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• Understanding Determinants of Racial Disparities in Lung Cancer Incidence

  This is a nested case-control study designed to evaluate the association between common genetic variants and the risk of lung cancer. The study included 1258 cases and 1252 controls selected from the Southern Community Cohort Study (SCCS), a large, prospective observational cohort. Cases were identified from cancer registries across the catchment area of the SCCS. Cases and controls were frequency matched on age, sex, race, and enrollment site (community health center vs general population).

  Study phs003789

• Whole genome sequencing of PDAC tissues an PDOs

  whole genome sequencing (WGS) on 48 PDOs (established from 39 tumors) and 4 tissues samples. The majority of PDOs were established from treatment-naive and localized tumors. Histopathologically, the majority of PDAC tumors from which PDOs were established displayed a conventional morphological pattern, with two containing squamous components (defined as adenosquamous), and one classified as a signet-ring tumour. 7 of the PDOs were grown in a culture medium lacking both WNT3A and RSPO1.

  Study EGAS50000000193

• 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

• scRNAseq of acute myeloid leukemia

  This study analyzes T-cell transcriptional state in acute myeloid leukemia (AML) and healthy donors. The goal of the study is to correlate T-cell transcriptional states abundances with response to chemotherapy. 12 samples (5 baseline and post-treatment, 2 baseline-only) from AML patients and 3 samples from healthy donors were collected and sequenced on Illumina platforms. The files were created using the GRCh38 reference through CellRanger count (10xGenomics).

  Study EGAS50000000357

• Whole genome sequencing data of pediatric TCF3::PBX1 acute lymphoblastic leukemia

  TCF3::PBX1 leukemia is a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL), occurring in approximately 3–5% of pediatric cases. It results from a chromosomal translocation t(1;19)(q23;p13), generating the TCF3::PBX1 fusion gene, which disrupts normal transcriptional regulation and contributes to leukemogenesis. Although historically associated with poor prognosis, contemporary risk stratification and intensified therapy have significantly improved outcomes, and both 5-years DFS and OS are nowadays ≥ 0.96.

  Study EGAS50000001257

• DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded (FFPE) tissues followed by targeted sequencing

  To overcome the challenges of low DNA yields, degraded DNA by formalin fixation and diluted signal of genomic aberrations by non-carcinoma components in the heterogeneous FFPE samples, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from 9 primary and metastatic breast cancer and 3 primary ovarian high-grade serous carcinomas. This was followed by a targeted panel for somatic mutation and sCNA analysis (7 samples), subject to cell availability. Mutation analysis was performed successfully in 6/7 samples and somatic mutations were detected in all of them.

  Dataset EGAD50000001888

• DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded (FFPE) tissues followed by targeted sequencing

  To overcome the challenges of low DNA yields, degraded DNA by formalin fixation and diluted signal of genomic aberrations by non-carcinoma components in the heterogeneous FFPE samples, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from 9 primary and metastatic breast cancer and 3 primary ovarian high-grade serous carcinomas. This was followed by a targeted panel for somatic mutation and sCNA analysis (7 samples), subject to cell availability. Mutation analysis was performed successfully in 6/7 samples and somatic mutations were detected in all of them.

  Dataset EGAD50000001890

• DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded (FFPE) tissues followed by targeted sequencing

  To overcome the challenges of low DNA yields, degraded DNA by formalin fixation and diluted signal of genomic aberrations by non-carcinoma components in the heterogeneous FFPE samples, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from 9 primary and metastatic breast cancer and 3 primary ovarian high-grade serous carcinomas. This was followed by a targeted panel for somatic mutation and sCNA analysis (7 samples), subject to cell availability. Mutation analysis was performed successfully in 6/7 samples and somatic mutations were detected in all of them.

  Dataset EGAD50000001896

• DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded (FFPE) tissues followed by targeted sequencing

  To overcome the challenges of low DNA yields, degraded DNA by formalin fixation and diluted signal of genomic aberrations by non-carcinoma components in the heterogeneous FFPE samples, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from 9 primary and metastatic breast cancer and 3 primary ovarian high-grade serous carcinomas. This was followed by a targeted panel for somatic mutation and sCNA analysis (7 samples), subject to cell availability. Mutation analysis was performed successfully in 6/7 samples and somatic mutations were detected in all of them.

