1567 results for "Sweden+NDA+enforceability+one+party+signed"

in 31.03 milliseconds.

• Microsatellite unstable colorectal cancers

  Immune escape has been recognised as one of the hallmarks of cancer. Overcoming this immunomodulatory process by tumour cells has become a major therapeutic target. Here we utilize organoid technology to study immune-cancer interactions and assess immunomodulation by colorectal cancer (CRC). Transcriptional profiling and flow cytometry revealed that organoids maintain differential expression of immunomodulatory molecules present in primary tumours. Finally, we established a method to model antigen-specific epithelial cell killing and cancer immunomodulation in vitro using CRC organoids co-cultured with cytotoxic T cells. Our method may serve as a first step to rebuilding the tumor microenvironment in vitro.

  Study EGAS00001003366

• Illumina Human OmniExpress genotyping data from the Cretan Greek isolate collection HELIC MANOLIS

  Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina Human OmniExpress BeadChip array. The HELIC (Hellenic Isolated Cohorts) MANOLIS (Minoan Isolates) collection focuses on Anogia and surrounding Mylopotamos villages. Recruitment of this population-based sample was primarily carried out at the village medical centres. All individuals were older than 17 years and had to have at least one parent from the Mylopotamos area. www.helic.org **The data may not be used for population genetics analyses**

  Study EGAS00001000687

• Transcriptome sequencing of intravenous leiomyomatosis and uterine myoma

  Up to now, there are two hypothesis about the pathogenesis of the relationship of intravenous leiomyomatosis and uterine myoma. One theory suggests that the IVL comes from the smooth muscle cell in the vessel wall.The other theory indicates that the IVL derives from the uterine myometrium. However, limited to the technology, few studies have been deeply explore the underlying relation. In this study, we employ the RNA sequencing to explore the molecule relationship between IVL and uterus myoma. In order to identify the molecule relationship between IVl and uterine myoma we conducted transcriptome sequencing and bioinformaitc analysis

  Study EGAS00001002504

• Pulmonary atypical carcinoid multi-omic dataset on up to 42 tumours from same patient

  Pulmonary atypical carcinoid. DNA WES and RNA-Seq on 42 tumour samples collected at autopsy, 10x Chromium linked read whole genome sequencing on four tumours plus one normal sample, and targeted DNA sequencing on two clinical biopsies and one blood plasma sample. Note – RNA-Seq dataset features complex batch effect attributable to tissue processing artefacts, as described in "Complex patterns of genomic heterogeneity identified in 42 tumor samples and ctDNA of a pulmonary atypical carcinoid patient" - Robb et al., 2022 and detailed in Supplementary Table S3. Note – RNA-Seq dataset features complex batch effect attributable to tissue processing artefacts, as described in "Complex patterns of genomic heterogeneity identified in 42 tumor samples and ctDNA of a pulmonary atypical carcinoid patient" - Robb et al., 2022 and detailed in Supplementary Table S3.

  Dataset EGAD00001009296

• Genomic and Transcriptomic sequencing of neuroblastoma patient

  Genomic and Transcriptomic single-cell sequencing of neuroblastoma patient. Data represents one 96-well plate that was processed with G&T sequencing, resulting in genomic and transcriptomic data from the same single cells. Dataset contains 95 bam files containing the DNA sequencing data and 95 bam files containing the RNA sequencing data.

  Dataset EGAD50000000728

• APP p.V742L and control fibroblasts RNA-seq

  This dataset consists of 16 FASTQ file pairs containing 3` RNA-sequencing data of patient-derived fibroblasts and three age- and sex-matched control fibroblast lines (CTR1, CTR2, and CTR3). The patient and CTR1 fibroblast lines have three biological replicates, while CTR2 and CTR3 lines both have one sample. Each sample has two lanes.

  Dataset EGAD50000001825

• Whole-genome sequencing data of metastatic salivary gland cancer

  This dataset contains whole-genome sequencing data of three patients with metastatic salivary gland cancer who underwent autopsy to harvest tumor biopsies from spatially separated metastatic sites and biopsies from healthy skin as a control. Two patients had the subtype adenoid cystic carcinoma (patients 1 and 4) and one patient had the subtype myoepithelial carcinoma.

  Dataset EGAD50000002056

• Post Mortem brain data used in paper "Significant and pervasive effects of RNA degradation on Nanopore direct RNA sequencing"

  This dataset contains data used in the paper titled "Significant and pervasive effects of RNA degradation on Nanopore direct RNA sequencing. The data consists of one post mortem sample that was sequenced with direct RNA sequencing form Oxford Nanopore Technologies on a promethION flow cell.

  Dataset EGAD00001009308

• Epigenomics and Single-cell Sequencing Define Cellular Heterogeneity in Langerhans Cell Histiocytosis

  Epigenomic and transcriptomic analysis of Langerhans cell histiocytosis (LCH) biopsies. Single-cell RNA-seq (10x Genomics) of seven LCH biopsies. ATAC-seq data from four sorted cell populations (in duplicate) from one LCH biopsy.

  Dataset EGAD00001005280

• ICR Exome Optimization series

  Exome sequencing of 142 samples with corresponding Sanger sequencing results for 416 variants and 288 negative sites. DNA library preps prepared with Illumina TruSeq sample preparation kit. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers. Sequencing was performed with an Illumina HiSeq2000 (SBS Kit v3, one pool per lane) generating 2x101-bp reads.

  Dataset EGAD00001001462

• ICR1000 UK exome series

  Exome sequencing of 1000 samples from the UK 1958 Birth Cohort. DNA library preps prepared with Illumina TruSeq sample preparation kit. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers. Sequencing was performed with an Illumina HiSeq2000 (SBS Kit v3, one pool per lane) generating 2x101-bp reads.

  Dataset EGAD00001001021

• San Francisco Bay Area Latina Breast Cancer Study

  The genome-wide association study (GWAS) includes participants enrolled into two different studies. The first study, the San Francisco Bay Area Cancer Study (SFBCS) is a population-based case-control study of breast cancer conducted in the San Francisco Bay Area and included women ages 35-79 years from three racial/ethnic groups: Non-Hispanic whites, African Americans, and Hispanics/Latinas. For the GWAS, only Hispanic/Latina women were included. Women diagnosed with invasive breast cancer between 1995 and 2002 were identified through the Greater Bay Area Cancer Registry. Controls were identified by random digit dialing and were frequency-matched to cases by age in 5 year increments and by race/ethnicity. Hispanic/Latina ethnicity was assessed by self-report. 175 Hispanic/Latina cases and 307 Hispanic/Latina controls from the SFBCS had given adequate consent and provided biospecimens that were used in the GWAS to be included in this data submission. The second study is the Northern California site of the Breast Cancer Family Registry (NC-BCFR). This population-based family study recruited breast cancer cases ages 18-64 years diagnosed from 1995-2009 that were identified through the Greater Bay Area Cancer Registry. Cases included all women at increased genetic susceptibility for breast cancer who met one or more of the following criteria: (a) being diagnosed with breast cancer at age <35 years; b) having a personal history of ovarian cancer or childhood cancer; (c) being diagnosed with two different breast cancers (bilateral breast cancers), with the first one diagnosed at age <50 years; and d) having one or more first-degree relatives with breast cancer, ovarian cancer or childhood cancer. Cases not meeting these criteria were randomly sampled and racial/ethnic minorities were oversampled. Controls were recruited by random digit dialing and were matched by 5-year age increments and by race/ethnicity. For the current GWAS only Latina/Hispanic cases and controls were included. Latina/Hispanic ethnicity was assessed by self-report. 631 Hispanic/Latina cases and 61 Hispanic/Latina controls from the NC-BCFR had given adequate consent and provided biospecimens that were used in the GWAS to be included in this data submission.

  Study phs000912

• University of Utah Pelvic Organ Prolapse Disorder Study

  The overall purpose of this University of Utah Pelvic Organ Prolapse Disorder Study was to identify and localize predisposition genes contributing to pelvic organ prolapse (POP). POP cases recruited for this study were identified by one of three methods: high-risk POP pedigree cases, POP sister pairs, and surgically-treated POP cases reporting a family history of POP. High-risk POP pedigree cases were identified using the Utah Population Database (UPDB), a genealogy database of residents in Utah that has been linked to diagnostic ICD9 and CPT codes in medical records at the University of Utah and Intermountain Healthcare. We identified families with a significant excess number of POP cases compared to matched population rates and targeted these individuals for recruitment as well as any other POP cases in the family. POP sister pair cases were identified at the University of Utah Urogyncology clinic for women who had undergone POP surgery and also self-reported one or more sisters who were also surgically treated for POP. POP affection status of all sisters was confirmed either by physical examination or by chart review. Surgically treated-POP cases reporting a family history of POP were identified at the University of Utah Urogyncology clinic by self-report of a family history of POP. Efforts were made to recruit other affected family members and confirm affection status. To obtain DNA, subjects provided either a blood specimen or saliva. Medical records were reviewed by a urogynecologist and diagnostic information for pelvic organ prolapse and stress and overactive bladder were obtained. Collected DNA was genotyped and analyzed. To maintain confidentiality of the familial data, genetic data from only one subject per family has been submitted to dbGaP. Use of the University of Utah Pelvic Organ Prolapse Disorder Study data is limited to investigators studying pelvic floor disorders. These pelvic floor disorders include pelvic organ prolapse, urinary and anal incontinence, and other conditions related to weakening or injury to the muscles and connective tissue in the pelvis as a result of pelvic surgery, pregnancy, or vaginal delivery of a child. These data will be used only for research purposes related to pelvic floor disorders. They will not be used to determine the individual identity of any person or their relationship to another person or for research on non-disease traits.

