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• A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours

  We generated a single-cell RNA-seq atlas capturing over 100,000 cells spanning all stages of the mouse cerebral development. By examining data from over 100 cerebral tumour samples, our study reveals that, despite the phenotypic/genotypic differences between the tumour types, they are all comprised of developmental sublineages that map most closely to embryonic or juvenile stages of development.

  Study EGAS00001006237

• Understand Paratyphoid Disease - host responses to human challenge with S. Paratyphi A (2019-08-28)

  This project aims to evaluate the transcriptional response to disease measured in whole blood of participants who developed enteric fever after challenge and, importantly, those who were challenged but stayed well throughout the challenge period. This data will provide unique coverage of the transcriptome and will yield invaluable insight after integration with a wealth of clinical data collected during this trial. 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 2019-08-28.

  Dataset EGAD00001005298

• Investigating low frequency variants in CAD/MI cases, controls and pedigrees using whole exome sequencing and custom pulldowns

  The Cardiogenics re-sequencing study will consist of three parts: Eight pools of 25 individuals will be sequenced using a Nimblegen hybrid-capture solution specific to miRNA sequences, 80 pools of 25 individuals will be sequenced using a custom Agilent SureSelect array covering genes associated with coronary artery disease (CAD) and myocardial infarction (MI), 10 individuals from families with a history of CAD/MI will be exome sequenced using the Sanger exome array. The experiment will use the early onset patients from the German MI cohort and the UK BHF CAD/MI cohort both of which have strong family history. For controls we will consider individuals from the UKBS and KORA cohorts.

  Dataset EGAD00001000400

• DPY30 ChIP-seq

  H9 human embryonic stem cells (hESCs) were cultured in feeder-free chemically-defined conditions in medium containing 10ng/ml Activin A and 12ng/ml FGF2 (Vallier L. 2011, Methods in Molecular Biology, 690: 57-66). Chromatin immunoprecipitation was performed as described in Brown S. et al. 2011. Stem Cells 29: 1176-85 by using 5ug of anti-DPY30 antibody (Sigma, cat. number HPA043761). This protocol was performed in control hESCs (expressing a scrambled shRNA) and in hESCs stably expressing an shRNA against DPY30 (Sigma, clone n. TRCN0000131112).This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001001268

• Tumor-derived cell lines as pharmacogenomic models to predict therapeutic vulnerabilities in hepatocellular carcinoma

  Hepatocellular carcinoma (HCC) is a heterogeneous aggressive malignancy with low efficacy of current therapies at advanced stages. We integrated molecular and pharmacological profiling of a large panel of liver cancer cell lines (LCCL) to assess their clinical relevance as HCC preclinical models and identify new effective therapies and biomarkers of response. Here, we performed multi-omic analysis including whole-exome, RNA and microRNA sequencing in a series 34 LCCL. Molecular profiles of LCCL and primary HCC were compared and we searched for molecular features associated with drug response. Our panel of LCCL faithfully recapitulated the most aggressive molecular “proliferation class” of HCC.

  Dataset EGAD00001004938

• Genome-Wide Association Study of Leprosy and Dapsone Hypersensitivity Syndrome (DHS) in Chinese population