  Dataset EGAD50000001897

• DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded (FFPE) tissues followed by targeted sequencing

  To overcome the challenges of low DNA yields, degraded DNA by formalin fixation and diluted signal of genomic aberrations by non-carcinoma components in the heterogeneous FFPE samples, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from 9 primary and metastatic breast cancer and 3 primary ovarian high-grade serous carcinomas. This was followed by a targeted panel for somatic mutation and sCNA analysis (7 samples), subject to cell availability. Mutation analysis was performed successfully in 6/7 samples and somatic mutations were detected in all of them.

  Dataset EGAD50000001898

• DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded (FFPE) tissues followed by targeted sequencing

  To overcome the challenges of low DNA yields, degraded DNA by formalin fixation and diluted signal of genomic aberrations by non-carcinoma components in the heterogeneous FFPE samples, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from 9 primary and metastatic breast cancer and 3 primary ovarian high-grade serous carcinomas. This was followed by a targeted panel for somatic mutation and sCNA analysis (7 samples), subject to cell availability. Mutation analysis was performed successfully in 6/7 samples and somatic mutations were detected in all of them.

  Dataset EGAD50000001899

• Idiopathic Scoliosis (SNP-array & WES study)

  This study aimed to investigate the genetic basis of severe idiopathic scoliosis (IS) using whole exome sequencing (WES) and SNP array methods. We intended to identify structural and point genetic variations contributing to the development of IS. By analyzing intraoperatively collected articular processes (AP) and blood (BL) samples from 70 unrelated individuals with IS, we sought to uncover pathogenic copy number variants (CNVs), regions of homozygosity (ROH), and single-nucleotide variants (SNVs) linked to the condition. EGAD00001015758

  Study EGAS00001008152

• Multi-omics analysis reveals immune programs delineating disease severity in extrapulmonary tuberculosis

  This study investigates the immune response in extrapulmonary tuberculosis (EPTB) using a combination of bulk and single-cell RNA sequencing. Hierarchical clustering of patient transcriptomes identified three distinct levels of disease severity, uncovering immunological pathways involved in disease progression, including interferon and IL-1β-mediated signaling. The findings also led to the development of a diagnostic gene expression signature for both EPTB and pulmonary TB, offering potential improvements in TB diagnosis and treatment.

  Study EGAS50000000668

• Whole Transcriptome Sequencing of NXF1 or CRM1 depleted Cell

  mRNA exporters, NXF1 and CRM1 are known to function in mRNA export. However, since each target mRNA has not been identified genome-widely, it is not clear whether they export exclusive mRNA subsets. To reveal this point, we prepared the nuclear and the cytoplasmic RNAs under either exporter inhibited condition and carried out RNA-seq. In these experiments, we also focused in the export machinery of aberrant transcripts that usually retained and decayed in the nucleus.

  Study JGAS000294

• An efficient procedure for the recovery of DNA from formalin-fixed paraffin-embedded tissue sections

  We investigated the effects of different incubation temperatures and duration, and formalin scavenger (Tris) concentrations on the recovery of DNA from FFPE tissue sections. We optimized the conditions for preserving the integrity and maximizing the yield of DNA from FFPE tissue sections. Furthermore, DNA obtained using the optimized procedure was compared with that obtained using a commonly used extraction procedure with regard to their performance in whole-genome and targeted gene panel sequencing.

  Study JGAS000520

• Whole exome sequencing of Zimbabwean patients with suspected Mendelian disorders

  This study presents whole exome sequencing data from Zimbabwean individuals with suspected Mendelian disorders, including sickle cell disease, Fanconi anemia, haemophilia, and muscular dystrophy. The dataset includes both affected individuals and family members to support inheritance-based analyses. Variant calling was performed using the Illumina DRAGEN pipeline, with downstream variant prioritisation and interpretation conducted using the Zi-Mendelian bioinformatics pipeline. This study supports rare disease genomics and precision medicine efforts in African populations.

  Study EGAS50000001708

• Whole_Genome_Sequencing_of_JK_Family

  In collaboration with Dr David Savage, we have identified a patient with a very unusualphenotype, lacking almost all visceral fat, but showing a massive accumulation of white fattissue behind her neck and significantly elevated liver fat.Whole exome sequencing of the proband and her unaffected parents and brother has beenrun previously, however no causative variant has been found and the sequencing coveragewas generally poor. We propose to conduct whole genome sequencing of all 4 familymembers at a depth of 30X.

  Study EGAS00001001323

• Sequencing of liver cancer cell lines

  Liver cancer is a dreadful disease with limited therapeutic options. How to translate genomic findings into biomarkers and precision treatment is challenging. A large cell line-based platform was established, termed as Liver Cancer Model Repository. Heterogeneities in patients were faithfully recapitulated by 81 liver cancer cell lines at genomic and transcriptomic levels. This platform provides a rich resource and models to study cancer drivers and drug responses in liver cancer.