  Study phs001439

• VESPA: Vanderbilt Electronic Systems for Pharmacogenomic Assessment

  The Vanderbilt Electronic Systems for Pharmacogenomic Assessment (VESPA) Project is a large electronic medical record (EMR)- and biobank-based initiative for translational pharmacogenomics discoveries. Key research resources utilized in this effort include the BioVU DNA databank and associated Synthetic Derivative database of clinical information, and software tools developed to identify drugs and clinical events using EHR-derived structured and unstructured ("free text") data. Cohorts include subjects with primarily drug-response phenotypes, and most cases and controls identified include three data types: ICD-9 codes, medication regimens, and medical test results. Advanced informatics methods, such as natural language processing, were also used for some phenotypes. Algorithms used event-sequence analyses to establish temporal relationships between drugs and phenotypes. Both cases and control algorithms excluded records that contained specific comorbidities and were refined to achieve positive predictive value (PPV) > 90%. For automated algorithms failing to meet this threshold, manual review was coupled with algorithms to validate that the included cases were true positives. A total of 11,639 subjects met phenotyping criteria for a least one of the 28 phenotypes investigated. Across all phenotypes cases and controls, 90% were reused as either a case or control for a least one other phenotype. Data are deposited for individual phenotypes in the VESPA substudies. Substudies: VESPA: Genome Wide Association Study of Serum Creatinine during Vancomycin Therapy and Vancomycin Pharmacokinetics - phs000894 VESPA: Genome Wide Study of Clinically Diagnosed Ace Inhibitor Cough - phs000992

  Study phs000991

• NHLBI GO-ESP: Lung Cohorts Exome Sequencing Project (Lung Health Study of Chronic Obstructive Pulmonary Disease)

  The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. The Lung Health Study I was a randomized multicenter clinical trial with 5887 participants carried out from October 1986 to April 1994, designed to test the effectiveness of smoking cessation and bronchodilator administration in smokers aged 35 to 60 with mild lung function impairment. Participants were randomly assigned to one of three groups: usual care, who received no intervention smoking intervention with the inhaled bronchodilator ipratroprium bromide smoking intervention with an inhaled placebo The effect of intervention was evaluated by the rate of decline of forced expiratory volume in one second (FEV1).

  Study phs000291

• Rapid Whole Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units

  Monogenic diseases are frequent causes of neonatal morbidity and mortality, and disease presentations are often undifferentiated at birth. More than 3,500 monogenic diseases have been characterized, but clinical testing is available for only some of them and many feature clinical and genetic heterogeneity. As such, an immense unmet need exists for improved molecular diagnosis in infants. Because disease progression is extremely rapid, albeit heterogeneous, in newborns, molecular diagnoses must occur quickly to be relevant for clinical decision-making. We describe 50-hour differential diagnosis of genetic disorders by whole-genome sequencing (WGS) that features automated bioinformatic analysis and is intended to be a prototype for use in neonatal intensive care units. Retrospective 50-hour WGS identified known molecular diagnoses in two children. Prospective WGS disclosed potential molecular diagnosis of a severe GJB2-related skin disease in one neonate; BRAT1-related lethal neonatal rigidity and multifocal seizure syndrome in another infant, identified BCL9L as a novel, recessive visceral heterotaxy gene (HTX6) in a pedigree, and ruled out known candidate genes in one infants. Sequencing of parents or affected siblings expedited the identification of disease gene in prospective cases. Thus, rapid WGS can potentially broaden and foreshorten differential diagnosis, resulting in fewer empirical treatments and faster progression to genetic and prognostic counseling. Reprinted from Saunders et. al, Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units. Sci. Transl. Med. 4, 154ra135 (2012; PMID: 23035047) with permission from AAAS.

  Study phs000564

• Extent and Significance of Bacterial DNA Integrations in the Human Cancer Genome

  The integration of exogenous DNA into the human genome can cause somatic mutations associated with oncogenesis. For example, the insertion of HPV DNA into human chromosomes is the single most important event leading to tumorigenesis in cervical cancer. It is also now preventable with vaccines against HPV. In contrast to viral DNA integrations, the instances and repercussions of bacterial DNA integration into the somatic human genome are less clear. Yet bacterial DNA integrations (BDI) found to be associated with tumorigenesis could also be prevented using therapeutics like vaccines that limit exposure to the bacteria. Previous analysis of publicly available sequencing data from the Cancer Genome Atlas (TCGA) showed BDIs from Pseudomonas spp. rRNA into the 5'-UTR of four proto-oncogenes as well as in Ig (the immunoglobulin gene) of gastric cancer samples. The original samples from TCGA were not available to validate these findings. Therefore, a different cohort of gastric cancer patients was identified in order to establish the presence BDIs. Whole exome sequencing was completed on seven tumor samples and six adjacent gastric samples, as well as one intestinal metaplasia sample and one non-atrophic gastritis sample. Four of those samples were also investigated with transcriptomics and whole genome sequencing. Given that 15-20% of cancers worldwide are linked to infections, more work is needed to understand the role of infectious agents in oncogenesis and the mechanisms underlying that role.

  Study phs001936

• Trisomy 21 Dosage Compensation Map (T21DoCoMap)

  Excess gene dosage from human chromosome 21 (HSA21), due to trisomy or translocation of HSA21 material, causes Down syndrome (DS). We derived trisomy 21 (T21) induced pluripotent stem cells (iPSCs) alongside otherwise isogenic euploid controls from mosaic DS fibroblasts (GM00260, first described in Lubiniecki et al., PMID: 225951) of the NIGMS genetic cell repository, to enable analysis of whole-chromosomal and individual gene dosage imbalance in the context of in vitro models of DS development. Virtual karyotyping (by Infinium CytoSNP-850k), and phased genotyping (by linked-read whole-genome sequencing) of the resulting iPSC lines provide a deeply-characterized genomic platform for dissection of HSA21 gene dosage. We apply this highly unique resource to allelic analysis of mRNA sequencing of iPSCs and differentiated neural lineages, and demonstrate its utility in the context of inducible HSA21 dosage compensation. To this end, we equipped one distinct HSA21 copy with a doxycycline-inducible XIST transgene, which endogenously silences one X in 46,XX females. Standard and allele-specific RNA-seq analysis confirms mono-allelic T21 silencing to be virtually complete and irreversible, further supported by DNA methylation data (Infinium methylEPIC). This full-length HSA21 map of phased single-nucleotide and insertion/deletion variants enables allele-specific applications for gene-level dissection T21 dosage effects. Because our XIST remains inducible in post-mitotic T21 neurons and astrocytes, we perform single-nuclei RNA-seq to demonstrate XIST efficiently represses genes even after terminal differentiation.

  Study phs002397

• UCSF Database for the Advancement of JMML - Integration of Metadata with Omic Data

  Juvenile myelomonocytic leukemia (JMML) is a rare and frequently fatal myeloproliferative/myelodysplastic disorder of early childhood with an estimated incidence of 1.2 cases per million. It is associated with a spectrum of diverse outcomes ranging from spontaneous resolution in rare patients to transformation to acute myeloid leukemia in others. The overwhelming majority of JMML patients (~95%) will harbor mutations in canonical Ras pathway genes, including NF1, NRAS, KRAS, PTPN11, and CBL. As Ras proteins are mutated in more than 30% of human cancers, the information gleaned from the study of JMML has provided insights into Ras signaling in cancer as well as a group of congenital diseases with tumor predispositions known as the “Rasopathies”. While oncogenic Ras is one of the most common mutations in human cancer, it remains one of the most vexing targets for efficacious therapy. To better understand this disease, a JMML tissue bank was established at UCSF that allows for consenting of subjects, biobanking of tissue and collection of follow up data from patients both locally and at other institutions. Through the collection and analysis of specimens, knowledge about the genetic, epigenetic, and biochemical basis of JMML has been gained. This integrated database will enable future JMML research, and importantly, additional Ras/MAPK pathway research by depositing linked, processed data to well annotated anonymized patients in an easily accessible online database

  Study phs002504

• RNA Transcriptomic and DNA Methylation Landscape in FTLD-TDP and Controls

  Frontotemporal lobar degeneration (FTLD) is one of the leading causes of dementia in individuals younger than 65 years, with the aggregation of TDP-43 as one of the most common forms of FTLD. FTLD-TDP is clinically, genetically and pathologically heterogeneous, with GRN and C9orf72 as the most common genetic forms (although more than 50% of the cases are genetically unexplained), and A, B and C as the most common pathological subtypes. To investigate the molecular differences between the different forms of FTLD-TDP, we performed bulk RNA sequencing (RNAseq) and reduced representation bisulfite sequencing (RRBS) from different brain regions of FTLD-TDP patients and controls. The RNAseq dataset includes samples from the frontal cortex of 149 individuals, comprising 127 FTLD-TDP cases (genetically unexplained types A (27), B (20) and C (22), 24 GRN mutation carriers, and 34 C9orf72 expansion carriers) and 22 controls. The RRBS dataset includes samples from the frontal cortex of 158 individuals —119 FTLD-TDP cases (genetically unexplained types A (25), B (24), and C (25), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 39 controls; and from the cerebellum of 151 individuals —113 FTLD-TDP cases (genetically unexplained types A (24), B (21), and C (23), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 38 controls. In total, the study consists of data from 183 unique individuals, with some overlap across the different datasets.

