AR-negative/low samples as well as their respective masterTFs. Additional analysis revealed a model in which YAP, TAZ, TEAD and AP-1 function together and drive oncogenic growth in CRPC-SCL samples. Overall, we show here how an approach to stratify CRPC patients into four subtypes using their transcriptomic signatures can potentially inform upon appropriate clinical decisions.

  Study EGAS00001006059

• Gene expression-based prediction of pazopanib efficacy in sarcoma (HIPO, H021)

  The multi-receptor tyrosine kinase (RTK) inhibitor pazopanib is approved for the treatment of advanced non-adipocytic soft-tissue sarcoma and has also shown activity in other sarcoma subtypes. However, its clinical efficacy is highly variable, and no reliable predictors exist to date to select patients who are most likely to benefit from this drug. We analyzed the molecular profiles and clinical outcomes of pazopanib-treated sarcoma patients enrolled in a prospective observational study by the German Cancer Consortium, DKTK MASTER, that employs whole-genome/exome sequencing (WGS/WES) and transcriptome sequencing to inform the care of adults with advanced cancer across histologies who are younger than 51 and patients with rare tumors, including rare subtypes of more common entities, regardless of age.​ Among a total of 109 patients with available WGS/WES data, there was no correlation between clinical parameters, specific genetic alterations, or mutational signatures and clinical outcome. In contrast, analysis of a subcohort of 62 patients who underwent molecular analysis before pazopanib treatment and had transcriptome sequencing data available showed that mRNA levels of NTRK3 (hazard ratio [HR]=0.53, p=0.021), IGF1R (HR=1.82, p=0.027), and KDR (HR=0.50, p=0.011) were independently associated with progression-free survival (PFS). Based on the expression of these RTK genes, i.e., the features NTRK3-high, IGF1R-low, and KDR-high, we developed a pazopanib efficacy predictor (PEP) that stratified patients into three groups with significantly different PFS (p<0.0001). Application of the PEP to an independent cohort of pazopanib-treated sarcoma patients from DKTK MASTER (n=43) confirmed its potential to separate patient groups with significantly different PFS (p=0.02), whereas no such association was observed in sarcoma patients from DKTK MASTER (n=77) or The Cancer Genome Atlas sarcoma cohort (n=256) who were not treated with pazopanib. A score based on the combined expression of NTRK3, IGF1R, and KDR allows identification of sarcoma patients with good, intermediate, and poor outcome following pazopanib therapy and warrants investigation as a predictive tool in prospective studies to optimize the use of this drug in the clinic.

  Study EGAS00001005836

• Characterization of Cell Free Plasma Methyl-DNA From Xenografted Tumors to Guide the Selection of Diagnostic Markers for Early-Stage Cancers

  Circulating cell-free methyl-DNA (mcfDNA) contains promising cancer markers but its low abundance and possibly diverse origin pose challenges toward the accurate diagnosis of early stage cancers. By whole-genome bisulfite sequencing (WGBS) of cell-free DNA (cfDNA) from about 0.5 mL plasma of mice xenografted with human tumors, we obtained and aligned the reads to the human genome, filtered out the mouse and carrier bacterial sequences, and confirmed the tumor origin of methyl-cfDNA (mctDNA) by methylation-sensitive restriction enzyme digestion prior to species-specific PCR. We estimated that human tumor-specific reads (ctDNA) or mctDNA comprised about 0.29 or 0.01%, respectively of the xenograft mouse cfDNA, and about 0.029 or 0.001% of the cfDNA of human early stage cancer patients. Similar WGBS of early stage (0-II, node- and metastasis-free) breast, lung or colorectal cancer samples identified hundreds of specific DMRs (differentially methylated regions) compared to healthy controls. Their association with tumourigenesis was supported by stage-dependent methylation, tumor suppressor or oncogene clusters, and genes also identified in the xenograft samples. Using 20 three-cancer-common and 17 colorectal cancer-specific DMRs in combination (top 0.0018% of the WGBS methylation clusters) was sufficient to distinguish the stage I colorectal cancers from breast and lung cancers and healthy controls. Our data thus confirmed the tumor origin of mctDNA by sequence specificity, and provide a selection threshold for authentic tumor mctDNA markers toward precise diagnosis of early stage cancers solely by top DMRs in combination. Biological Materials were provided by the Ontario Tumour Bank, which is funded by the Ontario Institute for Cancer Research Reference for citation: Ling Liu, Jinghua Feng, Julian Polimeni, Manli Zhang, Hai Nguyen, Urmi Das, Xu Zhang, Harminder Singh, Xiao-Jian Yao, Etienne Leygue, Sam K.P. Kung, and Xie J. Characterization of cell free plasma methyl-DNA from xenografted tumours to guide the selection of diagnostic markers for early-stage cancers. Frontiers in Oncology, 2021 Feb. 5. DOI: 10.3389/fonc.2021.615821.

