1297 results for "monedas en FC Visité Buyfc26coins.com. Confiabilidad total. Cumplen lo que prometen..AdhH"

in 24.10 milliseconds.

• The Genomic Landscape of Core-Binding Factor Acute Myeloid Leukemias

  Pediatric de novo acute myeloid leukemia (AML) is a heterogeneous disease that can be divided into clinically distinct subtypes based on the presence of specific chromosomal abnormalities or gene alterations. One of the best characterized subtypes of AML involves leukemias with alterations of the core-binding factor (CBF)-complex, which comprises the FAB subtypes M2 and M4Eo and associates with a favorable outcome. Patients with the AML M2 subtype harbor a translocation between chromosomes 8 and 21 [t(8;21)] that yields the chimeric fusion gene RUNX1(AML1)-RUNX1T1(ETO), while patients with AML M4Eo express the chimeric fusion gene CBFβ-SMMHC(MYH11) as a result of an inversion/translocation event of chromosome 16 [inv(16)/t(16;16)]. In an effort to define the total complement of genetic changes in CBF-leukemia, we performed paired-end whole genome sequencing (WGS) on diagnostic leukemia blasts and matched germ line samples from 17 pediatric CBF-leukemia patients using the Illumina platform. Somatic alterations, including single nucleotide variations (SNVs) and structural variations (SVs), including insertions, deletions, inversions, and inter- and intra-chromosomal rearrangements, were detected using complementary analysis pipelines (Bambino, CREST and CONSERTING). Recurrent screening of identified mutations will be performed in a cohort of approximately 94 cases of CBF-leukemias.

  Study EGAS00001000349

• 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.

  Study EGAS00001000935

• Genomic profiling of Acute Lymphoblastic Leukemia in Ataxia Telangiectasia patients reveals tight link between ATM mutations and chromothripsis

  Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared to tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities.

  Study EGAS00001002270

• CancerDetector: Ultrasensitive and Non-Invasive Cancer Detection at the Resolution of Individual Reads using Cell-free DNA Methylation Sequencing Data

  The detection of tumor-derived cell-free DNA in plasma is one of the most promising directions in cancer diagnosis. The major challenge in such approach is how to identify the tiny amount of tumor DNAs out of total cell-free DNAs in blood. Here we propose an ultrasensitive cancer detection method, termed “CancerDetector”, using the DNA methylation profiles of cell-free DNAs. The key of our method is to probabilistically model the joint methylation patterns of multiple adjacent CpG sites on an individual sequencing read, in order to exploit the pervasive nature of DNA methylation for signal amplification. Therefore, CancerDetector can sensitively identify a trace amount of tumor cfDNAs in plasma, at the level of individual reads. We evaluated CancerDetector on the simulated data, and showed a high concordance of the predicted and true tumor burden. Testing CancerDetector on real plasma data demonstrated its high sensitivity and specificity in detecting tumor DNAs. In addition, the predicted tumor burden showed great consistency with tumor size and survival outcome. Note that all of those testing were performed on sequencing data at low to medium coverage (1X to 10X). Therefore, CancerDetector holds the great potential to detect cancer early and cost-effectively.

  Study EGAS00001002728

• Exploring the role of mtDNA variation in Multiple Sclerosis in a large cohort of discordant monozygotic twins

  Several lines of evidence indicate that mitochondrial DNA (mtDNA) variants might predispose to multiple sclerosis (MS). We examined this in 49 monozygotic (MZ) twin pairs clinically discordant for MS at study entry. Since the nuclear DNA of MZ twins is identical, our study provides a unique setting to functionally associate unique mtDNA variants and skewed heteroplasmy with MS development. In order to identify mtDNA variants in the twin cohort, we deeply sequenced the mitochondrial genome in blood of all 49 MZ twin pairs using next generation sequencing (Illumina, HiSeq or MiSeq) with an average coverage depth of ~25,000 sequences per base. Heteroplasmic variants were validated using targeted deep sequencing (TDS) (Illumina, MiSeq) in DNA isolated from blood and buccal swabs. In addition, whole blood was also available of 5 additional MS-affected or healthy siblings and 1 dizygotic twin pair discordant for MS, comprising in total 6 non-identical sib pairs. Moreover, all cases were screened for pathogenic mtDNA polymerase gamma (POLG) mutations. The data provides valuable insights in the possible involvement of mtDNA variants in the pathogenesis of MS, and gives information on the segregation of heteroplasmic variants within MZ twins and non-identical siblings and across different tissues.

