15038 results for "cancer studies using rna-seq"

in 44.50 milliseconds.

• DNA methylation (RRBS) data for the validation the glioblastoma progression study (GBMatch).

  Genome-wide profiling of DNA methylation levels by RRBS in 150 glioblastoma tumor samples. Patients were selected to represent the general population of glioblastoma patients based on Austrian Brain Tumor Registry. These DNA methylation profiles were created for the validation of the glioblastoma progression study (GBMatch) and consist of 106 profiles from FFPE samples and 44 profiles from fresh-frozen samples. For the 44 fresh-frozen samples also WGS data (43 genomes) and RNA-seq data (37 transcriptomes) have been produced for validation purposes.

  Dataset EGAD00001004074

• Gene expression in CSF and whole blood of adults with proven bacterial meningitis in Malawi

  Dataset of BAM files from patients with proven bacterial meningitis in Malawi. Samples consist of BAM files from PolyA RNA seq runs from patients classifed as admission whole blood or CSF on admission (pre-antibiotics) in the Emergency Department. Subsequent BAM files are identical runs from whole blood from the same patients, taken at either day 10 or day 40 post admission to hospital. All patients have disease, they are divided into survivors and non-survivors at the day 40 time point.

  Dataset EGAD00001004488

• RNAseq from PDAC samples

  BAM files from RNA-seq of PDAC samples used in the COMPASS hENT1 study

  Dataset EGAD00001009409

• RNA-seq dataset of Characterization of UV DNA damage in B-cell precursor acute lymphoblastic leukemia

  Extensive characterization of mutational signature SBS7a in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) samples. We aimed to describe the presentation of SBS7a in BCP-ALL, identify other pediatric cancers presenting with SBS7a, look into the link of SBS7a and UV-light in the context of BCP-ALL and cancers with provable UV exposure, and pinpoint when SBS7a was acquired.

  Dataset EGAD00001015598

• Epigenetic Profiling of Human Colorectal Cancer

  DNA methylation, together with chromatin modifications, constitute the epigenome that functions to regulate gene expression and genome integrity. DNA methylation alterations are ubiquitous in human cancers, as many genes acquire DNA methylation in a cancer-specific manner. DNA methylation at these sites in the genome of cancer cells not only serves as a marker for tumor identification, but together with gene mutation and gene expression data, can also be used to describe subsets of tumors of the same organ source. We have previously shown distinct human colorectal cancer subtypes based on DNA methylation differences. Correlating these DNA methylation differences with clinical co-variates will serve to further understand how these distinct subtypes are generated. We have collected 100 colorectal tumor tissues (for which clinical information is known) and have obtained (unprotected) genome-wide DNA methylation and chromatin modification information for each sample for the purposes of identifying and classifying unique tumor subtypes of colorectal cancers. In addition, we have determined mutations of key genes relevant to colorectal cancer as well as gene expression profiles. We will use the clinical data for each de-identified sample to correlate with the DNA methylation, mutation and gene expression information so as to understand the driving forces behind these distinct colorectal subtypes. We have selected the most promising tumors for whole-genome bisulfite sequencing using next-generation sequencing technology to obtain complete maps of colon cancer methylomes. Researchers will be unable to identify the subjects because the samples and associated information have been de-identified and anonymized by the tissue source site. In addition, upon receipt by the USC Epigenome Center, we have assigned new random identifiers for each sample. The data generated using these new codes are not traceable to the patient identity.

  Study phs000385

• Effects of Metformin on Transcriptomic and Metabolomic Profiles in Breast Cancer Survivors Enrolled in the Randomized Placebo-Controlled MetBreCS Trial

  Metformin reduces the incidence of breast cancer in patients with obesity and type 2 diabetes. However, our knowledge of the effects of metformin on breast cancer recurrence is limited. Within the randomized double-blind placebo-controlled phase II trial MetBreCS, we examined changes in breast tissue from breast cancer survivors with BMI >25 kg/m2 after treatment with metformin. To identify metformin-regulated signaling pathways, we integrated the transcriptomic, metabolomic and steroid hormone profiles using bivariate and functional analyses. We identified MS4A1, HBA2, MT-RNR1 and MT-RNR2 expression to be differentially expressed in breast tissues from metformin-treated women. We also found metformin-associated down-regulation of EGFL6 and FDCSP in postmenopausal women. The integration of transcriptomic and metabolomic profiles revealed down-regulation of immune response genes associated with reduced levels of arginine and citrulline in the metformin-treated group. The integration of transcriptomic and steroid hormone profiles showed an enrichment of steroid hormone biosynthesis and metabolism pathways with highly negatively correlated CYP11A1 and CYP1B1 expression in breast tissue from postmenopausal metformin-treated women. Our results indicate that breast cancer survivors treated with metformin have specific changes in breast tissue gene expression that may prevent the development of new tumors. Within the randomized double-blind placebo-controlled phase II trial MetBreCS, we examined changes in breast tissue from breast cancer survivors with BMI >25 kg/m2 after treatment with metformin using bulk RNAseq (total mRNA sequencing), that is deposited in Federated EGA. The steroid hormones, and metabolomics and the insulin sensitivity serum biomarker data underlying this article may be shared upon reasonable request to the PI of the MetBreCS study (Dr. Bernardo Bonanni), following approval by the Data and Safety Monitoring Board at IEO, Milan.

  Study EGAS50000000874

• Cancer genome scanning in plasma: detection of tumor-associated copy number aberrations, single nucleotide variants and tumoral heterogeneity by massively parallel sequencing

  Tumor-derived DNA can be found in the plasma of cancer patients. We explored the use of shotgun massively parallel sequencing of plasma DNA obtained from cancer patients to scan a cancer genome noninvasively. We achieved the profiling of copy number aberrations and point mutations, in a genomewide manner using this approach. By measuring the genomewide aggregated allelic loss and point mutations, we determined the fractional tumor-derived DNA concentrations in plasma and correlated these values with tumor size and surgical treatment. We have also demonstrated the application of this approach to monitoring a complex oncologic scenario, in a patient with two synchronous cancers. In particular, through the use of multi-regional sequencing of tumoral tissues and shotgun sequencing of plasma DNA, we have shown that plasma DNA sequencing is a valuable approach for studying tumoral heterogeneity. Shotgun plasma DNA sequencing is thus a powerful tool for cancer monitoring and research.

  Study EGAS00001000370

• Whole-genome sequencing of tumour, germline and plasma samples from a BRCA1-mutant breast cancer patient

  This data set contains the fastq files from whole-genome sequencing of temporally matched tumour (fresh frozen biopsies), blood germline and plasma samples collected from a BRCA1-mutant breast cancer patient to directly compare mutation signature analysis using gold-standard tumour-germline paired variant calling with a novel ctDNA-based method (MisMatchFinder).

  Dataset EGAD50000000811

• Whole genome sequencing of circulating cell-free DNA on Illumina and Ultima platforms

  The dataset includes Illumina (n=1) and Ultima (n=92) sequencing of circulating cell-free DNA. The dataset was generated through standard whole genome sequencing (Illumina n=1 & Ultima n = 15) and using a duplex unique molecular identifier whole genome sequencing workflow (Ultima, n=77). This dataset includes cancer samples and cancer-free control samples.

  Dataset EGAD50000001234

• The dataset of Detection and characterization of lung cancer using cell-free DNA fragmentomes on NovaSeq 6000 at 1-2x coverage

  The dataset contains 364 CRAM files from whole-genome next-generation sequencing on the Illumina NovaSeq 6000 at 1- 2x coverage. These are plasma samples from healthy individuals and patients with cancer.

  Dataset EGAD50000001961

• Biomodal duet +modC sequencing of endometrial cancer plasma cfDNA samples

  This dataset contains biomodal sequencing data generated using the duet + modC assay from plasma-derived cell-free DNA of endometrial cancer patients and healthy donors. Sequencing was performed on an Illumina NovaSeq 6000. Dataset includes raw sequencing FASTQ files. Duet +modC output enables whole-genome profiling of both genetic variation and DNA methylation.

  Dataset EGAD50000002261

• CNV detection in targeted NGS panel data

  We present targeted NGS panel data from 170 samples that were processed using the TruSightTM Cancer (TSC) panel (Illumina, San Diego, CA, USA), which targets 94 genes and 284 SNPs associated with a predisposition towards cancer. The samples are enriched for CNVs in the genes of interest. All CNVs have previously been assessed with MLPA and can therefore be considered as confirmed.

  Dataset EGAD00001003400

• Targeted Pulldown Validation of mutations found in whole genome sequencing

  This experiment is to inform us of the validity of using pre-made library material to perform a bespoke pulldown experiment to validate the mutations found between the whole genome sequencing of the DNA from the same individuals cancer and normal material. This is to identify the valid and informative mutations in cancer genomes.

  Dataset EGAD00001001061

• Whole-exome sequencing of liver cancer organoids

  Whole-exome sequencing was performed from organoids derived from 10 liver cancer biopsies (7 hepatocellular carcinoma and 3 cholangiocarcinoma), corresponding liver and non-tumoral biopsies. For 3 of the organoids, both early and late passage organoids were sequenced. Whole-exome sequencing was performed using the Agilent Clinical Research Exome capture kit followed by Illumina sequencing. BAM files are provided in this dataset.

  Dataset EGAD00001004205

• Dataset Gene-Breakpoint Panel

  In this study we analysed patients with metastatic prostate cancer to scan their tumor genomes noninvasively in plasma DNA. We enriched 1.3 Mbp of seven plasma DNAs (4 CRPC cases: CRPC1-3 and CRPC5; 3 CSPC cases: CSPC1-2 and CSPC4) including exonic sequences of 55 cancer genes and 38 introns of 18 genes, where fusion breakpoints have been described using Sure Select Custom DNA Kit.

  Dataset EGAD00001000365

• Determining off-target effects of splice-switching antisense oligonucleotides using short read RNAseq in neuronally differentiated human induced pluripotent stem cells

  Neuronal cells derived from female healthy control hiPSC lines LUMCi003-A, LUMCi003-B and LUMCi023-A were transfected with in total four different splice-switching AONs targeting three different human transcripts. Untransfected samples as well as samples transfected with a scrambled AON were included as controls. Three days after transfection, RNA was isolated for sequencing using Illumina Novaseq6000 in order to perform differential gene expression analysis and differential splicing analysis to determine off-target effects. Sequencing was performed in two batches: one containing the samples from cell line LUMCi003-A and the other containing cell lines LUMCi003-B and LUMCi023-A.

  Dataset EGAD50000001742

• Target-capture sequencing of FFPE tumor samples from patients diagnosed with NKTL

  211 NKTL FFPE specimens were screened for somatic mutations using deep targeted capture sequencing. FFPE rolls or slides were extracted using QIAamp DNA FFPE Tissue kit (QIAGEN). The FFPE genomic DNA was treated with NEBNext FFPE DNA Repair Mix and assessed by Quant-it PicoGreen dsDNA Assay Kit (Invitrogen). The library was generated from 10-200 ng DNA with SureSelectXT Low Input Target Enrichment System for Illumina Paired-End Sequencing Library (Agilent Technologies) according to manufacturer’s instructions. RNA based probe was designed with SureDesign (Agilent Technologies) to target-capture 140 genes. Next, the captured libraries were pooled in equimolar concentration and sequenced on Illumina Novaseq 6000 platform with SP or S1 chip.

  Dataset EGAD00001005303

• CCDG CVD: VIRGO - Variation in Recover-Role of Gender on Outcomes of Young Acute Myocardial Infarction (AMI) Patients

  The VIRGO study is a four year research project funded by the NHLBI to study young women and men with heart attacks. A total of 2,000 women who are 18 - 55 years of age and a smaller comparison group of 1,000 similarly aged men will be enrolled in this multi-site observational study from approximately 120 different hospitals across the country. Young women have a much greater risk of dying after an acute myocardial infarction (AMI) than similarly aged men. Their mortality risk is markedly higher than that of young men, and limited data on young minority women suggest that they may have the highest risk of any young subgroup. Findings from the small number of published studies of young women with ischemic heart disease suggest that the biology, epidemiology, care, and outcomes of this group are distinct from those of men. To date, there have been no large studies of this population, even as the death toll is comparable to that from breast cancer in this country. This study will help researchers identify key factors that influence recovery from a heart attack and potentially improve the care and outcomes of young women and men with AMI. Specific Aims: To investigate the excess risk in young women with AMI and to identify key demographic, clinical, metabolic, psychosocial, health care delivery, and biological determinants of prognosis, we propose a national, prospective, observational study of 2,000 women who are 55 years or younger with AMI and a smaller comparison group of 1,000 men. Our prior work and preliminary studies indicate that the sex differences are most prominent in this age group and suggest that by 1 year after discharge, there are substantial sex differences in outcomes. We will also develop risk stratification tools that will help clinicians to identify young women with the highest and lowest risk. Specific Aim 1: Determine sex differences in outcomes following AMI. Specific Aim 2: Determine sex differences in the prevalence and prognostic importance of demographic, clinical, and psychosocial risk factors. Specific Aim 3:Determine sex differences in quality of care. Specific Aim 4: Determine sex differences in the prevalence and prognostic importance of selected biochemical biomarkers following AMI. These samples have been whole genome sequenced as part of the NHGRI's Center for Common Disease Genetics at the Broad Institute.

