14662 results for "PLOS+ONE+Pennsylvania+German+ACS+language+code+pdc+open+access+study"

in 34.46 milliseconds.

• Matched Pair Cell Line Tumour RNAseq

  In this study we will sequence the transcriptome of Verified Matched Pair Cancer Cell line tumour samples. This will be married up to whole exome and whole genome sequencing data to establish a full catalog of the variations and mutations found.

  Dataset EGAD00001000630

• 200PG : WGS Aligned Sequence (fastq)

  200PG : WGS Aligned Sequence (fastq) : Aligned WG sequence data (bam) in this dataset are from the 124 CPCGene Tumour/Normal Pairs used in the 200PG Study. https://www.ncbi.nlm.nih.gov/pubmed/28068672

  Dataset EGAD00001003139

• Carcinoid study - WGS dataset

  Fernandez-Cuesta et al., 2014, Nature Communication, Whole genome sequencing was performed using a read length of 2x100 bp for all samples. On average, 110 Gb of sequence were produced per sample, aiming a mean coverage of 30x for both tumour and matched normal.

  Dataset EGAD00001000813

• Exome sequencing in bipolar disorder families

  In the present study two large, multiply affected bipolar disorder families from Cuba were investigated using whole exome sequencing (Illumina HiSeq2500 v4). The variant calling files (VCFs) of 15 individuals provided here were generated using the Varbank exome pipeline from the Cologne Center for Genomics (CCG, https://varbank.ccg.uni-koeln.de).

  Dataset EGAD00001004276

• Colorectal organoids and tumoroids - pulldown (2018-08-13)

  Targeted capture of cancer gene panel bait set in single cell derived organoids from colon tissue and colorectal cancer from 1 patient. . This dataset contains all the data available for this study on 2018-08-13.

  Dataset EGAD00001004292

• Tam-seq of germline samples for HGSOC copy-number signatures study

  This dataset contains targeted amplicon sequencing of Germline DNA extracted from 56 blood samples. They were sequenced on Illumina HiSeq 2500 and aligned to human genome assembly GRCh37 (hg19)to produce 127 bam files (2-3 technical replicates per sample).

  Dataset EGAD00001004172

• The landscape of LAM disease

  Tumor biopsies from LAM disease were retrospectively analyzed by multiple techniques to characterize the alterations in patients ,to elucidate the landscape of genetic/genomic alterations.

  Study EGAS00001003534

• Non-coding RNAs in breast cancer

  Using RNA CaptureSeq we annotated non-coding RNAs transcribed from genome intervals surrounding breast cancer risk signals in a range of mammary-derived tissue and cell lines.

  Study EGAS00001003353

• Bioinformatics analysis of chimerism in monochorionic dizygotic twins

  We conducted a bioinformatics analysis of hematopoietic chimerism of the monochorionic dizygotic twins. Whole-genome sequencing was used to understand the genomic compositions of the chimeras.

  Study EGAS00001005997

• Kidney_Single_Cell_Study

  We intend to use single cell transcriptome analysis to explore the heterogenity of different cell types within the kidney.

  Study EGAS00001002325

• MNM - Temporal variability in Quantitative Microbiome Profiles

  Daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over six weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics.

  Study EGAS00001005686

• Exome and transcriptome sequencing of Desmoplastic Small Round Cell Sarcoma

  To conduct exome and transcriptome profiling to identify secondary recurrent mutations, multi-site phylogenetic analyse and immune characterization of Desmoplastic Small Round Cell Sarcoma.

  Study EGAS00001004575

• Co-infection of fungi and bacteria in brain tissue of Alzheimer’s patients.

  Metagenomics analysis reveals co-infection of fungi and bacteria isolated from different regions of brain tissue from elderly persons and patients with Alzheimer's disease.

  Study EGAS00001002766

• The integrated genomic and immune landscapes of lethal metastatic breast cancer.

  We report on the extensive molecular profiling of multiple individual metastases from 10 warm autopsies of patients with lethal multi-therapy resistant breast cancers.

  Study EGAS00001002703

• Genomic and transcriptomic profiling of combined hepatocellular and intrahepatic cholangiocarcinoma reveals distinct molecular subtypes

  We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes.

  Study EGAS00001003093

• The_Little_Princess_Knowledge_Bank_

  We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome data with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours.

  Study EGAS00001004237

• Whole-genome landscape of adult T-cell leukemia/lymphoma

  Whole-genome sequencing (WGS) data of tumor-normal pairs from 139 ATL patients and RNA sequencing (RNA-seq) data of tumors from 28 ATL patients.

  Study EGAS00001005237

• Organoid_Derivation_Project___GRCh38___RNAseq

  Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines.

  Study EGAS00001004677

• Single-cell RNA sequencing of bronchoalveolar lavages from COVID-19 patients

  Discriminating mild-moderate from critical COVID-19 disease by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.

  Study EGAS00001004717

• Genomics analysis of mucinous tumours of the ovary and related neoplasms

  To perform genetic and gene expression analyses on mucinous ovarian tumours to determine a progression model, cell of origin and novel therapeutic targets.

  Study EGAS00001003545

• Single Cell Sperm sequencing try 2

  Sequence single cell sperm using a 10X Chromium. As a pilot test, we used samples from men who have had children with autism and normal controls.

  Study EGAS00001004035

• Epigenomic data of HEMa_LP

  To profile the epigenomic landscape of Human Epidermal Melanocytes , adult, lightly pigmented(HEMa-LP), whole genome bisulphite sequencing (WGBS) and ChIP-seq of histone marks data were generated.

  Study EGAS00001004016

• RNA-seq of Ewing sarcoma tumors (ICGC)

  Ewing sarcoma (ES) is a primary bone tumor initiated by an EWSR1-ETS gene fusion. To characterize the transcriptome of Ewing sarcoma, RNA-seq was performed.

  Study EGAS00001003333

• Organoid_Derivation_Project___GRCh38___TGS

  Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines.

  Study EGAS00001007349

• Organoid_Derivation_Project___GRCh38___WGS

  Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines

  Study EGAS00001004712

• Bulk and single-cell AML RNA-seq post ex vivo culture

  Bulk and single-cell RNA-seq performed on primary AML blasts cultured ex vivo for 3 days in standard or niche-like conditions.

  Study EGAS00001006265

• Neuroblastoma Evolution

  Here, we quantify the somatic evolution of neuroblastomas by deep (80x) whole-genome sequencing, molecular clock analysis and population-genetic modeling in a comprehensive cohort (Hipo_K09R) covering all subtypes.

  Study EGAS00001006533

• Covid19 WGS BAM files

  The Samples were collected from Saint James's Hospital, Dublin, and after informed consent Extracted Genomic DNA samples were prepared and sequenced using the Automated Illumina TruSeq PCR-free methodology.

  Study EGAS00001007048

• DECONVOLUTION OF HEMATOPOIETIC STEM/PROGENITOR CELL SIGNALING IN HUMAN AML

  A comprehensive taxonomy of the predicted interactions between LEPR + stromal niches, HSPCs and adaptive/innate immune cells in the human NBM and AML

  Study EGAS00001007330

• Sequencing of patient tissue and patient derived organoids in colon cancer

  Multiome (ATAC + RNA) sequencing of cancerous primary tissue and cancer organoids derived from the same patient. Nanopore and whole exome sequencing of selected samples.

  Study EGAS00001008067

• IFNL4 Organoid Transcriptome Profiles

  RNAseq of liver organoids with a dG genotype (B20, nt115, U15) and with a TT genotype (nt5, U16, U19) was performed, which was used to study the impact of IFNλ4 on the cellular response to Sendai viral infection.