  Leprosy GWAS (1) Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae). Due to M. leprae's narrow host range and an inability to be cultured in vitro, the biological investigation of this disease has been difficult. Host genetic factors have been suggested to play an important role in disease development, but few have been identified. In this study, we attempted to identify the host genetic factors by performing a two-stage genome-wide association study (GWAS) in Chinese population. The initial genome-wide scan was done by genotyping 706 patients and 1225 controls using the Illumina HumanHap610 BeadChip, and the follow-up study was performed by genotyping 93 SNPs in three independent samples consisting of 3254 cases and 5955 controls. We identified significant association (P < 10-10) within six genes CCDC122 (13q14), C13orf31 (13q14), NOD2(16q12), TNFSF15 (9q32), HLA-DR (6p21) and RIPK2 (8q21), and suggestive association (P = 5.68x10-6) within LRRK2 (12q12). We also revealed suggestive evidence for C13orf31, LRRK2, NOD2 and RIPK2 to show stronger association in the multibacillary form than the paucibacillary form of leprosy. Our findings highlight the importance of the innate immune response, particularly NOD2-mediated signaling, in leprosy and suggests a new therapeutic target for leprosy. DHS GWAS Dapsone (DDS), as both an antibiotic and an anti-inflammatory agent, has been widely used for preventing and treating pathogen-caused infectious diseases and chronic inflammatory diseases. Currently, about 0.5-3.6% of individuals treated with DDS develop severe dapsone hypersensitivity syndrome (DHS) and the mortality rate is up to about 11-13%. However, until now, no tests are available to predict the risk of DHS. To identify the genetic risk factors of DHS, we performed a two-stage GWAS in Chinese population. In this study, the initial genome-wide scan was done by genotyping 39 DHS cases and 833 controls using Illumina Human 660W-Quad Beadchips and imputed human leukocyte antigen (HLA) molecules. Validation was performed by genotyping 24 SNPs using the Sequenom MassARRAY platform in additional 31 DHS cases and 1,089 controls through genotyping and 32 four-digit HLA-B alleles in an independent series of 37 DHS cases and 201 controls through Roche 454 sequencing. We identified significant association (OR =6.18, P = 3.84x10-13) with SNP rs2844573, which located between the HLA-B and MICA loci. HLA-B*13:01 was confirmed to be a strong risk factor for DHS (OR = 20.53, P = 6.84x10-25) and responsible for the association at rs2844573. The presence of HLA-B*13:01 had a sensitivity of 85.5% and specificity of 85.7% as a predictor for DHS, and its absence can reduce the risk by 7 fold (from 1.4% to 0.2%). HLA-B*13:01 is strongly associated with the development of DHS and can be used as a risk predictor of DHS in the individuals of Chinese and other Asian populations. Leprosy GWAS (2) This is a three-stage GWAS of leprosy in the Chinese population. The genome-wide discovery analysis involved two independent data sets: the new unpublished data set by genotyping 842 leprosy patients and 925 controls from northern and southern China using the Human660w-quad beadchips and a previously published GWAS data set of 706 leprosy cases, 1,225 healthy controls and 4,362 individuals with immune-related diseases as population controls from northern China of Chinese Han descent. Further validation studies were performed in two stages in a total of 6,765 cases and 9,505 controls from Chinese Han and minority descent in multiple areas of China, similar to the discovery stage. From this study, we discovered six new susceptibility loci with a combined P-value from discovery and validation stage surpassing genome-wide significance, including BATF3 at 1q32.3, CDH18 at 5p14.3, DEC1 at 9q32, EGR2 at 10q21.3, CCDC88B at 11q13.1 and CIITA at 16p13.13. Our current study has advanced the genetic understanding of leprosy by substantially increasing the number of confirmed genetic susceptibility loci. Leprosy GWAS (3) To discover additional leprosy susceptibility loci, we carried out a large-scale three-stage GWAS analysis of leprosy in Chinese population. The genome-wide discovery analysis (Stage 1) involved a new GWAS data set of 1,197 leprosy cases and 1,426 controls from northern and southern China conducted by using Illumina Omni Zhonghua chips with 900,015 single-nucleotide polymorphisms (SNPs), two published GWAS dataset (GWAS2 data set including 706 leprosy cases, 1,225 healthy controls genotyped by Illumina HumanHap610 beadchips, GWAS3 data set including 842 leprosy patients and 925 controls from northern and southern China genotyped by the Human660w-quad beadchips). Further validation studies were performed in two stages in a total of 5,413 cases and 9,771 controls from Chinese Han descent in multiple areas of China. In this study, we identified four novel associations at genome-wide significance (P < 5 x 10-8), all of which can indicate candidate genes within the susceptibility loci, SYN2 (3p25.2), BBS9 (7p14.3), CTSB (8p23.1) and MED30 (8q24.11), through a differential gene expression and eQTL analysis. Altogether, these findings have provided new insight and significantly expanded our understanding of the genetic basis of leprosy. Leprosy GWAS (4) In this study, we attempted to systematically investigate the contribution of protein-coding variants to leprosy susceptibility by performing a three-stage genome-wide association study (GWAS) of protein-coding variants in Chinese population. The initial genome-wide scan was done by genotyping 1,670 persons affected by leprosy and 2,321 controls using the Illumina Infinium Human Exome Beadchips (v1.0).The validation study was performed by genotyping 39 SNPs in an additional 3,169 leprosy patients and 9,814 healthy controls from the northern region of China, and the replication study was performed by genotyping eight SNPs in three independent samples from the southern regions of China consisting of 2,231 cases and 2,266 controls. We identified significant association (P < 1.23 x 10-6) within seven genes FLG (Gene ID: 2312), IL23R (Gene ID: 149233), CARD9 (Gene ID: 64170), NCKIPSD (Gene ID: 51517), TYK2 (Gene ID: 7297), SLC29A3 (Gene ID: 55315), IL27 (Gene ID: 246778). Our findings discover novel involvement of skin barrier and endocytosis/phagocytosis/autophagy, besides known innate and adaptive immunity, in the pathogenesis of leprosy, highlight the merits of protein coding variant studies for complex diseases. Here, the summary statistics from the five genome-wide association analyses were published.