  Study phs001259

• Next Generation Sequencing Characterization of Tregs in Human Peripheral Blood during Autoimmunity

  Tregs were sorted as CD4+CD25+CD127- cells from peripheral blood of 14 healthy individuals, 8 patients with systemic lupus erythematosus, 9 patients with rheumatoid arthritis, and 11 patients with multiple sclerosis. RNA was extracted and polyA libraries were prepared using the Illumina Truseq sample preparation kit v.2. Single-end sequencing was performed on NextSeq500.

  Dataset EGAD00001006193

• Somatic Mutation Profile by Next Generation Sequencing in HER2+ Breast Cancer

  The HER pathway is the driving force behind 30% of human breast cancers. It is important to understand how targeted therapies block different cellular pathways, and mechanisms of escape from this blockage. Therapies directed at HER2 establish a successful treatment paradigm, but de novo and acquired resistance exist. The HER signaling system is a complex network with four receptors and eleven ligands, a phosphorylation signaling cascade, and many transcription factors, all complicated by both positive and negative feedback circuits. Analysis of genomes, exomes and transcriptomes by next generation sequencing is aimed at uncovering the genetic factors responsible for patient responses to HER2-directed therapies. We are sequencing HER2-overexpressing cancers, in order to identify potential somatic changes that may better select patients who will benefit from therapy, to determine new targets that may overcome resistance, and to improve outcomes with known current HER2-targeted therapies. Whole exome capture sequencing will determine somatic mutation profiles in HER2-overexpressing tumors, to comprehensively characterize the somatic alterations, with the goal of identifying those patients most likely to respond, as well as discovering new targets that may overcome resistance to HER2-directed therapy. We augment the whole exome data with RNA-seq data to determine expression levels of somatic mutations we discover.

  Study phs000770

• Germline WES of serrated polyposis syndrome

  The serrated polyposis syndrome (SPS) is a disease with a mainly unknown inherited genetic basis characterized by the presence of multiple and/or large serrated polyps in the colon and a higher associated risk for colorectal cancer (CRC). The objective of the present study was to identify new SPS/CRC germline predisposition genes by using whole-exome sequencing in two affected SPS patients from the same family.

  Study EGAS50000000765

• WES analysis of tumor samples from ER+ breast cancer patients treated with CDK4/6 inhibitor

  We performed whole exome sequencing of paired fresh frozen tumor from 4 ER+ advanced breast cancer patients. Samples were obtained for each patient prior to combined CDK4/6 inhibitor and endocrine therapy and at disease progression (N=8). DNA was extracted using the Maxwell® RSC FFPE and Tissue DNA Kit (Promega). WES was performed at the Department of Molecular Medicine, Aarhus University Hospital on matched tumor DNA (derived from primary fresh frozen and FFPE tissue) and buffy coat DNA. Libraries of tumors and matching germline DNA were prepared using 50 ng DNA and captured by Twist Comprehensive Exome with custom spike-ins, sequenced on the Illumina NovaSeq 6000 platform to an average coverage of 413x (range: 148-515x). The dataset include the analysis data files (vcf files).

  Dataset EGAD50000000622

• Reproducibility of variant calls in replicate next generation sequencing experiments

  In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.

  Study EGAS00001000826

• The Landscape of Genetic Alterations in Hepatocellular Carcinoma, 88 matched HCC tumour/normal pairs WGS belongs to ICGC LICA-CN project

  Hepatocellular carcinoma (HCC) is the most common malignancy of the liver. Genomic analysis is conducted to identify genetic alterations in driver genes which are all druggable targets for cancer therapy. Whole genome shotgun sequencing (WGS) and the landscaple of somatic mutations in 88 paired samples from HCC patients including tumors and matched adjacent normal tissues using Illumina HiSeq 2000 platform were performed.

  Study EGAS00001002218

• Functionally Active Copy Number Variants Associated with Prostate Cancer Risk

  Prostate cancer is a leading cause of cancer death in males throughout the world and has the largest estimated effect of heritability among the most common tumor types. Copy Number Variants (CNVs) are a recently recognized class of human germline polymorphisms (Iafrate AJ, et al. (2004) Nat Genet 36, 949-951; Sebat J, et al. (2004) Science 305, 525-528.) and are associated with a variety of human diseases, including cancer. This study characterized 1,903 individuals from the Tyrol Early Prostate Cancer Detection Program (Bartsch G, et al. (2008) BJU Int 101, 809-816) using a computational framework (Banerjee S, et al. (2011) PLoS One 29;6(3)). The study results establish non-coding and coding germline CNVs as significant risk factors for prostate cancer susceptibility and implicate their role in disease development and progression. The study "Identification of functionally active, low frequency copy number variants at 15q21.3 and 12q21.31 associated with prostate cancer risk," Demichelis F, Setlur SR, Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6686-91.

  Study phs000487

• Longitudinal genome-wide analysis of progressive chronic lymphocytic leukemia under uniform front-line therapy of pentostatin, cyclophosphamide, and rituximab

  Samples from two-center prospective phase 2 clinical trail conducted at Ohio State University (Columbus, OH) and Mayo Clinic (Rochester, MN) were analyzed in 12 cases. All patients had progressive CLL as defined by National Cancer Institute (NCI) Working Group criteria. Patients provided written informed consent for correlative studies according to the Declaration of Helsinki on an institutional review board approved protocol for the collection and use of samples for research purposes from both participating institutions. Eligible patients received a regimen consisting of pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) provided intravenously on day 1 of a 21-day cycle for a maximum of 6 cycles. Responses were assessed by NCI Working Group criteria and included a bone marrow evaluation and two-color flow cytometry 2 months after completion of therapy. Peripheral blood samples from these patients collected longitudinally before (Pre-Baseline), at (Baseline) and after therapy (Relapse) were analyzed for genomic heterogeneity and clonal complexity by high throughput Exome sequencing.

  Study phs000794

• Cancer cell and tumor microenvironment biomarkers associated with disease-free survival with adjuvant nivolumab in the phase 3 CheckMate 274 trial

  In the CheckMate 274 trial, adjuvant nivolumab versus placebo demonstrated an improvement in the primary endpoint of disease-free survival (DFS) in patients with high-risk muscle-invasive urothelial carcinoma after radical resection. An extensive analysis of tumor biomarkers, including their associations with DFS, was performed. Analysis of genome-wide differential gene expression and known gene signatures found that immune-related genes and pathways, in particular an IFNγ signature, were predictive of DFS in nivolumab-treated patients. Predictive and prognostic associations, respectively, were found for tumor-infiltrating CD4 and CD8 T cells. Analysis of a composite predictive model suggested that CD4 gene expression and tumor cell PD-L1 expression had the greatest contributions to predicting outcomes in nivolumab-treated patients. These results reinforce recent studies establishing the importance of biomarkers of adaptive immunity, and in particular CD4 T cells, in influencing response to PD-1/PD-L1 blockade and establish the potential predictive rather than solely prognostic nature of such findings.

  Study EGAS50000000560

• UK10K NEURO IMGSAC

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The IMGSAC cohort is an international collection of families containing children ascertained for ASDs (autism spectrum disorders). The affected individuals are have been phenotyped, including using the ADI-R and ADOS instruments. Individuals with a past or current medical disorder of probable etiological significance or TSC have been excluded. Where possible, karyotyping has been performed on one affected individual per family to exclude Fragile X syndrome. Many of the samples have been genotyped, using the Affymetrix 10k and Illumina 1M platforms. All samples to be included in the current study are of UK origin.For further information on this cohort please contact Jeremy Parr (jeremy.parr@newcastle.ac.uk).

  Study EGAS00001000120

• Single_cell_measurements_to_characterise_B_cell_repopulation_in_SLE_after_rituximab_therapy__a_pilot_study

  Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by autoantibodies against DNA and nuclear proteins. Kidney involvement (lupus nephritis) is one of the most serious manifestations and is the leading determinant of long-term prognosis. Therapies targeting B cells (e.g. rituximab) are used in the treatment of severe lupus, including lupus nephritis. Rituximab is a monoclonal antibody that targets the CD20 surface protein on the surface of B cells. Following rituximab treatment, there is near complete depletion of B cells in peripheral blood. Peripheral blood B cells slowly return over a period of months. The speed of repopulation varies but typically B cells have returned to baseline levels between 9 and 12 months post rituximab therapy. Return of B cells may be associated with increased disease activity, but this is not always the case. For example, some patients remain in clinical remission for several years following one cycle of rituximab, despite B cell repopulation, whilst others relapse as soon as the B cell number reaches the normal range. The reasons for the different response remain unclear. The B cell subpopulations that return following B cell depleting therapy have been previously studied using flow cytometry but have never been characterised using single cell -omic technologies and thus no data on their molecular signatures are available. Previous studies have shown that naïve B cells were the predominant repopulating B-cells, indicating de novo production of B cells. Obtaining an integrated understanding of the molecular programs of these cells at the single cell level will enhance our ability to predict disease outcome, to identify patients with poorer B-cell drug responses, understand disease heterogeneity and design more effective B-cell targeted therapies approach.

  Study EGAS00001006798

• IBD-dysplasia

  This data set concerns DNA copy number alterations and mutation data from 30 IBD-associated dysplastic lesions and 13 IBD-associated cancers. DNA was isolated from formalin-fixed, paraffin-embedded material. Whole-genome shallow seq and Truseq amplicon cancer panel (Illumina) were used for detection of DNA copy number alterations and gene mutations, respectively.

  Dataset EGAD00001005196

• Shallow whole genome sequencing from plasma DNA of BC, CRC and NSCLC patients

  This is the raw data obtained from shallow whole-genome sequencing of plasma DNA (plasma-Seq) for calling of somatic copy number alterations as well as focal amplifications and deletions from patients with breast, colorectal and non-small cell lung cancer.

  Dataset EGAD00001006288

• Genomic Landscape of High-Grade Neuroendocrine Neoplasms

  This project is a multi-omics study of high grade (grade 3) neuroendocrine neoplasms across diverse organs. Genomic analysis using low-pass whole genome sequencing for copy number analysis, whole exome sequencing and whole transcriptomic sequencing using RNAseq were performed. As high grade neuroendocrine neoplasms are highly lethal with a median survival of approximately 7 months, new insights are urgently needed for better prognosis, diagnosis and management. This study focuses on gene and pathway discoveries in this cancer, and includes samples from a diverse set of organs, including the lungs, gastroenteropancreatic tract, breast, prostate, head and neck and bladder. This study was made possible by a generous donation from The Helen B. Rodde Fund.

  Study phs002070

• Epiclomal: probabilistic clustering of sparse single-cell DNA methylation data

  We present Epiclomal, a probabilistic clustering method arising from a hierarchical mixture model to simultaneously cluster sparse single-cell DNA methylation data and infer their corresponding hidden methylation profiles. Using synthetic and published single-cell CpG datasets we show that Epiclomal outperforms non-probabilistic methods and is able to handle the inherent missing data feature which dominates single-cell CpG genome sequences. Using a recently published single-cell 5mCpG sequencing method (PBAL), we show that Epiclomal discovers sub-clonal patterns of methylation in aneuploid tumour genomes, thus defining epiclones. We show that epiclones may transcend copy number determined clonal lineages, thus opening this important form of clonal analysis in cancer.

  Study EGAS00001003504

• Dental Caries: Whole Genome Association and Gene x Environment Studies

  Dental caries (also known as tooth decay) remains the most common chronic disease of childhood, five times more common than asthma and seven times more common than environmental allergies, with more than 40% of children exhibiting caries when they enter kindergarten. In 2005, it was estimated that dental health care costs were approximately $84 billion, of which 60% or about $50 billion were related to treatment of dental caries. Although overall caries prevalence has declined over the last 40 years, dental caries in the primary dentition and mean caries rates in children ages 2-11 has increased markedly over the past 12 years. Childhood caries is a serious public health issue because of associated health problems and because disparities in oral health have led to substantially higher average disease prevalence among children in poverty and in under-served racial and ethnic groups. These issues are of such concern that in 2005, the American Academy of Pediatrics made children's oral health one of their top areas of focus, as it is for the majority of the NIDCR "Disparities Centers". The etiology of dental caries has been studied for many years. Multiple factors contribute to a person's risk for caries, including: 1) environmental factors such as diet, oral hygiene, fluoride exposure and the level of colonization of cariogenic bacteria and 2) host factors such as salivary flow, salivary buffering capacity, position of teeth relative to each other, surface characteristics of tooth enamel and depth of occlusal fissures on posterior teeth. In spite of all that is known about this disease, there are still individuals who appear to be more susceptible to caries and those who are extremely resistant, regardless of the environmental risk factors to which they are exposed, implying that genetic factors also play an important role in caries etiology. This conclusion is supported by studies in both humans and animals, with the most compelling evidence coming from studies of twins reared apart in which investigators found significant resemblance within monozygotic (MZ) but not dizygotic (DZ) twin pairs for percentage of teeth and surfaces restored or carious and estimated the genetic contribution to caries as 40%. Other recent studies of twins reared together estimated the heritability for caries, adjusted for age and gender, as ranging from 45-64%. Despite the strong evidence of a genetic component to risk for dental caries, there have been only a few studies of candidate genes in caries, and no published genome-wide scans. A comprehensive genome wide search is the only approach that will allow us to identify those genetic regions likely to harbor genes increasing the risk for dental caries, and eventually to identify the etiologic genes and to explore the interaction of those genes with microbiological, dietary, fluoride, and behavioral factors that are known to be associated with caries risk and progression. Therefore, the goal of this study is to perform genome-wide association (GWA) studies of dental caries with a large panel of SNP's (610,000) in families and individuals ascertained through multiple US sites (University of Pittsburgh and University of Iowa). The v2 release of this study includes 96 additional individuals who were genotyped with the CCDG: Dental Caries and CL/P in Guatemala project (dbGaP accession number phs000440) to augment the data initially presented here. These subjects were genotyped on the Illumina 610 platform to make their data comparable. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org), which was developed through the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to dental caries through large-scale genome-wide association studies of well-characterized families and individuals at multiple sites in the U.S. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). The study was supported by the National Institute of Dental and Craniofacial Research (NIDCR, U01-DE018903). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington. Samples of some participants in this study were selected for further genomic analysis. These results will be available in the dbGaP CIDR study: Center for Oral Health Research in Appalachia (COHRA) Genomic Studies of Oral Health and Disease (phs001591).