  Study EGAS00001001240

• Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

  We studied a group of melanoma patients treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n=51), and observed significantly higher rates of major pathologic response (MPR= <10% viable tumor at resection) and improved recurrence-free survival (RFS) in females versus males (MPR-66% versus 14%, p=0.001; RFS-64% versus 32% at 2 years, p=0.021). Findings were validated in a several additional cohorts 2-4 patients with unresectable metastatic melanoma treated with BRAF and/or MEK-targeted therapy (n=664 patients in total), demonstrating improved progression-free survival (PFS) and overall survival (OS) in females versus males in several of these studies. Studies in pre-clinical models demonstrated significantly impaired anti-tumor activity in male versus female BRAF/MEK-treated mice (p=0.006), with significantly higher expression of androgen receptor (AR) in tumors of male and female BRAF/MEK-treated mice versus control (p=0.0006 and 0.0025). Pharmacologic inhibition of AR signaling improved responses to BRAF/MEK-targeted therapy in male and female mice (p=0.018 and p=0.003), whereas induction of AR signaling (via testosterone administration) was associated with significantly impaired response to BRAF/MEK-targeted therapy in males and females (p=0.021 and p<0.0001).

  Study EGAS00001006196

• RNA-Seq of vocal fold fibroblasts in Reinke’s edema and control subjects

  The voice disorder Reinke’s edema (RE) is a smoking- and voice-abuse associated benign lesion of the vocal folds, defined by an edema of the Reinke space, accompanied with pathological microvasculature changes and immune cell infiltration. Vocal fold fibroblasts (VFF) are the main cell type of the lamina propria and play a key role in the disease progression. Current therapy is restricted to symptomatic treatment. Hence, there is an urgent need for a better understanding of the molecular causes of the disease. In the present study, we investigated differential expression profiles of RE and control VFF by means of RNA sequencing. In addition, fast gene set enrichment analysis (FGSEA) was performed in order to obtain involved biological processes, mRNA and protein levels of targets of interest were further evaluated. We identified 74 differentially regulated genes in total, 19 of which were upregulated and 55 downregulated. Differential expression analysis and FGSEA revealed upregulated genes and pathways involved in extracellular matrix (ECM) remodeling, inflammation and fibrosis. Downregulated genes and pathways were involved in ECM degradation, cell cycle control and proliferation. The current study addressed for the first time a direct comparison of VFF from RE to control and evaluated immediate functional consequences.

  Study EGAS00001005130

• WES, sWGS and RNA-seq of Asian breast cancer

  The dataset contains a full genomics characterization of 527 Asian breast tumours. This includes whole-exome sequencing of tumour tissue at 80X, whole-exome sequencing of matched normal (blood) tissue at 40X, shallow-whole genome sequencing at 0.1X for copy number analyses, and RNA-seq of tumour tissue at 40X coverage (>15 million reads). Whole-exome libraries were prepared using the Nextera Rapid Capture Exome Kit; exome capture was performed in pools of 3 and subjected to paired end 75 sequencing on a HiSEQ4000 platform. RNA libraries were prepared using the TruSeq Stranded Total RNA HT kit with Ribo-Zero Gold as per manufacturer’s instructions and also subjected to paired end 75 sequencing on a HiSEQ4000 platform. Uploaded bam files have been mapped to the hs37d5 human genome and processed using the standard GATK pipelines. Paired clinical, demographic, genotyping, and overall survival data for these patients are available from the associated publications or by request.