  Study phs004075

• Copy number profiling of putative cancer stem from pleural effusion aspirates from breast cancer patients

  A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. In pleural effusions malignant cells can be detected, which indicates a metastatic spread from the primary tumor site. Beside the usefulness for investigation of the metastatic process, it has been a source to isolate cells with putative cancer stem cell (CSC) properties. For this study, pleural effusion aspirate from 25 metastatic breast cancer patients were processed to establish in vitro culture. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were sorted for cancer stem cell populations ALDH1+ and CD44+CD24-/low and sphere forming efficiency of CSC and non-CSC subpopulation was determined. Unsorted cells had a higher potential to form spheres compared to CSC subpopulations. Subsequently, DNA was isolated from pleural effusions before and after cell sorting, to compare their copy number profiles generated by low-coverage whole genome sequencing to DNA from FFPE primary tumors or bone metastasis. Unbalanced profiles could be detected in four pleural samples before sorting, in two ALDH1+ sorted samples, in one CD44+CD24-/low and in all control samples. Additionally, spheroid culture from one pleural sample could be passaged on and was characterized. Therefore, pleural effusions are an appropriate media for enrichment of putative CSC. However, low-coverage sequencing is difficult due to low quantities of abnormal cells compared to normal cells.

  Study EGAS00001002343

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

  Starting point is one patient from which iPSC cells are created, some received a genome correction to be called iCtrl from those two batches (DJ1 and iCtrl). 3 independent differentiation to Microglia cells were done, named R1, R2 and R3. On top, growing conditions were either untreated or LPS, leading to the 12 samples.

  Dataset EGAD50000000291

• Single-cell RNA sequencing of 16 NPM1 mutated AML patients

  This dataset contains paired-end fastq files for single-cell RNA-seq of 16 NPM1 mutated AML patients. 19 fastq pairs are included, with two samples split into two lanes and a second (technical) replicate for one patient. Libraries were constructed using 10x Genomics Chromium Next GEM Single cell 3’ v3.1 and sequencing was performed using Illumina NovaSeq6000.

  Dataset EGAD50000000478

• WGS data of paediatric TCF3::PBX1 acute lymphoblastic leukemia (set2)

  The dataset includes FASTQ and BAM files from diagnostic and matched remission (control) samples of one TCF3::PBX1 ALL patient (ALLT-376). Sequencing library was made using PCR free-based WGS library preparation (PCR-), using NEB Next® Ultra™ DNA Library Prep Kit. Both diagnostic (90x) and remission (30x) samples were sequenced using HiSeq X.

  Dataset EGAD50000001795

• WGS data of pediatric TCF3::PBX1 acute lymphoblastic leukemia (set1)

  The dataset includes FASTQ and BAM files from diagnostic and matched remission (control) samples of one TCF3::PBX1 ALL patient (ALLT-335). Sequencing library was made using standard PCR-based WGS library preparation (PCR+), using NEB Next® Ultra™ DNA Library Prep Kit. Both diagnostic (90x) and remission (30x) samples were sequenced using HiSeq X.

  Dataset EGAD50000001796

• WGS data of paediatric BCR::ABL1 acute lymphoblastic leukemia

  The dataset includes FASTQ and CRAM files from diagnostic and matched remission (control) samples of one BCR::ABL1 ALL patient (ALLT-399). Sequencing library was made using PCR free-based WGS library preparation (PCR-), using Novogene NGS DNA Library Prep Set Kit (Cat No. PT004). Both diagnostic (90x) and remission (30x) samples were sequenced using NovaSeqX Plus.

  Dataset EGAD50000002185

• WGS data of paediatric ETV6::RUNX1 B cell acute lymphoblastic leukemia (set2)

  The dataset includes FASTQ and CRAM files from second relapse and matched remission (control) samples of one ETV6::RUNX1 ALL patient (ALLK-104). Sequencing libraries were made using using NEBNext® Ultra™ II DNA Library Prep Kit (Cat No. E7645). Both second relapse (90x) and remission (30x) samples were sequenced using Illumina NovaSeq 6000.

  Dataset EGAD50000002286

• Whole Exome Sequencing of Mixed Histology Lung Cancer

  We conducted whole-exome sequencing (WES) and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histologic patterns including 6 LUAD, 6 LCNEC, 3 SCLC, 3 LUSC, and one poorly differentiated NSCLC-NOS.

  Dataset EGAD00001007076

• ChIP-seq in colorectal cancer and paired adjacent normal mucosa

  This dataset includes ChIP-seq data for H3K27ac and H3K4me1 on 20 paired samples of colorectal cancer and adjacent normal mucosa. One tumor sample that failed QC is not available.

  Dataset EGAD00001007707

• Nuclease deficiencies alter plasma cell-free DNA methylation profiles (Human samples)

  The dataset contains 2x75bp paired-end sequencing data in DNASE1L3-deficient human subjects. We performed bisulfite sequencing of plasma samples from three DNASE1L3-deficient subjects and one heterozygous parent to investigate how nuclease deficiencies alter plasma cell-free DNA methylation profiles.

  Dataset EGAD00001007750

• Long read mRNA sequencing of blood cells exposed to different immune stimuli

  Long-read (PacBio) RNA sequencing dataset of in vitro stimulated PBMC cells. 5 samples consisting of 1 RPMI control and 4 stimulus conditions (lipopolysaccharide (LPS), polyI-polyC, S. aureus and C. albicans) all originating from one donor. Files are raw BAM format files generated by Sequel 2 machine.

  Dataset EGAD00001009998

• PIK3R4 (VPS15)

  WES of human: A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi WES (Agilent SureSelect All Exon XT2 50 Mb kit) has been realized on three affected siblings (II.1, II.3, II.5) and one healthy sister (II.4). Raw data (BAM files) are provided: - II.1.aligned.sorted.dedup.realign.recal.bam - II.3.aligned.sorted.dedup.realign.recal.bam - II.5.aligned.sorted.dedup.realign.recal.bam - II.4.aligned.sorted.dedup.realign.recal.bam

  Dataset EGAD00001002736

• Exome sequencing data

  Exome sequencing fastq files from 6 mutation carriers and 5 non-carriers from 2 families. One µg DNA was used for library preparation using the TruSeq DNA LT Sample Prep Kit v2 according to the manufacturer’s instructions (Illumina). Hybridization was performed using Nimblegen SeqCap EZ Exome v3 (Roche) and Paired-end Sequencing (2x100 bp) on the Illumina HiSeq 2000 with TruSeq v3 chemistry (Illumina).

  Dataset EGAD00001003745

• exome sequence of female patients suffering from Ovarian Meiotic Defects

  Exome sequencing was performed on 15 unrelated female patients suffering from primary infertility due to Ovarian Meiotic Defects (OMD). Each reference number corresponds to one of the tested subject. DNA was extracted from Saliva using Oragene saliva DNA collection kit (DNAgenotek Inc., Ottawa, Canada).Exome capture was performed with the Agilent V5 kit and sequencing was performed on Illumina HiSeq 2000.

  Dataset EGAD00001004035

• Exome sequencing data from tumor progression cohort

  This dataset, named Stockholm tumor progression cohort, contains exome-sequencing samples of matched primary and metastasis samples from 20 metastatic breast cancer patients. All patients have one or more sequenced normal samples as well. The total number of samples is 125. The dataset has been used, apart from other studies, to explore tumor evolution patterns in metastatic breast cancer at Karolinska Institute Stockholm.

  Dataset EGAD00001003837

• Genetic Diseases of Immune Homeostasis and Autoimmunity Caused by GIMAP Deficiency

  We investigated 17 affected individuals in 9 kindreds with lymphopenia, splenomegaly, liver disease, thrombocytopenia, lymphadenopathy, severe recurrent lung infections, skin diseases, and lymphoma. Whole-exome sequencing of the cohort revealed mutations in GIMAP5. We also found another patient from one kindred with a unique mutation in the gene GIMAP6, discovered by whole-exome sequencing. A comprehensive investigation of this gene mutation through in vivo and in vitro experiments revealed that GIMAP6 deficiency results in defects in autophagy in patient T cells and interruption of GIMAP7 and GABARAPL2 interactions. GIMAP6 deficiency leads to affected patients to present with clinical phenotypes such as recurrent infections, lymphoproliferation, autoimmunity, and inflammation.