  Study phs000095

• A Genome-Wide Association Study of Heroin Dependence

  This collaboration of Australian and American investigators aims to identify genes associated with liability for heroin dependence. The project uses a case-control design in which cases met lifetime DSM-IV criteria for heroin dependence. Controls included assessed individuals who did not meet DSM-IV heroin dependence criteria and unassessed general population controls. Cases and controls were obtained from the several large investigations including: The Comorbidity and Trauma Study, Heroin Dependence in Western Australia, the OZ-ALC Study, a Twin Study of Mole Development in Adolescence, and ongoing genetic studies of substance dependence conducted by investigators at Yale and collaborating institutions. These projects are briefly described below. The Comorbidity and Trauma Study (PI: Elliot Nelson), a retrospective case-control study examining genetic and environmental factors contributing to heroin dependence liability. The study was funded by the National Institute on Drug Abuse (NIDA), and was run in collaboration with Washington University, the Queensland Institute of Medical Research (QIMR), and the National Drug and Alcohol Research Centre (NDARC), University of New South Wales. Case participants were recruited from maintenance clinics in the greater Sydney area. Control participants were recruited from employment centres and community centres, open street malls, and local press servicing the same geographical area as the opioid maintenance treatment clinics and either denied recreational use of opioids or had used these drugs recreationally fewer than 11 times lifetime. The prevalence in these individuals of non-opioid licit drug dependence and illicit drug dependence as well as childhood trauma exposure and other psychiatric disorders is elevated considerably versus estimates of similar measures in Australian general population samples. Participants provided blood samples as a source of DNA and completed a comprehensive psychiatric diagnostic interview based on the Semi-Structured Assessment of the Genetics of Alcoholism - Australia (SSAGA-OZ) augmented with sections drawn from other instruments assessing childhood trauma exposure, family history, and screening for borderline personality disorder. Heroin Dependence in Western Australia (PI: Sybille Schwab) is a study focusing both on genetic contributions to heroin dependence and response to naltrexone treatment of the disorder. Participants completed a clinical assessment and provided blood samples during their treatment at the Perth Naltrexone Clinic now name as the Fresh Start Recovery Programme. Funding for the project was provided by the Australia Government's National Health and Medical Research Council (Grant # 513862; PI: Sybille Schwab) Affected subjects from ongoing genetic studies of substance dependence conducted by investigators at Yale (PI: Joel Gelernter) and collaborating institutions were collected in the course of several NIDA-funded studies. Those included in the current set were assessed by means of the SSADDA (Semi-Structured Assessment for Drug Dependence and Alcoholism). All are opioid dependent European-Americans, and all list heroin as the opioid must used. Most were collected at Yale University School of Medicine or University of CT School of Medicine under the supervision of Drs Joel Gelernter and Henry Kranzler. Control subjects were also collected in the course of several NIDA- and NIAAA-funded studies. Those included in the current set were assessed by means of the SSADDA (Semi-structured Assessment for Drug Dependence and Alcoholism). Most were collected at Yale University School of Medicine or University of Connecticut School of Medicine under the supervision of Drs Joel Gelernter and Henry Kranzler. The OZ-ALC Study (PI: Andrew Heath) consists of a large group of twins and their family members ascertained from the general population Australian Twin Registry who have participated in ongoing research projects. For the control investigation, we have selected individuals who do meet criteria for illicit drug dependence who have had GWAS genotyping with the Illumina Human CNV370-Quad. Inclusion of individuals with alcohol dependence or nicotine dependence was minimized. For a more detailed description of the study, please see: http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000181.v1.p1 The Twin Study of Mole Development in Adolescence (PI: Nick Martin) is an ongoing investigation of melanocytic naevi funded by the Australian Government's National Health and Medical Research Council (Grant # 389891; PI: Nick Martin). For the current project, unassessed parents of these twins will serve as a control group. These individuals will either have been previously genotyped with the Illumina Human 610-Quad BeadChip or will be genotyped as part of the current project. Parents have largely survived the period of risk for heroin dependence and, by virtue of their participation in this research, are very likely to have a prevalence of heroin dependence lower than that in the general population (i.e., <0.7%). In order to understand the immune modulatory effect of opioids across peripheral blood immune populations, a second study (PI: Christine S. Cheng) analyzed single cell RNA-seq profiles from the PBMCs of a subset of case participants and control participants from the Comorbidity and Trauma Study (PI: Elliot Nelson). The study assessed and identified transcriptional changes between opioid dependent and control samples across naive and LPS stimulated immune populations.

  Study phs000277

• Reconstructed VDJ sequences from Smart-seq2 data

  The dataset contains reconstructed VDJ sequences (fasta files) and accompanying metadata for each cell (csv file) from scRNA-seq data generated with the Smart-seq2 protocol. The VDJ sequences were reconstructed with the computational tool BraCeR using raw fastq files as input. The dataset contains sequences from 355 IgA+ peripheral blood B-lineage cells of two untreated celiac disease patients. The sequences comprise both IgA+ transglutaminase 2-specific and other IgA+ B cells.

  Dataset EGAD50000000341

• Human brain development single cell sequencing additional samples

  69 tissue samples from various parts of the developing human embryo brain were dissociated and single cells were collected and processed without bias for mRNA-seq using 10X chromium 3' protocol. Libraries were sequenced on Illumina NovaSeq and reads aligned against the human GRCh38 genome. This is an addition to EGAD00001006049 Human development single cell sequencing, consisting of samples added after the original submission to EGA, but included in final paper.

  Dataset EGAD50000001295

• FFPE

  The mutational status of 112 recurrently mutated genes in B-cell lymphoma was examined by targeted next-generation sequencing (NGS). Libraries were performed with 150 ng of genomic DNA (gDNA) obtained from formalin-fixed paraffin-embedded (FFPE) biopsy using molecular-barcoded library adapters (ThruPLEX Tag-seq kit; Takara) coupled with a custom hybridization capture based method (SureSelect XT Target Enrichment System Capture strategy, Agilent Technologies Inc.) and sequenced in a MiSeq instrument (Illumina, 2x150bp).

  Dataset EGAD00001006565

• COVID-19 Challenge Project Single Cell Profiling

  Single-cell profiling of sero-negative and sero-positive humans that were inoculated with SARS-CoV-2. The cellular response during SARS-CoV-2 is profiled using single-cell transcriptomics, CITE-seq and single cell immune profiling, by sampling PBMCs and nasal swabs before and at multiple time points during SARS-CoV-2 infection. This one-of-a-kind cellular map will give unique temporal resolution of how nasal and immune cells respond to SARS-CoV-2 exposure and infection.

  Dataset EGAD00001012227

• Acquired RAD51C promoter methylation loss causes PARP inhibitor resistance in high grade serous ovarian carcinoma

  Analysis of RAD51C promoter methylation using targeted bisulfite sequencing (amplicon sequencing) in ovarian cancer pre-clinical models and patient samples.

  Dataset EGAD00001007799

• 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

• Deep Sequencing of 3 Cancer Cell Lines on 2 Sequencing Platforms (Illumina HiSeqX and NovaSeq)

  To test the performance of a new sequencing platform, develop an updated somatic calling pipeline and establish a reference for future benchmarking experiments, we performed whole-genome sequencing of 3 common cancer cell lines (COLO-829, HCC-1143 and HCC-1187) along with their matched normal cell lines to great sequencing depths (up to 278X coverage) on both Illumina HiSeqX and NovaSeq sequencing instruments. This dataset can be used for benchmarking purposes by the genomic community and as a reference call set for scientists using these 3 cell lines.

  Study phs001839

• ProstOmics - DNA methylation v1

  Bulk methylation array data from 64 prostate tissue samples from 16 patients (5 with post-surgery relapse). Methylation data were acquired using the microarray kit Illumina Infinium MethylationEPIC BeadChip (n=64 ). The individual samples have information on patient origin and sample type (cancer, cancer-adjacent field-effect normal or normal sample far from cancer). Patient metadata include information of age at surgery, time (months) until reported relapse, pre-surgery PSA and post-surgery T-stage.

  Dataset EGAD50000000605

• ProstOmics - DNA methylation v2

  Bulk methylation array data from 32 prostate tissue samples from 8 patients (3 with post-surgery relapse). Methylation data were acquired using the microarray assay Illumina Infinium MethylationEPIC v2.0 Kit. The individual samples have information on patient origin and sample type (cancer, cancer-adjacent field-effect normal or normal sample far from cancer). Patient metadata include information of age at surgery, time (months) until reported relapse, pre-surgery PSA and post-surgery T-stage.

  Dataset EGAD50000000606

• WES data of pediatric cancer patients with P/LP variants in HBOC-related genes

  The current study aimed to identify (likely) pathogenic germline variants(LP/PVs) in 25 adult-onset HBOC-related genes within a cohort of 372 pediatric cancer patients. For this purpose we performed (paired-end) whole exome sequencing (WES) using Ilumina sequencing technology. The files uploaded here belong to the 27 individuals with such a LP/PV. The project provides insight into the prevalence and spectrum of such variants in childhood cancer, contributing to the understanding of genetic predisposition in pediatric oncology.

  Dataset EGAD50000001561

• Error-corrected targeted sequencing of rectal mucus from patients suspected to have colorectal cancer

  This dataset contains error-corrected next-generation sequencing (ecNGS) data generated from 161 rectal mucus samples. These samples belong to colorectal cancer, adenoma, and control participants. Genomic DNA was extracted and processed using a hybrid-capture panel targeting 50 colorectal cancer–associated genes, incorporating unique molecular identifiers (UMIs) for duplex consensus error correction. Libraries were sequenced on an Illumina NovaSeq 6000 (paired-end 150 bp) producing paired-end FASTQ files. These data support analyses of DNA mutations in CRC detection and progression.

  Dataset EGAD50000002032

• Whole exome and RNA sequencing of organoid samples derived from TRACERx patients

  Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of >20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘hot’) and non-evading (‘cold’) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.

  Study EGAS00001008092

• scRNA-seq of CD4+ T cells from blood and tumor of NSCLC patients

  This study explore the CD4+ T cells diversity in paired blood and tumor of 5 different NSCLC patients. After FACS-sorted of Tregs (DAPI- CD45+ CD4+ CD25hi CD127lo) and Tconvs (DAPI- CD45+ CD4+CD25lo CD127lo/hi), cells were mixed in equal proportion (fifty/fifty ratio) and processed with 10X Chromium (10X Genomics) gene expression kit (3 bloods and 2 tumors) or immunoprofiling kit (2 bloods and 3 tumors) and sequenced using Illumina platforms.

  Study EGAS50000000293

• Single-cell RNA sequencing data of peripheral blood mononuclear cells obtained from 30 ATL patients, 11 HTLV-1-infected asymptomatic carriers, and 4 healthy donors.

  Single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) obtained from 30 ATL patients (34 samples including 4 sequential ones), 11 HTLV-1-infected asymptomatic carriers, and 4 healthy donors.

  Dataset EGAD00001007015

• Capturing the Genetic Diversity of the Himba Population

  The Himba people are a semi-nomadic, Bantu-speaking pastoralist group from the northwestern Kunene region of Namibia. Because of their limited population size, restricted geographic distribution, and endogamy, founder populations represent an ideal system for genetic analyses due to reduction of the confounding environmental and cultural variables. The original study used genotype data and demographic interview data to understand family dynamics and ancestry in a population of Himba pastoralists. HLA allele calls and genome-wide methylation array data were later generated for a subset of the initial dataset for 2 additional studies. These 3 molecular datasets, available through dbGaP, are relevant to broader studies of ancestry, allele frequencies and the relationship of Himba to other ethnic groups in sub-Saharan Africa. The Himba population provides a unique opportunity to study questions regarding extra-pair paternity and mate selection because Himba culture allows both men and women, married and not, to take multiple partners. Previous estimates of extra-pair paternity rates in human populations have been very low, but these estimates lack global and cultural diversity in population representation. Thus, investigating the rate of extra-pair paternity in the Himba greatly aids in understanding the global variation in non-paternity rates among human populations. Saliva samples were collected from parents and children, and were genotyped on Illumina SNP array platforms (MEGAex and H3Africa). In total, 678 individuals' genotype array data are deposited. Paternity results were de-identified and protected by a double blind protocol (no researcher has full knowledge of individual paternity results). Due to the sensitive nature of this study, paternity assertions are not available for access. For a subset of 360 individuals, HLA class 1 (A, B, C) and class 2 (DPA1, DPB1, DQA1, DQB1, DRB1) genes were targeted for DNA sequencing using a probe-based capture method. HLA alleles at the four field resolution were determined from the sequence capture using the consensus calls obtained from two algorithms: NGSengine® 2.10.0 (GenDX, Utrecht, the Netherlands) and HLA Explore™ (Omixon Biocomputing Ltd. Budapest, Hungary). These data were used to investigate evidence for mate selection based on HLA dissimilarity in the Himba. Himba cultural norms permit concurrent arranged marriages and chosen sexual partnerships allowing us to directly test for evidence of disassortative mate selection based on HLA genotype. Due to the sensitive nature of this study, partnership data are not available for access.For a subset of 51 Himba individuals methylation array data was generated from the saliva-derived DNA. These data were generated in order to investigate the accuracy of epigenetic age predictors in this population and to construct population-specific epigenetic age predictors in a subsequent publication. Chronological ages are available for these 51 individuals.