  Dataset EGAD00001006399

• RNA sequencing on colonic biopsies from inflammatory bowel disease patients treated with vehicle control, MEK inhibitor, or infliximab

  This dataset consists of RNA sequencing data (FASTQs) from intestinal mucosal biopsies from 9 IBD patients. All patients endoscopically active disease and were not receiving immunosuppressive or biologic therapies. All biopsies (6 per donor) were collected from a single inflamed site. Biopsies were cultured for 18 hours at an air-liquid interface in media containing either DMSO (vehicle control), PD-0325901 (0.5uM) or infliximab (10ug/ml; MSD) - two biopsies per condition. Sequencing was performed on a NovaSeq 6000 (100bp, PE reads). After 18 hours, biopsies were harvested and snap frozen. After lysis, RNA was extracted using an AllPrep DNA/RNA Mini Kit (Qiagen). Sequencing libraries were prepared from 10ng RNA using the SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian (Takara) following the manufacturer’s instructions. The quality and molarity of all libraries was assessed using a BioAnalyzer 2100 and the libraries were sequenced on a NovaSeq 6000 (100bp, PE reads).

  Dataset EGAD00001011333

• Mongolia and Western Dataset

  Total collection of Samples. Exome sequencing and RNAseq from Mongolia and Western HCC samples.

  Dataset EGAD00001007830

• RNA sequencing in primary inflammatory (TPP) macrophages following deletion of a disease-associated gene desert at chr21q22, disruption of ETS2, or treatment of ETS2-edited macrophages with a HIF1α stabiliser.

  This dataset comprises raw RNA sequencing data (FASTQs) from primary inflammatory (TPP) macrophages that were unedited (non-targeting control, NTC), edited to delete the disease-associated chr21q22 enhancer region (n=5), or edited to disrupt ETS2 with 1 of 2 independent gRNAs (n=9). We also performed RNA-sequencing in NTC or ETS2-edited TPP macrophages that were treated for 12 hours with vehicle (DMSO) or roxadustat (30 uM, n=3). Macrophages were detached using Accutase and lysed. RNA was extracted from cell lysates using an AllPrep DNA/RNA Mini Kit (Qiagen). Sequencing libraries were prepared from 10ng RNA using the SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian (Takara) following the manufacturer’s instructions. The quality and molarity of all libraries was assessed using a BioAnalyzer 2100 and the libraries were sequenced on a NextSeq500. Raw data are provided as 50 bp paired-end Illumina reads.

  Dataset EGAD00001011338

• GoNL release 5 haplotype panel

  The samples in this panel come from 250 families: 248 parents-child trios and 2 parent-child duos. As the children do not provide additional haplotypes or population information, they were excluded from the panel. The samples present in the release are composed of 248 couples, 2 single individuals and 1 sample composed from the 2 haplotypes from the duo's children transmitted by their missing parent. The composed sample is named gonl-220c_223c.The files contain a total of 18.9M SNVs and 1.1M INDELs in autosomal chromosomes. They were generated by phasing/imputing the SNVs (a) and INDELs (b) using MVNCall. Only sites passing filters are reported. Sites filtered as part of the GoNL inaccessible genome were kept (but flagged as filtered) and still may contain true positive calls but should be used with care as they are located in parts of the genome that are less well captured (systematic under or over-covered or low-mapping quality)

  Dataset EGAD00001000744

• Targeted resequencing of Cardiomyopathies associated genes

  In this study, we present the results of a custom “pan-cardiomyopathy panel” in a molecular screening of 38 unrelated patients, 16 affected by DCM, 14 by HCM, and 8 by ARVC. The panel was designed using the Design Studio Tool (Illumina, San Diego, CA,USA). Coding regions and intron–exon boundaries of 115 genes, known to be associated with 7 DCM, HCM, and ARVC as well as channelopathies, were selected for targeted gene enrichment. For genes with multiple transcripts, all exons included in transcripts expressed in cardiac muscle were considered in the gene panel design. Total DNA was extracted from peripheral blood samples using the Wizard Genomic DNA Purification Kit (Promega, Mannheim, Germany) according to the manufacturer’s instructions, quantified, and qualitatively checked using NanoDrop 2000c (Thermo Fisher Scientific, Waltham, MA, USA). Custom targeted gene enrichment and DNA library preparation were performed using the Nextera Capture Custom Enrichment kit (Illumina) according to the manufacturer’s instructions. Targeted regions were sequenced using the Illumina MiSeq platform, generating approximately two millions of 150-bp paired-end reads for each sample (Q30 ≥90%).