  Study EGAS00001006175

• Non Dystrophic Myotonias: Genotype-Phenotype Correlation and Longitudinal

  NMD are rare ion channel disorders. The optimal management and treatment of these disorders are not known. This multi-center proposal will allow the prospective collection of standardized data from a critical number of patients to help better define the clinical features of NDM. The data will also be used to establish clinically relevant endpoints for use in therapeutic trials. The identification and genetic characterization of patients will facilitate recruitment of participants for future therapeutic trials. Ultimately, the information gained will lead to the improvements in the treatment and management of NMD with an associated reduction in morbidity and improvement in patient quality of life.

  Study phs000578

• GCAT | Genomes for life

  The GCAT project is a prospective cohort study that was designed to recruit the general population of Catalonia, the north-east region of Spain. This study is a long-term genomic, environmental and lifestyle cohort project that aims to evaluate and track multiple pathologies as well as biologically related traits. By the end of 2017, the GCAT Study had recruited a total of 20 000 participants aged 40–65 years. Participants who agreed to take part in the study completed a self-administered computer-driven questionnaire, and underwent blood pressure, cardiac frequency and anthropometry measurements. For each participant, blood plasma, blood serum and white blood cells are collected at baseline. The GCAT Study has access to the electronic health records of the Catalan Public Healthcare System. Participants are followed biannually for/during, at least, 20 years after recruitment. Therefore, the GCAT Study offers a unique opportunity to integrate diverse data to allow the identification of novel relations among different biomarkers and conditions. Results may lead to the development of new genetic, genomic, epigenomic and proteomic diagnoses and screening tests, as well as new public health recommendations. The only currently available population-based prospective cohort study in Spain to the date, including more than 4899 genotyped participants and 800 whole genome sequences is now stored in the EGA archive under accession id EGAS00001003018.

  Blog gcat-genomes-for-life

• Carcinoma of Unknown Primary (CUP): A comparison across tissue and liquid biomarkers (CUP-COMP) study

  The Carcinoma of Unknown Primary (CUP): A comparison across tissue and liquid biomarkers (CUP-COMP) study (NCT: NCT04750109) was sponsored by The Christie NHS Foundation Trust and funded by Innovate UK. Data generated include: A) Whole genome sequencing* of paired germline blood and tumour tissue B) Whole genome sequencing *of germline blood only C) Next-generation sequencing of circulating tumour DNA (FoundationOne Liquid CDX) D) Next-generation sequencing of tumour tissue (FoudationOne CDX) *Whole genome sequencing - germline sample at 30x coverage and somatic sample at 75x coverage performed by Illumina NovaSeq 6000 instrument in the 150bp PE read mode.

  Study EGAS00001008239

• Single-cell atlas of penile cancer reveals TP53 mutations as driver for an aggressive phenotype, irrespective of HPV status, and provides clues for treatment personalization

  Our aim was to identify molecular differences in the microenvironment of penile squamous cell carcinoma (PSCC) stratified by TP53 loss-of-function (TP53LOF) mutations and HPV-status. Hence, we present a first single-cell transcriptomic atlas of PSCC. Stratification based on TP53 and HPV-status uncovered differences in CSS and underlying molecular pathways. Our data indicate that TP53LOF tumors are characterized by worse biological behavior regardless of HPV-status. These findings and further research are essential for trial design in PSCC, allowing us to move away from the current one-size-fits-all approach.

  Study EGAS50000000217

• Genomic analysis of head and neck squamous cell carcinoma upon acquired resistance to cetuximab

  Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab) remain the only FDA-approved targeted therapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Unfortunately, most patients develop acquired resistance to cetuximab and there is currently no further therapeutic option for these patients (unmet clinical need), thereby highlighting the need to better understand resistance-causing mechanisms. Here, we carried out whole-exome sequencing on 2 cetuximab-sensitive and -resistant patient-derived xenograft models of HNSCC. Our data reveal several genetic alterations (mutations and copy number variations) associated with acquired resistance to anti-EGFR therapy.

  Study EGAS50000000800

• Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals

  This study presents a methodology for detecting circulating tumor DNA (ctDNA) using deep whole-genome TET-Assisted Pyridine Borane Sequencing (TAPS), a less destructive alternative to bisulphite sequencing. The method enables simultaneous analysis of genomic and methylomic data for multi-cancer detection and monitoring minimal residual disease. In a diagnostic accuracy study across various cancer types, it achieved 85.3% sensitivity and 88.8% specificity, with validation done using matched tumour biopsies. Additionally, in silico validation showed strong discrimination at low ctDNA levels. The approach also successfully tracks tumour burden and ctDNA shedding from precancerous lesions post-treatment, making it ready for further clinical testing.