  Study phs002816

• Lysosomal Disease Network (LDN6719) Immune Response to Intrathecal Enzyme Therapy in Mucopolysaccharidosis 1 Patients

  In this study we characterized the immune response to intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) in mucopolysaccharidosis I (MPS I) subjects with spinal cord compression who had been previously treated with intravenous rhIDU. Concentrations of specific antibodies and cytokines were measured in serum and cerebrospinal fluid (CSF) collected before monthly IT rhIDU infusions. These serologic findings were compared with clinical adverse event (AE) reports to establish temporal correlations with clinical symptoms. We found that IT rhIDU was generally well tolerated in the subjects studied although one subject had moderate to severe clinical symptoms and serologic abnormalities consistent with an immune response.

  Study phs000862

• Characterization of Prostate Cancer Organoids

  Using models from the LuCaP series as well as those generated at the National Cancer Institute, we have established organoids for in vitro mechanistic testing, including drug screening and genetic manipulation. The major findings from these continuing studies is the durability of organoids for maintaining complex subpopulation and intratumoral heterogeneity and the parallels between in vitro testing and patient outcomes. Existing data from prior releases includes whole-genome sequencing, whole-exome sequencing, single-cell and bulk RNA-seq, single-cell ATAC-seq, and SNP array. New data in this release is ChIP-seq data from three models and RNA-seq data from one model.

  Study phs001587

• NHLBI TOPMed: Childhood Asthma Management Program (CAMP)

  The Childhood Asthma Management Program (CAMP) was designed to evaluate whether continuous, long-term treatment (over a period of four to six years) with either an inhaled corticosteroid (budesonide) or an inhaled noncorticosteroid drug (nedocromil) safely produces an improvement in lung growth as compared with treatment for symptoms only (with albuterol and, if necessary, prednisone, administered as needed). The primary outcome in the study was lung growth, as assessed by the change in forced expiratory volume in one second (FEV1, expressed as a percentage of the predicted value) after the administration of a bronchodilator. Secondary outcomes included the degree of airway responsiveness, morbidity, physical growth, and psychological development.

  Study phs001726

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

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

  Study EGAS50000000217

• Mitochondrial DNA mosaicism in human somatic cells

  Genomic alterations accumulate in the somatic cells throughout an individual’s lifetime. Recent sequencing studies have documented widespread mutations in the nuclear genome and the frequent clonal competition of normal cells carrying mutations. However, the landscape of mitochondrial DNA (mtDNA) heteroplasmy in normal human tissues is poorly understood. This study investigated the whole genome sequences (WGSs) of 2,096 clones established from non-neoplastic healthy single cells obtained from 31 donors. In addition, we analyzed 31 WGSs of neoplastic cells, including 12 clones established from adenomatous polyps from one individual with MUTYH-associated polyposis and 19 matched colorectal carcinomas from individuals who donated normal colorectal clones.

  Study EGAS50000000254

• Single-Cell Transcriptomic Characterization of Microscopic Colitis

  Patients with microscopic colitis (MC), chronic diarrhea without histological signs of MC, or unaffected controls were profiled using single-cell RNA sequencing (scRNA-seq; inDrops and 10X Genomics were used). One profiled patient without clinical symptoms was found to have histological signs of MC (asymptomatic MC). Some of the subjects from dbGaP study phs003418 are controls in this study. T-Cell Receptor sequencing (TCR-Seq) was also performed on a subset of patients. Individual transcriptomes were analyzed to characterize the cellular profile associated with MC and search for mediators of disease pathology. Raw reads and processed count matrices will be available through dbGaP.

  Study phs003876

• Transcriptomic Profiling after B-Cell Depletion Reveals Central and Peripheral Immune Cell Changes in Multiple Sclerosis

  We investigated the immunological effects of B cell depletion therapy using ocrelizumab in treatment-naïve relapsing-remitting multiple sclerosis (RRMS) patients. Our primary aim was to delineate transcriptomic alterations in immune cell populations in peripheral blood before and after therapy, using single-cell RNA sequencing (scRNAseq). This study included 18 newly diagnosed, treatment-naïve RRMS patients who provided matched pre- and 6-month post-treatment peripheral blood mononuclear cells (PBMCs). A secondary cohort of five patients also contributed paired cerebrospinal fluid (CSF) samples. All RRMS patients were treated with ocrelizumab, except one patient in the CSF cohort who received rituximab.

  Study phs003938

• A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer (D-Beyond)

  This is a prospective, single arm phase IIa trial in which patients with early breast cancer will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart (maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be collected at baseline and at surgery. Post-operative treatment will be at the discretion of the investigator.Primary objective: to determine if a short course of RANKL inhibition with denosumab can induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry (IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.

  Study EGAS00001003252

• Meisal temporal lobe epilepsy sequencing study

  Our understanding of mesial temporal lobe epilepsy (MTLE) is one of the most common forms of drug-resistant epilepsy in humans. Using RNA- and small RNA-sequencing in parallel, we explored differentially expressed genes in the hippocampus and cortex of MTLE patients who had undergone surgical resection and non-epileptic controls. We found significant enrichment for astrocytic and microglial genes amongst up-regulated genes and down-regulation of neuron-specific genes in the hippocampus of MTLE patients. The transcriptome profile of the small RNAs reflected disease state more robustly than mRNAs, even across brain regions which show very little pathology.

  Study EGAS00001003922

• Native_American_Ancient_DNA_sequencing

  The morphology of the first humans in the Americas (Paleoamericans) differs from that of Native Americans, and has raised the question of whether or not there are also differences in origin or genetics. A few populations who survived until relatively recently have been suggested to retain Paleoamerican morphology. One of these populations is from La Jolla. Here, we have generated genome sequence data from four La Jolla individuals in order to investigate these questions 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/

  Study EGAS00001001802

• PTPN22 SNPs and outcome after lung transplantation

  Obstructive chronic lung allograft dysfunction (BOS) is the major limiting factor for lung transplantation (LTx) outcome. PTPN22 is described as the hallmark autoimmunity gene, and one specific single nucleotide polymorphism (SNP), rs2476601, is associated with multiple autoimmune diseases, impaired T cell regulation and autoantibody formation. Taking into consideration the contribution of autoimmunity to LTx outcome, we hypothesized that polymorphisms in the PTPN22 gene could be associated with BOS incidence. We selected six SNPs within PTPN22 and analyzed both patient and donor genotypes on BOS development post-LTx. A total of 144 patients and matched donors were included, and individual SNPs and haplotype configurations were analyzed.

  Study EGAS00001003380

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

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

  Study EGAS00001003490

• Mutational landscape of renal cell carcinoma with venous tumor thrombus

  Renal cell carcinoma with venous tumor thrombus opens the unique opportunity to investigate the clonal evolution of a tumor in two fundamentally different compartments i.e., within the confinement of an organ and inside a large blood vessel. We performed multiregion whole exome sequencing of a total of 37 samples from five consecutive patients (normal tissue, n=5; primary tumors, n=16; tumor thrombi, n=16) to >35-fold target coverage. Four patients had a clear cell RCC, one patient had a poorly differentiated type II papillary RCC (RCC-VTT-04). The latter patient had a friable thrombus, the others were of solid consistency.

  Study EGAS00001001950

• RNA sequencing in primary inflammatory (TPP) macrophages treated with a MEK1/2 inhibitor

  By investigating an intergenic haplotype on chr21q22, independently linked to inflammatory bowel disease (IBD), ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis, we discover that the causal gene, ETS2, is a master regulator of inflammatory responses in human macrophages and delineate how the risk haplotype increases ETS2 expression. Using a database of cellular signatures, we identified drugs that could modulate this pathway. To validate the anti-inflammatory activity of one class of small molecules in vitro, we treated TPP macrophages with vehicle control or a selective, non-ATP competitive MEK inhibitor (PD-0325901) at 2 doses (100nM and 500nM) and performed RNA sequencing.

  Study EGAS00001007552

• Single Cell Sequencing of Sperm (scSperm)

  The aim of this project is to genotype and sequence single spermatozoa from two men, one in his twenties and the other in his seventies. The resulting data is used to quantify the mutations that have arisen in the gametes of both individuals in order to better understand the effect of aging on mutation rates and modes.Project Outline. In order to quantify mutations, semen from two individuals are sequenced. 48 single sperm cells are isolated from each individual, and their DNA is extracted. The resulting genomes are amplified using PicoPlex, GenomiPhi MDA, Repli-G MDA, and MALBAC. QC step is applied to check the quality of WGA DNA using standard Sequenom plex (26 SNPs). A subset of 32 amplification products which pass the intiall QC, are genotyped using Affymetrix SNP6 chips. 12 of the genotyped amplification products are also sequenced. In addition, one multi-cell sample per individual is sequenced as a reference and for validation purposes.Altogether, 12 single cell sperm genomes and two multi-cell genomes are sequenced, coming to a total of 14 genomes. Of the single cell sperm genomes, 2 are sequenced to 50x coverage, and the other 10 to 25x coverage. Both multi-cell genomes are sequenced to 25x coverage.