  Dataset EGAD00001003359

• The mutational landscape of normal human endometrial epithelium

  All normal somatic cells are thought to acquire mutations. However, characterisation of the patterns and consequences of somatic mutation in normal tissues is limited. Uterine endometrium is a dynamic tissue undergoing cyclical shedding and reconstitution lined by a gland-forming epithelium. Whole genome sequencing of normal endometrial glands showed that most are clonal cell populations derived from a recent common ancestor, with mutation burdens differing from other normal cell types and many fold lower than endometrial cancers. Mutational signatures found ubiquitously account for most mutations. Many, in some women all, endometrial glands are colonised by cell clones carrying driver mutations in cancer genes, often with multiple drivers. Total and driver mutation burdens increase with age, but are also influenced by other factors, including body mass index and parity, and clones with drivers often originate during early decades of life. The somatic mutational landscapes of normal cells differ between cell types and are revealing the procession of neoplastic change leading to cancer.

  Dataset EGAD00001004547

• A Study to Assess the Cardiovascular, Cognitive, and Subjective Effects of Atomoxetine in Combination with Intravenous Methamphetamine

  The Study to Assess the Cardiovascular, Cognitive, and Subjective Effects of Atomoxetine in Combination with Intravenous Methamphetamine started in 2007 and ended in 2011. It was a small pilot study that included methamphetamine abusing individuals and healthy control participants aged 18-50 years. Participants who qualified over the telephone were scheduled to visit the London Laboratory at the UCLA Semel Institute for Neuroscience and Human Behavior for the In-Person Screening Phase. The screening procedures, usually scheduled over two visits, determined if participants were eligible to complete the subsequent study visits. Both groups completed identical screening procedures, including a SCID diagnostic interview to rule out any major psychiatric disorders. Methamphetamine users also answered questionnaires specific to their drug use. Urine toxicology for marijuana, opiates, cocaine, methamphetamine, and benzodiazepines were monitored at the beginning and throughout the study. Additionally, participants had blood samples to test for Rapid Plasma Reagin (exposure to syphilis), purified protein derivative (PPD), HIV and Hepatitis-C (HCV). Positive test results were relayed by a study physician and resulted in termination from continuing in the study. The inpatient portion of the study lasted a total of 24 days. To confirm compliance with abstinence from illicit and prescription drug use for the duration of the study, urine and breath alcohol testing was performed for both inpatient (methamphetamine users) and outpatient (healthy control) groups. Each subject was randomized to receive either atomoxetine (80 mg daily) or placebo. During inpatient days of the study, a study physician oversaw research subjects daily and experimental procedures were conducted in the General Clinical Research Center (GCRC). During drug administration sessions, heart rate and blood pressure were assessed at frequent intervals. Experimental sessions lasted around three hours and were conducted at approximately the same time of day for a given participant. Lunch was provided to participants at 11:30am with the prohibition of caffeine on study days involving methamphetamine administration. Participants were provided with smoke breaks as needed to assure that acute nicotine withdrawal did not negatively impact performance on cognitive testing. The following outlines the day to day procedures for a methamphetamine inpatient: Phase I Inpatient Study (15 days total) Days 1-3: On the day of admission, participants received blood tests and an EKG in order to determine that they had no occult medical conditions which would make their participation in the study medically contraindicated. A three day washout period was provided at the beginning of the study to establish an appropriate methamphetamine-free baseline for testing. Days 4-6: Participants completed cognitive test batteries to assess inhibitory control including self-report measures and cognitive testing, as well as up to three MRI scanning sessions. Day 7: On day 7, at 9AM and 1PM, participants received methamphetamine in a single-blinded condition. It was administered as two IV infusions of 15mg separated by a 60min break. The total dose of IV methamphetamine was 30mg. Participants were clinically evaluated by continuous cardiac telemetry, serial EKG and measurement of vital signs, during and after infusions, in order to determine the medical safety of methamphetamine infusion in the absence of study medication. Day 8: On day 8 we evaluated the safety and residual effects of the methamphetamine administered on the previous day. Days 9-10: After demonstrating medical and psychiatric stability of the initial methamphetamine infusion, participants were then randomized to receive placebo or atomoxetine (0 or 40mg) under double-blind conditions, which would be given at 8AM on both study days. Days 11-12: On days 11 and 12, participants remained in the GCRC and took two doses of test compound atomoxetine (0 or 40mg) at 8AM and 8PM. On the morning of day 12, participants completed a series of cognitive