  Study phs000217

• Genetic Causes of Growth Disorders

  Description of the disorder: A very common disorder presenting to pediatricians/pediatric endocrinologists is childhood growth failure. Sometimes the cause is evident, for example, growth hormone deficiency. In other children, the etiology remains unknown despite extensive evaluation, resulting in the unhelpful diagnosis of severe idiopathic short stature (SISS). These conditions are quite heterogeneous, including children with isolated growth failure and others who also have other abnormalities such as developmental delay or a constellation of congenital anomalies (syndromic short stature). Sometimes, the disorder appears to primarily affect the growth plate, which drives skeletal growth and thereby determines overall body proportions, whereas in other children, the disorder affects skeletal and non-skeletal tissues equally. Some cases of SISS have a polygenic inheritance while others appear to follow a Mendelian inheritance model, recessive, dominant or X-linked. Very recently, genome-wide analysis for copy number variants (CNVs) and whole-exome sequencing have begun to identify some of the molecular etiologies of these disorders.1 Identifying the molecular etiology of growth disorders has clinical and scientific value. Clinically, identifying a molecular cause prevents extensive further testing and may direct anticipatory care for associated medical problems. For example, we recently studied aggrecan (ACAN) gene mutations in families with autosomal dominant short stature and accelerated skeletal maturation. These mutations affect both growth plate cartilage, causing linear growth failure, and also articular cartilage, causing osteochondritis dissecans and early-onset osteoarthritis.1 Etiological classification of idiopathic growth failure allows more precise characterization of prognosis and response to treatment, which are currently highly imprecise because of the locus heterogeneity. In some cases, finding the genetic etiology points to a novel treatment approach that targets the specific molecular pathway involved. The proposed project is central to the main focus of our group, the Section on Growth and Development, NICHD. Our primary goal is to investigate cellular and molecular mechanisms governing childhood growth and to gain insight into the many human genetic disorders causing childhood growth failure. The proposed project is well suited for the intramural program because it takes advantage of Clinical Center expertise to phenotype subjects with SISS. Study subjects: We will study subjects with SISS and nuclear family members. SISS will be defined by height SDS < -2.5 for age without evident cause after routine evaluation including: growth hormone axis evaluation; thyroid function testing; celiac disease screening; urinalysis; CBC; chemistry; karyotype (girls, for Turner syndrome); and testing for single gene defects based on the clinical evaluation (for example, SHOX or Noonan-associated genes). Candidate families will include isolated growth disorders and growth disorders that are accompanied by congenital anomalies, developmental delay, or other syndromic short stature. Strong preference will be given to subjects with a severe phenotype and a pedigree that indicates a Mendelian inheritance. Multiple independent families with the same phenotype will have priority. The pool of applicants for recruitment is large, and we receive many inquiries by emails and phone consultations from pediatric endocrinologists for advice regarding diagnosis and management of unusual growth disorders, including familial disease. Often these families are seeking further evaluation and are willing to participate in a research study. From this pool, we will be selecting pedigrees with very favorable Mendelian characteristics, for example de novo dominant occurrences where two normal parents have a child with SISS, and the child grows up to be an adult who passes this phenotype on to multiple grandchildren in the next generation. Subjects and family members will be brought to the NIH Clinical Center (NIHCC) for outpatient