  Study phs001995

• Characterization of X Chromosome Inactivation Using Integrated Analysis of Whole-Exome and mRNA Sequencing

  This study of DNA and RNA sequencing of 5 parent-offspring trios is a single center study. The goal of this study is to characterize X chromosome inactivation (XCI) ratio in females using phased genomic variations obtained through whole genome or exome sequencing in trios, followed by allele-specific expression analysis of the phased, heterozygous alleles in the mRNA of the female offspring, and to apply this method to clinical diagnosis. The distribution of allele ratios across X obtained from mRNA sequencing allows for the estimation of X inactivation status of inherited X chromosomes, and the parameters of each parental allele distributions in the offspring's mRNA data can be used as determinants for XCI ratio. This approach was used to evaluate the contribution of skewed XCI ratio to phenotypic heterogeneity in an undiagnosed, mild neurological condition.

  Study phs000816

• CNCD Recall by Genotypes

  This is a DAC to handle recall by genotype studies by the conducted by the Center for Non-Communicable Disease Karachi, Pakistan.

  Dac EGAC50000000937

• WXS and RNA-seq raw sequence data for TG project

  WXS sequence data from 112 samples, RNA-seq sequence data from 117 samples, all sequence data are raw sequence data in fastq format, sequenced by Illumina platform.

  Dataset EGAD00001007989

• DAC for human-derived clonal organoid studies

  This is the DAC for human-derived clonal organoid culture studies. It includes the study to investigate the clonal evolution of metastatic CRC at the single-cell level, where we performed WGS in 58 clonal organoids and 18 fresh-frozen (FT) bulk-tissue samples from surgically resected primary and metastatic tumors before and after anticancer therapies in 6 patients. This approach enabled detailed phylogenetic reconstruction of individual clones. We discovered the timing and burden of treatment-related mutations as well as the heterogeneous evolution in driver mutations and genomic rearrangements in late-stage clonal evolution under anticancer therapies in metastatic CRC.

  Dac EGAC50000000628

• Comprehensive genetic analysis of pediatric germ cell tumors

  Germ cell tumors (GCTs) are relatively rare tumors in children. Previous studies showed that adult testicular GCTs had some genomic alterations, but genetic basis of pediatric GCTs is still to be elucidated. We applied DNA methylation array analysis, whole-transcriptome sequencing, targeted capture sequencing, and SNP array analysis to fifty-one GCT samples.

  Study JGAS000204

• HipSci-RNAseq-healthy volunteers

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sup-study we perform RNAseq on iPS cells generated from skin biopsies from healthy volunteers.

  Study EGAS00001000593

• Targeted sequencing data and shallow whole genome sequencing data of Follicular lymphoma.

  Contain data of 2 studies 1: 82 nodal stage 1 FL cases and 139 stage III/IV cases 2: 44 watch and wait stage III/IV and 46 Immediate treatment stage III/IV targeted sequencing data of 369 genes and 12 translocation regions whole genome shallow sequencing data

  Study EGAS00001005755

• Precursor lesions, clonal architecture and relapse in Wilms nephroblastoma

  Targeted resequencing at high depth (21 genes, 9 chromosomal regions): at least 4 FFPE samples per case and matched germline DNA: * 100 cases with detailed outcome data, including 15 cases with tumour relapse (515 samples) * 40 cases with matched pre-chemotherapy biopsies (240 samples) * 50 nephrogenic rests matched to above cases (50 samples) We expect a proportion (possibly 10%) of cases to be mutationally silent on the above studies, and propose to subsequently carry out integrated whole-genome, methylome and transcriptome studies on matched frozen tissue from these cases

  Dataset EGAD00001003217

• RNA seq of intestinal biopsies and blood cells from patients with celiac disease and controls

  This study presents RNA sequenced from several intestinal phenotypes such as from patients with damaged intestinal mucosa as well as from those without a damaged intestine but still an autoantibody response to tissue transglutaminase (“potential celiac disease”) or those with treated celiac disease. By combining phenotypes in a much larger number of tissue samples from both peripheral blood and mucosal biopsies, we found highly differentially expressed genes, but also identify genes involved in controlling and triggering celiac disease associated changes. This study identifies molecular mechanisms involved in celiac disease and new possible targets for treatment and for identification of individuals at risk.

  Study EGAS50000001104

• Polygenic Risk Score for the Prediction of Breast Cancer Is Related to Lesser Terminal Duct Lobular Unit Involution of the Breast

  The Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center is an annotated biobank, which has recruited healthy women who provided demographic, lifestyle, and cancer-related information via self-administered questionnaire, blood samples and normal breast tissues. H&E slides of the normal breast tissues were scanned for image analysis and a pathologist measured the number of terminal duct lobular units (TDLUs) ("TDLU count"). The acini count per TDLU was quantified using the TDLU analyzer software. In this analysis, we computed the recently developed polygenic risk score (PRS) based on 313 common variants for the prediction of breast cancer and related this PRS to TDLU count and acini count per TDLU. We did this for the overall PRS, the ER-positive PRS and the ER-negative PRS.

  Study phs002062

• MYC Inhibition By Omomyc Causes DNA Damage And Overcomes PARPi Resistance In Breast Cancer.

  This study investigates the role of MYC dysregulation in DNA damage response (DDR) and PARP inhibitor (PARPi) resistance in breast cancer. Using Omomyc, a direct MYC inhibitor, we demonstrate that MYC inhibition shuts down DDR genes in triple-negative breast cancer (TNBC), causing DNA repair defects and inducing DNA damage that synergizes with PARPi treatment. Through patient-derived models and clinical samples from metastatic HR-altered breast cancer patients treated with PARPi, we identify MYC transcriptional activity as a predictive biomarker of PARPi resistance. Digital spatial profiling (DSP) analysis of pre-treatment tumor biopsies reveals that patients with progressive disease have significantly elevated MYC signatures compared to responders. These findings support the therapeutic strategy of combining MYC inhibition with PARPi in PARPi-resistant breast cancers where high MYC activity predicts poor response to therapy.

  Study EGAS50000001347

• Genome-wide Association Study for Non-syndromic Clefts in the African Population: CIDR

  The focus of this project is to identify genetic variants that are associated with orofacial clefts in African populations in sub-Saharan Africa. Most genetic studies of CLP (including the vast majority of GWAS) have been conducted in populations of European origin with only a few focused on Asian or African populations. We choose to study the genetics of these complex traits in African populations because, African populations have the greatest genetic variation amongst the various populations in the world by virtue of being the primary ancestral population to modern humans (Cavalli-Sforza and Feldman, 2003; Ramsay et al., 2011). Therefore, the potential for finding novel loci for CLP is quite high. To date 6 genome wide association studies (GWAS) for cleft lip with or without cleft palate (CL/P) have been conducted and 18 risk loci identified (Birnbaum et al., 2009; Grant et al., 2009 ; Beaty et al., 2010; Mangold et al., 2010; Ludwig et al., 2012; Sun et al., 2015). All these studies have either been conducted in European populations, Asian populations or both. There is currently no published GWAS for clefts in African populations. African populations represent a novel and richly productive populations for genetic and environmental exposure studies for CL/P. Investigating the presence of genetic variants in diverse population groups can identify novel variants and candidate genes that are population specific. Environmental factors may also increase the risks in certain population groups due to genetic susceptibility and/or specific exposures. Understanding the role these susceptibility genes play in the effects of environmental risk factors can inform strategies designed towards reducing the outcome of these complex traits, e.g. through the modification of the environmental influences. The study population comprises a large number of individuals (3205 individuals) from Africa (Ghana, Ethiopia and Nigeria). There are cases, case triads (nuclear families), as well as controls with no history of OFC nor other developmental defects.

  Study phs001090

• ARDSnet and the iSPAAR Consortium: Genomic Basis of Susceptibility and Outcomes in Patients with the Acute Respiratory Distress Syndrome (ARDS)

  Acute Respiratory Distress Syndrome (ARDS)/ Acute Lung Injury (ALI) is a syndrome defined by the presence of acute hypoxemic respiratory failure, bilateral pulmonary infiltrates on chest radiograph, a known clinical risk factor (e.g. sepsis, pneumonia, trauma, gastric fluid aspiration, pancreatitis, massive transfusion), and the absence of physiologic or clinical evidence of congestive heart failure. The Identification of SNPs Predisposing to Altered ALI Risk (iSPAAR) study is a multi-institutional cooperative study, funded through the NHLBI Recovery Act, that assembled samples and phenotype information from existing cohorts. The consortium included samples from patients with ARDS from the NIH NHLBI ARDS Clinical Trials Network (ARDSNet). Samples were obtained from 3 interventional treatment trials in patients with ARDS, including the Fluid and Catheter Treatment Trial (FACTT), the Albuterol to Treat Acute Lung Injury (ALTA) trial, and the Omega-3 Fatty Acid/Antioxidant Supplementation for ALI trial (Omega). In addition to ARDSnet samples, samples from the other cohorts included cases of established ARDS but also controls: critically ill patients who were at-risk for ARDS but who did not develop ARDS during their hospital course. These cohorts included the Molecular Epidemiology of Acute Respiratory Distress (MEA) Study enrolled at the Harvard University/Massachusetts General Hospital, the Systemic Inflammatory Immune Response Syndrome (SIRS) Patient Database and ICU Traumatic Injury cohorts from Harborview Medical Center, and cohorts collected from the ALI research programs at the University of Pennsylvania and the University of California, San Francisco. The Cohort is utilized in the following dbGaP sub-studies. To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" box located on the right hand side of this top-level study page phs000631 ARDSnet iSPAAR Consortium. phs000334 ESP_LungGO_ALI phs000686 ALI_GeneticRisk

  Study phs000631

• Count Me In (CMI): The Metastatic Prostate Cancer (MPC) Project (CMI-MPCproject)

  Count Me In - The Metastatic Prostate Cancer Project: A Patient-Driven Research Initiative to Accelerate Metastatic Prostate Cancer Research The Metastatic Prostate Cancer Project (MPCproject; http://mpcproject.org/) is a research study that empowers men with metastatic and advanced prostate cancer to partner directly with researchers by sharing their samples and clinical information, with the ultimate goal of accelerating scientific discoveries that have clinical impact. The MPCproject enables any man with metastatic or advanced prostate cancer in the US and Canada to participate in cutting-edge genomic and molecular research, regardless of where they live. Metastatic or advanced prostate cancer patients visit the project website and complete an online questionnaire of basic information about themselves and their cancer. Enrolled patients are mailed saliva and blood draw kits, which can be used to extract germline DNA and cell-free DNA (cfDNA), respectively. The study team contacts participants' healthcare institutions to obtain medical records and a portion of archived tumor samples. Whole exome sequencing is performed on tumor DNA, germline DNA, and cfDNA, and transcriptome sequencing is performed on tumor RNA. De-identified data, including linked genomic, clinical, and patient-reported data, are shared via public databases on a recurring pre-publication basis. Participants are regularly provided with updates on the study.

  Study phs001939

• Comprehensive gene analysis of colorectal cancer cases

  Colorectal cancer is the third most common morbidity and the fourth leading cause of cancer death in the world.To characterize the mutation profiles of colorectal cancer with liver metastasis,we performed both whole-exosome sequencing and RNA sequencing for 12 cases of colorectal cancer with liver metastasis (group A) and 16 cases of colorectal cancer without liver metastasis (group B). As a result of driver mutation search by Mutsig pipeline, PTEN was identified as a significant mutant gene in group A alone.ADAMTS10,NELL1 and RXFP3 were identified as candidate genes for metastasis by MuTect,SID and VarScan pipeline.Furthermore, in all samples, the copy number of chromosomes 1p,4,7,8,13,15, 17p,18,20 and 22q were significantly abnormal. Chromosomes 1p,4,15,18,17p,22q were deleted and chromosomes 7, 8,13 and 20 were amplified by CNV.Pathway analysed revealed Wnt/Ca2+ and PCP pathway was involved in metastasis of cl cancer.9 kinds of fusion genes were identified in deFuse pipeline. Among them, ADAP1 fusion genes were identified in 2 samples, and ADAP1 fusion genes were further identified in 3 samples by our in-house algorithm. It is suggested that new fusion genes present in such multiple samples may be involved in the development of colorectal cancer.