  Study EGAS00001002237

• Complex structural variation patterns in pediatric solid tumors

  In this study, we performed systematic characterization of chromoplexy, chromothripsis and extrachromosomal DNA across five types of pediatric solid tumors: neuroblastoma, Ewing sarcoma, Wilms tumor, hepatoblastoma and rhabdomyosarcoma. Almost half of all tumors had at least one complex SV and we identified candidate pathogenic events that affect genes or chromosomal alterations known to be relevant in these cancer types. In conclusion, complex SVs are prevalent and highly pathogenic in pediatric solid tumors.

  Study EGAS00001007565

• Molecular subtypes of malignant peritoneal mesothelioma

  Malignant Peritoneal Mesothelioma (PeM) is a rare but frequently fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no targeted therapies for PeM yet exist. This study performs comprehensive integrative analysis of genome, transcriptome, and proteome of treatment-naive PeM tumors with the aim of identifying mesothelioma-related molecular alterations and potentially identifying novel treatment strategies.

  Study EGAS00001002820

• WGS/RNA-seq pair of an inflammatory hepatocellular adenoma (IHCA)

  A 49 years old female patient consulted for diarrhea, rectal bleeding and lower limbs edema and was diagnosed with systemic AA amyloidosis. An inflammatory hepatocellular adenoma was further identified and resected, resulting in the improvement of amyloidosis-related symptoms. Molecular analyses of the tumor tissue revealed a somatic chromosome rearrangement responsible for interleukin-6 mRNA stabilization leading to an inflammatory acute response with serum amyloid A protein production by both neoplastic and normal hepatocytes.

  Study EGAS00001003025

• APCDR AGV Project: Whole genome sequencing of 3 African populations (curated data)

  The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA. As part of the AGVP we sequenced 3 African populations; Baganda from Uganda (4x), Zulu from South Africa (4x), Gumuz, Wolayta, Oromo, Somali and Amhara from Ethiopia (8x).

  Study EGAS00001000960

• Immunogenomic landscape of hematological malignancies

  We integrated over 8,000 transcriptomes and over 2,000 samples with multilevel genomic data of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival. For more detailed follow-up analyses in acute myeloid leukemia (AML), single-cell RNA sequencing was performed on 8 AML bone marrow samples at diagnosis to profile the phenotypes of blasts and infiltrating immune cells in different disease subtypes.

  Study EGAS00001004444

• APCDR AGV Project: The African Genome Variation Project(dense array genotyping data)

  The African Genome Variation Project (AGVP) aims to provide a global resource to understand population diversity and help design, implement and interpret genomic studies in sub-Saharan Africa (SSA), and worldwide. The AGVP represents dense genotyping data on 1,481 individuals from 18 ethno-linguistic groups and low coverage whole genome sequencing data on 320 individuals from 7 ethno-linguistic groups in SSA.

  Study EGAS00001000959

• Carcinoma of the oral tongue (OTSCC) genomic landscape characterisation

  Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smokers. Here, we sought to characterize the OTSCC genomic landscape and to determine factors that may delineate the genetic basis of this disease, inform prognosis and identify targets for therapeutic intervention.

  Study EGAS00001001329

• Functional analysis of GATA2 synonymous mutations

  Germline mutations in SAMD9 and SAMD9L (SAMD9/9L) genes predispose to myelodysplastic syndromes (MDS) and show high prevalence in pediatric MDS with monosomy 7. Here, we studied an international cohort of children with primary MDS to assess the prevalence, hematological features, genetics, clonal evolution and clinical outcome in patients with germline SAMD9/9L mutations compared to pediatric MDS with either germline GATA2 mutations or pediatric MDS with wildtype status in SAMD9/9L and GATA2 genes

  Study EGAS00001003817

• Preservation of stemness in high-grade serous ovarian cancer organoids requires low Wnt environment

  High-grade serous ovarian cancer (HGSOC) likely originates from the fallopian tube (FT) epithelium, but advanced stages are mostly found outside the FT. We used ex-vivo cultures of HGSOC and knock-out of tumor suppressors in FT organoids to study changes in epithelial cells and niche requirements for normal and transformed FT cells. We found that transformed cells require BMP signaling and are growth arrested in Wnt rich medium.