evaluation. Participants will be evaluated by pediatric endocrinology fellows (as part of our training program) and by senior staff to establish the clinical findings and construct a pedigree. Subjects will receive additional biochemical and imaging studies at the Clinical Center to complete the phenotyping and assign affected status. The growth abnormality will be evaluated by assessing body proportions, relative organ size, and skeletal imaging as indicated. Associated clinical abnormalities beyond altered growth will be characterized with the help of other Clinical Center subspecialists. Subjects and family members will be evaluated by SNP microarray and whole-exome sequencing. We anticipate 4-5 persons for each of 16-20 families, for a total of 72-90 whole-exome sequences. Half of the families will be recruited and studied within the first year and half in the second year. We will use freshly collected peripheral blood as the DNA source for SNP array and NextGen Sequencing. Analytic approach: The candidate genes will be chosen based on 1) inheritance state consistency, 2) population frequency in the ESP and UDP databases, and 3) predictions of deleteriousness. We will use VarSifter and the B road Institute Integrated Genome Viewer to filter and visualize these data. The genetic model will be dependent on the family's pedigree. For a simple trio, we will explore variants using genetic models including autosomal recessive, de novo (dominant), compound heterozygous, deletion/point mutation recessive, and X-linked (male only). The candidate variants will be identified using Boolean logic sets in VarSifter following intramural NHGRI/UDP methods. We will also use SNP microarray data to identify copy number variations, complete/single copy deletions, duplications, non-paternity, consanguinity for homozygosity mapping, uniparental isodisomy, mosaicism, and segregation patterns (bed file generation for use in VarSifter filter work). After a list of candidate sequence variants has been generated, annotation will include using the Exome Variant Server, Polyphen-2, MutationTaster, Sift, and CADD predictions of deleteriousness. Biological laboratory data will be included to prioritize candidate variants. Our group has expertise in the molecular mechanisms regulating both skeletal growth2,3 and growth of other tissues4,5, which may be helpful in this phase of the analysis. The most promising candidate mutations will be confirmed by Sanger sequencing and studied functionally, in vitro and/or in vivo. For mutations that affect skeletal growth, we will use experimental systems related to growth plate cartilage. For in vitro studies, we have experience transfecting chondrocyte cell lines, such as ATDC5, and primary chondrocytes. We will determine whether the mutation alters protein and/or cell function. In vivo studies can be used to explore pathophysiology. We have recently successfully used a new approach, the CAS9/CRISPR system to knockout multiple loci in mice (unpublished), which can be used again in the future to create mouse models efficiently. 1J Clin Endocrinol Metab, 2014 (PMID: 24762113) 2J Mol Endocrinol, 2014 (PMID: 24740736) 3Hum Mol Genet, 2012 (PMID: 22914739) 4Proc Natl Acad Sci U S A, 2013 (PMID: 23530192) 5Endocr Rev, 2011 (PMID: 21441345)

  Study phs001617

• Genomic Characterization of Patient-Derived Xenograft Models to Improve Targeted Therapy for HER2+ Breast Cancer Brain Metastases Treatments

  We have developed orthotopic patient-derived xenograft models of HER2 positive breast cancer metastasized into the brain of patients to test novel therapeutic strategies. In this study, we identified a novel combinatorial therapeutic strategy that has resulted in a durable remission and markedly increased overall survival in majority of patient-derived xenograft (PDX) models tested. We performed whole exome sequencing analysis of these PDX tumors and their matched blood and patient samples to investigate drug sensitive and resistance mechanisms. Our sequencing data revealed an interesting association of genotyping and phenotyping with tumors responses to drug treatment.