  Dataset EGAD00001001216

• BAM files of targeted next-generation DNA sequencing data of 13 chordoid gliomas of the third ventricle

  BAM files of targeted next-generation DNA sequencing data of 13 chordoid gliomas of the third ventricle (2 paired tumor-normal samples and 11 tumor-only samples). Genomic DNA was extracted from formalin-fixed, paraffin-embedded blocks of tumor tissue from 13 patients with chordoid glioma of the third ventricle using the QIAamp DNA FFPE Tissue Kit (Qiagen). Genomic DNA was also extracted from leukocytes in a peripheral blood sample from one of the patients and a non-neoplastic gastric biopsy specimen from one of the patients. Capture-based next-generation DNA sequencing was performed at the University of California, San Francisco Clinical Cancer Genomics Laboratory, using an assay that targets all coding exons of approximately 500 cancer-related genes, select introns of 47 genes, and TERT promoter with a total sequencing footprint of 2.8 Mb (UCSF500 Cancer Panel). Sequencing libraries were prepared from genomic DNA, and target enrichment was performed by hybrid capture using a custom oligonucleotide library (Nimblegen SeqCap EZ Choice). Captured libraries were sequenced as paired-end 100 bp reads on an Illumina HiSeq 2500 instrument. Duplicate sequencing reads were removed computationally to allow for accurate allele frequency determination and copy number calling.

  Dataset EGAD00001003818

• Neuroblastoma cell-lines and healthy cfDNA used for the benchmarking study

  This dataset comprises nine neuroblastoma cell lines used to construct the reference matrix for the RRBS-CL dataset in the corresponding benchmarking study. In addition, it includes one extra neuroblastoma cell line and a pooled cfDNA sample from multiple donors, which were used to generate the in silico mixtures. All the samples were profiled using DNA methylation sequencing.

  Dataset EGAD50000002199

• Transcriptome Changes in ASD (NRXN1α+/-) iPSC-derived neurons

  This dataset contains 10 fastq files from 10 cell lines (4 cell lines from 3 patients and 6 cell lines from 4 controls) that have undergone 50bp single end sequencing with PolyA enrichment strategy (BGI project number HUMpcsN). *please note one of the samples (Patient_4) was named in error and should be corrected to Patient_3 during analysis

  Dataset EGAD00001007993

• Targeted DNA sequencing on bulk bone marrow and peripheral blood

  Targeted DNA sequencing was performed on 195 bone marrow samples to identify cases of clonal haematopoiesis, and on 99 paired peripheral blood samples. The SeqCap EZ HyperCap protocol was followed, and targeted capture performed against a panel of 97 genes recurrently mutated in myeloid malignancies and clonal hematopoiesis. One BAM file (mapped to the hg38 reference genome) is provided per sample.

  Dataset EGAD00001011083

• Somatic mutations reveal embryonic genetic bottlenecks generating placental mosaicism

  The human placenta harbours chromosomal aberrations that are absent from the fetus in one to two percent of pregnancies. This confined mosaicism suggests that embryonic genetic bottlenecks exist, which phylogenetically segregate placental tissue. Here, we studied the somatic genetic landscape of human placentas by whole genome sequencing of 86 placental biopsies and of 106 microdissections.

  Dataset EGAD00001006337

• Genome Denmark Phase II - alignments

  Alignment of Genome Denmark Phase II dataset to GRCh38. The dataset consists of 150 Danish individuals (50 trios) sequenced to 80X. The BAM-file contains data from multiple libraries created from one individual with libraries of 180, 500, 800, 2000, 5000, 10000 and 20000 bp. The libraries were created using standard Illumina protocols for paired end reads (180-800bp libraries) and mate pair libraries (2kb-20kb).

  Dataset EGAD00001003157

• Environmental Arsenic and Diabetes Mellitus (Chihuahua Cohort)

  The Chihuahua Cohort was established as part of a larger NIEHS-funded project that used laboratory models (tissue culture and mice) and human subjects to examine the association between exposure to arsenic and diabetes, including identification of mechanisms underlying this association. All procedures involving human subjects were approved by institutional review boards at the University of North Carolina at Chapel Hill and Cinvestav-IPN (Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico). All participants provided signed informed consent. A total of 1,160 adults (≥ 18 years old) with a minimum 5-year uninterrupted residency in the Chihuahua study area were recruited between 2008 and 2012. Samples of drinking water were obtained from the participants' households. Data on residency, occupation, drinking-water sources and use, smoking, alcohol consumption, and medical history were recorded by a study questionnaire. Spot urine and fasting venous blood were collected during medical examination that included an oral glucose tolerance test (OGTT) with blood drawn 2 hr after a 75-g glucose dose. Plasma from both fasting and 2-hr blood samples was collected. Body mass index (BMI) of each participant was calculated from body weight and height. BMI cutoffs of ≥ 25.0, ≥ 30, and < 18.5 kg/m2 were used to define overweight, obese, and underweight individuals, respectively. Participants' waist circumference was also measured. Blood pressure was assessed using a manual sphygmomanometer. Three measurements were taken at intervals of at least 1 min, with a 5-min rest before obtaining the first reading; the mean of the last two measurements was used. The concentrations of arsenic in drinking water and arsenic species in urine were measured by hydride generation-atomic absorption spectrometry. The limit of detection for As in water as well as for As species in urine was 0.01 µg As/L. Creatinine concentration in urine was determined using an established colorimetric assay. DNA was isolated from blood for genotyping analysis.The following measures were taken: glucose concentration in fasting blood (FBG) and in blood collected 2 hours into OGTT (2HBG); concentrations of triglycerides, HDL and total cholesterol (TC) in fasting plasma; and LDL was calculated using the Friedewald equation. Diabetes was classified by FPG ≥ 126 mg/dL, 2HPG ≥ 200 mg/dL, or self-reported diabetes diagnosis or medication use (WHO/International Diabetes Federation 2006). Prediabetes was defined as the absence of diabetes with FPG ≥ 110 mg/ dL or 2HPG ≥ 140 mg/dL. Elevated fasting levels of each lipid were defined as plasma TG ≥ 150 mg/dL, TC ≥ 200 mg/dL, and LDL ≥ 130 mg/dL. Fasting HDL < 40 mg/dL in men and < 50 mg/dL in women were designated as low. Hypertension was defined by systolic blood pressure (SBP) > 140 mm Hg, diastolic blood pressure (DBP) > 90 mmHg, or self-reported use of anti-hypertensive medication. Genotyping analysis, which will be available in version 2 of this study, was carried out in a subset of ~600 subjects with focus on enzymes involved in the metabolism of arsenic, including AS3MT, GSTs.All data collected during the medical exams or generated by the above-described chemical and biochemical analysis of water, urine and blood/plasma, as well as results of the genotyping analysis are included in dbGaP. Data generated by metabolomics and epigenetic analyses in small subsets of the Chihuahua cohort are not included, but are available in published articles.

  Study phs002139

• International Verapamil SR/Trandolapril [INVEST] Genes Study

  INternational VErapamil SR-Trandolapril STudy (INVEST) was a prospective, multicenter, randomized, open-label, parallel-clinical trial that evaluated blood pressure response and adverse outcomes in patients randomized to either an atenolol-based or a verapamil SR-based hypertension treatment strategy in 22,576 patients with documented coronary artery disease and hypertension (PMID: 9809930,14657064). Hydrochlorothiazide and trandolapril were added as needed to achieve BP control or end organ protection in a protocol-defined manner. Briefly, the protocol required patients to be followed up at bassline, 6, 12, 18 and 24 weeks and then every 6 months thereafter until 2 years after the last patient was enrolled. At each visit, patients had BP and heart rate measured, clinical assessment performed, and additional antihypertensive medications added as needed to meet JNC VI blood pressure goals. The primary outcome was the first occurrence of all-cause death, nonfatal myocardial infarction (MI), or nonfatal stroke (clinicaltrials.gov identifier: NCT00133692). The genetic substudy of INVEST, INVEST-GENES, collected genomic DNA samples from 5,979 INVEST study participants. INVEST-GENES samples were genotyped on the Illumina OmniExpressExome GWAS chip. This data release includes 1529 samples that passed quality control including 657 whites, 537 Hispanics and 155 blacks. Two case-control subsets were created: one for the primary outcome of all-cause death, nonfatal MI or nonfatal stroke; the other one is for new-onset diabetes. Resistant hypertension was also evaluated in 1349 participants based on the medication use and blood pressure measurements at the visit prior to experiencing study outcomes or censoring (PMID:30237584).

  Study phs002319

• Strabismus, CCDD and other anomalies

  Strabismus is one of the most common ophthalmological diseases affecting our population. It has many detrimental effects for affected individuals, including functional visual loss from amblyopia, secondary psychosocial difficulties, and limited employment opportunities. Strabismus also imposes a significant economical burden on society from the cost of screening programs, surgical correction, and lost productivity. Congenital incomitant strabismus is a broad term that encompasses congenital ocular motility disorders with restricted movement in one or more directions of gaze, and includes various forms of Duane's retraction syndrome, horizontal gaze palsy, congenital fibrosis of extraocular muscles, and Moebius syndrome. Incomitant strabismus together with a group of related disorders such as congenital ptosis and congenital facial palsy have been collectively redefined as congenital cranial dysinnervation disorders (CCDDs). This redefinition stemmed from previous studies in the Engle lab showing that these disorders can be caused by mutations in genes encoding transcription factors critical to ocular cranial motor neuron development and by genes that encode proteins essential to the proper growth and guidance of developing axons. Thus, while these disorders account for only a small percent of strabismus, understanding their genetic etiology has led to our ability to provide genetic testing and counseling, and has provided the first insights into the molecular etiologies of strabismus. While the Engle lab has identified all seven CCDD genes published to date, our cohort still includes >100 familial CCDD pedigrees that are mutation-negative. We continue to utilize co-segregation analysis and whole exome or whole genome sequencing technologies to identify new disease genes in this mutation-negative cohort.