  Study JGAS000128

• Efficacy of two different FGFR-inhibitors in a patient with extrahepatic cholangiocarcinoma harboring an FGFR2 mutation

  Cholangiocarcinomas (CCAs) is a type of cancer with few effective systemic therapies. Elucidation of the molecular landscape of the disease from genomic studies based on next generation sequencing (NGS) has contributed to the introduction of new targeted therapies. One of these treatments consists of a class of small molecules that target members of the FGFR family of receptor tyrosine kinases. These drugs are effective and have been approved for cholangiocarcinomas with fusions or rearrangements of FGFR genes. In contrast, the role of these inhibitors in cholangiocarcinomas with mutations in FGFR genes is less well defined. We report here a patient with a cholangiocarcinoma bearing a FGFR2 p.Ser252Trp mutation. The patient was treated with two different FGFR inhibitors, as the first caused ocular toxicity. She obtained clinical benefit from both. This case illustrates the efficacy of FGFR inhibitors on cholangiocarcinoma with specific point mutations. This is the first case to report the clinical benefit of these drugs in FGFR2 p.Ser252Trp mutation. Clinical benefit can be sustained, as seen in our patient. Our case also shows that FGFR inhibitors-induced adverse effects, such as ocular toxicities, may not recur after re-challenge with an alternative drug of the same class.

  Study EGAS50000000015

• Comprehensive NGS Profiling to Enable Detection of ALK Gene Rearrangements and MET Amplifications in Non-Small Cell Lung Cancer

  We evaluate the analytical performance of the PGDx™ elio™ tissue complete assay, a 505 gene next-generation sequencing (NGS) tissue-based assay, that has now been FDA-cleared for use by physicians to help guide treatment decisions for cancer patients, using a NSCLC cohort of 38 patients.

  Dataset EGAD50000000016

• WGS of single CTCs from 4 patients with metastatic cancer

  This dataset contains 352 paired fastq files sequenced by illumina Novoseq6000. Single-cell low-pass WGS analysis (illumina platform, PE150, 1-2x coverage) was performed on CTCs enriched using high-throughout microfluidic device from entire leukopak from patients with metastatic prostate cancer (GU-1 and GU-2) and metastatic hepatocellular carcinoma (HCC-1 and HCC-2). Patient matched white blood cells (WBC) served as internal controls.

  Dataset EGAD50000001006

• Total RNAseq data from 8 patients with muscle invasive bladder cancer

  For this dataset we performed total RNAseq on blood samples from 8 patients with muscle invasive bladder cancer. The data consists of 8 sets of paired fastq files with accompanying UMI fastq files. Sequenced on the Illumina NoveSeq6000 platform using S2 flow cells (v1.5,2x150 cycles), with a mean yield of 313 million reads.

  Dataset EGAD50000001380

• High-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform

  Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes that are essential for the stability as well as the complete replication of the human genome. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length in clinics and research laboratories due to the lack of accurate and high-throughput telomere length measurement method. Here, we describe a novel workflow to capture and analyze telomeres accurately at the single-nucleotide resolution. By using newly designed telobaits that are complementary to the single-stranded G-rich 3’ telomeric overhangs, we can specifically and efficiently capture full-length telomeres and subject them to single-molecule real-time (SMRT) sequencing. We show that the telomere length can be measured at nucleotide resolution using the PacBio high fidelity (HiFi) sequencing platform, which provides the necessary accuracy and throughput to uncover the steady-state telomere length distribution in human culture cell lines as well as clinical patient samples. This new method is a valuable tool not only in population-wide epidemiology studies but also for the longitudinal assessment of telomere attrition in individuals. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that is dispersed throughout the telomere repeat region. Importantly, the unique distribution pattern and sequence of TVSs in individuals may be used as a fingerprint for sample identification. In addition, the presence of TVSs disrupts the continuity of the canonical (5’-TTAGGG-3’)n telomere repeats, which could affect the binding of shelterin complexes at the chromosomal ends. Therefore, TVSs may act as a form of genetic polymorphisms that impairs telomere protection. Together with the absolute telomere length in each individual, TVSs may have profound implications in human aging and diseases.

  Study EGAS00001006103

• High-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform, P49-P104 and run1 replicates

  Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes that are essential for the stability as well as the complete replication of the human genome. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length in clinics and research laboratories due to the lack of accurate and high-throughput telomere length measurement method. Here, we describe a novel workflow to capture and analyze telomeres accurately at the single-nucleotide resolution. By using newly designed telobaits that are complementary to the single-stranded G-rich 3’ telomeric overhangs, we can specifically and efficiently capture full-length telomeres and subject them to single-molecule real-time (SMRT) sequencing. We show that the telomere length can be measured at nucleotide resolution using the PacBio high fidelity (HiFi) sequencing platform, which provides the necessary accuracy and throughput to uncover the steady-state telomere length distribution in human culture cell lines as well as clinical patient samples. This new method is a valuable tool not only in population-wide epidemiology studies but also for the longitudinal assessment of telomere attrition in individuals. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that is dispersed throughout the telomere repeat region. Importantly, the unique distribution pattern and sequence of TVSs in individuals may be used as a fingerprint for sample identification. In addition, the presence of TVSs disrupts the continuity of the canonical (5’-TTAGGG-3’)n telomere repeats, which could affect the binding of shelterin complexes at the chromosomal ends. Therefore, TVSs may act as a form of genetic polymorphisms that impairs telomere protection. Together with the absolute telomere length in each individual, TVSs may have profound implications in human aging and diseases.

  Study EGAS00001006595

• A small cell lung cancer genome reports complex tobacco exposure signatures

  Cancer is driven by mutation. Worldwide, tobacco smoking is the major lifestyle exposure that causes cancer, exerting carcinogenicity through 60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. 22,910 somatic substitutions were identified, including 132 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in-frame, and another two lines carrying PVT1-CHD7 fusion genes, suggesting that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.

  Study EGAS00000000051

• A Translational, Pharmacodynamic and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer

  This phase IB clinical trial studied the pharmacodynamic changes induced by everolimus in patients with previously untreated, resectable non small cell lung cancer. Using a combination of in vivo and ex vivo assessments with FDG PET, immunohistochemistry and genomic assays, evidence of mTOR pathway perturbation was assessed in patients treated with everolimus, an allosteric mTOR inhibitor. Untreated patients served as controls for comparison. Key results from this work include a dose-dependent biologic effect of everolimus, signal of activity in RAS mutant tumors as well as near complete metabolic and pathologic response in a case of sarcomatoid lung cancer. These findings represent novel translational insights that can guide future development of mTOR inhibitors in lung cancer and other tumor types. Additionally, metabolic response and anatomic tumor shrinkage observed in a significant proportion of patients following a short of duration of therapy with everolimus suggests potential clinical utility of this agent in carefully-selected lung cancer patients.

  Study phs000829

• Whole exome sequencing of Finnish hereditary breast cancer families

  Dataset contains Whole Exome Sequencing(WES) data from 37 individuals as aligned bam-files. The reads have been aligned using bowtie2 to human genome hg19 build.

  Dataset EGAD00001002133

• Exome Sequencing of Statin-Induced Myopathy Cases

  Severe myopathic events occur in 0.1-0.5% of patients taking statins. Although genetic association studies have identified some possibly associated gene loci, these have not been reproducible in additional studies with independent patient cohorts. A more reasonable explanation for susceptibility to statin-induced myopathy is the presence of rare pathogenic variants in genes important for skeletal muscle structure and function. In support of this, we have previously reported an increased incidence of pathogenic variants in genes causing metabolic myopathies in patients with statin-induced myopathy (Vladutiu et al.,2006). We also reported a patient with statin myopathy who had an RYR1 variant known to be causative of malignant hyperthermia susceptibility (MHS) (Vladutiu et al., 2011). There are a number of genes associated with metabolic myopathies triggered by various factors such as extreme exercise, fasting, extremes in temperature, viral infection and exposure to volatile anesthetics. In addition, many of the genes causing congenital myopathies, myofibrillar myopathies and muscular dystrophies have overlapping phenotypes with these genes. We propose that statins act as an additional trigger inducing myopathic symptoms and many patients with severe statin-induced myopathy have causative genetic variants within similar genes associated with MHS and congenital myopathy. We have analyzed the resultant data using a disease model in which rare pathogenic variants, possibly within multiple genes, are causative of statin-induced myopathy. In this study, we have identified potentially causative genetic variants in greater than 50% of the statin-induced myopathy cases and in particular, rare and possibly pathogenic in the RYR1 and CACNA1S genes were present in 25% of the patient samples studied. Vladutiu, G. D., Simmons, Z., Isackson, P.J., Tarnopolsky, M., Peltier, W.L., Barboi, A.C., Sripathi, N., Wortmann, R.L., Phillips, P.S., (2006). "Genetic risk factors associated with lipid-lowering drug-induced myopathies." Muscle Nerve 34: 153-162. Vladutiu, G. D., Isackson, P.J., Kaufman, K., Harley, J.B., Cobb, B., Christopher-Stine, L., Wortmann, R.L, (2011). "Genetic risk for malignant hyperthermia in non-anesthesia-induced myopathies." Mol Genet Metab 104: 167-173.

  Study phs001342

• Identification of germline variants in Medullary thyroid carcinoma (MTC) by whole- exome sequencing

  Medullary thyroid cancer (MTC) is a rare malignant tumor that arises from parafollicular cells. Approximately 8% of thyroid cancer cases are MTC, and about 25% of these have a hereditary component. Incorporating molecular parameters into tumor classification is important. Besides, the presence of pathogenic germline variants can impact directly on cancer prevention. Thus, the aim of this study was to perform whole exome sequencing (WES) on a consecutive series of hereditary RET wild-type MTC patients to identify genetic variants that may be involved in the carcinogenesis of this tumor. WES was performed on 28 patients negative for germline RET pathogenic variants using the NovaSeq 6000 platform. Variant classification followed American College of Medical Genetics and Genomics guidelines.Our study represents a significant advancement in gene discovery for MTC genetics.

  Study EGAS50000000061

• RP-1843 Arcagen - Gastrointestinal rare cancers (GI)

  Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here we are submitting two datasets that contain NGS files from gastrointestinal rare cancers (n=119): - Dataset 1 (32 patients): Mesothelioma of the peritoneum (n=21) and Pseudomyxoma peritonei/mucinous adenocarcinoma of the appendix (n=11) - Dataset 2 (87 patients): Intra-hepatic cholangiocarcinoma (n=47), Extra-hepatic, cholangiocarcinoma (n=16), Not specified Cholangiocarcinoma (n=9), Small bowel adenocarcinoma (n=6) and other rare GI cancer (n=9)

  Study EGAS00001006299

• Custom long non-coding RNA capture enhances detection sensitivity in different human sample types.

  Long non-coding RNAs (lncRNAs) are a heterogeneous group of transcripts that lack protein coding potential and display regulatory functions in various cellular processes. As a result of their cell- and cancer-specific expression patterns, lncRNAs have emerged as potential diagnostic and therapeutic targets. The accurate characterization of lncRNAs in bulk transcriptome data remains challenging due to their low abundance compared to protein coding genes. To tackle this issue, we describe a unique short-read custom lncRNA capture sequencing approach that relies on a comprehensive set of 565,878 capture probes for 49,372 human lncRNA genes. This custom lncRNA capture approach was evaluated on various sample types ranging from artificial high-quality RNA mixtures to more challenging formalin-fixed paraffin-embedded tissue and biofluid material. The custom enrichment approach allows the detection of a more diverse repertoire of lncRNAs, with better reproducibility and higher coverage compared to classic total RNA-sequencing.

  Study EGAS00001005418

• Study of the Human Skin Metagenome Associated with Acne

  Studies have emphasized the importance of disease-associated microorganisms in perturbed communities, however, the protective roles of commensals are largely under recognized and poorly understood. Using acne as a model disease, we investigated the determinants of the overall virulence property of the skin microbiota when disease- and health-associated organisms coexist in the community. By ultra-deep metagenomic shotgun sequencing, we revealed higher relative abundances of propionibacteria and Propionibacterium acnes phage in healthy skin. In acne patients, the microbiome composition at the species level and at P. acnes strain level was more diverse than in healthy individuals, with enriched virulence-associated factors and reduced abundance of metabolic synthesis genes. Based on the abundance profiles of the metagenomic elements, we constructed a quantitative prediction model, which classified the clinical states of the host skin with high accuracy in both our study cohort (85%) and an independent sample set (86%). Our results suggest that the balance between metagenomic elements, not the mere presence of disease-associated strains, shapes the overall virulence property of the skin microbiota. This study provides new insights into the microbial mechanism of acne pathogenesis and suggests probiotic and phage therapies as potential acne treatments to modulate the skin microbiota and to maintain skin health.

  Study phs001655

• A Large Data Resource of Genomic Copy Number Variation across Neurodevelopmental Disorders

  This study presents the first genome-wide copy number variation (CNV) analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD). A total of 2,691 subjects diagnosed with a neurodevelopmental disorder (NDD), and a total of 1,769 unaffected family members from Ontario, Canada were assayed using the Affymetrix CytoScan HD array. We identified rare CNVs, (< 0.1% frequency in 10,851 population control samples), and found clinically relevant CNVs in 10.5% of total subjects. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence) are NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244, NRON, and PTCHD1-AS. We demonstrated that identical CNVs or genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants and clinical interpretations.CNV data from this study are available through dbVar at https://www.ncbi.nlm.nih.gov/dbvar/studies/nstd173/.