  Study phs001063

• Genome-Wide Association Study of Schizophrenia

  The goal of the study is to find susceptibility genes for schizophrenia. Dataset versioning Version 1: European-American (EA) ancestry only Version 2: Version 1 plus African-American (AA) ancestry Consent groups and participant set General research use (GRU): 4591 cases and controls (1217 EA cases, 1442 EA controls, 953 AA cases, 979 AA controls) This consent group includes a subset of schizophrenia cases and all controls (which overlap with Bipolar study controls in Bipolar: GRU dataset). Schizophrenia and related disorders (SARC): 475 cases (187 EA cases, 288 AA cases) This consent group includes a subset of schizophrenia cases.

  Study phs000021

• GSCAN GWAS Meta-analysis of Tobacco and Alcohol use (GSCAN-GWAS)

  This study was a meta-analysis of genome-wide association study (GWAS) of substance use across 1.2 million total participants with European ancestry (some phenotypes are based on fewer participants). The phenotypes were chosen to represent different stages and kinds of substance use from initiation (age of smoking initiation) to regular use (cigarettes per day and drinks per week) to cessation (smoking cessation). For each of those phenotypes, collaborators shared their GWAS summary statistics, which were then meta-analyzed using a method that incorporates into the meta-analytic weighting the sample size, allele frequency and imputation quality score.

  Study phs001809

• Biology and Molecular Analysis of Human Hematopoiesis Genetics

  In this study we have performed exome sequencing using the hybrid capture method that has previously been described (Gnirke et al., Nature Biotechnology, 2009) on genomic DNA samples from patients with the congenital bone marrow failure syndrome that affects the erythroid lineage, specifically, Diamond-Blackfan anemia. This disease is characterized by a hypoplastic anemia and approximately 50% of cases are attributable to mutations in ribosomal protein gene subunits. The other 50% of cases do not have a known genetic etiology and the purpose of this study is to attempt to delineate such causes.

  Study phs000474

• Whole Genome Sequencing of Skull-Based Chordoma

  Chordoma is a rare bone tumor, which is believed to originate from notochordal remnants. Based on the United States Surveillance Epidemiology and End Results (SEER) data, the incidence of chordoma varies by gender and race; however, little is known about the etiologic factors that predispose to it. Genomic profiling studies of chordoma are limited, particularly in the Chinese population. We therefore conducted a detailed molecular characterization of paired chordoma tumor/normal tissues using fresh frozen tissues and blood collected from skull-based Chinese chordoma patients. These analyses included whole exome sequencing and RNA sequencing analyses.

  Study phs002301

• Biesecker Lab (NHGRI) Whole Genome Medical Sequencing for Gene Discovery

  We aim to use whole-genome medical sequencing (WGMS) to discover causative molecular lesions for a set of rare, severe phenotypes hypothesized to be caused by either somatic mutations, germline de nova heterozygous mutations, germline inherited recessive, or germline inherited dominant mutations in currently unknown or uncharacterized genes. The goal of this research is threefold: to identify causative sequence variants for disorders whose molecular etiology was previously unknown, to apply this insight to both the rare disorders under study and more common phenotypes, and to enhance the study of mutation on a genome-wide level.