  Dataset EGAD00001007820

• Neuroblastoma hybrid capture sequencing panel

  Patient neuroblastoma hybrid capture sequencing panel. 5 samples from 2 donors (BAM files). For each donor, we obtained neuroblastoma tumor samples and neuroblastoma ALKi resistant samples. This dataset was used to study ALKi resistance in neuroblastoma.

  Dataset EGAD00001008343

• WES CRAM files of HUG-CEL Covid-19 Genomics Study

  Whole Exome Sequencing Dataset (CRAM files) of 415 admixed Brazilians with Covid-19 extreme phenotypes from recovered nonagenarians and centenarians to deceased adults.

  Dataset EGAD00001009652

• miRNA and mRNA transcriptome data

  This dataset contains 278 miRNA and 20 mRNA transcriptomes generated as part of the study "miR-374a-5p regulates inflammatory genes and monocyte function in inflammatory bowel disease."

  Dataset EGAD00001008683

• Bulk RNAseq with monocyte spike-ins

  This dataset contains bulk transcriptomes from the operable cohorts of the LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19), used to verify the deconvolution method used for the scRNA-seq dataset.

  Dataset EGAD00001010306

• Organoid Derivation Project: TGS (2023-06-22)

  Sequencing of tissue samples and their derived organoids from oesophageal, pancreatic and colorectal cancer patients. . This dataset contains all the data available for this study on 2023-06-22.

  Dataset EGAD00001011089

• Systematic analysis of paralogous regions in 41,755 exomes uncovers clinically relevant variation

  As part of the study "Systematic analysis of paralogous regions in 41,755 exomes uncovers clinically relevant variation" we wanted to identiffy the SNVs that are located in STRC and which ones in STRCP1. For this we applied targeted long-read sequencing.

  Dataset EGAD00001011305

• Possible DNA Damage after paternal exposure to ionizing radiation in Radar technicians

  This dataset contains whole genome sequences from Illumina NovaSeq Devices sequenced at the WGGC Bonn to study effects of prolonged paternal exposure to ionizing radiation. Here we provide the reads, mapped to the hg19 reference genome of all samples.

  Dataset EGAD00001011043

• Harnessing transposons for drug resistance gene discovery in cancer

  This study involves a forward genetic screen to identify common insertion sites in drug resistant clones. We will be utilising piggybac transposon systems in order to generate multiple drug resistant clones in a range of human cancer cell lines.

  Dataset EGAD00001000980

• Whole Exome Sequencing of healthy Spanish individuals - Fastq files

  The need for a detailed catalogue of local variability for the study of rare diseases within the context of the Medical Genome Project motivated the whole exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population.

  Dataset EGAD00001001012

• Somatic Genetics of lesions from a POT1 patient (2016-04-20)

  In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1). This dataset contains all the data available for this study on 2016-04-20.

  Dataset EGAD00001002050

• Role of HPV and Interferon in APOBEC mutational signature (2019-04-11)

  The aim of this project is to test whether HPV oncogenes and /or interferon induce the APOBEC mutational signature in vitro, and to test the role of APOBEC3A in this process. . This dataset contains all the data available for this study on 2019-04-11.

  Dataset EGAD00001004955

• ESGI - Whole Genome Sequencing of samples from the INGI-Val Borbera genetic isolate (X10) (2019-08-19)

  Whole genome sequencing of sampels from an isolated population from the Val Borbera valley in Italy. The samples are sequenced using the Illumina HiSeq X Ten system. . This dataset contains all the data available for this study on 2019-08-19.

  Dataset EGAD00001005268

• Comparison of 133/144bp dominant phenotype vs 166bp dominant phenotype.

  The sequencing results provided in this study is enriched through liquid phase hybridization capture. The data set shows 35 clinical cfDNA samples showing a dominant peak at 166bp and 35 clinical cfDNA samples showing a dominant peak at 134/144bp.

  Dataset EGAD00001005798

• Dedifferentiated Melanoma (2021-02-02)

  De- and transdifferentiation of melanoma is a rare histopathological phenomenon that has not be characterised genetically. In this project we plan to sequence the genomes of de and transdifferentiated cases so as to define their genetic make-up. . This dataset contains all the data available for this study on 2021-02-02.

  Dataset EGAD00001006931

• Autism Post-Mortem Brain RNA-Sequencing: SRRM4 Splicing Study

  Purpose: The goal of this study was to assess the status of splicing changes in microexons in the cortex of individuals with autism. Methods: We performed RiboZero Gold (rRNA depleted) 50bp PE RNA-seq in a larger set of case and control samples to define 12 autism and 12 control samples showing the greatest global differential gene expression change. These samples, which show differential expression of the splicing regulator SRRM4, were used to evaluate global splicing changes. Results: Within these samples, 126 of 504 (30%) detected alternative microexons display, a mean ΔPSI > 10 between ASD and control subjects of which 113 (90%) also display neural-differential regulation. By contrast, only 825 of 15,405 (5.4%) longer (i.e. > 27 nt) exons show such misregulation, of which 285 (35%) correspond to neural-regulated exons. Notably, we also observe significantly higher correlations between microexon inclusion and nSR100 mRNA expression levels across the stratified ASD samples and controls, for those microexons regulated by nSR100 relative to those microexons that are not regulated by this factor (p=1.4x10-7, Wilcoxon Sum Rank test). Conclusions: These data suggest microexon regulation is a potentially important mechanism underlying ASD and likely other neurodevelopmental disorders.

  Study phs000872

• Microbiome-Host Interactions in Oral Squamous Cell Carcinoma: a Metatranscriptomic Exploratory Study

  Oral cancer (predominantly squamous cell carcinoma; OSCC) is the 14th most prevalent malignancy worldwide, accounting for more than 300,000 new cases and 145,000 deaths annually. Despite advances in cancer treatment modalities, OSCC continues to have poor prognosis with 5-year survival rates less than 50%. Although use of tobacco and alcohol consumption constitute the major risk factors, there is emerging evidence for the role of the microbiome in OSCC. However, studies on the association between the microbiome and OSCC has so far focused on compositional analysis and has been largely limited to the bacterial component of the microbiome. The aim of this study is to characterize the transcriptional activity (function) as well as composition of the multi-kingdom microbiome associated with OSCC and correlate it with the gene expression of the host using ultra-deep metatranscriptome sequencing, which will provide new insight into the role of the microbiome in OSCC and the possible mechanisms by which the tumor’s microbial community may influence on its behavior. This project comprises RNA-Seq data from twenty OSCC tumor/normal tissue pairs and twenty tongue scraping samples from healthy controls. However, due to consent constraints, the human sequences from the control data are filtered out.

  Study phs002678

• Genome-Wide Association Study of the Taste and Hedonic Ratings of the Low-Calorie Sweetener Acesulfame Potassium

  Acesulfame potassium (Ace-K) is a low-calorie sweetener (LCS) widely used as an additive in foods and beverages and an excipient in pediatric medicines. Because genetic variants play a role in individual variation in the taste of Ace-K, we sought to identify genetic contributions to its taste using a genome-wide association study (GWAS). 141 adult panelists rated the taste of an aqueous solution of Ace-K using the general labelled magnitude scale (gLMS) and its palatability using the hedonic gLMS. Genotypes were assayed on the Infinium Global Screening Array. Imputation of genotypes was performed on the Michigan Imputation Server with 1000 Genomes Project phase 3 genotype data as reference. Linear regression was performed to test genetic associations between genotyped and imputed variants with three gLMS ratings (bitterness (square-root-transformed), hedonic, sweetness) of Ace-K using PLINK2, adjusting for standardized age, sex, and the first 10 principal components of genetic ancestry. We identified that a locus spanning several TAS2R (Taste receptor 2) genes was associated with bitterness ratings of Ace-K and a locus within the gene ELMO1 (Engulfment and Cell Motility Protein 1) was associated with hedonic ratings of Ace-K (p-values 40594245).