  Study phs001881

• snRNA: A Cultured Leukemia Stem Cell Model Enables Validation of CDK6 as a Stemness Target Against Acute Myeloid Leukemia

  Acute myeloid leukemia (AML) represents a group of aggressive hematological malignancies, the clinical management of which is made challenging due to the persistence of rare and therapy resistant leukemia stem cells (LSCs) which serve as a source of disease relapse and poor outcomes. There are currently a paucity of methods to reliably enrich and study LSCs, hindering the development of therapies that specifically target LSCs. In this study, we deeply characterize the OCI-AML8227 culture model, which maintains a functional stemness hierarchy originating from its highly primitive CD34⁺CD38⁻ cells, to elucidate LSC biology and uncover LSC-specific therapeutic vulnerabilities. We analyzed both bulk and single-cell proteomics, transcriptomics, and epigenomics to generate a LSC protein-protein interaction network, which was then integrated with an LSC-focused small molecule screen using this model. From these findings, CDK6 was discovered as a therapeutic vulnerability specific to LSCs, which was validated in findings from the BEAT-AML cohort and a patient-derived xenograft (PDX) panel of AML samples through palbociclib treatment. Taken together, our studies validate CDK6 as a druggable vulnerability in LSCs, and authenticate OCI-AML8227 cells as a LSC target discovery engine.

  Study EGAS50000000786

• bulk ATACseq: A Cultured Leukemia Stem Cell Model Enables Validation of CDK6 as a Stemness Target Against Acute Myeloid Leukemia

  Acute myeloid leukemia (AML) represents a group of aggressive hematological malignancies, the clinical management of which is made challenging due to the persistence of rare and therapy resistant leukemia stem cells (LSCs) which serve as a source of disease relapse and poor outcomes. There are currently a paucity of methods to reliably enrich and study LSCs, hindering the development of therapies that specifically target LSCs. In this study, we deeply characterize the OCI-AML8227 culture model, which maintains a functional stemness hierarchy originating from its highly primitive CD34⁺CD38⁻ cells, to elucidate LSC biology and uncover LSC-specific therapeutic vulnerabilities. We analyzed both bulk and single-cell proteomics, transcriptomics, and epigenomics to generate a LSC protein-protein interaction network, which was then integrated with an LSC-focused small molecule screen using this model. From these findings, CDK6 was discovered as a therapeutic vulnerability specific to LSCs, which was validated in findings from the BEAT-AML cohort and a patient-derived xenograft (PDX) panel of AML samples through palbociclib treatment. Taken together, our studies validate CDK6 as a druggable vulnerability in LSCs, and authenticate OCI-AML8227 cells as a LSC target discovery engine.

  Study EGAS50000000787

• scATAC: A Cultured Leukemia Stem Cell Model Enables Validation of CDK6 as a Stemness Target Against Acute Myeloid Leukemia

  Acute myeloid leukemia (AML) represents a group of aggressive hematological malignancies, the clinical management of which is made challenging due to the persistence of rare and therapy resistant leukemia stem cells (LSCs) which serve as a source of disease relapse and poor outcomes. There are currently a paucity of methods to reliably enrich and study LSCs, hindering the development of therapies that specifically target LSCs. In this study, we deeply characterize the OCI-AML8227 culture model, which maintains a functional stemness hierarchy originating from its highly primitive CD34⁺CD38⁻ cells, to elucidate LSC biology and uncover LSC-specific therapeutic vulnerabilities. We analyzed both bulk and single-cell proteomics, transcriptomics, and epigenomics to generate a LSC protein-protein interaction network, which was then integrated with an LSC-focused small molecule screen using this model. From these findings, CDK6 was discovered as a therapeutic vulnerability specific to LSCs, which was validated in findings from the BEAT-AML cohort and a patient-derived xenograft (PDX) panel of AML samples through palbociclib treatment. Taken together, our studies validate CDK6 as a druggable vulnerability in LSCs, and authenticate OCI-AML8227 cells as a LSC target discovery engine.

  Study EGAS50000000788

• Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis thymoma

  Myasthenia gravis (MG) is known to be epidemiologically associated with abnormalities of the thymus, an organ that maintains central tolerance. However, due to the complexity of the thymus, specific characteristics related to the pathogenesis of MG remain elusive. In our study, we attempted to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We found that the majority of thymomas were constituted by the cortical region, whereas the medullary region was localized in comparatively restricted areas. Moreover, the medullary region contained polygenic enrichment, MG-specific germinal center structures, and a supporting immune microenvironment. Additionally, neuromuscular medullary thymic epithelial cells (nmTECs), previously identified as MG-specific autoantigen-producing cells, were situated at the cortico-medullary junction. The immune microenvironment in the medulla was characterized by a specific chemokine pattern and specific immune cells, such as CCR7+ migratory dendritic cells (migDCs) and effector regulatory T (Treg) cells. Furthermore, similar germinal center structures and immune microenvironments were observed in the medulla during thymic hyperplasia. This study indicates that the medulla and junction areas are related to the pathology of MG, suggesting that these areas should be the focus of future studies on MG pathogenesis and drug targeting.

  Study JGAS000672

• Unifying recovery dynamics in heterogeneous diseases exemplified by COVID-19

  Studying the recovery dynamics in different diseases poses many difficulties, as patients often display high heterogeneity in their recovery courses. Moreover, most attempts to study disease dynamics focus on disease progression rather than disease recovery mechanisms. To model recovery dynamics, using severe COVID-19 as the example, we align heterogeneous recovery trajectories via a novel computational scheme applied to longitudinally sampled blood transcriptomes. We thus generate pseudotime trajectories, which we then link to cellular and molecular mechanisms based on cell deconvolution analysis and molecular pathway prediction, thus presenting a unique framework for studying recovery processes over time. Specifically, mature neutrophils displayed a gradual decrease during recovery, allowing superior useability for outcome prediction compared to currently used clinical markers. Further, we discovered a recovery-related regulatory change in gene programs resulting in immune rebalancing between interferon and NFkB activity and the restoration of cell homeostasis. We thus propose regulatory mechanisms governing COVID-19 recovery and suggest mature neutrophils and additional gene markers, as novel clinical biomarkers for disease outcome. Overall, we present a novel clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues.

  Study EGAS00001005735

• CRISPR/Cas9-mediated genome editing of Schistosoma mansoni acetylcholinesterase

  Here we report successful gene knock-in (KI) in the eggs of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We targeted the acetylcholinesterase (AChE) gene of S. mansoni using two synthetic guide RNAs (gRNAs), X5 and X7, respectively. Liver eggs of S. mansoni were exposed to CRISPR-vector containing X5 or X7 by electroporation. Simultaneously, eggs were transfected with a ssODN donor encoding a stop codon in all six frames. Next generation sequencing analysis revealed that CRISPR/Cas9-mediated editing in S. mansoni eggs resulted in Homology-Directed Repair (HDR) when template DNA ssODN provided. Furthermore, soluble egg antigen (SEA) from AChE-modified eggs exhibited markedly reduced AChE activity compared with controls, indicative that programmed Cas9 cleavage mutated the AChE gene. Following injection of modified schistosome eggs into the tail veins of mice, a significant decrease in granuloma size in the lungs of these animals. Notably, an enhanced Th2 response induced by eggs in lung, and splenocytes small intestine-draining mesenteric lymph node cells was also generated in mice injected with X5-KI eggs in different methods. These findings further demonstrate the power and utility of CRISPR/Cas9-based genome editing for undertaking functional genomics studies in schistosomes.

  Study EGAS00001004455

• Identification of Rare Germline Variants in Familial Patients with Non-medullary Thyroid Cancer

  As the most common malignancy of the endocrine system, thyroid cancer is classified into two major categories, non-medullary thyroid cancer (NMTC) and medullary thyroid cancer (MTC) according to the origins and clinical features. NMTC includes papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), and anaplastic thyroid cancer (ATC). Sporadic non-medullary thyroid cancer (SNMTC) accounts for ~90% of all thyroid cancers. Compared to SNMTC, familial non-medullary thyroid cancer (FNMTC) is rare, constituting only 3 - 9%. FNMTC is a complex genetic disease that often shows an autosomal dominant mode of inheritance. Characterization of the germline variants causing the disease is still challenging given the heterogeneity of affected families. In recent years, some mutations in known cancer susceptive coding genes have been reported using targeted DNA sequencing method in FNMTC cases. Still, little is known for the novel mutations in other thyroid cancer predisposition genes. With the decreasing cost and rapid development of next generation sequencing technology, more rare germline mutations underlying different types of cancer susceptibility in families had been discovered by whole genome sequencing (WGS). In this study, we performed WGS in familial NMTC patients in the U.S. Our aim is to identify rare germline variants with high penetrance that may contribute to thyroid cancer predisposition in NMTC families.

  Study phs001758

• Bulk RNASeq of metastatic colorectal cancer organoids with ATOH1 knockout

  Bulk RNA sequencing was performed on mCRC organoids subjected to cetuximab treatment, comparing ATOH1 knockout and control conditions. The dataset is intended to elucidate the contribution of ATOH1-regulated secretory cell population to cetuximab persistence mechanisms.

  Dataset EGAD50000002060

• Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk paediatric cancer

  Zero Childhood Cancer is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Utilising tumour and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumours from high-risk paediatric cancer patients, we identified 968 reportable molecular aberrations (39.9% in WGS and RNAseq, 35.1% WGS-only, 25.0% RNAseq-only). 93.7% of patients had at least one germline or somatic aberration, 71.4% had therapeutic targets and 5.2% had a change in diagnosis. WGS identified pathogenic cancer-predisposing variants in 16.2% of patients. In 76 CNS tumours, methylome analysis confirmed diagnosis in 71.1% and contributed to a change of diagnosis in two cases (2.6%). To date 43 patients have received a recommended therapy, 38 of whom could be evaluated. A small but encouraging proportion of 31% showed some evidence of clinical benefit. Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, which in some cases has significant clinical impact.

  Study EGAS00001004572

• Drug-induced epigenomic plasticity reprograms circadian rhythm regulation to drive prostate cancer towards androgen-independence (ChIP-seq)

  Understanding how prostate cancer cells adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenetic plasticity towards pro-survival signaling, and uncovered circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel clinical lead for therapeutic development.

  Study EGAS00001006017

• Chromatin Accessibility Landscape of Human Pancreatic Ductal Adenocarcinoma (PDAC)

  Therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we discovered a signature of 1092 chromatin loci displaying differential accessibility between patients with disease-free survival (DFS) < 1 year and patients with DFS > 1 year. Using this signature, we further develop a chromatin accessibility microarray methodology termed “ATAC-Array”, an easy-to-use platform obviating the time and cost of next-generation sequencing. PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.

  Study phs002394

• Transcriptome profiling of head and neck squamous cell carcinomas with paired patient-derived xenografts

  This dataset includes transcriptome profiling of 88 head and neck primary patient tumor samples and 45 paired patient-derived xenograft samples that successfully engrafted in mice. NGS was performed using the Illumina TruSeq stranded total RNA sample preparation kit on the Illumina NovaSeq X Plus platform at the Princess Margaret Genomics Centre. This dataset consists of paired-end fastq files.

  Dataset EGAD50000000995

• Single-cell RNA sequencing of cytokine-induced T cell responses

  Cytokines affect T cell responses by polarising them to different phenotypes. We isolated T cells from healthy platelet donors and cultured them in resting and stimulated condition, as well as in the presence of Th2, iTreg and Th17 polarizing cocktail. To characterize the efficacy of cytokine induced porization and subpopulation specific response, we profiled single cell transcriptome five days following polarization using 10x platform (3' v2).

  Dataset EGAD00001005290

• Raw sequencing data for donor and patient fecal samples

  Microbiome analysis was performed on the patient samples collected pre-FMT and on days after FMT, and on samples collected from the FMT donor. Genomic bacterial DNA was extracted from fecal samples using the QIAamp DNA Stool kit (Qiagen, Hilden, Germany), with the addition of a bead-beating lysis step. Genomic 16S ribosomal-RNA V4 variable regions were amplified and sequenced on the Illumina MiSeq platform.

  Dataset EGAD00001004371

• Diseased heart analysis: RNA Adult (2025-10-14)

  Samples for this project are taken from adult human hearts which have been preserved using 2 different methods (cold static storage on ice, and hypothermic perfusion). Samples have been acquired at various time points during post-preservation normothermic perfusion. The aim of the project is to assess the transcriptional changes caused by these differing methods of preservation. . This dataset contains all the data available for this study on 2025-10-14.