  Study phs000478

• Molecular Evolution of Cancer

  Recently developed methods that utilize partitioning of long genomic DNA fragments, and barcoding of shorter fragments derived from them, have succeeded in retaining long-range information in short sequencing reads. These so-called read cloud approaches represent a powerful, accurate, and cost-effective alternative to single-molecule long-read sequencing. We developed software, GROC-SVs, that takes advantage of read clouds for structural variant detection and assembly. We apply the method to two 10x Genomics data sets, one chromothriptic sarcoma with several spatially separated samples, and one breast cancer cell line, all Illumina-sequenced to high coverage. Comparison to short-fragment data from the same samples, and validation by mate-pair data from a subset of the sarcoma samples, demonstrate substantial improvement in specificity of breakpoint detection compared to short-fragment sequencing, at comparable sensitivity, and vice versa. The embedded long-range information also facilitates sequence assembly of a large fraction of the breakpoints; importantly, consecutive breakpoints that are closer than the average length of the input DNA molecules can be assembled together and their order and arrangement reconstructed, with some events exhibiting remarkable complexity. These features facilitated an analysis of the structural evolution of the sarcoma. In the chromothripsis, rearrangements occurred before copy number amplifications, and using the phylogenetic tree built from point mutation data, we show that single nucleotide variants and structural variants are not correlated. We predict significant future advances in structural variant science using 10x data analyzed with GROC-SVs and other read cloud-specific methods.

  Study phs001255

• Intra-tumor heterogeneity and clonal evolution of papillary renal cell carcinoma

  Limited knowledge of intratumor heterogeneity (ITH), and clonal evolution of papillary renal cell carcinoma (pRCC) and rare kidney tumor subtypes hinders understanding of tumorigenesis and therapeutic efficacy. We conducted an integrative genomic and epigenomic ITH analysis and studied clonal evolutionary history of pRCC and rare kidney tumor subtypes. We dissected multiple consecutive samples from the center of the tumor towards the tumor's periphery, a normal sample ~5 cm distant from the tumor, and, where feasible, metastatic regions in the adrenal gland. Specifically, we performed 60X multi-region whole-genome sequencing (mWGS), both genome-wide methylation and SNP array profiling, and deep targeted sequencing (average 500X coverage) of 254 cancer driver genes (PMID:24390350). The study population comprises 39 patients with kidney cancers, including 23 with papillary type 1 (pRCC1), 12 with papillary type 2 (pRCC2), one of which also had areas of clear cell, and one each with collecting duct tumor (cdRCC), renal fibrosarcoma rSRC, mixed pRCC1/pRCC2, and an unclassified renal cancer with mixed features of pRCC2 and cdRCC. Based on DNA sample availability, we conducted whole genome sequencing (WGS) on 124 samples from 29 subjects, deep targeted sequencing on 139 samples from 38 subjects, SNP array genotyping on 101 samples from 38 subjects, and genome-wide methylation profiling on 139 samples from 28 subjects. All assays were performed on tumor, metastasis and normal tissue samples, with the exception of the SNP array genotyping, which was conducted only on tumor samples.

  Study phs001573

• Center for Craniofacial and Dental Genetics: Exome Sequencing of Orofacial Cleft Families

  Orofacial Clefts (OFCs) are genetically complex structural birth defects caused by genetic factors, environmental exposures, and their interactions. OFCs are the most common craniofacial anomalies in humans. Affect about 1 in 800 newborns, OFCs are also one of the most common structural birth defects worldwide. OFCs can impose a substantial personal cost resulting from the associated emotional and financial burden. On average a child undergoes 6 surgeries, spends 30 days in hospital, receives 5 years of orthodontic treatment, and participates in ongoing speech therapy, leading to an estimated total lifetime treatment cost of about $200,000. Individuals born with an OFC have higher infant mortality (especially in developing countries with limited access to care), higher mortality rates at all other stages of life, increased incidence of mental health problems, and higher risk for other disorders (notably including breast, brain, and colon cancers). Prior genetic studies have focused on the contribution of common genetic variants through genome-wide linkage and association studies. These studies have revealed a significant etiologic heterogeneity. One promising approach to dissect the etiology of OFCs into focus on subclinical phenotypic features present in the non-cleft family members of affected individuals. These subclinical features are subtle phenotypic features that may represent mild manifestations of the same risk genes; thus, their inclusion in family-based studies may clarify the inheritance patterns in OFC families. In this project, we conducted whole exome sequencing in multiplex families with both overt OFCs and subclinical phenotypes to identify high-impact genes causing OFCs.

  Study phs001675

• Bayesian-Based Noninvasive Prenatal Diagnosis of Single-Gene Disorders

  In the last decade, non-invasive prenatal diagnosis (NIPD) has emerged as an effective procedure for early detection of inherited diseases during pregnancy. This technique is based on using cell-free DNA (cfDNA) and fetal cfDNA (cffDNA) in maternal blood, and hence, has minimal risk for the mother and fetus compared with invasive techniques. NIPD is used today for identifying chromosomal abnormalities (in some instances) and for single-gene disorders (SGDs) of paternal origin. However, for SGDs of maternal origin, sensitivity poses a challenge that limits the testing to one genetic disorder at a time. Here we present a Bayesian method for the NIPD of monogenic diseases that is independent of the mode of inheritance and parental origin. Furthermore, we show that accounting for differences in the fragment length distribution of fetal- and maternal-derived cfDNA results in increased accuracy. Our model is the first to predict inherited insertions-deletions (indels). The method described can serve as a general framework for the NIPD of SGDs; this will facilitate easy integration of further improvements. One such improvement that is presented in the current study is a machine learning model that corrects errors based on patterns found in previously processed data. Overall, we show that next generation sequencing (NGS) can be used for the NIPD of a wide range of monogenic diseases, simultaneously. We believe that our study will lead to the achievement of a comprehensive NIPD for monogenic diseases. (Reprinted from Bayesian-based noninvasive prenatal diagnosis of single-gene disorders, with permission from Genome Research)

  Study phs001659

• Pediatric Papillary Thyroid Carcinoma Whole Exome Sequencing

  BACKGROUND: Pediatric papillary thyroid carcinoma (PPTC) is distinct from adult-onset disease. Despite higher rates of regional and distal metastases and more frequent recurrence, there is, paradoxically, a highly favourable prognosis. Historically, only 40-50% of childhood PTC are driven by genomic variants common to adult PTC, while the oncogenic drivers in the remainder are unknown. METHODS: Fifty-two PPTCs were genotyped by candidate gene testing, followed, in a subset (n=32), by whole exome (WES) and transcriptome sequencing (RNASeq) to identify oncogenic variants in driver-unknown tumors and to explore gene expression patterns. FINDINGS: Thirty-one tumors (60%) carried variants identified by candidate gene testing, specifically: BRAFV600E(22%), NRASQ61R(2%), RET-CCDC6(19%), RET-NCOA4(15%) and PAX8-PPARG. Among the 21 remaining tumors with negative first-line genotyping, oncogenic variants were identified in 19 (90%). These were enriched with oncogenic fusions, with 11 non-recurrent fusion transcripts identified, including two that had not been previously described: STRN-RET and TG-PBF. Most fusions were associated with 3’ receptor tyrosine kinase (RTK) moieties: RET, MET, ALK and NTRK3. Gene expression analysis defined three distinct clusters, which demonstrated differing expression of genes involved in thyroid differentiation and MAPK signaling. INTERPRETATION: Exome and transcriptome-wide sequencing identify genomic drivers of PPTC in 98% of tumors, whereas conventional genotyping leaves many tumors genetically unexplained. PPTC is driven, in the majority of cases, by oncogenic fusion transcripts involving one of a limited number of RTKs. These observations have broad implications for diagnostic testing and for therapeutic options in children with advanced disease.

  Study EGAS00001005187

• Next-Generation Sequencing of AV Nodal Reentry Tachycardia patients

  Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients below 40 years of age. Familial clustering, early onset of symptoms, and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System.In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes.This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling.

  Study EGAS00001002745

• Non-viral precision T cell receptor replacement for personalized cell therapy

  The T cell receptor (TCR) provides the fine specificity of T cells to recognize mutations in cancer cells 1-3. We developed a clinical-grade approach based on CRISPR/Cas9 non-viral precision genome editing to simultaneously knock-out the two endogenous TCR genes, TCRα (TRAC) and TCRβ (TRBC), and insert in the TRAC locus the two chains of a neoantigen-specific TCR (neoTCR), isolated from the patient’s own circulating T cells using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with refractory solid cancers received up to three distinct neoTCR-transgenic cell products, each expressing a patient-specific neoTCR, in a cell dose-escalation, first-in-human phase 1 clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome, and one grade 3 encephalitis. All had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease, and the other 11 had disease progression as best response on therapy. NeoTCR-transgenic T cells were detected in tumour biopsies post-infusion at frequencies higher than the native TCRs pre-infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs recognizing mutational neoantigens, the simultaneous knock-out of the endogenous TCR and knock-in of the neoTCRs using single-step, non-viral precision genome editing, the manufacturing of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene edited neoTCR T cell products, and the ability of the transgenic T cells to traffic to the patients’ tumours.