  Study phs004031

• The Role of E2F4 in Controlling Resistance to Irinotecan (CPT-11) in Human Colon Cancer

  This study reports the results of RNA sequencing (RNA-seq) experiments performed on three isogenic clones of the human HT29 colon cancer cell line, genetically engineered to achieve the selective inactivation of the adenovirus early 2 (E2) gene transcription factor 4 (E2F4) protein, a key functional component of the multimeric transcriptional repression complex known as the dimerization partner (DP), retinoblastoma-like (RB-like), E2F and multi-vulva class B (MuvB) complex (DREAM). In previous studies, we identified E2F4 as a key regulator of colorectal cancer (CRC) resistance to irinotecan (CPT-11), a cytotoxic agent that stands at the backbone of multiple chemotherapy regimens for the treatment of metastatic CRCs. The molecular mechanisms linking E2F4 to irinotecan resistance, however, remain poorly understood. The present study was designed to identify which genes are under the transcriptional control of E2F4, either at baseline or following exposure to SN38 (i.e., the active metabolite of irinotecan, generated in vivo by biotransformation in the liver) in order to clarify the role played by E2F4 in shaping colon cancer resistance to chemotherapy. The cell line used for this study (HT29) is aneuploid and contains three copies of the E2F4 gene, because of a trisomy of chromosome 16, where the E2F4 gene is located (Kawai et al., Genes, Chromosomes & Cancer, 34:1-8, 2002; PMID: 11921276). HT29 cells were infected with lentivirus vectors encoding for CRISPR/Cas9 constructs designed to selectively inactivate the E2F4 gene, using three distinct guide-RNAs (gRNAs), each targeting a different sequence within the proximal exons of the E2F4 gene (exon 1, exon 2). Lentivirus-infected cells were sub-cloned by single-cell fluorescence-activated cell sorting (FACS), based on the differential expression of a fluorescent reporter (EGFP) expressed in tandem with the gRNAs. Isogenic clones (EGFP+) were then screened to identify those with a tri-allelic knock-out, as revealed by both genetic sequencing of the E2F4 gene (revealing the presence of three distinct frameshift mutations) and Western blot (revealing complete loss of E2F4 protein expression). The study includes twelve (n=12) RNA-seq experiments, representative of 3 experimental replicates (i.e., three distinct isogenic clones of the HT29 cell line, each displaying complete loss of E2F4 expression) and 3 negative controls (i.e., three independent preparations of the parent HT29 cell line, infected with a lentivirus vector encoding for a non-targeting gRNA) exposed to 2 distinct in vitro cell culture conditions: a) treatment with SN38 resuspended in dimethyl sulfoxide (DMSO); or b) treatment with DMSO alone (negative control). The in vitro treatment regimen used for SN38 (32 nM, 24 hours) was designed so that the exposure to SN38 experienced in vitro by HT29 cells would mirror the exposure to SN38 experienced in vivo by malignant tissues, as measured, for example, in metastatic CRC patients receiving a standard dose of irinotecan (180 mg/m2) administered by intravenous infusion over 90 minutes (Deyme et al., Cancer Chemotherapy and Pharmacology, 88:247-258, 2021; PMID: 33912999).

  Study phs003560

• Nurminen et al ("GP2Men") Study Primary and Metastatic Prostate Cancer Whole Genome Sequence Data

  We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones.

  Study EGAS50000000005

• Human scMultiome data (GEX and ATAC paired) from CD34+ Bone Marrow (BM) and mobilized peripheral blood (mPB), including CITE-Seq data from mPB CD34+ samples

  We analyzed healthy CD34+ samples from Bone Marrow (BM) and mobilized Peripheral Blood (mPB) in gene therapy experiments within the X-PAND project. BM samples underwent scMultiome analysis, providing paired GEX and ATAC data. For the mPB samples, both scMultiome and CITE-Seq were performed on the same donors, offering additional protein marker information. These datasets allow for an in-depth exploration of chromatin accessibility, gene expression, and surface protein profiling in hematopoietic progenitor cells from healthy donors.

  Study EGAS50000000750

• Sequencing Study in COPD cases and controls

  Since smokers with COPD have a higher risk of developing lung cancer than those without, we hypothesized that they carry more mutations in affected tissue. We called somatic mutations in airway brush samples from medium-coverage whole genome sequencing data from healthy never and ex-smokers (n=8), as well as from ex-smokers with variable degrees of COPD (n=4). Owing to the limited concordance of resulting calls between the applied tools we built a consensus, a strategy that was validated with high accuracy for cancer data.

  Study EGAS00001003406

• Cystic fibrosis multi-omics study

  Cystic fibrosis (CF) is a genetic disorder affecting approximately 1 in 2,500 people in the UK. Here, we generated a number of high-throughput sequence data sets for monocytes and neutrophils from CF patients and matched healthy volunteers (HV); including ChIP-Seq (H3K27Ac), chromatin accessibility (ATAC-Seq), and transcript/gene expression (RNA-Seq) data. Analysis of gene expression and epigenetic profiles demonstrates a robust innate immune gene expression profile that distinguishes CF and HV during periods of disease exacerbation. Upregulation of pathways responsible for the production of proinflammatory cytokines is described.

  Study EGAS00001006421

• Leukemia sequencing study

  A custom single-cell amplicon DNA sequencing panel was designed to cover relevant somatic mutations and common single nucleotide polymorphisms (panel CO303). Frozen bone marrow mononuclear cells were thawed, stained using the antibody-derived tags panel TotalSeq™-D Human Heme Oncology Cocktail, V1.0 (Biolegend) and loaded into Tapestri single-cell DNA genotyping platform (Mission Bio) to perform microfluidic encapsulation, lysis, and barcoding according to the manufacturer’s protocol (Chemistry V2, PN_3360A). DNA and ADT libraries were prepared and underwent 2x150bp paired-end sequencing on a NextSeq 500 platform (Illumina).

  Study EGAS00001006784

• AfricanNeo aDNA Study

  With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ~4000 years ago in western Africa. We have generated whole-genome sequences from 12 Late Iron Age individuals. Our comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.

  Study EGAS00001007519

• RNAseq of circulating monocytes of familial hypercholesterolaemia (FH) patients before and after treatment, and healthy controls.

  RNAseq of circulating monocytes of familial hypercholesterolaemia (FH) patients before and after treatment, and healthy controls. Please cite original paper: Monocyte and macrophage lipid accumulation results in downregulated type-I interferon responses. Willemsen et al. Frontiers in Cardiovascular Medicine (2022) Familial hypercholesterolemic patients (n=10) and healthy subjects (n=9): the study population, design, and further processing of these human study subjects and their samples have been extensively described (Stiekema et al., 2021). Briefly, untreated FH patients who indicated to start lipid-lowering therapy (statin, PCSK9 antibody, and/or ezetimibe) according to their treating physician were included. The healthy controls were age, sex, and body mass index (BMI) matched with the FH patients. After inclusion, FH patients fasted for at least 9 hours before blood samples were drawn for lipid measurements and monocyte isolation. This was repeated after 12 weeks of lipid-lowering therapy. RNA-seq was performed on circulating monocytes. V1 = visit 1. V2 = visit 2.