  Study phs001348

• High-Throughput RNA Isoform Sequencing using Programmable cDNA Concatenation

  MAS-ISO-seq is a novel technique for programmably concatenating cDNAs into single molecules for optimal long-read sequencing. In practice, this boosts throughput >15 fold to nearly 40 million cDNA reads per run on the PacBio Sequel IIe sequencer. We have validated this method via application to synthetic RNA isoforms and single-cell sequencing of tumor-infiltrating T cells. Results demonstrated a >30 fold boosted discovery of differentially spliced genes and robust cell clustering, as well as canonical PTPRC splicing patterns across T cell subpopulations and the concerted expression of the associated hnRNPLL splicing factor.

  Study phs003200

• Mosaic Chromosomal Aneuploidies Detection in Clinical Samples

  Mosaic chromosomal aneuploidy occurs when only a subset of cells carries an abnormal number of chromosomes. Mosaic aneuploidy has been reported in multiple types of diseases. Here we have developed a new sequencing-based approach to identify, characterize and quantify mosaic aneuploidy events in human tissue samples. This ongoing study has begun with results from sequencing data from two clinical patients, one with autism spectrum disorder (ASD) and the other with hemihyperplasia (OMIM 235000). We captured ~100,000 common SNPs from the samples to identify the nature of the mosaic aneuploidy events in each of the samples.

  Study phs001557

• NHLBI TOPMed: Children's Health Study (CHS) Effects of Air Pollution on the Development of Obesity in Children (Meta-AIR)

  The Effects of Air Pollution on the Development of Obesity in Children (Meta-AIR) study was proposed to study a subset of the Children's Health Study (CHS) participants representing the extremes of long-term traffic-related air pollution exposure occurring in Southern California CHS communities. The primary aim of the Meta-AIR study was to investigate whether lifetime exposure to air pollution increases risk for obesity and metabolic dysfunction at 17-18 years of age. A total of 56 Hispanic White participants (16 asthma cases and 40 controls) were included in the TOPMed project.

  Study phs001604

• Detection of Somatic Mutations In Vitro Aging Cells

  Deep sequencing was performed to analyze the prevalence of somatic mutations during in vitro cell aging. Primary dermal fibroblasts from healthy subjects of young and advanced age, from Hutchinson-Gilford progeria syndrome, and from Xeroderma Pigmentosum complementation group A (XPA) and C (XPC), were first restricted in number and then expanded in vitro. DNA was obtained from cells pre- and post-expansion and sequenced at high depth, over a cumulative 290 kb target region, including the exons of 44 aging-related genes. Allele frequencies of 58 somatic mutations differed between the pre- and post-cell culture expansion passages.

  Study phs001867

• Molecular Features of Hepatocellular Carcinoma Associated with 18F-Fluorocholine PET/CT Imaging Phenotype

  Molecular imaging with 18F-fluorocholine PET/CT reveals two distinct imaging phenotypes for hepatocellular carcinoma (HCC) as a potential source of non-invasive insight into its molecular heterogeneity. Using gene set enrichment analyses, we found 18F-fluorocholine-avid tumors to be significantly enriched by genes comprising a subset of previously published HCC-related gene signatures. Significant gene sets included those from existing molecular classification systems for HCC as well as gene signatures predictive of clinical outcomes after tumor resection. PET/CT imaging using 18F-fluorocholine might therefore provide surrogate information about tumor molecular characteristics and prognosis in HCC.

  Study phs001784

• Single-Cell Transcriptomics of Adult Recurrent Respiratory Papillomatosis

  These single-cell sequencing data were generated from diseased respiratory tract papilloma tissue caused by chronic infection with HPV 6 or 11. Patients from which this tissue was derived participated in a phase I clinical trial using a novel therapeutic vaccine, but these samples were acquired before this experimental treatment. The aim of performing this single-cell sequencing study was to characterize the papilloma cells and other cells in the papilloma microenvironment with single-cell analyses using the 10X Genomics platform. The single-cell gene expression raw data files for each sample will be available in this submission.