  Dataset EGAD00001015738

• DNA Methylation in Prostate Tumor and Paired Benign Tissue for African and European Ancestry Men

  We recruited prostate cancer (PCa) patients undergoing robotic-assisted laparoscopic radical prostatectomy at the University of Chicago Medical Center Urology Clinic between 2011 and 2017. Our study includes 76 African American (AA) and 75 European American (EA) men with PCa of Gleason Score (GS) ≥7, recruited by the Epidemiology Research Recruitment Core at the University of Chicago. All patients consented to the collection of questionnaire data, prostate tissue, and medical records. The study was approved by the Institutional Review Board of the University of Chicago. Following prostatectomy, prostate tissue was sent to the Human Tissue Research Center (HTRC) at the University of Chicago. Each sample underwent histological examination and Gleason scoring by University of Chicago genitourinary pathologists. The presence of adenocarcinoma was confirmed by overexpression of alpha-methylacyl-coenzyme-A racemase (AMACR) and areas for DNA extraction were marked. Tissue samples used for DNA extraction were obtained using with either a 1mm biopunch or laser microdissection of a 100 µm2 area of tissue. Genome-wide DNA methylation profiles were generated using Illumina's Infinium MethylationEPIC BeadChip array kit. Genome-wide SNP data was generated (from benign tissue DNA) using the Illumina Infinium Multi-Ethnic Global-8 v1.0 array at the University of Chicago Genomics Core Facility. We performed imputation using the Haplotype Reference Consortium (HRC, Version r1.1 2016) panel, which includes all samples from the 1,000 Genomes Project (Phase 3), using the Michigan Imputation Server. The imputed SNP data for mQTL analysis was imputed based on genotype SNP data which was all from benign tissue DNA and the methylation data was identified in both tumor and benign tissue, both AA and EA men, and identified QTLs co-occuring with prostate cancer susceptibility loci.Data including SNP genotypes, DNA methylation, tissue type, and participant characteristics will be available in dbGaP.

  Study phs003516

• Dataset for other_cancer-EXON

  Rare cancer sequencing data of 137 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008896

• Dataset for neuroendocrine_adrenal_tumor-EXON

  Rare cancer sequencing data of 164 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008891

• Combination Immune Checkpoint Inhibition in Australian Rare Cancers_WES

  Combination immune checkpoint inhibition (ICI) with anti-CTLA-4 and anti-PD-1 blockade has demonstrated significant clinical activity across tumour types. Rare cancer patients have limited treatment options due to the scarcity of studies of novel treatment options, so they are often offered chemotherapies untested in their disease. ONJ2016-001/CA209-538 is a prospective, multicentre clinical trial of combination ICI (ipilimumab and nivolumab) in patients with advanced rare cancers, including biliary tract, adrenocortical, rare gynaecological and neuroendocrine cancers (https://clinicaltrials.gov/ct2/show/NCT02923934). The primary endpoint is clinical benefit rate (complete response + partial response + stable disease >3 months) by RECIST 1.1. This study involves generation and analysis of pre-treatment formalin fixed paraffin embedded (FFPE) tumour DNA sequencing data, paired with germline DNA sequencing data, to potentially identify genomic biomarkers that may associate with clinical benefit or other clinical efficacy / toxicity metrics.

  Dataset EGAD00001015465

• National Heart, Lung, and Blood Institute SNP Health Association Asthma Resource Project (SHARP)

  SNP Health Association Resource (SHARe) Asthma Resource project (SHARP) is conducting a genome-wide analysis in adults and children who have participated in National Heart, Lung, and Blood Institute's clinical research trials on asthma. This includes 1041 children with asthma who participated in the Childhood Asthma Management Program (CAMP), 994 children who participated in one or five clinical trials conducted by the Childhood Asthma Research and Education (CARE) network, and 701 adults who participated in one of six clinical trials conducted by the Asthma Clinical Research Network (ACRN). There are three study types. The longitudinal clinical trials can be subsetted for population-based and/or case-control analyses. Each of the childhood asthma studies has a majority of children participating as part of a parent-child trio. The ACRN (adult) studies are probands alone. Control genotypes will be provided for case-control analyses.

  Study phs000166

• Comparison of fresh and slow-frozen cancer samples for different applications

  Surplus tissues from multiple solid human cancers directly slow-frozen after resection can subsequently be used for different types of methods including the establishment of 2D, 3D, and ex vivo cultures as well as single cell RNA sequencing (scRNAseq) with similar results when compared to freshly analyzed material.

  Study EGAS00001005891

• Personalised Mapping of Tumour Development in Synchronous Colorectal Cancer Patients

  We performed an in-depth characterisation of 12 tumours from 3 syCRC patients by analysing histopathological, whole genome sequencing and RNA-sequencing data. We assessed the extent of genetic overlap between synchronous tumours and examined associations between clinicopathological information and the molecular, microbial and immune features of each tumour genome.

  Study EGAS00001004413

• Whole Genome Sequencing of Multiple Myeloma patients treated with T-cell redirecting immunotherapies

  Samples was collected at the Arnie Charbonneau Cancer Institute (University of Calgary). Whole Genome Sequencing was performed at the New York Genome Center, and libraries were prepared using the Truseq DNA Nano Library Preparation Kit. Libraries were sequenced on an Illumina Novaseq 6000 sequencer using 2 x 150-bp cycles. The dataset consists in 85 BAM files from patients with Multiple Myeloma treated with bi-specific and CAR-T therapies. Reference Genome: GRCh38.

  Dataset EGAD50000000776

• Molecular profiling of HGBCL-DH-BCL2 patients treated in the HOVON-152 trial

  Using targeted sequencing and shallow whole genome sequencing for simultaneous screening of mutations, copy number alterations, and translocations, this study aims to identify genomic alterations associated with outcome in HGBCL-DH-BCL2 patients of the HOVON-152 trial.

  Study EGAS50000001453

• ESGI___Whole_Genome_Sequencing_of_samples_from_the_ORCADES_cohort__X10__

  Deep whole genome sequencing of sampels from the Orkney Complex Disease Study (ORCADES), each with data on up to 300 quantitative traits and other risk factors associated with cardiovascular, metabolic and other complex diseases. The samples are sequenced using the Illumina HiSeq X Ten system.

  Study EGAS00001001125

• Warm_Autopsy_Single_Cell_X10

  Study of cell lineage and embryogenesis using biopsy samples from sites across the whole body (post mortem). Sample donors are recruited sensitively through the Phoenix study and consent to samples being taken after their death for both the Phoenix study and this WTSI study.

  Study EGAS00001001698

• Clonal expansion of mutated cell population in bladder urothelium

  1cm biospies of from patients undergoing bladder cystectomy will be collected. The underlying muscle and stroma will be removed and the remaining epithelia dissected into small sequential areas which will be sent for ultra-deep exome sequencing using a panel of known cancer and viral genes. Sequence analysis using similar methods to Martincorena I et al (Science 2015, 348:880) will provide an idea of the somatic mutational landscape in these patient samples. Individual patient muscle samples will also be sequenced as a reference.

  Dataset EGAD00001003250

• Understanding_Self__Organising_Capacity_of_Stem_Cells_during_Implantation_and_Early_Post_implantation_Development_in_vitro_and_in_vivo__Implications_for_Human_Development_

  The aim of this project is to differentiate human embryonic stem cells to an extra-embryonic fate, specifically the hypoblast. This is of uttermost importance given the current lack of human hypoblast stem cells. We hypothesized that the pluripotent characteristics of the starting human embryonic stem cell population may dictate the competency for extra-embryonic cell fate specification. Based on this hypothesis and using human embryonic stem cells maintained in different naïve-like culture regimes, we have now developed conditions that allow the differentiation of human embryonic stem cells to a stable GATA6+ SOX2- population. This suggests that these cells may be putative human hypoblast stem cells. To validate this finding here we propose to perform RNA sequencing experiments of the differentiated human embryonic stem cells. By comparing their RNA expression profile to the single cell sequencing data of the human embryo that we are currently generating, we will be able to determine the identity of our GATA6+ SOX2- cells, and establish whether they represent the in vivo human hypoblast.

  Study EGAS00001003571

• Genomic landscape of poorly differentiated thyroid carcinoma

  Poorly differentiated thyroid carcinoma (PDTC) is a rare and aggressive subtype of thyroid cancer with limited molecular characterization. This study aims to define the somatic mutational landscape of PDTC using whole-genome sequencing. Paired tumour and matched normal blood samples were collected from six patients undergoing surgery. The overarching goal is to identify recurrent mutations, structural variants, and other genomic alterations associated with tumour aggressiveness and poor clinical outcomes.

  Study EGAS50000001134

• Development of New Diagnostics, Therapeutics, and Prevention Methods for Personalized Medicine Based on Comprehensive Cancer-Related Gene Exome Analysis and Information Analysis Using Cancer Specimens Stored in TMDU Biobank.

  Biobanked tumor samples are a valuable resource in real-world solid tumor research. Panel-based genomic profiling enables the identification of clinically significant alterations that inform personalized diagnostic and treatment decisions. This study aimed to characterize the genomic landscape of solid tumors collected through the TMDU Biobank by summarizing mutational, copy number, and gene fusion alterations in a large and diverse patient cohort. This dataset contains summary-level genomic information from 1,996 tumor samples analyzed by ACT Genomics and ACT med using the ACTOnco Comprehensive 440-Gene Cancer Panel. Data provided includes (1) gene-level mutation counts, (2) a summary of copy number alterations, and (3) a summary of detected fusion events. Clinical attributes such as ICD-10 codes, age group, sex, tumor mutational burden (TMB), and microsatellite instability (MSI) status were included at the aggregate level. Summary statistics were generated from three source tables (gene, sample, and copy number data) using standardized processing rules. Due to contractual and ethical considerations, individual-level mutation locations and raw sequence data are not included; only summary-level information is provided. This dataset will support future research in tumor-type-specific genomic patterns, molecular characterization of solid malignancies, and precision oncology.

  Study JGAS000863

• CSER: Evaluating Utility and Improving Implementation of Genomic Sequencing for Pediatric Cancer Patients in the Diverse Population and Healthcare Settings of Texas: The KidsCanSeq Study

  Through this Clinical Sequencing Evidence-Generating Research (CSER) with Enhanced Diversity project we are completing a clinical study (The Texas KidsCanSeq Study) comparing the results of targeted cancer panel sequencing versus genome-scale testing in pediatric cancer patients across diverse clinical settings. We will compare the targeted pediatric cancer panel to germline whole exome sequencing (WES) of unselected childhood cancer patients. We will also compare an RNA/DNA targeted pediatric cancer panel versus WES, transcriptome sequencing and copy number array of FFPE tumor samples for the subset of patients with high-risk tumors. Exome sequencing is performed from a blood or saliva sample of the pediatric age (0-18) patient. We are building on our success completing the CSER program BASIC3 exome sequencing trial (which included 60% Hispanic and African-American patients from a single large academic center) in this large multi-institutional study of an even more diverse patient population from six pediatric oncology healthcare settings across Texas. Data from the Texas KidsCanSeq study will be submitted through the CSER Data Coordinating Center for access in NIH-supported databases.

  Study phs002378

• Pan Cancer Investigation of Human Leukocyte Antigen Loss of Heterozygosity

  Cancer cells can escape immune recognition through human leukocyte antigen (HLA) loss of heterozygosity (LOH) which results in deletion of HLA alleles, causing a reduction in presentation of tumor neoantigens. Despite its influence on immunotherapy response, few methods exist to detect HLA LOH, and accuracy of the approaches is poorly defined. Here, we present DASH (Deletion of Allele-Specific HLAs), a machine learning-based algorithm developed to detect HLA LOH from paired tumor-normal sequencing data. Using DASH to characterize HLA LOH in 610 patients across 15 cancer types, we found that 18% of patients had loss of heterozygosity in at least one HLA allele, suggesting the HLA LOH is a widespread, and potentially key immune resistance strategy in multiple cancers.

  Study phs002783

• Deciphering the genomic, epigenomic and transcriptomic landscapes of pre-invasive lung cancer lesions to determine prognosis

  Background: Lung carcinoma-in-situ (CIS) lesions are the pre-invasive precursor to lung squamous cell carcinoma. However, only half progress to invasive cancer in three years, while a third spontaneously regress. Whether modern molecular profiling techniques can identify those pre-invasive lesions that will subsequently progress and distinguish them from those that will regress is unknown. Methods: Progressive and regressive CIS lesions were laser-captured and their genome, epigenome and transcriptome interrogated. We analysed 83 progressive lesions, 41 regressive and 33 normal epithelial control samples. DNA methylation and gene expression profiles were further validated using publicly available lung cancer data. Results: Somatic mutation burden was higher in progressive lesions than regressive CIS lesions, across base substitutions, rearrangements, and copy number changes. Driver mutations were present in both progressive and regressive CIS lesions, but were more numerous in progressive cases. Progressive and regressive CIS lesions had distinct epigenomic and transcriptional profiles, with a strong chromosomal instability signature. Gene expression, methylation and copy number profiles can all predict accurately which CIS lesions will progress to lung cancer. Conclusion: Pre-invasive CIS lesions that will subsequently progress to invasive lung cancer can be distinguished from those that will regress using molecular profiling. Progression is associated with a strong chromosomal instability signature. These findings inform the development of novel therapeutic targets.

  Dataset EGAD00001003883

• Evolution and clinical impact of genetic epistasis within EGFR-mutant lung cancers: multi-timepoint exome sequencing of a single patient's disease

  This dataset is a time-series of EGFR-mutant NSCLC clinical specimens from an individual patient profiled using tumor-based whole exome sequencing and the data is in BAM format. DNA was extracted from FFPE for primary tumor and frozen tumor tissue samples and matched non-tumor tissue using the Qiagen Allprep DNA/RNA Mini Kit.  The library preparation protocol was based on the Agilent SureSelect Library Prep and Capture System. DNA was resuspended in a low TE buffer and sheared (Duty Cycle 5%; Intensity 175; Cycles/Burst: 200; Time: 300s, Corvaris S2 Utrasonicator).  Bar-coded exome libraries were prepared using the Agilent Sure Select V5 library kit per manfucaturer’s specifications. The libraries were run on the HiSeq2500. Raw paired end reads (100bp) in FastQ format generated by the Illumina pipeline were aligned to the full hg19 genomic assembly obtained from USCS, gencode 14, using bwa version 0.7.12. Picard tools version 1.117 was used to sort, remove duplicate reads and generate QC statistics. Tumor DNA was sequenced to median depth of 303X (range 114.39-383.41) and the matched germline DNA to average depth of 231.65.