  Dataset EGAD00001008967

• Convergent somatic evolution from early life in a germline ribosomopathy

  Clonal tracking of stem cells and their progeny by whole genome sequencing permits exploration of evolutionary genetics in human disease. In this study, we performed phylogenetic reconstruction of haematopoiesis using somatically acquired mutations in 323 single haematopoietic stem and progenitor cell-derived colonies from 10 individuals with an inherited disorder of ribosome assembly, Shwachman-Diamond syndrome. We observed numerous clonal expansions, with recurrent acquisition of mutually exclusive mutations (EIF6, TP53, RPL5, RPL22, PRPF8, chromosomes 7 and 15) in multiple different clones in utero or early childhood converging on the p53-dependent nucleolar surveillance pathway that monitors ribosome integrity. In contrast to clones carrying biallelic TP53 mutations, genomes derived from colonies carrying mono-allelic TP53 mutations displayed no increase in mutation burden or specific mutational signatures. Our study highlights striking loss of clonal diversity with convergent somatic evolution on the p53-dependent nucleolar surveillance pathway from early life to offset the deleterious effects of a germline mutation in a Mendelian haematopoietic disorder.

  Dataset EGAD00001009061

• Understanding the development of resident memory T cells (Trm) in the human small intestine using integrative multiomic approaches: Adult RNA (2025-10-14)

  Animal studies have demonstrated that resident memory T (Trm) cells provide enhanced protective responses to a broad array of tissue-tropic pathogens, thus making Trm cells promising targets for novel vaccination strategies. However, the biological pathways that enable the long-term survival of Trm cells are poorly understood in humans. Here, we will employ a unique human intestinal transplantation setting that allows us to study the retention of persistent T cells in the grafts and the temporal development of resident T-cell populations from recruited recipient T cells. We will integrate high resolution transcriptomics, epigenetics, proteomics and immune repertoire single-cell data from purified intestinal T cells. These single-cell multiomics approaches will uncover the diversity and differentiation of the T cell populations in the human intestine, allowing us to temporally resolve the generation and maintenance of gut resident T cells. . This dataset contains all the data available for this study on 2025-10-14.

  Dataset EGAD00001015739

• Gene expression QTL mapping in stimulated iPSC-derived macrophages

  Immune cells sense and respond to external stimuli, initiating an inflammatory response, with genetic variants potentially altering these responses. Traditional QTL mapping often uses naïve cells, missing condition-specific variants detectable post-stimulation. Our study uses a high-throughput platform to map eQTLs across 24 conditions using iPSC-derived macrophages, identifying that 76% of eQTLs in stimulated conditions were also present in naïve cells. We found response eQTLs (reQTLs) vary widely across conditions, with rare single-condition reQTLs being overrepresented among disease-colocalizing eQTLs. This study nominates 21.7% more disease effector genes at GWAS loci through reQTL colocalization, with 38.6% not found in the GTEx catalogue, highlighting the importance of condition-specific regulatory variation in understanding disease risk alleles. Our findings underscore the value of condition-specific studies in elucidating the genetic mechanisms underlying complex 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/

  Dataset EGAD00001015380

• Bladder Cancer Organoids as a Functional System to Model Different Disease Stages and Therapy Response

  The study 'Bladder Cancer Organoids as a Functional System to Model Different Disease Stages and Therapy Response' reports the genomic characterization at the single allele level upon Whole Exome Sequencing of Bladder Cancer (BLCa) Patient Tumor (PT) samples obtained from 18 patients and corresponding Patient Derived Organoids (PDOs), implementing the SPICE pipeline (Ciani Y et al). Our cohort included 21 PTs and 22 PDOs. In this study, we generated a unique biobank resource of BLCa organoids that encompasses a broad spectrum of disease stages. We demonstrated that PDOs retain cancer heterogeneity and mutational burden. Furthermore, we observed that BLCa PDO can have different morphologies which may reflect tumor-specific features. Indeed, a solid morphology may be associated with more advanced tumors, as supported by the high PDO genomic burden and high primary tumor stage. Moreover, with our drug screening pipeline, we demonstrated the clinical relevance and feasibility of using a BLCa PDO-based drug assay for comparing the standard of care (SOC) drugs with compounds not currently in use for BLCa. Response to SOC was highly heterogeneous with approximately 50% of non-muscle invasive bladder cancer and 33% of muscle invasive bladder cancer PDOs showing no or minimal response. The most effective targeted therapy was lapatinib. We used an integrative analysis of drug response profiles with matched PDO genomic analysis to determine enrichment thresholds for candidate markers of therapy resistance and sensitivity. Importantly, by assessing the clinical history of longitudinally sampled cases, the clonal evolution of the disease could be determined and matched with PDO drug response profiles.

  Study phs003149

• Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension

  Patients with chronic autonomic failure (CAF) often have disabling orthostatic hypotension (OH). OH in CAF patients is often associated with supine hypertension (hypertension while lying down), which can be severe. Drugs to treat OH worsen supine hypertension. Therefore, the combination of OH with supine hypertension poses a difficult therapeutic challenge. This protocol is a first step toward development of a way to maintain blood pressure during standing without worsening hypertension while lying down. The research question is will a drug (norepinephrine) given intravenously (IV) prevent blood pressure from falling in patients with orthostatic hypotension. This is a placebo controlled, blinded study of 15 patients with neurogenic orthostatic hypotension. The study consists of two experimental days per participant. On a day before the day of norepinephrine (NE) infusion, the patient undergoes head-up tilting while blood pressure is monitored. Tilt angles are increased until the patient has orthostatic symptoms, systolic pressure decreases to less than 90 mm Hg, or systolic pressure decreases by more than 80 mm Hg. On the day of NE infusion patients, receive NE and placebo with the sequence of treatments randomized. If the patient has severe supine hypertension (more than 200 mm Hg systolic), then NE is infused beginning with the patient at whatever tilt angle is required for baseline pressure to be less than 200 mm Hg. NE is infused at doses titrated to keep directly recorded systolic blood pressure at or above the baseline value during exposure to higher tilt angles. When placebo is given, angles of tilt are increased until the patient has orthostatic symptoms, systolic pressure decreases to less than 90 mm Hg, or systolic pressure decreases by more than 80 mm Hg.

  Study phs001769

• Identifying Novel Small RNA Biomarkers Unique to Patients with Gastric Cancer

  The biomarker development study consisted of two parts: discovery and validation. The first part was the discovery and verification phase of biomarkers using two different platforms: transcriptomic and miRNA. The salivary transcriptomes of 63 GC samples and 31 non-GC controls were profiled using Affymetrix HG U133+2.0 microarrays (Affymetrix, Santa Clara, CA). The identified exRNA candidates were verified by quantitative real-time PCR (RT-qPCR) using all 94 of the original samples. In the discovery phase for the miRNA biomarkers, 10 early-stage GC samples and 10 non-GC controls were selected. The salivary miRNAs of these samples (n=20) were profiled using the TaqMan MicroRNA Array (Applied Biosystems, Foster City, CA). MicroRNA candidates were verified using TaqMan miRNA Assay (Thermo Scientific, Grand Island, NY). The second part of the study was to validate these verified exRNA biomarker candidates with exRNA samples extracted from an independent cohort of 100 GC and 100 non-GC saliva samples. The cohort was not balanced for demographics on gender and smoking history but more accurately reflected the diagnostic setting where our proposed final model could be implemented. Reprinted from "Li F, Yoshizawa MJ, Kim K, Kanjanapangka J, Grogan T, Wang X, Elashoff D, Ishikawa S, Chia D, Liao W, Akin D, Yan X, Lee M, Choi R, Kim S, Kang S, Bae J, Sohn T, Lee J, Choi M, Min B, Lee J, Kim J, Kim Y, Kim S, Wong D. (2018) Development and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer. Clin Chem. PMID: 30097497 DOI: 10.1373/clinchem.2018.290569", with permission from American Association for Clinical Chemistry (United States).