  Study EGAS00001006898

• SNP array

  The whole study comprises of two patient cohorts. Screening cohort: 40 patients of Germany; validation cohort: 40 patients from Asia. Further, bile duct and CCA cell lines have been analyzed.
This dataset contains SNP array data for tumor/normal pairs for a subset of 36 patients from the screening cohort plus an additional relapse tumor of one of those 36 patients. Data was generated on a OmniExpress-24 v1.1 Bead Array (Illumina) and is stored in IDAT file format.

  Dataset EGAD00010002597

• iPSC and iPSC derived pericytes

  Bulk RNA sequencing of iPSCs and iPSC derived pericytes from three cell lines MNZTASi019-A, MNZTASi021-A and MNZTASi022-A. Data includes one iPSC data set per cell line and iPSC derived pericyte differentiations per cell line (3 differentiations from MNZTASi019-A and MNZTASi021-A, 2 from MNZTASi022-A). RNA-seq data was generated using an Illumina Stranded mRNA 150bp paired-end library preparation.

  Dataset EGAD50000000255

• paired-end FASTQ files from the study: Identification of the cause of juvenile parkinsonism in a case_SYNJ1

  The dataset consists of three samples: two controls and one case of juvenile Parkinsonism. Whole Exome Sequencing (WXS) was performed on these samples using hybrid selection for library preparation. Sequencing was carried out on the Illumina NextSeq 500 platform. For each sample, two FASTQ files containing paired-end reads (R1 and R2) were generated. The data deposited consists of the corresponding FASTQ files.

  Dataset EGAD50000000413

• ST dataset from subcortical white matter MS lesions (CA & CI) and controls

  This dataset contains the FASTQ files, the correspondent H&E pictures with the fiducial frames and the json files that were used for the spatial transcriptomic analysis in our paper (n=19). Within the json files names, one can find the information about the slide name (V11M111-111) and the capture area (A1) for each sample.

  Dataset EGAD50000000520

• IMPRESS_all

  Dataset containing tumor, normal and blood sample data, for various tissue and tumor types. Data is targeted methylation data, using smMIP probes to target informative CpG sites in the genome. Sample type can be inferred from the name, with 'W' being normal samples and 'TC' tumor samples. Dataset contains 259 samples in duplicate, with one half of the runs being cut by MSRE's, and the other not. For every sample paired fastq files are present.

  Dataset EGAD50000000882

• Shallow whole genome sequencing DETECT samples

  Shallow whole genome sequencing of samples from the paper Beddowes et al. A large-scale retrospective study in metastatic breast cancer patients using circulating tumour DNA and machine learning to predict treatment outcome and progression-free survival. Mol. One 2025. This includes 1048 longitudinal plasma samples from 149 patients and 35 normals. Samples were sequenced with shallow whole genome sequencing for copy number estimation. All the files are single-end fastq files.

  Dataset EGAD50000001333

• APS-1 Immune Panel Sequencing

  Single cell sequencing of expanded regulatory T cells (Tregs) in 8 APS-1 patients and 8 age and gender matched controls (same patients and controls as for global gene expression and TCR sequencing, excluding one for each group (control sample and patient sample #13)). Each Sample has two technical repeats. 10x Genomics Target Hybridization Kit and Human Immunology Panel was used with GEX libraries.

  Dataset EGAD50000000262

• Whole Exome Sequencing of Human Gastro-esophageal Cancer PDXs

  The dataset includes 51 whole exome sequencing datasets generated using Illumina paired-end sequencing technology. These data derive from 26 patient-derived xenograft (PDX) tumors and their matched normal tissues, which consist of either normal gastric mucosa or blood samples. In one case (GTR0607), the matched normal tissue data are unavailable. As a result, the dataset comprises 102 FASTQ files, providing raw sequencing reads for comprehensive genomic analysis.

  Dataset EGAD50000001407

• WGS data of pediatric T-ALL acute lymphoblastic leukemia (set1)

  The dataset includes FASTQ and BAM files from diagnostic and matched remission (control) samples of one T-ALL patient (ALLT-317). Relapsed (BM ALLT-317L and Tonsil ALLT-3107L) sample files are in dataset set2 of this submission. Sequencing library was made using PCR free-based WGS library preparation (PCR-), using TruSeq DNA PCRfree library preparation kit v1 (PE150). Both diagnostic (60x) and remission (30x) samples were sequenced using HiSeq X.

  Dataset EGAD50000002013

• This dataset includes FASTQ for single-nucleus RNA-seq of normal controls, and multiple system atrophy (MSA) or Parkinson's disease (PD) patients.

  The dataset includes more than 130k nuclei isolated using 10x Genomics Chromium Next GEM Single Cell 3' Reagent Kits v3.1. In total, 30 samples are included from 10 controls, 8 MSA (including one sample that was omitted during QC), or 12 PD patients. Samples were sequenced on Illumina Novaseq 6000 or NextSeq 550 instruments.

  Dataset EGAD50000002041

• 10X single-cell Multiome (RNA+ATAC) of bone marrow-derived HSPC

  10X genomics chromium single-cell ATAC+RNA (Multiome) was use to prepare single-nucleus RNA- and ATAC-seq libraries, sequenced on an Illumina NovaSeq 6000 platform. BAM files are provided. Samples from 6 donors were sequenced after sorting for primitive HSPCs in 5 libraries; each library comprises a single donor, except one with cells from 1 male and 1 female donor.

  Dataset EGAD50000002326

• Whole transcriptome and 97 antibodies of one healthy bone marrow

  Whole transcriptome sequencing using BD Rhapsody with 97 antibodies of a healthy young adult bone marrow (Young3/BM3) mononuclear cells from iliac crest aspirations. Please note raw and integrated gene expression data, cell type annotation, metadata and dimensionality reduction are available as Seurat v3 objects through figshare. Access links is https://figshare.com/s/901bcddb9ee18e226031.

  Dataset EGAD00001008186

• Single-cell RNA-seq of patient-derived organoids across three generations

  Single-cell RNA-seq of first-, second-, and third-generation patient-derived organoids. Obtained using the 10X Genomics single-cell 3' expression solution (v3 chemistry). First- and second-generation PDOs from one patient and first-, second-, and third-generation PDOs from three additional patients.

  Dataset EGAD00001008431

• WGS data subfolder HF3J5CCXY from multifocal ileal NETs study

  This dataset includes linked-read whole-genome sequencing data (subfolder HF3J5CCXY) for multifocal ileal tumor samples from one patient. Samples were sequenced using the 10x Genomics linked-read whole-genome sequencing (WGS) approach.

  Dataset EGAD00001008493

• WGS of off-target analysis of base editing in organoids

  Seven clonal organoid lines and one bulk wild-type control sample were paired-end whole-genome sequenced using the Illumina Novaseq 6000 system. We sequenced four clonal intestinal organoid lines harbouring engineered TP53 and FBXW7 mutations as well as three lines targeted for oncogenic APC/TP53/PIK3CA/SMAD4 mutations. The reads were mapped to hg38 genome assembly and data is provided as BAM files.

  Dataset EGAD00001009827

• Paired WGS data of 45 samples and 2 paired WES sample of RRMM (multiple myeloma)

  Here is mostly paired WGS data of RRMM, 45 samples (tumors and controls) in 86 runs. This data was produced by using Illumina TruSeq Nano DNA and NovaSeq6000 or HiSeq X Ten for sequencing. One tumor/control pair is WES data using Agilent SureSelect V5+UTRs and NovaSeq6000 for sequencing.

  Dataset EGAD00001009682

• Whole exome sequencing (WES)

  The whole study comprises of two patient cohorts. Screening cohort: 40 patients of Germany; validation cohort: 40 patients from Asia. Further, bile duct and CCA cell lines have been analyzed. This dataset contains whole exome sequencing data of 37 tumor/normal pairs from the screening cohort plus an additional relapse tumor of one of those 37 patients. Data was generated on Illumina HiSeq 2000 device in paired-end mode and is stored in BAM file format.

  Dataset EGAD00001011324

• Whole genomes sequencing BAM files (blood and lung brushings) of COPD cases and controls (EvA)

  Dataset of 27 whole genome sequencing files (BAM), which cover 12 individuals out of which four suffer from COPD. From 9 individuals, there are sequencing data from blood and from lung brushings at one single site available, from another 3 there is additionally a lung brushing sequencing file from a second site available. Comparison of blood with lung brushings allows the calling of somatic mutations within a tissue.

  Dataset EGAD00001004535

• Circular RNA characterization in functionally distinct brain regions

  RNA extracted from middle temporal gyrus (MG) brain region of healthy elderly controls. Three pairs of samples were generated, each pair consisting of one sample that was enriched for circular RNAs using RNase R, and a second sample that was not enriched (total N=6). Remaining samples in the study from other functionally distinct brain regions are currently under process and will be released soon.