  Study EGAS50000000715

• Peripheral blood DNA transcriptomics of ustekinumab treatment response in patients with Crohn's disease

  Data pertains longitudinal transcriptomic data measured from blood obtained from patients with Crohn's disease that were starting treatment with ustekinumab. Samples were obtained prior to treatment and approximately 26 weeks into treatment during response assessment. At response assessment, patients were classified as responders (R) or non-responders (NR) based on a strict combination of endoscopic, biochemical and clinical criteria: ≥50% reduction in the endoscopic SES-CD score, corticosteroid-free clinical remission (≥3 point drop98 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 mg/L and fecal calprotectin ≤250 µg/g). Modified response was defined as a combination of corticosteroid-free clinical- (HBI ≤4) and biochemical (CRP ≤5 mg/L and/or fecal calprotectin ≤250 µg/g) remission between week 26-52 without treatment change through week 52. Transcriptomic analyses was conducted through RNA sequencing, wherein mRNA was extracted utilizing the QIAsymphony system, converted into cDNA and sequenced in a paired-end format on the Illumina NovaSeq6000 at the Amsterdam UMC Core Facility Genomics, generating a dataset comprising 40 million 150 bp-reads.

  Dataset EGAD50000000386

• Peripheral blood DNA transcriptomics of vedolizumab treatment response in patients with Crohn's disease

  Data pertains longitudinal transcriptomic data measured from blood obtained from patients with Crohn's disease that were starting treatment with vedolizumab. Samples were obtained prior to treatment and approximately 26 weeks into treatment during response assessment. At response assessment, patients were classified as responders (R) or non-responders (NR) based on a strict combination of endoscopic, biochemical and clinical criteria: ≥50% reduction in the endoscopic SES-CD score, corticosteroid-free clinical remission (≥3 point drop98 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 mg/L and fecal calprotectin ≤250 µg/g). Modified response was defined as a combination of corticosteroid-free clinical- (HBI ≤4) and biochemical (CRP ≤5 mg/L and/or fecal calprotectin ≤250 µg/g) remission between week 26-52 without treatment change through week 52. Transcriptomic analyses was conducted through RNA sequencing, wherein mRNA was extracted utilizing the QIAsymphony system, converted into cDNA and sequenced in a paired-end format on the Illumina NovaSeq6000 at the Amsterdam UMC Core Facility Genomics, generating a dataset comprising 40 million 150 bp-reads.

  Dataset EGAD50000000385

• Novel driver variants in the histone 3.3 genes, H3F3A and H3F3B, define bone and cartilage cancer sub-types

  A selection of human cancers harbours somatic driver mutations in genes encoding histones, most notably childhood brain tumours with K27M substitutions of the histone 3.3 gene, H3F3A. We performed whole genome sequencing of the benign cartilage tumour, chondroblastoma, and targeted sequencing of histone 3.3 genes, H3F3A and H3F3B, in seven further skeletal tumour types. We identified an exceptionally high prevalence of novel histone 3.3 driver mutations at glycine 34 and at lysine 36. Histone 3.3 gene mutations were found in 91% in giant cell tumours of bone (48/53), mainly H3F3A G34W variants, and in 92% of chondroblastoma (73/79), predominantly K36M mutations in H3F3B. H3F3B is paralogous to the cancer gene H3F3A. However, H3F3B driver variants have not previously been reported in human cancer. Our observation demonstrate remarkable tumour-specificity of mutations, with respect to which histone 3.3 gene and residue is mutated, indicating that the advantage these mutations confer is tumour dependent. Moreover, tumour-specific mutation of H3F3A and H3F3B suggests, that although both genes encode identical proteins, they are likely non-redundant and employed differentially during skeletal development.

  Dataset EGAD00001000646

• cell-free DNA Target sequencing from primary and recurrent/metastatic breast cancer patients

  Breast cancer is one of the most common cancers occurring worldwide in women. Even after curative treatment based on clinical subtypes according to molecular features, the risk of relapse still remains. Cell-free DNA (cfDNA) is an emerging tool for clinical cancer detection to monitor the risk of recurrence, therapeutic efficacy and tumor progression. In occurrence of relapse, genomic, transcriptomic and epigenetic profiles are altered, and reflected in cfDNA fragmentation patterns. In this study, we focus on the transcriptionally dynamic loci associated with therapy resistance in breast cancer, and develop the target sequencing approach using cfDNAs to detect individuals with recurrent/metastatic breast cancer.