  Study phs001767

• Single-Cell Analysis of CD19-Specific CAR T Cell Treatment of Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia

  By leveraging single-cell transcriptome and T cell receptor (TCR) sequencing, we aimed to track the transcriptional signatures of chimeric antigen receptor (CAR) T cell clonotypes throughout the course of treatment and furthermore identify molecular patterns leading to potent CAR T cell cytotoxicity. The data presented in this study encompass blood and bone marrow samples from patients ≤ 21 years of age with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) participating in the SJCAR19 phase I/II clinical trial (NCT03573700). In brief, patients enrolled in the clinical trial received either 1 x 10^6 (dose level 1) or 3 x 10^6 (dose level 2) per kilogram of body weight following successful generation of autologous CAR T cell products and lymphodepleting chemotherapy. Peripheral blood was drawn from each participant every week until week 4 post-infusion, at week 6 or 8, and month 3 or 6 if feasible. At week 4 post-infusion, blood marrow was also collected from participants. Total T cells (CD3+) were sorted from each post-infusion sample, as well as the pre-infusion CAR T cell products, and processed through 10x Genomics’ single-cell gene expression and V(D)J sequencing platform using the standard protocol. We identified a unique and unexpected transcriptional signature in a subset of pre-infusion CAR T cells that shared TCRs with post-infusion cytotoxic effector CAR T cells. Functional validation of cells with even a subset of these pre-effector markers demonstrated their immediate cytotoxic potential and resistance to exhaustion. The data deposited into dbGaP include all raw single-cell expression and V(D)J sequencing generated from samples obtained from 16 study participants.

  Study phs002966

• Warfarin Pharmacogenetics: Pharmacogenetic Optimization of Anticoagulant Response (POAT) and Genetic and Environmental Determinants of Warfarin Response (GEDWR)

  Although the efficacy of warfarin in the treatment and prevention of thromboembolic disorders is proven, it is vastly underutilized with difficulties in management and risk of complications being the main deterrents. Recognition of genetic regulation of warfarin response has fueled efforts to quantify this influence, but the focus has been restricted to select genes and outcomes mainly in European Americans. Race appears to influence warfarin dose requirements with African Americans requiring larger and Asians requiring lower doses compared to Europeans. This variation in dose requirement by race may at least partially be explained by genetic differences. The Genetic and Environmental Determinants of Warfarin Response (GEDWR) and the Pharmacogenetic Optimization of Anticoagulation Therapy (POAT) are prospective cohort study aimed at defining the influence of CYP2C9, VKORC1 and other genes. All patients were followed at monthly intervals from initiation of therapy. At each visit factors influencing warfarin response such as warfarin dose, INR, concurrent medications, etc. were documented. Information on concurrent medications was updated at every clinic visit by self-report and verified by medical record review. Concomitant use of drugs such as drugs that alter warfarin pharmacokinetics, including CYP2C9 inhibitors (e.g., amiodarone), and pharmacodynamics such as antiplatelet agents (e.g. aspirin). Although the a priori hypothesis focused on the candidate-gene approach, with the recognition that the candidate-gene approach is bound by the assumption that our knowledge of genetic influences on warfarin response is complete. Among African Americans known variation in candidate genes (CYP2C9 and VKORC1) explain substantially less variability in warfarin dose requirements. Therefore a genome-wide association study (GWAS) was conducted on African American patients to identify novel variants associated with warfarin dose requirements.

  Study phs000708

• Epigenetics of Cocaine and Nicotine Addiction

  This project characterizes DNA methylation and gene expression changes that occur in the human brain, specifically in neurons from the rostral striatum. Major advances from NIDA funded initiatives for noninvasive neuroimaging studies have made it possible to study neuroanatomical, neurochemical and functional changes in the human brain that contribute to the vulnerability to abuse drugs, together with the neurotoxic consequences of years of drug misuse. Animal models have been developed to explain the fundamental behavioral and biological mechanisms of addiction, including reward, tolerance and dependence. From these studies, we learned that cocaine abuse not only alters the epigenetic status of genes, but also induces particular epigenetic modifications depending on the frequency of the drug's administration. Certain genes are switched on by infrequent (short-term exposure) administration, while others are switched on only after chronic administration (addiction/dependence). Animal studies have also suggested that cocaine-seeking habits modeling chronic cocaine addiction in humans depend upon dopamine-dependent serial connectivity linking the ventral (nucleus accumbens) with the dorsal striatum (caudate nucleus). The primary goal of this study is to identify DNA methylation and gene expression changes that occur in the transition from recreational cocaine use to cocaine addiction. High throughput sequencing studies were designed to investigate unique postmortem human brain specimens from individuals that met criteria for cocaine dependence, as compared to unaffected age-matched controls. Brain biospecimens were available from the University of Miami Brain Endowment BankTM, from a collection of phenotypically well-characterized postmortem tissues sampled from chronic cocaine abusers that came to autopsy. This biobank of postmortem brain specimens and annotated genomic data serve as a research resource to support NIDA's scientific mission.

  Study phs001377

• Integration of Genomics and Transcriptomics in unselected Twins and in Major Depression

  Our goals are to develop a comprehensive understanding of the genomics of transcription in a population based unselected sample and to discover DNA and RNA biomarkers for major depressive disorder (MDD). This work is essential to developing a more complete understanding of the biological basis of MDD, a common complex trait associated with considerable morbidity, mortality, and personal/societal cost. All biological samples have been collected from well-defined populations, and are now available. First, we conduct a "genetical genomics" or eQTL study of ~800 MZ and ~800DZ twin pairs. Each subject has been assayed for genome-wide SNPs and CNVs and gene expression from peripheral blood sampled under standardized conditions. We determine the genetic architecture (genetic and non-genetic proportions of variance via twin analyses) for every transcript, and the genome-wide associations (i.e., SNP-transcript eQTL pairs). These analyses will be expanded to consider transcriptional modules. The key deliverable is a detailed catalogue of the general and specific architecture of transcription plus raw intensity files. Second, we seek to discover DNA and RNA biomarkers relevant to MDD, capitalizing on the results of a large MDD study with repeated clinical and biological assessments; we have previously shown that PB is a reasonable proxy for CNS expression and employ an advanced modelling framework: (a) Using baseline data, we identify biomarkers for MDD by comparing ~1000 controls with ~1400 MDD cases via comparisons of SNP, CNV, expression transcripts, and transcriptional modules. (b) Using longitudinal data, we contrast gene expression signatures assessed at baseline and two years later in ~200 controls and ~500 MDD cases.

  Study phs000486

• Genome Studies in Hereditary Spastic Paraplegia

  Next-generation sequencing technology is opening up new opportunities to rethink the way we identify disease causing genetic variation. An early application, whole exome sequencing, has now been established by a small number of research labs, including ours. Exome sequencing allows obtaining a near complete set of protein coding genomic variation in single individuals for less than $5,000. Promising targets for exome sequencing studies are Mendelian diseases, such as hereditary spastic paraplegias (HSP). HSP comprise a genetically very heterogeneous set of neurological disorders with currently 39 different HSP chromosomal loci being reported; yet, the identified genes explain only 60% of the genetic effect at best. Traditional methods of gene identification require linkage analysis of large families, but face increasing difficulties to identify such extended pedigrees for rare HSP forms. However, the innovative approach described in this application will overcome some of these limitations and utilize relatively small pedigrees for highly effective gene identification. We will apply exome sequencing, which will characterize all coding changes and flanking exonic variation in two individuals of a family. We have developed a multi-tiered strategy to reduce the number of identified novel variants to the very causative change in an individual family. We propose to study at least 60 HSP families, which are too small to yield conclusive results with linkage analysis. If the developing technology permits we will consider a larger sample or perform whole genome sequencing. Beyond the important benefit to genetics of HSP, this study will allow us to further establish this new method, which will benefit a large range of additional disease studies.