testing. Day 13: On day 13, participants remained in the GCRC, and took two doses of the test compound atomoxetine (0 or 40mg) at 8AM and 8PM. At 9AM and noon, they received methamphetamine under double-blind conditions administered non-contingently as two infusions of 0 or 15mg by IV (intravenously), with each infusion separated by 60min. The total dose of IV methamphetamine that each participant received was 30mg. As before, participants were clinically evaluated by continuous cardiac telemetry, serial EKG and measurement of vital signs, during and after infusions, in order to determine the medical safety of methamphetamine infusion in those participants receiving study medication. Day 14: On day 14 at 8AM, participants received their final dosing of the first test compound (atomoxetine 0 or 40mg). At 9AM and 1PM, participants selected between methamphetamine infusion or money using double-blind conditions in a multiple-choice self-administration paradigm. Participants were able to take up to two infusions of 0 or 15mg of methamphetamine, separated by 60min. The total dose of IV methamphetamine that each participant received on day 14 was 30mg. Participants were clinically evaluated by continuous cardiac telemetry, serial EKG and measurement of vital signs, during and after infusions, in order to determine the medical safety of methamphetamine infusion in those participants receiving study medication. At 5pm on day 14 discharge laboratory studies were drawn. Day 15: On day 15, a final EKG was performed as well as a review of discharge laboratory studies, including review of the EKG and continued medical and psychiatric stability. Upon clearance from a physician, participants were discharged on day 15. Participants spent at least 2 weeks (14 days) out of the hospital prior to returning to the UCLA GCRC for inpatient Phase II. Phase II Inpatient Study (9 days total) Day 1-2: On the day of re-admission, participants received blood tests and an EKG. A two day washout period was provided at the beginning of the study to establish an appropriate methamphetamine free condition for safe administration of the second test compound condition. Days 3-4: On days 3 and 4, given medical stability, participants were then switched to the opposite test compound (atomoxetine 0 or 40mg) under double-blind conditions, in the same manner as in Days 9-10 in Phase I. Days 5-6: Same procedure as in Days 11-12 in Phase I but with opposite medication condition. Day 7: Same procedure as in Day13 in Phase I but with opposite medication condition. Day 8: Same procedure as in Day14 in Phase I but with opposite medication condition. Day 9: Same procedure as in Day14 in Phase I but with opposite medication condition. For healthy control participants, the study consisted of 30 days or fewer of out-patient testing. Healthy control participants had an extensive screening, including a history and physical exam performed by a study physician, an EKG, and laboratory studies performed to assess for medical or psychiatric conditions. Control participants meeting criteria were invited back to UCLA to undergo cognitive testing, and some participants received fMRI scans. Participants were required to refrain from illicit and prescription drug use for the duration of the study, which was confirmed with urine toxicology and breath alcohol level testing on examination days. Caffeine was restricted on study days for least 2 hours prior to cognitive testing and MRI scans. Participants were permitted to drink their normal daily intake of caffeine, given the caveat above. On study days, cigarette smoking was permitted to match conditions used with methamphetamine users. The incorporation of smoke breaks during the test day assured that acute nicotine withdrawal did not negatively impact performance on cognitive tests or neuroimaging. The following outlines procedures for healthy control participants: For normal controls, participation involved one day of outpatient screening, and one day of baseline cognitive testing and possible MRI scans. After these procedures were completed, participants were randomized to the first test compound (atomoxetine 40mg or placebo), to be taken once daily in the morning for 2 days. It was then increased to twice daily for the next 3 days, followed by a final dose (40mg or placebo) on the sixth day of study medication. Participants were also asked to bring their pill packages to assess compliance with the study medication. Additionally, control participants completed a series of repeated-measures cognitive testing (on placebo or atomoxetine, respectively) and possibly two fMRI sessions (separated by a short break). After at least a four-day washout period, control participants were instructed to start the opposite test compound (atomoxetine 40mg or placebo), again to be taken once daily in the morning for two days, then twice daily for 3 days, reaching the final dose (40mg or placebo) of the second test compound in the morning. Participants were again asked to bring their pill packages to assess compliance and had blood drawn to assess atomoxetine levels. Control participants then completed another series of cognitive testing and fMRI testing sessions. They were subsequently discharged from the study. Normal control participants returned two weeks after completion of both study phases in order to complete assessments to their physical and psychological status following treatment.