  Study phs003349

• Ancient genomes reveal insights into ritual life at Chichén Itzá

  To better understand the origin and biological relationships of the sacrificed children from Chichén Itzá to each other and to present-day inhabitants of the region, here we used a combined bioarchaeological and genomics approach to investigate 64 subadults interred within a chultún near the Sacred Cenote and compare them to 68 present-day Maya inhabitants of the nearby town of Tixcacaltuyub, as well as to other available ancient and contemporary genetic data from the region. The community of Tixcacaltuyub has been collaborating with our research team for many years, and their perspectives informed the development of this project.

  Study EGAS50000000296

• Epigenomics of Prostate Cancer from Cell Free Plasma

  We sought to perform epigenomic characterization of prostate cancers by profiling circulating nucleosomes isolated from patient plasma using cell free chromatin immunoprecipitation followed by sequencing (cfChIP-seq). Our major findings include identification of prostate-cancer specific regulatory elements using a novel statistical method accounting for variable tumor DNA fraction in plasma, inferring transcription factor activity based on binding motif enrichment within regulatory elements, and epigenetically phenotyping patients based on clinical and genomic features. Data available in dbGaP will include cfChIP-seq and targeted sequencing from approximately 50 patients with a known diagnosis of cancer and healthy patient controls.

  Study phs003482

• Oncogene activated human breast luminal progenitors contribute basally located myoepithelial cells

  Basal-like breast cancer originates in luminal progenitors, frequently with an altered PI3K pathway, and focally in close association with genetically altered myoepithelial cells at the site of tumor initiation. The exact trajectory behind this bi-lineage phenomenon remains poorly understood. Here we used a breast cancer relevant transduction protocol including hTERT, shp16, shp53, and PIK3CA(H1047R) to immortalize FACS isolated luminal cells, and we identified a candidate multipotent progenitor. We found that the apparent luminal phenotype of these oncogene transduced progenitors was metastable giving rise to basal-like cells dependent on culture conditions.

  Study EGAS50000000505

• NHLBI TOPMed - NHGRI CCDG: Groningen Genetics of Atrial Fibrillation (GGAF) Study

  Atrial fibrillation (also called AFib or AF) is a quivering or irregular heartbeat (arrhythmia) that can lead to blood clots, stroke, heart failure and other heart-related complications. The Groningen Genetics of Atrial Fibrillation (GGAF) cohort is a cohort composed from 5 different sources of individuals with atrial fibrillation (AF) and age and sex-matched controls. Written informed consent was provided from all participating individuals, and all 5 studies were approved by the ethical committee at the University Medical Center (www.atrialfibrillationresearch.nl) and Maastricht University. All samples selected for TOPMed WGS are from individuals with atrial fibrillation.

  Study phs001725

• Single-cell Analysis of Neoplastic Plasma Cells Identifies Novel Myeloma Pathobiology Mediators and Potential Targets

  Newly diagnosed symptomatic and relapsed/refractory myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors which have been studied utilizing bulk or single-cell (sc) techniques. By combining scRNA-sequencing with scB-cell receptor (BCR)-sequencing, we found more dysregulated genes in monoclonal PCs compared with analyses of the entire CD138+ population, which includes non-neoplastic/polyclonal PCs. Paired tumor and non-tumor WGS was performed to evaluate the presence of IgH-associated translocations and hyperdiploidy events, initially detected by FISH, in a subset of samples included in this study.

  Study EGAS50000000801

• Young Boost Trial for Breast Cancer patients

  The Young Boost Trial (YBT, YOUNG BOOST / BOOG 2004-01 (Borstkanker) | Kanker.nl investigated the optimal radiation dose for breast cancer patients aged 50 years or younger, treated with breast-conserving therapy (BCT). In this randomized study, participants were assigned to receive either a 26 Gy or a 16 Gy radiation boost, with the primary endpoint being local recurrence. To explore potential predictive biomarkers of treatment response in this patient group, whole exome sequencing (WES) was performed on tumor samples to identify genetic factors that could guide personalized treatment strategies and improve clinical outcomes for these young breast cancer patients.

  Study EGAS50000000797