  Study EGAS00001003821

• Genetic regulation of RNA splicing in human pancreatic islets

  Genetic variants that influence transcriptional regulation in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D). For many susceptibility loci, however, the mechanisms are unknown. To this end, we examined splicing and gene expression QTLs (sQTLs and eQTLs) in pancreatic islets from 399 human donors from publicly available cohorts and in-house data. Here we provide newly generated RNA-seq data and genotyping array data from 101 donors.

  Study EGAS00001006440

• Whole blood transcriptomic analysis of ANCA-associated vasculitis

  Whole blood mRNA sequencing from 30 patients with AAV (granulomatosis with polyangiitis/GPA, n=22) and microscopic polyangiitis (MPA, n=8) combined with functional enrichment and network analysis for aberrant pathways. Key genes and pathways were validated in an independent cohort of 18 AAV patients. Co-expression network and hierarchical clustering analysis, identified molecular endotypes. Multi-level transcriptional overlap analysis to SLE was based on our published data from 142 patients.

  Study EGAS00001006704

• Cell of Origin and Early Evolution of Leukemia in Down Syndrome

  To investigate the mechanism by which GATA1s and STAG2 deficiency contribute to Down Syndrome leukemogenesis, specifically within the propagating CD34/CD117 cell fractions from primary xenografts, we carried out transcriptional and epigenetic profiling by RNAseq and ATACseq. The chromatin accessibility landscape was compared to bulk ATACseq of individually sorted N-FL HSPC subpopulations. To investigate the mechanism underlying the synergy between T21 and GATA1s in driving preleukemia development, we analyzed the binding occupancy of GATA1. We performed Cut&Run assays to profile genome-wide GATA1 binding sites and also to quantify binding changes upon GATA1s editing in N-FL and T21-FL CD34+ enriched HSPCs. Lastly, we profiled miRNAs from N-FL and T21-FL CD34+ enriched HSPCs by miRNA-Seq.

  Dataset EGAD00001006555

• NGS data of human NES cells and tumors

  Raw RNA-seq data for WT and 2 Gorlin NES cells, tumors derived from MYCN mis-expressed WT NES cells, tumors derived from Gorlin NES cells, and tumors derived from Gorlin NES cells transduced with mutant DDX3X (R351W and R534S) and CRISPR/Cas9 targeting GSE1 (each sample has 3 replicates/tumors except Gorlin NES cell tumors have 4). Raw whole exome sequencing data for WT and Gorlin 1 NES cells, tumors derived from MYCN mis-expressed WT NES cells, and tumors derived from Gorlin NES cells (each sample has 3 replicates/tumors except Gorlin NES cell tumors have 4). Raw data for amplicon sequencing of GSE1 and KDM3B at regions targeted by CRISPR/Cas9 in Gorlin NES cells.

  Dataset EGAD00001004990

• Estimating transcription factor variability in PC-9 cells using scRNA-seq

  PC-9 cells were barcoded following protocol from Chang et al. Nature Biotech. 2021, which does not affect downstream analysis. PC-9 cells were trypsinized into single-cell suspensions and processed using Chromium Single Cell Gene Expression 3’ Library and Gel Bead Kit V2.0 following the manufacturer’s instructions (10X Genomics). Cells were counted and checked for viability using Vi-CELL XR cell counter (Beckman Coulter), and then injected into microfluidic chips to form Gel Beads-in-Emulsion (GEMs) in the 10X Chromium instrument. Reverse transcription was performed on the GEMs, and RT products were purified and amplified. Expression libraries were made from the cDNA and profiled using the Bioanalyzer High Sensitivity DNA kit (Agilent Technologies) and quantified with Kapa Library Quantification Kit (Kapa Biosystems). Illumina HiSeq2500 (Illumina) was used to sequence the libraries.

  Dataset EGAD00001011041

• Organ maturation in preparation for birth (Peds RFA) to develop a tissue resource and a single-cell atlas of organ development and maturation for dissemination among the scientific and clinical community: RNA (2025-10-14)

  Knowledge about abnormal organ development is important to understand pathology and to develop novel treatment approaches for individuals with congenital and acquired disease. Most of our current understanding is based on examination of tissues from the embryo and early foetus, collected from women undergoing termination of pregnancy in the first trimester (third) of pregnancy. There is very little known about normal and abnormal organ development from a developmental perspective during the crucial last two-thirds of pregnancy when much remodelling of foetal tissues occurs. This study will generate a single-cell atlas of late-foetal lungs, blood, heart, bone and immune organs. . This dataset contains all the data available for this study on 2025-10-14.