  Study phs001195

• The Finland-United States Investigation of NIDDM Genetics (FUSION) Study - Islet Expression and Regulation by RNAseq and ATACseq

  This study evaluates gene expression and its regulation in human pancreatic islets, a tissue relevant in the study of genetic risk factors contributing to diabetes. We obtained pancreatic tissue sections and purified pancreatic islets from deceased donors and processed these biological samples to generate various data types. We generated spatial transcriptomic data from pancreatic tissue samples using the 10X Genomics VISIUM technology with sequencing on the Illumina NovaSeq platform. We also generated multiple data types from the purified pancreatic islets using genome-wide SNP chips, bulk RNA-Seq, microRNA (miRNA)-Seq, whole genome sequence, DNA methylation (methyl)-Seq, cap analysis of gene expression (CAGE)-Seq, single cell RNA-seq, and single nuclei ATAC-seq approaches. These data include ATAC-seq of two islet subjects, RNA-seq of 31 additional subjects, genome-wide chip genotypes, and imputed genotypes of the 33 subjects released with phs001188.v1. For genotyping, 500-1000 islet equivalents (IEQ) were cultured as in Gershengorn (Science, 2004, PMID: 15564314); genomic DNA isolated from islet cultures. For RNA analyses, 2500-5000 IEQ from each islet source were used for bulk or single-cell RNA isolation. Messenger RNA was isolated with trizol extraction and 12-plex libraries were generated using the Illumina TruSeq directional mRNA-seq library protocol. Bulk RNA sequencing was performed on HiSeq2000/HiSeq2500/Hiseq4000/NovaSeq6000 sequencers using paired-end reads at the NIH Intramural Sequencing Center (NISC). miRNA libraries were prepared from total RNA from 68 samples, pooled and sequenced 50bp single-end reads on Illumina HiSeq2500. CAGE libraries were prepared from total RNA samples using the nAnT-iCAGE protocol at DNAFORM, Japan. CAGE libraries were sequenced at the NIH Intramural Sequencing Center (NISC) on the HiSeq2000 sequencer. Genotyping on the Illumina Omni2.5M array was performed at the NHGRI Genomics Core facility. Genotypes were imputed using the HRC.r1.1.2016 reference panel. To assess regions of open chromatin in islets, we performed bulk ATAC-seq on HiSeq2000 sequencers using paired-end reads at NISC. Single-nuclei ATAC-seq libraries were prepared using single-cell-combinatorial-indexing (sci-) ATAC-seq protocol and sequenced on Illumina NextSeq using paired-end reads. scRNA-seq libraries were generated using the 10X Genomics platform and sequenced on Illumina HiSeq3000 at the Genomics Technology Core of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Greater than 90% of the loci associated with T2D through genome-wide association studies occur in non-coding regions, suggesting a strong regulatory component to disease susceptibility. Therefore, there is a critical need to understand the full spectrum of genetic variation and regulatory element usage in T2D-relevant tissues. To that end, this study contains multiple genomic and transcriptomic data sets from pancreas tissue sections and pancreatic islets, a resource that will contribute to our efforts to investigate the genetic risk factors for type 2 diabetes.