  Study phs001080

• NHLBI TOPMed: Coronary Artery Risk Development in Young Adults (CARDIA)

  CARDIA is a study examining the etiology and natural history of cardiovascular disease beginning in young adulthood. In 1985-1986, a cohort of 5115 healthy black and white men and women, aged 18-30 years, were selected to have approximately the same number of people in subgroups of age (18-24 and 25-30), sex, race, and education (high school or less, and more than high school) within each of four US Field Centers. These same participants were asked to participate in follow-up examinations during 1987-1988 (Year 2), 1990-1991 (Year 5), 1992-1993 (Year 7), 1995-1996 (Year 10), 2000-2001 (Year 15), 2005-2006 (Year 20), 2010-2011 (Year 25) and 2015-2016 (Year 30). In addition to the follow-up examinations, participants are contacted regularly for the ascertainment of information on out-patient procedures and hospitalizations experienced between contacts. Within the past five years, 95% of the original surviving cohort has been contacted. While the specifics of each examination have differed somewhat, data have been collected on a variety of factors believed to be related to heart disease. These include conditions with clear links to heart disease, such as blood pressure, cholesterol and other lipids. Data have also been collected on physical measurements, such as weight and skinfold fat, as well as lifestyle factors such as substance use (tobacco and alcohol), dietary and exercise patterns, behavioral and psychological variables, medical and family history, and other chemistries (e.g., insulin and glucose). In addition, subclinical atherosclerosis was measured via echocardiography during Years 5, 10, and 25, computed tomography during Years 15 and 20, and carotid ultrasound during Year 20.Comprehensive phenotypic data for study participants are available through dbGaP phs000285.

  Study phs001612

• ChiLDReN/BA: Genetic Studies of Biliary Atresia in the Childhood Liver Disease Research Network

  Biliary atresia (BA) is a progressive necroinflammatory process initially involving the extra-hepatic biliary tree. Little is known about the factors that cause BA or the factors that influence disease progression. A variety of genetic, autoimmune, and environmental influences have been hypothesized to be important. Most studies to date have focused on the neonate and young child with BA, yet the older surviving child with BA can provide important information about genetics as well as natural history.The Childhood Liver Disease Research Network (ChiLDReN) conducts two longitudinal and observational studies that include BA patients: Biliary Atresia Study in Infants and Children (BASIC) and A Prospective Database of Infants with Cholestasis (PROBE). Using samples from participants in these two protocols, we have formed the largest known data set of biliary atresia patients in the world. ChiLDReN is performing a series of genomic analyses, with subsequent analyses being released as subsequent versions of this registration, phs003356. Version 1 concerns PKD1L1.About the PKD1L1 Analysis (phs003356.v1): While multiple factors have been implicated in the perinatal biliary injuries that characterize BA, a definitive etiology has not yet been established. This study is part of a larger project to characterize the largest cohort of pediatric BA patients through whole-exome sequencing (WES). In this analysis, we examine the WES of those with various laterality defects to determine whether genetic factors could be identified to explicate the etiopathogenesis of BA in biliary atresia splenic malformation (BASM) syndrome. We specifically explored variations in the PKD1L1 gene, which recently has been identified in mouse models as playing a role in laterality.

  Study phs003356

• Cholesterol homeostasis and lipid raft dynamics at the basis of tumor-induced immune dysfunction in chronic lymphocytic leukemia

  Autologous T-cell therapies show limited efficacy in chronic lymphocytic leukemia (CLL), where acquired immune dysfunction prevails. In CLL, disturbed mitochondrial metabolism has been linked to defective T-cell activation and proliferation. Recent research suggests that lipid metabolism regulates mitochondrial function and differentiation in T cells, yet its role in CLL remains unexplored. This comprehensive study compares T-cell lipid metabolism in CLL patients and healthy donors, revealing critical dependence on exogenous cholesterol for human T-cell expansion following TCR-mediated activation. Using multi-omics and functional assays, we found that T cells present in viably frozen samples of patients with CLL (CLL T cells) showed impaired adaptation to cholesterol deprivation and inadequate upregulation of key lipid metabolism transcription factors. CLL T cells exhibited altered lipid storage, with increased triacylglycerols and decreased cholesterol, and inefficient fatty acid oxidation (FAO). Functional consequences of reduced FAO in T cells were studied using samples from patients with inherent FAO disorders. Reduced FAO was associated with lower T-cell activation but did not affect proliferation. This implicates low cholesterol levels as a primary factor limiting T-cell proliferation in CLL. Consequently, CLL T cells displayed fewer and less clustered lipid rafts, potentially explaining the impaired immune synapse formation observed in these patients. Our findings highlight significant disruptions in lipid metabolism as drivers of functional deficiencies in CLL T cells, underscoring the pivotal role of cholesterol in T-cell proliferation. This study suggests that modulating cholesterol metabolism could enhance T-cell function in CLL, presenting novel immunotherapeutic approaches to improve outcome in this challenging disease.

  Study EGAS50000000933

• Genomic Landscape of Multiple Myeloma and of its Precursor Conditions, and its Clinical Implications

  Reliable strategies to capture patients at risk of progression from precursor stages of multiple myeloma (MM) to overt disease are still missing. In this study, we generated whole-genome sequencing (WGS) data from matched tumor and normal samples from 98 individuals from the PCROWD study (Precursor Crowd, NCT02269592). These individuals have either a precursor condition for MM, which can be a monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM), or an active multiple myeloma (MM). To do so, we enriched tumor plasma cells from the bone marrow by magnetic bead selection (CD138+), sequenced the DNA of these samples to a target depth of 60X (tumor), and analyzed them against normal white blood cells (peripheral blood mononuclear cells) from the same individuals sequenced to a target depth of 30X (normal). In our first publication [Alberge, Dutta, Poletti, et al., 2025], we integrated and homogeneously analyzed these data together with data from mostly publicly available datasets (phs003084 and phs000748) to reach 1,030 total samples. We used these data to identify recurrent coding and non-coding candidate drivers, as well as significant hotspots of structural variation, and used those drivers to define and validate a simple “MM-like” score which we could use to place patients' tumors on a gradual axis of progression toward active disease. Our MM precursor genomic map provides new insights on the time of initiation and cell of origin of the disease, on the order of acquisition of genomic alterations, and on mutational processes found across stages of the transformation. Taken together, we highlight here the potential of genome sequencing to better inform risk assessment and monitoring of MM precursor conditions.

  Study phs003846

• Field Studies of Human Immunity to Amebiasis in Bangladesh

  Amebiasis is a common cause of diarrhea and is associated with malnutrition in grade-school aged children in an urban slum of Dhaka, Bangladesh. Field Studies of Human Immunity to Amebiasis in Bangladesh was designed to determine the contribution of amebiasis to illness in the first 2 years of life when most deaths due to diarrhea occur, and understand the immunologic and genetic factors that protect children from amebiasis. The hypothesis underlying the study is that susceptibility to amebiasis is determined by host innate and acquired immune responses that vary between individuals in part due to: human genetic polymorphisms; environmental influences including malnutrition and concurrent geohelminth infection; and virulence differences among Entamoeba histolytica genotypes. Specific aims proposed in the design of the study were to: a) Measure the incidence of amebiasis and correlate it with human and parasite genetic polymorphisms, immune responses, and environmental factors such as geohelminth infection and malnutrition; b) Test the hypothesis that protective immunity is mediated both by innate immune responses initiated via TLR stimulation as well as by mucosal IgA against the Gal/GalNAc lectin and systemic IFN-γ; c) Test for the association of common genetic polymorphisms in host innate and acquired immune genes with incidence of amebiasis. 629 newborn babies were enrolled and followed regularly through bi-weekly surveillance for diarrheal episodes, anthropometry at 3-month interval until 60 months of age. The infants that were consented for GWAS analysis were genotyped in 3 separate batches at different times, on 3 different arrays. Quality control was performed on the 3 separate data sets and then jointly after merging. Genetic data available on 447 infants together with their phenotype data is made available in this submission.