  Dataset EGAD00001015737

• BLUE CORAL: Biology and Longitudinal Epidemiology of PETAL COVID-19 Observational Study

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.Available Data: Long Term Follow-up data has been added with version 2. Biospecimens: Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from PETAL BLUE CORAL include: Bronchial Lavage, Plasma, Tracheal Aspirate, Urine, Whole Blood Buffy Coat, DNA, Plasma, Serum, Urine, and Whole Blood. Please note that use of biospecimens is tiered for both non-genetic and genetic research.Objectives: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19–related hospitalization.Background: For many individuals, the effects of COVID-19 persist after the acute phase and result in prolonged symptoms and disability. This has led to widespread efforts to characterize the epidemiologic characteristics of such post-COVID-19 sequelae. However, accurate data were limited, hindering the ability to counsel patients, caregivers, and policy makers and to plan relevant recovery-focused clinical research. Thus, the BLUE CORAL study was intended to address the knowledge gaps and provide critical data to help guide clinical care, public health, and scientific efforts.Participants: A total of 1376 COVID-19 patents were enrolled, with 825 (444 male, and 379 female) that completed at least one follow-up survey.A subset of the BLUE CORAL adult participants were enrolled in the extension study, FIRE CORAL. FIRE CORAL was a multicenter prospective cohort study of participants recovering from COVID-19 disease after discharge from the hospital. Design: BLUE CORAL was a prospective cohort study. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Posthospital surveys were administered by trained interviewers in English or Spanish to patients or their proxies at 1, 3, and 6 months after enrollment. Cardiopulmonary symptoms were assessed using the Airways Questionnaire 20, the Kansas City Cardiomyopathy Questionnaire, and the Seattle Angina Questionnaire. Fatigue was assessed using the Patient Health Questionnaire-9. Disability was assessed by self-report of limitations in activities of daily living (ADLs) or instrumental activities of daily living (IADLs). Financial problems were assessed using the World Health Organization Disability Assessment Schedule 2.0 question and questions regarding job changes, time off work, and insurance coverage developed with the Mi-COVID-19 study using qualitative interviews. Quality of life was measured using the European Quality of Life 5-dimension 5-level instrument.The primary outcomes were new or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Symptoms that were not present before hospitalization or specifically reported as increased in severity were counted as new or worsened. Conclusions: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.

  Study phs003419

• Center for Craniofacial and Dental Genetics: Study of Dental Caries and Cleft Lip/Palate in Guatemala

  This study provides an opportunity to investigate the genetics of both dental caries and orofacial clefts (OFCs) in one set of families ascertained in Guatemala. 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). Furthermore this study brings together multiple research priorities of the University of Pittsburgh Center for Craniofacial and Dental Genetics (www.ccdg.pitt.edu). A genome-wide panel of 610,000 SNPs was genotyped at the Broad Institute to be comparable to our other pertinent GENEVA studies that are also part of dbGaP (dbGaP accession number phs000095, "Dental Caries: Whole Genome Association and Gene x Environment Studies" and dbGaP accession number phs000094, "International Consortium to Identify Genes and Interactions Controlling Oral Clefts"). The goal of this study is to investigate genetic determinants to dental caries and to OFCs in a novel study population. To date, most genetic studies of dental caries have been conducted in Caucasians, and of OFCs in Caucasians and Asians. The Guatemalan population under study is rural and ethnically mixed with a high proportion of Native-South-Americans. Thirty-six Guatemalans from this dataset were also part of the recent GWAS studies of cleft lip and cleft palate (Beaty et al., 2010 and 2011, dbGaP Study Accession: phs000094, "International Consortium to Identify Genes and Interactions Controlling Oral Clefts"). In addition to the families ascertained in Guatemala, some subjects were genotyped with this cohort to augment the data in the parent GENEVA study (Dental Caries: Whole Genome Association and Gene x Environment Studies, dbGaP accession number phs000095), in particular individuals from the IOWA and PITT GENEVA study sites. Their data are available with the parent study. 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. 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%. In our study populations of families, we also estimated caries heritability as approximately 54%-70% of variation in primary dentition caries scores and 35%-55% in the permanent dentition (Wang et al., 2010). Orofacial clefts (OFCs), particularly cleft lip with or without cleft palate (CL/P) and isolated cleft palate (CP) are a major public health problem, affecting one in every 500-1000 births worldwide thus representing the most common facial birth defect and one of the most common of all congenital anomalies. CL/P is a major structural birth defect that is notable for significant lifelong morbidity and complex etiology. The extensive psychological, surgical, speech and dental involvement emphasize the importance of understanding the underlying causes of CL/P. Therefore, many research groups have attempted to elucidate the etiology of CL/P, with some recent success by our research group and others (see Beaty et al., 2010, 2011; Dixon et al., 2011). It is clear that CL/P can occur as part of Mendelian syndromes, that certain chromosomal abnormalities include CL/P in the phenotype, and that certain teratogens can increase the risk of having an offspring with CL/P. However, phenotypes of known etiology comprise only a small portion of all individuals with a CL/P or CP, and the major focus of research into OFCs is to develop an understanding of the etiology of nonsyndromic (NS) forms of clefting. A major focus of the University of Pittsburgh CCDG has been to study additional phenotypes within nonsyndromic OFC families in order to identify sub-clinical expressions of OFC risk genes or risk variants, e.g. SNPs (see Weinberg et al., 2006). A detailed oral exam is conducted as part of these extended phenotypic studies, including a dental caries exam. Note that although there are some reports in the literature of higher caries experience in individuals with clefts, the most recent meta-analysis of those literature reports concluded that individuals born with these defects do not have a higher frequency of caries (Hasslöf and Twetman, 2007). Notably, we investigated the association of CL/P and caries in three of our study populations (including part of the Guatemalan population in this GWAS study) and also found no increase in caries rates of CL/P cases versus controls (Jindal et al., 2011). 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 and oral clefts through large-scale genome-wide association studies of well-characterized Guatemalan families and individuals. Genotyping was performed at the Broad Institute of MIT and Harvard. 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.