  Dataset EGAD00001003769

• Pediatric Papillary Thyroid Carcinoma RNA-Seq

  Papillary thyroid carcinoma (PTC) is the most common malignancy amongst adolescent and young adult women. Clinical and genomic features of PTC in children differ from those in adults. Historically, a substantial proportion (~50%) of pediatric PTC (PPTC) lack any of the common driver mutations typical of adult PTC. Thus, molecular diagnostics developed for adults may not be valid in children. We applied novel bioinformatic pipelines to RNASeq analysis of pediatric thyroid tumors to identify known and novel fusion oncogenes as drivers of tumorigenesis and to define gene expression patterns among tumors. Analysis of 38 samples resulted in identification of 16 previously reported oncogenic fusions and three novel candidate fusions. In conducting these analyses, we reduced the proportion of cancers with unknown drivers from approximately 50% to 6%. Gene expression analysis identified three distinct categories of tumors. These studies represent the first unbiased genomic approach to childhood PTC. Novel bioinformatic pipeline. GEC Identified 3 distinct classes. DICER1, PTEN segregated with benign tumors. >90% of PPTC carry identifiable ongognic driver variants, however, the landscape differs from that in adults and existing tools for tumor genotyping in adults may not be applicable to pediatric tumors. BACKGROUND: Papillary thyroid carcinoma demonstrates clinically distinct behaviour in pediatric patients when compared to adults, with increased regional and distal metastases, more frequent recurrence, yet overall highly favourable prognosis. Recent tumor genotyping has demonstrated that in pediatric tumors, ***-*** do not carry the most common genomic variants found in adult PTC, leaving a substantial proportion of driver-unknown or “dark matter” tumors. METHODS: We established a cohort of 52 pediatric PTC and performed quantitative-PCR genotyping followed in a subset by whole exome and whole transcriptome (RNASeq) sequencing using a novel, robust bioinformatic pipeline to identify oncogenic fusion transcripts. Gene expression analysis was used to derive distinct clusters. RESULTS: In 52 pediatric PTC, genotyping identified BRAFV600E(21%), NRASQ61R(2%), RET/PTC1 (21%), RET/PTC3 (17%) or PAX8-PPAR in 33 (63%) of tumors. Among the remaining 19 tumors, oncogenic variants were identified in /19 (%). The variants included SNVs in DICER1, ETV6-NTRK3, PTEN and 9 additional oncogenic fusions including two previously-undescribed fusion transcripts, *** and ***. CONCLUSIONS: The genomic landscape of PTC differs between children and adults. In children, there is a substantial fraction of tumors that are unexplained by variants typical of adult PTC. This discrepancy is explained largely by uncommon oncogenic fusions which can be identified by whole-transcriptome analysis.

  Study EGAS00001005182

• 10X whole single cell RNA-seq from pre-frontal cortex biopsy

  The biopsy procedure was performed by a standard operative procedure under general anaesthesia. The placement of burr hole on the frontal lobe, opening of dura and cortex was performed in a routine fashion for VP shunt or VCS surgery. The biopsy was sharp dissected with knife through the leptomeninges, forming a tissue block consisting of cortex and subcortex, and placed in a sterile tube containing CSF. Fresh tissue sample processing was performed within the hours after surgery. The tissue was dissociated followed by red cell and debris removal and counting of the cells to be sequenced with (scRNA-seq; 10x Genomics). After dissociation only non neuronal cells were retrieved.

  Study EGAS50000001058

• Accurate detection of tumor-specific fusion genes reveals strongly immunogenic personal neo-antigens

  Fusion genes arising from cancer-associated somatic mutations are a potential rich source for highly immunogenic neo-antigens. However, their exploitation as targets for personalized cancer immunotherapy is currently limited by the lack of computational tools allowing transcriptome-wide identification of unique fusion genes in an accurate and sensitive manner. Here, we present EasyFuse, a computational pipeline, to detect individual and cancer-specific fusion genes in next-generation-sequencing transcriptome data obtained from human cancer samples. Using machine learning, EasyFuse predicts personal fusion genes with high precision and sensitivity and outperforms previously described approaches as qualified by an unprecedented ground-truth dataset of >1500 verification experiments in relevant patient samples. By testing immunogenicity with autologous blood lymphocytes from cancer patients we detected pre-established CD4+ and CD8+ T cell responses for 10 of 21 (48%), and for 1 of 30 (3%) of identified fusion genes, respectively. In conclusion, we demonstrate accurate detection of cancer-specific fusion genes. The high frequency of T cell responses detected in cancer patients support the relevance of private fusion genes as neo-antigens for personalized immunotherapies, especially for tumors with low point mutation burdens.

  Study EGAS00001004877

• Examination of Engineered LINE-1 Integration Events in HeLa Cells

  Long Interspsesed Element-1 (LINE1 or L1) encodes two proteins (ORF1p and ORF2p) required for its mobilization (i.e. retrotransposition) in the human genome. Human ORF2p, a 150kDa protein, has endonuclease (EN) and reverse transcriptase (RT) activities. L1 EN is classified as apurinic/apyrimidin-like endonuclease (APE) and is responsible for initiating target-site primer reverse transcription (TPRT) during the L1 retrotransposition cycle. During canonical TPRT, the L1 EN activity makes a single-strand endonucleolytic nick at a double-strand DNA target sequence in genomic DNA. The endonucleolytic nick is typically made at an L1 EN degnerate consensus cleavage sequence (5'-TTTT/A-3') exposing a free 3' hydroxy group that can be used as a primer by the ORF2p L1 RT activity to reverse transcribe the associated L1 RNA. Here, we characterized over 21,000 de novo engineered L1 retrotransposition events in HeLa cells to determine if L1 exhibits overt integration preferences in the human genome. Bru-seq of HeLa cells to determine actively transcribed regions of the genome was also performed. This Bru-seq data was used to determine if engineered L1 integration events preferentially integrate into transcribed regions of the genome, and to determine which strand during transcription may present itself as preferential during L1 retrotransposition.

  Study phs001669

• Data Use Ontology (DUO)

  Data Use Ontology Data Use Ontology at EGA The EGA is committed to its involvement in the work of GA4GH. In an effort to enhance data discoverability and streamline data access, EGA have implemented the use of the Data Use Ontology (DUO), based on consent codes as described in Dyke et al. 2017. The Data Use Ontology codes will be displayed on the live dataset page of your submission to advise any would be requestor on how the data can be used and also to enhance data discoverability as users will be able to search on these codes to find applicable datasets. DUO can be browsed online via the Ontology Lookup Service Learn more reading the Data Use Ontology publication and the GA4GH Machine-Readable Consent Guidance! Check our DAC Portal Take The Tour and learn how to add DUO codes to your policy! Term Shorthand Label Description DUO:0000004 NRES no restriction This data use permission indicates there is no restriction on use. DUO:0000042 GRU general research use This data use permission indicates that use is allowed for general research use for any research purpose. DUO:0000006 HMB health or medical or biomedical research This data use permission indicates that use is allowed for health/medical/biomedical purposes; does not include the study of population origins or ancestry. DUO:0000007 DS disease specific research This data use permission indicates that use is allowed provided it is related to the specified disease. DUO:0000011 POA population origins or ancestry research only This data use permission indicates that use of the data is limited to the study of population origins or ancestry. DUO:0000012 RS research specific restrictions This data use modifier indicates that use is limited to studies of a certain research type. DUO:0000015 NMDS no general methods research This data use modifier indicates that use does not allow methods development research (e.g., development of software or algorithms). DUO:0000016 GSO genetic studies only This data use modifier indicates that use is limited to genetic studies only (i.e., studies that include genotype research alone or both genotype and phenotype research, but not phenotype research exclusively) DUO:0000018 NPUNCU not for profit, non commercial use only This data use modifier indicates that use of the data is limited to not-for-profit organizations and not-for-profit use, non-commercial use. DUO:0000019 PUB publication required This data use modifier indicates that requestor agrees to make results of studies using the data available to the larger scientific community. DUO:0000020 COL collaboration required This data use modifier indicates that the requestor must agree to collaboration with the primary study investigator(s). DUO:0000021 IRB ethics approval required This data use modifier indicates that the requestor must provide documentation of local IRB/ERB approval. DUO:0000022 GS geographical restriction This data use modifier indicates that use is limited to within a specific geographic region. DUO:0000024 MOR publication moratorium This data use modifier indicates that requestor agrees not to publish results of studies until a specific date. DUO:0000025 TS time limit on use This data use modifier indicates that use is approved for a specific number of months. DUO:0000026 US user specific restriction This data use modifier indicates that use is limited to use by approved users. DUO:0000027 PS project specific restriction This data use modifier indicates that use is limited to use within an approved project. DUO:0000028 IS institution specific restriction This data use modifier indicates that use is limited to use within an approved institution. DUO:0000029 RTN return to database or resource This data use modifier indicates that the requestor must return derived/enriched data to the database/resource. DUO:0000043 CC clinical care use This data use modifier indicates that use is allowed for clinical use and care. DUO:0000044 NPOA population origins or ancestry research prohibited This data use modifier indicates use for purposes of population, origin, or ancestry research is prohibited. DUO:0000045 NPU not for profit organisation use only This data use modifier indicates that use of the data is limited to not-for-profit organisations. DUO:0000046 NCU non-commercial use only This data use modifier indicates that use of the data is limited to not-for-profit use. Point to Notice: For the consent code DUO:0000007 where data is restricted to use on a specific disease, please accompany it with an appropriate ontology from MONDO e.g., If the data is restricted to the use of research into juvenile idiopathic arthritis the code should be displayed as DUO:0000007; MONDO:0011429.

  Documentation access/data-access-committee/data-use-ontology

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

  ONT whole-genome sequencing data for "HPV integration induces gene fusions" . We sequenced five HPV-positive head and neck cancer samples using Oxford Nanopore platform. The sequences was submitted in fastq format.

  Dataset EGAD50000001302

• FFPE CPA Accreditation Study

  FFPE CPA accreditation of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing.

  Dataset EGAD00001000678

• Cell-free DNA sequencing data of healthy control, atrophic gastritis, and gastric cancer patients’ blood

  Sample cohort (n=48) is consisted of healthy, atrophic gastritis and gastric cancer patients. Some of the gastric cancer patients samples are collected at the separate time points: -1 before the operation; -2 after the operation; -3 during the control visit. For the hybridisation capture of the genes unique 15 gastric cancer-related gene panel was developed and very deep sequencing using TruSight Oncology Unique Molecular Identifier (UMI) Reagents (Illumina) was used.

  Dataset EGAD00001011153

• Smart-seq 2 single cell sequencing of CD4 and CD8 T cells from the blood and synovial fluid of 4 psoriatic arthritis patients.

  This dataset was used to characterise T cell gene expression and clonality at sites of active inflammation within the joints of psoriatic arthritis (PsA) patients, and to compare these results with T cells from the peripheral blood of those same patients. Freshly sorted CD45RA negative CD3+CD4+ and CD3+CD8+ single cells from four patients were individually flow sorted into 96-well full-skirted plates (Eppendorf) containing 10µL of a 2% Dithiothreitol (DTT, 2M Sigma-Aldrich), RTL lysis buffer (Qiagen) solution. Cell lysates were sealed, mixed and spun down before storing at -80 ºC. Paired-end multiplexed sequencing libraries were prepared following the Smart-seq 2 protocol using the Nextera XT DNA library prep kit (Illumina). A pool of barcoded libraries from four different plates were sequenced across two lanes on the Illumina HiSeq 2500.

  Dataset EGAD00001006342

• PD-associated regulatory variants in human dopaminergic neurons reveals modulators of SCARB2 and BAG3 expression

  SNPs have been associated with the risk of Parkinson’s disease but not in regulatory regions. While those potentially disrupt TFBS altering gene expression and contributing to cis-regulatory variation. To study changes in A and B compartment interactions and in topologically associated domains (TADs), we sequenced: - 3D chromatin contact using LowC, 6 samples. 3 replicates for each condition: smNPC (controls) cells and differentiated neurons after 30 days. Resulting paired-end are provided as BAM files. In order to confirm the predicted impact of the PD-associated allele of rs144814361 on BAG3 promoter, we proceeded with genome editing of the TH-REP1 cell line by using prime editing to insert the “T” allele at the position chr10:119651405 in the BAG3 promoter. - Chromatin accessibility using ATAC-seq, 9 samples of derived cell line TH-REP1. 3 replicates for each condition: 1) iPSC Wild Type 2) SNP-BAG3 variant in iPSC 3) SNP-BAG3 variant in smNPC. BAG3 variant: heterozygous for the SNP variant: rs144814361 (chr10 119651405) Resulting sequencing are provided as paired-end FASTQ files.

  Dataset EGAD50000002258