  Study phs001476

• Involvement of the FGF8/FGF Receptor Signaling Pathway in the Maintenance and Progression of Fusion-Positive Rhabdomyosarcoma

  In our previous work, we used a myoblast model of fusion-positive rhabdomyosarcoma (FP-RMS) to demonstrate that FGF8, a target of the PAX3-FOXO1 (P3F) transcription factor, is essential for tumorigenicity driven by P3F. When aberrantly expressed, FGF8 can also sustain tumorigenicity in recurrent tumors that are independent of P3F. In this study, we report that FGF8, along with its receptors FGFR1 and FGFR4, is often highly expressed in FP-RMS tumors. We found that high levels of FGF8 expression in FP-RMS cells correlate with increased sensitivity to an FGFR4 inhibitor and a pan-FGFR inhibitor. Conversely, downregulating FGF8 led to a loss of sensitivity to these inhibitors. Interestingly, when FGF8 was upregulated in myoblasts, it resulted in decreased FGFR4 expression and sensitized the cells to an FGFR1 inhibitor and a pan-FGFR inhibitor. The downregulation of FGFR4 expression mediated by FGF8 could be reversed by inhibiting FGFR1, MEK, or ERK, thereby defining a signaling pathway through which FGF8 exerts its regulatory effects. Additionally, we discovered that high FGF8 expression in P3F-independent recurrent tumors is due to a rearrangement of viral long terminal repeat (LTR) sequences into the 3' untranslated region (UTR) of FGF8, leading to increased stability of FGF8 mRNA. These findings indicate that FGF8 plays an oncogenic role in FP-RMS through FGFR4 and may also exert oncogenic effects in P3F-independent relapses via FGFR1. Our study highlights the functional significance of FGF8 in FP-RMS and supports the rationale for preclinical investigations of FGFR inhibitors in treating this type of cancer.

  Study phs004009

• Induced Pluripotent Cells Derived from Differentiated Rod Photoreceptors Undergo Efficient Retinogenesis in Three-Dimensional Cultures

  "Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are used to study lineage-specific differentiation in culture. We developed a standardized quantitative protocol called STEM-RET to compare eye field specification, optic cup formation, and retinal differentiation across stem cell populations. We reprogrammed individual rod photoreceptors into iPSCs by inducible expression of Oct3/4, Klf4, Sox2, and Myc. We also developed ESC lines from rods by somatic cell nuclear transfer. Using the STEM-RET protocol, we compared the abilities of ESCs, fibroblast-derived iPSCs (f-iPSCs), rod photoreceptor-derived iPSCs (r-iPSCs), and rod photoreceptorderived ESCs to form retinae using STEM-RET. r-iPSCs were the most efficient at producing differentiated retina. Retinae derived from f-iPSCs lacked an inner nuclear layer (INL) and had a concomitant reduction in amacrine cells and other INL cell populations. The INL-specific LIM homeobox gene, Lhx9, was hypermethylated in fiPSCs and concomitantly downregulated in retinae derived from those stem cells. ChIP-seq analysis for H3K36me3, H3K4me1, H3K4me3, H3K9/14Ac, H3K27me3, H3K9me3, CTCF and 5 hydroxymethyl cytosine showed that the major difference between the r-iPSCs and the f-iPSCs were in the genes marked by the CTCF insulator protein. Importantly, CTCF binding enrichment at rod photoreceptor specific genes was at least 10-fold higher in r-iPSCs relative to f-iPSCs. Taken together, our data suggest that both inhibitory and permissive epigenetic marks important for retinal development can be retained in iPSCs and such marks can be exploited to select the most favorable stem cell population to study retinal development or produce photoreceptor precursors for cell transplantation."

  Study EGAS00001001288

• Integrated genomic analyses reveal molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma

  Atezolizumab (anti–programmed death-ligand 1 [anti-PD-L1]) and bevacizumab (anti-vascular endothelial growth factor [anti-VEGF]) combination therapy has become the new standard of care in patients with unresectable hepatocellular carcinoma. However, potential predictive biomarkers and mechanisms of response and resistance remain less understood. We report integrated molecular analyses of tumor samples from 358 patients enrolled in the GO30140 phase 1b or IMbrave150 phase 3 trials who were treated with atezolizumab combined with bevacizumab, atezolizumab alone, or sorafenib. Pre-existing immunity assessed by high expression of CD274 (PD-L1 mRNA), T-effector signature, and intratumoral CD8+ T cell density were associated with response and better clinical outcomes with the combination treatment. Less clinical benefit was associated with high regulatory T cell (Treg) to effector T-cell ratio and high expression of oncofetal genes such as GPC3 and AFP. Improved outcomes from the combination vs atezolizumab alone appeared to be associated with high expression of KDR (VEGFR2), Treg, and myeloid inflammation signatures, indicating anti-VEGF may contribute by targeting these axes. These findings were further validated by transcriptome analysis of paired pre- and post-treatment biopsies, in situ analysis by multiplex IHC and digital pathology, and in vivo study of an immunogenic hepatocellular carcinoma mouse model. Our findings highlight that anti-VEGF therapy might augment antitumor immunity and enhance anti–PD-L1 immunotherapy by targeting VEGF-mediated angiogenesis, Treg proliferation, and myeloid cell inflammation. Furthermore, our study identified candidate biomarkers for predicting response and resistance to anti–PD-L1 and anti-VEGF combination therapy.

  Study EGAS00001005503

• Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients with Advanced Lung Adenocarcinoma

  We retrospectively collected patients (n=1047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r=0.403, P<0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT >6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤6.9 months set. This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

  Study EGAS00001004546

• Analysis of error profiles in deep next-generation sequencing data

  BackgroundSequencing errors are key confounding factors for detecting low-frequency genetic variants that are important for cancer molecular diagnosis, treatment, and surveillance using deep next-generation sequencing (NGS). However, there is a lack of comprehensive understanding of errors introduced at various steps of a conventional NGS workflow, such as sample handling, library preparation, PCR enrichment, and sequencing. In this study, we use current NGS technology to systematically investigate these questions.ResultsBy evaluating read-specific error distributions, we discover that the substitution error rate can be computationally suppressed to 10-5 to 10-4, which is 10- to 100-fold lower than generally considered achievable (10-3) in the current literature. We then quantify substitution errors attributable to sample handling, library preparation, enrichment PCR, and sequencing by using multiple deep sequencing datasets. We find that error rates differ by nucleotide substitution types, ranging from 10-5 for A>C/T>G, C>A/G>T, and C>G/G>C changes to 10-4 for A>G/T>C changes. Furthermore, C>T/G>A errors exhibit strong sequence context dependency, sample-specific effects dominate elevated C>A/G>T errors, and target enrichment PCR led to aprox 6-fold increase of overall error rate. We also find that more than 70% of hotspot variants can be detected at 0.1% - 0.01% frequency with the current NGS technology by applying in-silico error suppression.ConclusionsWe present the first comprehensive analysis of sequencing error sources in conventional NGS workflows. The error profiles revealed by our study highlight new directions for further improving NGS analysis accuracy both experimentally and computationally, ultimately enhancing the precision of deep sequencing.

  Study EGAS00001003444

• Exome sequencing from cfDNA blood samples. 159 samples at 2x101bp Illumina reads in Fastq format.