  Study phs001188

• Transcriptome of CD4+ T cells and CD8+ T cells in glioblastoma multiforme

  Patients included in this study were over 18 years of age and had a histology-confirmed diagnosis of glioblastoma multiforme (GBM). Exclusion criteria were the previous administration of any anti-tumor therapy including radiation therapy. All patients gave written informed consent. The study was approved by the local ethics committee (TUM Medical school) and conducted following the Declaration of Helsinki. During resection of the tumors, tumor tissue and tissue from normal appearing brain within the operative channel was collected. Blood was drawn during the surgical procedure. Single cell suspensions were prepared from the tumor tissue, the normal appearing brain, and the blood. CD4+ T cells and CD8+ T cells were sorted by flow cytometry. Only patients with a complete set of specimens (CD4+ tumor infiltrating lymphocytes (TIL), CD8+ TIL, CD4+ T cells from normal appearing brain, CD8+ T cells from normal appearing brain, blood-derived CD4+ and CD8+ T cells) containing a minimum of 1000 cells in each sorted sample were further analyzed (n=9). Total RNA was isolated from sorted cell populations using the RNAeasy Plus micro kit (Qiagen, 74034). Quality and integrity of total RNA was controlled on a Bioanalyzer 2100 (Agilent Technologies). Library preparation for bulk-sequencing of poly(A)-RNA was done as described previously (Parekh et al., 2016). Briefly, barcoded cDNA of each sample was generated with a Maxima RT polymerase (ThermoFisher Scientific, EP0742) using oligo-dT primer containing barcodes, unique molecular identifiers (UMIs) and an adaptor. Ends of the cDNAs were extended by a template switch oligo (TSO) and full-length cDNA was amplified with primers binding to the TSO-site and the adaptor. NEB UltraII FS kit was used to fragment cDNA. After end repair and A-tailing, a TruSeq adapter was ligated and 3'-end-fragments were finally amplified using primers with Illumina P5 and P7 overhangs. In comparison to previous descriptions (Parekh et al., 2016), the P5 and P7 sites were exchanged to allow sequencing of the cDNA in read 1 and barcodes and UMIs in read 2 to achieve a better cluster recognition. The library was sequenced on a NextSeq 500 (Illumina) with 59 cycles for the cDNA in read 1 and 16 cycles for the barcodes and UMIs in read 2. Data were processed using the published Drop-seq pipeline (v1.0) to generate sample- and gene-wise UMI tables (Macosko et al., 2015). Reference genome (GRCh38) was used for alignment. Transcript and gene definitions were used according to the Genecode Annotation Version 35.

  Dataset EGAD50000000226

• Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study (nuMoM2b Heart Health Study)

  Participants from study sites that recruited during the original study funded by NICHD of pregnant people, called nuMoM2b, participated in this study. The nuMoM2b-HHS1 was a prospective observational follow-up study of the nuMoM2b cohort consisting of interval contacts via phone or web every 6 months to about a year, and an in-person visit 2 to 7 years after the end of the nuMoM2b pregnancy including: Demographics Self-administered questionnaires Clinical measurements Lab results An in-home sleep breathing assessment for the subset of participants with at least one valid sleep breathing assessment during nuMoM2b Abstraction of medical records for pregnancies subsequent to nuMoM2b involving self-reported adverse pregnancy outcomes or multiple births Abstraction of medical records of selected cardiovascular risk-related events or procedures reported by participants. The study capitalized on the rich and unique data prospectively collected during nuMoM2b (biomarkers, uterine artery Doppler studies, fetal growth, psychosocial determinants, sleep, and blood pressure) and rigorous definitions of adverse pregnancy outcomes. These data are stored in the NICHD repository DASH (https://dash.nichd.nih.gov/study/226675). A total of 8,838 nuMoM2b participants were targeted for contact during nuMoM2b-HHS and 7,872 participants were reached, of whom 7,003 completed one or more interval contacts. Of these, 5,206 agreed to the visit, and 4,508 attended an in-person visit.