  Dataset EGAD00001004211

• RNA-sequencing of six Pilocytic astrocytoma tumors

  Total stranded TruSeq RNA sequencing by Illumina of six tumor samples from six cases of pediatric Pilocytic astrocytoma. The data is published in the following paper: Tomic TT, Olausson J, Wilzen A, Sabel M, Truve K, Sjogren H, Dosa S, Tisell M, Lannering B, Enlund F, Martinsson T, Aman P, Abel F. A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma. PLoS One. 2017 Apr 27;12(4):e0175638.

  Dataset EGAD00001003143

• Bajau and Saluan adaptation study data

  This dataset includes whole genome sequencing data from 93 Bajau and Saluan individuals that were used in the Ilardo et al 2018 study on adaptation to diving in Sea Nomads. Sequencing libraries were built using the TruSeq Nano DNA Library Preparation Kit on an Illumina NeoPrep instrument. Each pool was sequenced 125 Paired-End over one or two lanes on the Illumina HiSeq2500 (version 4 chemistry). Samples were sequenced to an average depth of 5x.

  Dataset EGAD00001004207

• Single-cell Multi-omics Sequencing of Human Early Embryos

  The whole blood of six female volunteers and sperm from one male volunteer were used to extract genomic DNA using a DNeasy Blood & Tissue Kit (QIAGEN). 500 ng gDNA was fragmented into 300 bp by Covaris. Then, the libraries were constructed using a KAPA Hyper Prep Kit (Kapa Biosystems). In total we have 7 samples and the files we uploaded are pair-end fastq files.

  Dataset EGAD00001004108

• CD49f single-cell methylomes

  74 CD49f single-cell methylomes are from cord blood of donor1, and 84 from cord blood of donor2. Samples from donor1 have one sequencing lane, and samples from donor2 have five sequencing lanes. This dataset was generated using Post-Bisulfite Adapter Ligation (PBAL), a bisulfite based whole genome protocol. In total this dataset consists of 494 runs.

  Dataset EGAD00001003913

• Alcohol Dependence GWAS in European- and African Americans

  This study includes SSADDA (Semi Structured Assessment for Drug Dependence and Alcoholism) assessed subjects (mostly unrelated, but including some affected sibling pairs) recruited in the course of several substance dependence genetics projects. The sample includes 1889 African-American (AA) subjects and 1020 European-American (EA) subjects. Among the AAs, 1397 meet DSM-IV criteria for alcohol dependence and 491 are controls. Among the EAs, 1010 meet the criteria for alcohol dependence and 9 are controls. (One in each population meets criteria for alcohol abuse and not dependence, and is therefore counted in neither category.) Although alcohol dependence is the major focus, the sample is informative also for cocaine, nicotine, and opioid dependence.

  Study phs000425

• Gene-Environment Interactions in COCCaINE Use Disorder: Collaborative Case-Control Initiative in Cocaine Addiction

  Drug addiction is a phenotype that has high heritability estimates. In recent years, association studies of candidate genes and some genome-wide association studies (GWAS) have identified a large number of SNPs associated with substance use, abuse or dependence, particularly in phenotypes related to alcohol and nicotine use. Regarding snorted or smoked cocaine dependency, only one GWAS has been conducted so far. In addition, genetic association studies that specifically evaluated smoked cocaine dependence (e.g. crack) are rare, because of characteristics related to the route of administration and duration of the effect of the drug. Thus, the main aim of this GWAS was to identify genetic variations that modulate the risk for the cocaine dependence.

  Study phs001810

• The Genomics of Pilocytic Astrocytoma Formation in Neurofibromatosis Type 1

  Neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome is one of the most common autosomal dominant tumor predisposition syndromes in which affected individuals develop brain tumors. These low-grade glial neoplasms (pilocytic astrocytomas) typically arise in children younger than 7 years of age and are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. In this study, whole genome sequence analysis was performed on three NF1-associated pilocytic astrocytoma tumors (NF1-PA) and matched normal blood samples to establish the genomic landscape of NF1-PA. These data support the existence of multiple distinct mechanisms (mutation, LOH, and methylation) underlying somatic NF1 inactivation in NF1-PA tumors.

  Study phs000563

• NHLBI TOPMed: Rare Variants for Hypertension in Taiwan Chinese (THRV)

  The THRV-TOPMed study consists of three cohorts: The SAPPHIRe Family cohort (N=1,271), TSGH (Tri-Service General Hospital, a hospital-based cohort, N=160), and TCVGH (Taichung Veterans General Hospital, another hospital-based cohort, N=922), all based in Taiwan. 1,271 subjects were previously recruited as part of the NHLBI-sponsored SAPPHIRe Network (which is part of the Family Blood Pressure Program, FBPP). The SAPPHIRe families were recruited to have two or more hypertensive sibs, some families also with one normotensive/hypotensive sib. The two Hospital-based cohorts (TSGH and TCVGH) both recruited unrelated subjects with different recruitment criteria (matched with SAPPHIRe subjects for age, sex, and BMI category).

  Study phs001387

• Phenotyping and Therapeutic Approaches for Patients with Sellar/Suprasellar Disorders

  The goal of the study is to phenotype and genotype patients with rare hypothalamic and pituitary disorders and identify biomarkers of disease diagnosis, presentation, and progression. We are investigating genetic mechanisms of pituitary tumorigenesis as well as genomic/transcriptomic markers of disease presentation and severity. Patients with suspected or confirmed hypothalamic and/or pituitary disorders and their family members are recruited. Biospecimens including peripheral blood, urine, tumor tissue (as available), and/or stool are collected. Genetic analysis may include a variety of techniques including peripheral blood or tumor tissue targeted Sanger sequencing of one or few genes, peripheral blood or tumor tissue whole exome sequencing, and other as applicable.

  Study phs003245

• Type 1 Diabetes Genetics Consortium (T1DGC): Case-only RNA-Seq Study

  Peripheral blood mononuclear cells (PBMC) from 82 T1D cases from the T1DGC study were fractionated by positive selection on magnetic beads into CD4+ T cells, CD8+ T cells and CD19+ B cells. RNA purification, library preparation and sequencing to an average of 50 million reads per sample were performed by the HudsonAlpha Genome Services Laboratory. The resulting dataset includes 82 subjects with data from at least one cell type; sequence data from all 3 cell types is available from 79 subjects. The individuals in this study can be linked to the phs000911 T1DGC ImmunoChip study via subject ids to obtain both genotypic and phenotypic information, including genotypes used for expression quantitative trait locus analysis.

  Study phs001426

• Epigenetic Analysis of Malnutrition

  The PROVIDE study (Dhaka, Bangladesh) is a randomized clinical trial platform which evaluated the efficacy of delayed-dose oral rotavirus vaccine as well as the benefit of an injectable polio vaccine replacing one dose of oral polio vaccine. This rigorous infrastructure supported the additional examination of hypotheses of vaccine underperformance. Primary and secondary efficacy and immunogenicity measures for rotavirus and polio vaccines were measured, as well as the impact of maternal and childhood malnutrition, environmental enteropathy, and additional exploratory variables. This study has been conducted to test the role of epigenetics in malnutrition, specifically the genome-wide role of histone modifications, which are known to provide a precise signature of metabolic state and immune system function.

  Study phs001073

• CADD/GADD centers on Antisocial Drug Dependence

  CADD (Center for Antisocial Drug Dependence): Funded through NIDA 011015 to study genetic influences on, and treatment of, antisocial drug dependence, studying both clinical probands and their families, and community samples of matched controls, twins, and participants in an ongoing longitudinal adoption study. A collaboration between three organizations at two campuses of the University of Colorado. Longitudinal with three waves of data collection completed. GADD (Genetics of Adolescent Antisocial Drug Dependence): Funded originally through NIDA 012845, s multisite collaboration including adolescent subjects at high-risk for antisocial drug dependence and their siblings, recruited in Denver, CO and San Diego, CA. Longitudinal with two waves of data collection completed, one in progress as of May, 2018.

  Study phs001841

• Sequence Analysis of Mutations and Translocations Across Breast Cancer Subtypes

  This study combined whole exome (103 samples) and whole genome (22 samples) sequencing over a total of 108 breast tumors and matched normal DNA to identify novel mutations and translocations. Samples were subjected to paired-end Illumina sequencing with goal of 30x coverage of tumor/normal for whole genomes and 100x tumor/normal coverage for whole exomes. From these sequences, we used various computational techniques to identify somatic point mutations, insertion/deletions and structural rearrangements in these tumors. From these data, we identified new insights into the rates of background mutations in these cancers, novel recurrent mutated genes, and multiple gene rearrangements. One of these rearrangements appears to be a recurrent event in breast cancer.

  Study phs000369

• National Institute of Mental Health (NIMH) Amish Mennonite Bipolar Genetics Study (AmBiGen)

  Bipolar affective disorder is a severe, heritable condition affecting about one percent of the population. The mode of inheritance is poorly understood and probably involves multiple loci of small to moderate effect. In this project, we use genetic mapping and sequencing methods to identify genetic markers and variations that contribute to the risk of bipolar disorder. Individuals diagnosed with bipolar disorder are studied, along with their relatives. Phenotypic information obtained from clinical interviews and family history is correlated with genotypic information obtained from genetic marker and sequencing methods. The goal is to identify genes involved in bipolar disorder and related conditions so that better methods of diagnosis, treatment, and prevention can be developed.

  Study phs000899