  Differential presence of exons (DPE) by next generation sequencing (NGS) is a method of interpretation of whole exome sequencing. This method has been proposed to design a predictive and diagnostic algorithm with clinical value in plasma from patients bearing colorectal cancer (CRC). The aim of the present study was to determine a common exonic signature to discriminate between different clinical pictures, such as non-metastatic, metastatic and non-disease (healthy), using a sustainable and novel technology in liquid biopsy. Through DPE analysis, we determined the differences in DNA exon levels circulating in plasma between patients bearing CRC vs. healthy, patients bearing CRC metastasis vs. non-metastatic and patients bearing CRC metastasis vs. healthy comparisons. We identified a set of 510 exons (469 up and 41 down) whose differential presence in plasma allowed us to group and classify between the three cohorts. Random forest classification (machine learning) was performed and an estimated out-of-bag (OOB) error rate of 35.9% was obtained and the predictive model had an accuracy of 75% with a confidence interval (CI) of 56.6-88.5. In conclusion, the DPE analysis allowed us to discriminate between different patho-physiological status such as metastatic, non-metastatic and healthy donors. In addition, this analysis allowed us to obtain very significant values with respect to previous published results, since we increased the number of samples in our study. These results suggest that circulating DNA in patient’s plasma may be actively released by cells and may be involved in intercellular communication and, therefore, may play a pivotal role in malignant transformation (genometastasis).

  Study EGAS00001006656

• Molecular Phenotyping to Accelerate Genomic Epidemiology (MolPAGE)

  MolPAGE is an integrated EU project that aims to develop methods and tools for discovery of biomarkers associated with diabetes (see www.ocdem.ox.ac.uk for MolOBB and www.twinsuk.ac.uk for MolTWIN).

  Study EGAS00000000102

• Paroxysmal Neurological Disorders - rare epilepsies

  We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.

  Dataset EGAD00001000647

• Whole-exome sequencing and microRNA profiling predicted relapse risk of stage I lung adenocarcinomas for the study and all the datasets.

  This dataset contains CEL files and rma normalized expression value for microarray of stage I lung adenocarcinomas from Asian patients. In total, there are 69 patients and 138 samples, including 69 tumor samples and 69 adjacent normal samples.

  Dataset EGAD00010001901

• Exome sequencing for heterogeneity and evolution of DNA mutation rates

  Dataset comprising 27 pairs of high-depth (300x) WES results obtained from 54 PDXs derived from primary CRCs resected synchronously with their corresponding metastases. These exoms sequences are part of a larger study on the heterogeneity and evolution of DNA mutation rates in microsatellite-stable colorectal cancer.

  Dataset EGAD50000000208

• Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

  Targeted cfDNA and WBC sequencing data from patients profiled in the study "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer". Note that 'Exome sequencing' is listed under Dataset Type since there is no option for targeted panel sequencing.

  Dataset EGAD50000000303

• RNA sequencing

  For RNA sequencing: All sample numbers starting with 6717 are tumor samples which has been sequenced using transcriptomics (see BAM files). It concerns biopsies of metastatic lesions from patients with BRAFV600 mutated melanoma, obtained before, during and after the study treatment (see samples metadata). RNA sequencing is performed using the Illumina Novaseq 6000 system.

  Dataset EGAD50000000383

• Tumor heterogeneity and immune-evasive microenvironment in T follicular helper cell lymphomas

  Single-cell analysis data for tumor and immune cells from lymph node and peripheral blood samples of 14 patients with T follicular helper cell lymphomas

  Study EGAS50000000275

• Somatic Mutations in Variant and IGHV4-34 Expressing Hairy Cell Leukemia

  To understand the genetic mechanisms driving variant and IGHV4-34 expressing hairy-cell leukemia, we performed whole exome sequencing of tumor/normal pairs from ten patients.

  Study phs000671

• Sputum RNA-Seq from Asthmatic Patients for Microbes and Genes

  RNA-seq files and other data associated with an investigation of the relationship between microbes, genes and immune cells present in the sputum of humans with asthma.

  Study phs002224

• Genetic Heterogeneity of Diffuse Large B Cell Lymphoma

  We sequenced exomes of 94 DLBCL tumors and cell lines. 34 of the tumors had paired normal tissue. Our work elucidates commonly occurring gene-coding mutations in DLBCL.

  Study phs000573

• Tumor heterogeneity and acquired drug resistance in FGFR2 fusion-positive cholangiocarcinoma through rapid research autopsy

  Whole exome sequencing was performed on blood and tumor specimens (collected from biopsy or rapid research autopsy) from a patient with FGFR2 fusion positive cholangiocarcinoma.

  Study phs001830

• RNA sequencing of Non-Small Cell Lung Cancer and adjacent normal tissue

  RNA sequencing was performed on 108 NSCLC tumor samples and their paired adjacent normal tissues (n=21) to identify associations with clinical and immune characteristics.

  Study EGAS50000000246

• ctDNA diva aggregate data

  ctDNA biomarker and relevant clinical data for divarasib phase I GO42144 study, including tumor type, KRAS G12C mutation detectability in plasma at baseline, baseline SLD, sites of metastasis, lines of therapy, best response, confirmed best response, PFS, ctDNA tumor fraction and KRAS G12C VAF at baseline/C1D15/C3D1.

  Dataset EGAD50000000454

• The evolution of ovarian high grade serous carcinoma from STIC lesions

  We performed shallow whole genome sequencing of normal fallopian tube, stroma, p53 signatures, STIL/STIC, invasive and metastasis carcinoma from 5 high grade serous carcinoma cases.

  Study EGAS50000000360

• GBM Study Complete Raw Data

  Tumors from 173 GBM patients were analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. Exome libraries for 173 glioblastoma tumors and matched normal DNA were sequenced on Illumina platform, alongside total RNA from the tumors.

  Dataset EGAD50000000650

• Disease recurrence after pathologic response

  In this study we aim to gain insight into the mechanisms of immune evasion after initial pathologic response to neoadjuvant immune checkpoint inhibition in macroscopic stage III melanoma by pooling data of the neoadjuvant OpACIN, OpACIN-neo and PRADO trials. Here we used RNAseq data from 21 patients(paired end)

  Dataset EGAD50000000698

• DAC-2020-03-26-Lemola (DAC-039))

  This is only the location. For the raw data and any check if the dataset may be relevant please refer to the Harvard Dataverse (https://dataverse.harvard.edu/dataverse/lemola).

  Study EGAS50000000635

• Cohort A RNA sequencing

  Cohort A includes glioma tumors of varied grading and pathology from male and female individuals. RNA was isolated from fresh frozen glioma tissue of each sample tumor block from Cohort A.

  Study EGAS50000000950

• Cohort B RNA sequencing

  Cohort B includes IDH-wild type, EGFR amplified, surgically derived glioblastoma tissue samples from male and female individuals. RNA was isolated from FFPE glioma tissue of each sample from Cohort B.

  Study EGAS50000000953

• Targeted DNA sequence

  Targeted DNA sequencing files that were used in our study. The cohort was composed of 36 cases of tumor-only targeted DNA sequencing data. All files are UMI processed. The panel is designed with Agilent Sure Select and the sequence was performed using DNBSEQ sequencer.

  Dataset EGAD50000000972

• Whole genome sequencing data using Adaptive sampling from 33 patients with hereditary cancer syndrome

  We performed whole genome sequencing using adaptive sampling with GridION on 33 patients with clinically suspected hereditary cancer syndromes to evaluate an efficient computational workflow.

  Study JGAS000654

• Elucidation of the association between viruses and autoimmune diseases and COVID-19

  We determined the presence of endogenous human herpesvirus 6 (eHHV-6) and calculated anellovirus load from whole-genome sequencing data of 1,164 patients with COVID-19.

  Study JGAS000739