  Study phs000440

• Center for Common Disease Genomics [CCDG] - Cardiovascular ATVB: Atherosclerosis Thrombosis and Vascular Biology

  Italian Atherosclerosis Thrombosis and Vascular Biology study is a prospective, nationwide, case-control study involving 125 coronary care units in Italy. The cases were patients who were hospitalised for a first MI before the age of 45 years and underwent coronary angiography. Acute MI was defined as resting chest pain lasting more than 30 minutes, accompanied by persistent electrocardiographic changes, and confirmed by an increase in total creatine kinase or in the MB fraction to more than twice the upper normal limits. The controls were healthy subjects without a history of thromboembolic disease who were unrelated to the patients, but individually matched with them by age, gender and geographical origin. They were enrolled from among the blood donors or staff of the same participating hospitals. Recruitment of cases and controls took place between 1994 and 2007. This site hosts data from ~60 whole exomes.

  Study phs001592

• Notch Signaling and Efficacy PD-1/PD-L1 Blockade in Relapsed Small Cell Lung Cancer

  Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine (NE) cancer that accounts for approximately 15% of all lung cancer, with an annual incidence of more than 34,000 in the United States alone. SCLC is characterized by loss of function of p53 and RB and high tumor mutational burden, which suggests that these tumors could be immunogenic and respond to immune checkpoint blockade (ICB). However, the benefit from ICB in an unselected SCLC population is modest. In this study, we evaluated the genomic features associated with clinical outcomes in relapsed SCLC to gain insight into the underlying mechanisms of ICB response. Exome, RNA and TCR sequencing data from a prospective clinical trial of relapsed SCLC treated with durvalumab and olaparib and RNA-sequencing data for second cohort of relapsed SCLC cohort treated with nivolumab are included.   

  Study phs002176

• The Two Sister Study: A Family-Based Study of Genes and Environment in Young-Onset Breast Cancer

  To study environmental and genetic causes of young onset breast cancer, we recruited women who had been young when recently diagnosed (under age 50 and within 4 years of enrollment), and had been identified as potentially eligible by a sister who was already participating in the ongoing Sister Study. The unaffected sister had already provided consent, questionnaire-based information and DNA (blood-based) when she enrolled in the Sister Study. Her case sister then provided comparable questionnaire-based information and DNA via a mail-back saliva collection kit. To enable family-based analyses, parents were also asked to (only) provide consent and a saliva sample. Because the cases were young-onset, most parents were alive, but unavailability of the parents was not a basis for exclusion. The study was funded in part by Susan G. Komen for the Cure.

  Study phs000678

• Natural History of and Genetic Modifiers in Spinocerebellar Ataxias

  Spinocerebellar ataxias (SCA) are genetic neurological diseases that cause imbalance, poor coordination, and speech difficulties. There are different kinds of SCA and this study will focus on types 1, 2, 3, and 6 (SCA 1, SCA 2, SCA 3, also known as Machado-Joseph disease and SCA 6). The diseases are rare, slowly progressive, cause increasingly severe neurological difficulties and are variable across and within genotypes. The purpose of this research study is to bring together a group of experts in the field of SCA for the purpose of learning more about the disease. The research questions are: How does the disease progress over time? What are the best ways to measure disease progression? Do some genes, other than the gene that is abnormal in the SCA disease, have any effect on the way the disease behaves?