  Study JGAS000812

• PAGE: Prenatal Assessment of Genomes and Exomes

  The Prenatal Assessment of Genomes and Exomes (PAGE) study is a multicentre prospective trial, performing exome sequence analysis on samples from 1000 families with structural anomalies in prenatal ultrasound screening but normal aneuploidy results. The data will enable discovery of novel genetic disorders and increase the diagnostic yield. Where appropriate, results will be reported back to the families at the end of the pregnancy, after thorough clinical review. Ultimately, the translation of the acquired know-how into cost-effective prenatal diagnostic sequencing will improve genetics-derived prognoses and allow more informed parental counselling as well as management of pregnancy and childbirth.

  Study EGAS00001001713

• Inter and intra - tumor heterogeneity in Colorectal Cancer

  We used high depth massive parallel sequencing analyses to study 27 CRC (colorectal cancer) patients, with a total of 97 tumors (both primary and matched metastases) in addition to healthy control samples. We found inter-tumor concordance for coding mutations; in contrast, gene copy numbers were found to be highly discordant between primary tumors and metastases as validated by fluorescent in-situ hybridization. in a further step, we dissected a single tumor into 68 spatially defined samples and sequenced them separately. Here we identify evenly distributed coding mutations in APC and TP53 in all tumor areas, yet highly variable gene copy numbers in numerous genes.

  Study EGAS00001002150

• Spatial and temporal genomic evolution in glioblastoma

  Tumor heterogeneity is a challenging barrier to successful targeted therapy in glioblastoma. Identifying the mechanisms that drive cancer cells as they genetically evolve and adapt in response to treatment is a vital goal of modern cancer research. Analysis of sequencing data provides a method for uncovering the mechanisms sustaining tumor heterogeneity and driving evolution. Here, we analyzed genomic profiles of GBM biopsies taken from pre- and post-treatment GBMs (with matched germline controls), to understand 1) the intratumoral clonal compositions of primary GBM and 2) how GBM responds to therapeutic intervention. Our results provide a molecular portrait of GBM recurrence.

  Study EGAS00001001033

• Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

  The human placenta is a dynamic and cellular heterogeneous organ, which is critical in fetomaternal homeostasis and the development of preeclampsia. Previous work has shown that placenta-derived cell-free RNA increases during pregnancy. We applied large-scale microfluidic single-cell transcriptomic technology to comprehensively characterize cellular heterogeneity of the human placentas and identified multiple placental cell-type–specific gene signatures. Analysis of the cellular signature expression in maternal plasma enabled noninvasive delineation of the cellular dynamics of the placenta during pregnancy and the elucidation of extravillous trophoblastic dysfunction in early preeclampsia.

  Study EGAS00001002449

• Predicting brain tumor recurrence: development and validation of a DNA-methylation based nomogram in meningioma

  Our work is the first to demonstrate the transformative utility of integrating clinical and molecular factors for use beyond simple classification into the realm of individualized prognostication for any brain tumor. Using our developed and validated tools that are publicly available, clinicians will be able combine clinical and molecular factors to determine an individualized probability of recurrence for patients with meningiomas. This represents a major advance in the field of personalized medicine for neuro-oncology, and the use of this tool can help clinicians overcome one of the most challenging limitations we face when treating patients with meningiomas.

  Study EGAS00001003490

• Control samples, breast cancer clinical samples and matched patient-derived tumour xenografts (PDTXs) to develop and test a computational approach to discriminate human and mouse sequences in PDTXs

  Patient-Derived Tumour Xenografts (PDTXs) have emerged as the pre-clinical models that best represent clinical tumour diversity and intra-tumour heterogeneity. The molecular characterization of PDTXs using High-Throughput Sequencing (HTS) is essential; however, the presence of mouse stroma is challenging for HTS data analysis. Indeed, the high homology between the two genomes results in a proportion of mouse reads being mapped as human. In this study we generated Whole Exome Sequencing (WES) and RNA sequencing (RNA-seq) data from samples with known mixtures of mouse and human DNA or RNA.

  Study EGAS00001002445

• Mapping Cells and Interactions in the Thymus Across Development and Aging (2025-07-28)

  Single cell RNA sequencing on thymic cells from children with syndromic diseases such as Trisomy 21 and inflammatory/autoimmune diseases such as myasthenia gravis. Our group has previously performed atlasing of the healthy human thymus using single cell transcriptomics and obtained an unprecedented understanding of human thymus throughout development. In this study, we intend to survey diseased human thymus and compare this to healthy to obtain a better understanding of thymic dysfunction in human diseases. The diseases we will survey include congenital conditions such as Down's syndrome, CHARGE syndrome, DiGeorge syndrome as well as acquired diseases such as myasthenia gravis and thymic hyperplasia. We intend to perform genetic and genomic study on the samples, including expression analysis. This will not only help us to understand the cells and molecular pathways affected in dysfunctional thymus; but may also lead to generalisable understandings in human genetic diseases and inflammatory/autoimmune diseases. 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/ . This dataset contains all the data available for this study on 2025-07-28.

  Dataset EGAD00001015660