  Study phs001332

• Genetic Analysis of Psoriasis and Psoriatic Arthritis: GWAS of Psoriatic Arthritis

  This study is a genome-wide study of genetic associations with psoriatic arthritis (PsA), an inflammatory musculoskeletal condition that develops in up to 30% of people who have chronic psoriasis skin lesions. 1,526 cases affected with psoriatic arthritis and 1,508 unaffected controls were recruited and typed on the Illumina HumanOmni1-Quad BeadChip array. After application of quality control measures to both samples and SNPs, genotypes for 791,217 autosomal SNPs were available for 1,430 PsA cases and 1,417 controls. Imputation using phased haplotypes for the EUR subpopulation of release 3, phase 1 of the 1000 Genomes Project as a reference, resulted in genotypes for 11,532,644 SNPs and 918,976 indels passing our imputation quality threshold (Mach r2 ≥ 0.3) that were available for downstream analysis. Association at a genome-wide threshold of significance was found for five regions (near genes TNIP1, IL12B, HLA-C, TRAF3IP2, and TYK2).

  Study phs000982

• Association Between Telomere Length and Falciparum Malaria Endemicity in Sub-Saharan Africans

  The goal of this study was to identify the genetic and environmental drivers of telomere length variation in an ethnically diverse African cohort. It comprises 1,818 participants from Cameroon, Tanzania, Ethiopia, and Botswana. For each participant, leukocyte telomere length was measured using the Southern blotting of the terminal restriction fragment methodology. 1,758 of the individuals with phenotype data also had genetic data, and these individuals were subjected to a genome-wide association study which accounted for age, sex, and genetic relatedness. Individuals were genotyped on one of two genotyping arrays (Illumina Infinium Omni5 array or Illumina H3Africa consortium array). Genetic datasets were merged, and missing genotypes were imputed for a final genetic dataset of 11,001,107 genetic variants. Correlations between telomere length and a variety of environmental factors, including malaria endemicity, were also examined in this study.

  Study phs003567

• Multiplexed scRNA-Seq Reveals Cellular and Genetic Correlates of SLE

  Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and cell states associated with SLE remains incomplete. We profiled over 1.2 million PBMCs (160 cases, 98 controls) with multiplexed single-cell RNA-seq (mux-seq). Cases exhibited prominent expression of type-1 interferon-stimulated genes (ISG) in monocytes, reduction of naïve CD4+ T cells that correlated with monocyte ISG expression, and expansion of repertoire-restricted cytotoxic GZMH+ CD8+ T cells. Cell-type-specific expression features accurately predicted case-control status and stratified patients into two molecular subtypes. We integrated dense genotyping data, mapping cell-type-specific cis-eQTLs and linked known and novel SLE-associated variants to cell-type-specific gene expression. These results demonstrate mux-seq as a systematic approach to characterize cellular composition, identify transcriptional signatures, and annotate genetic variants associated with SLE.

  Study phs002812

• Tissue-specificity and co-expression analyses identify human long non-coding RNAs related to inherited retinal disease genes

  The role of long non-coding RNAs (lncRNAs) in biological and pathological processes is still poorly understood. In this study, we aimed to identify lncRNAs that potentially contribute to retinal biology and Inherited Retinal Disease (IRD) by using two complementary strategies, tissue-specificity and location in topologically associating domains (TADs) containing IRD genes on one hand, and co-expression analyses on the other, applied to human retinal omics datasets. This combined approach resulted in the selection of 11 Retina Enriched IRD-gene Related (REIR) lncRNAs, one of which is novel. In-depth in silico and experimental characterization of REIRs identified novel REIR isoforms and confirmed retina-predominant (often photoreceptor-specific) expression as well as predicted functional association with visual function. Long-read direct cDNA sequencing (ONT) of three post-mortem human retina samples was used to delineate the novel REIR isoforms.

  Study EGAS50000000963

• The Formation and Propagation of Human Robertsonian Chromosomes

  Robertsonian chromosomes are a type of variant chromosome found commonly in nature. Present in one in 800 humans, these chromosomes can underlie infertility, trisomies, and increased cancer incidence. Recognized cytogenetically for more than a century, their origins have remained mysterious. Recent advances in genomics have allowed us to assemble three human Robertsonian chromosomes completely. We identify a common breakpoint and epigenetic changes in centromeres that provide insight into the formation and propagation of common Robertsonian translocations. Further investigation of the assembled genomes of chimpanzee and bonobo highlights the structural features of the human genome that uniquely enable the specific crossover event that creates these chromosomes. Resolving the structure and epigenetic features of human Robertsonian chromosomes at a molecular level will pave the way to understanding how chromosomal structural variation occurs more generally, and how chromosomes evolve.

  Study phs003920

• Anaplastic oligodendroglioma exome and RNA sequencing data

  Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. 80% of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frame shift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumor type. Our analysis provides further insights into the unique and shared pathways driving AO.

  Study EGAS00001001209

• Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML

  This study assessed molecular determinants of response in a cohort of patients with AML that were treated with venetoclax in combination with either DNA methyltransferase inhibitors or low dose cytarabine. RNA sequencing was performed on 31 patients from three different response classes [10 Group A - Durable remission (n=10), Group B - Relapsed (n=10) and Group C - Refractory (n=11)]. Library preparation and sequencing was performed at the Australian Genome Research Facility, using the Truseq Stranded mRNA library kit. Technical and batch replicate samples are included, and these replicates are designated in the sample name. Gene count data are provided with the original publication. The use of the sequencing data is subject to a data transfer agreement and is restricted to ethically approved research into blood cell malignancies and cannot be used to assess germline variants.

  Study EGAS00001003820

• Targeting AXL Kinase Uniquely Sensitizes Therapy-Insensitive Leukemic Stem and Progenitor Cells to Venetoclax Treatment in Acute Myeloid Leukemia

  The abundance of genetic abnormalities and phenotypic heterogeneities in AML pose significant challenges to developing improved treatments. Here we demonstrated that a key GAS6/AXL axis is highly activated in AML patient cells, particularly in leukemic stem cells. We developed a potent, selective AXL inhibitor that has excellent pharmaceutical properties and efficacy against preclinical patient-derived xenotransplantation models of AML. Importantly, inhibition of AXL sensitized AML stem/progenitor cells to venetoclax treatment, with strong synergistic effects in vitro and in vivo. Mechanistically, single-cell RNA-sequencing and functional validation studies uncovered that AXL inhibition or in combination with venetoclax potentially targets intrinsic metabolic vulnerabilities of AML stem/progenitor cells, which shows a distinct transcriptomic profile and inhibits mitochondrial oxidative phosphorylation. These findings have direct translational impact on the treatment of AML and other cancers with high AXL activity.

  Study EGAS00001004663

• Open Targets 020 Epigenomes of Cell Lines (2018-10-23)

  There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. The CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. Multiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ . This dataset contains all the data available for this study on 2018-10-23.

  Dataset EGAD00001004416

• Integrated clinical, whole genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer

  We report the first combined analysis of whole genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole genome and transcriptome sequence was obtained from 9 anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 years prior to death. Transcriptome analysis revealed increased expression of AR-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only 1 of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today given this knowledge, use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations is critical for actionability, and can only be determined through analysis of multiple sites of metastasis. Our findings suggest that a large set of deeply analyzed cases could serve as powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials.

  Dataset EGAD00001001869

• Reference Epigenomes and Regulatory Landscape of CLL

  Analysis of the reference epigenomes and regulatory landscape of CLL as a whole and its major clinico-biological subtypes (with mutated and unmutated IGHV) in the light of the normal B-cell differentiation. We have extensively characterized the reference epigenomes of seven primary chronic lymphocytic leukemia samples (CLLs) with mutated (n=5) and unmutated IGHV (n=2) as well as several mature B-cell subpopulations (naive B cells from blood and tonsil, germinal center B cells, memory B cells and plasma cells from tonsil) using genome-wide maps of six histone marks (H3K4me3, H3K4me1, H3K27ac, H3K36me3, H3K9me3 and H3K27me3), DNA accessibility (ATAC-seq), DNA methylation (whole-genome bisulfite sequencing) and gene expression (RNA-seq). Furthermore, we have mapped the regulatory chromatin landscape of 100 additional CLL cases using chIP-seq of H3K27ac and ATAC-seq and linked these data to additional layers of information (whole-genome and/or whole-exome sequencing (WGS/WES), RNA-seq and DNA methylation microarrays) studied in the context of the International Cancer Genome Consortium (ICGC).

  Dataset EGAD00001004046