  Study phs002808

• 3/7 Psychiatric Genomics Consortium: Finding Actionable Variation

  The goal of this study was to generate new therapeutic hypotheses by targeted sequencing of 161 genes most likely to harbor schizophrenia (SCZ) causal variants in multi-ancestry schizophrenia case-control cohorts. The gene panel was intended to contain putative SCZ risk genes, from within which, the majority of new discoveries from additional WES/WGS would come. To this end, we integrated current knowledge of the genetic architecture of SCZ (results from The Schizophrenia Exome Sequencing Meta-Analysis Consortium, or SCHEMA) and gene membership in gene sets that have been implicated in SCZ using a Bayesian framework. A total of 23,352 individuals selected to be non-overlapping with SCHEMA, as well as other previous and ongoing sequencing efforts in the field, were identified from over 20 individual study sites. Sequencing of the exonic regions of 161 prioritized genes was performed on the Ion Torrent platform in between June 2018 and April 2019. Sequencing plates were matched with respect to ancestry and case/control composition whenever possible. The average sequencing depth across all samples was 224x. Single sample calling was performed using Torrent Variant Caller v5.8.0, which is specially optimized to exploit the underlying flow signal information generated by the Ion Torrent sequencing. The schizophrenia case-control status was obtained from each original study site.

  Study phs003138

• Evolution of Core Archetypal Phenotypes in High-Grade Serous Ovarian Cancer (HGSOC)

  The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells in response to chemotherapy is only partially understood. To uncover phenotypic changes associated with chemotherapy resistance, we performed single-cell RNA-sequencing (scRNA-seq) or whole-genome sequencing of 23 total patients, with longitudinal samples collected from 9, treatment-naïve samples from 8 patients, and post-treatment samples from 6 patients. Our study revealed that the HGSOC transcriptome could be described using three core archetypal phenotypes, defined as oncogenic tasks that describe majority of the transcriptional data. We implemented a multi-task learning approach to identify the biological tasks of each archetype and identified metabolism and proliferation, cellular defense response, and DNA repair signaling. The “metabolism and proliferation” archetype evolved during treatment and was enriched in cancer cells from patients that received multiple-lines of treatment and had elevated tumor burden indicated by CA-125 levels. The emergence of archetypes was not consistently linked to specific whole-genome driver mutations. However, archetypes were closely associated with sub-clonal clusters at the single-cell level, indicating that cancer cell sub-populations specialize in particular biological tasks. Our study reveals a defining principle of ovarian tumor evolution using temporal scRNA-seq profiles, identifies the key phenotypic features across patients and links metabolic shifts with a response to chemotherapy.

  Study phs002294

• Center for Common Disease Genomics [CCDG] - Cardiovascular: Genetics of Coronary Heart Disease - Characterizaton of Coronary Prone Pedigrees

  The primary cohort includes samples from 499 men and 154 women who survived a myocardial infarction, percutaneous transluminal angioplasty, or coronary artery bypass grafting (CABG) by age 55 years for men or age 65 years for women. Patients were seen at least six months after their acute event. Samples from another 488 men and 541 women that showed a nearly identical age, gender, and measured blood pressure distribution were collected as population-based controls. These controls tended to live in urban Salt Lake City, where the vast majority of the population is Caucasian. Blood samples were collected in the morning after 12h to 16h of fasting and prepared according to guidelines of the Lipid Research Clinic's program Manual of Laboratory Operations. All samples have serum, DNA and/or white blood cells, and a host of measurements (e.g. standard clinical chemistries, LDL and HDL cholesterol, triglycerides, glucose, HbA1C, insulin, blood pressures, anthropometric data, information on medical conditions and drug use, etc.). Additional details about the cohort or sample preparation were published previously. Here we present in total 1,475 patients that were successfully sequenced. This number includes 228 women, 419 men, and 7 of unreported gender survivors as well as 339 women and 482 men that served as population-based controls.

  Study phs001901

• INdiana GENomics: Implementing an Opportunity for the Under Served (INGENIOUS)

  The INGenious trial planed to enroll a total of 6,000 patients, with 2,000 patients assigned to a pharmacogenetic testing arm and 4,000 to a control arm who will be followed, but not tested. It is randomized between an intervention arm and one that receives no intervention in order that the genotyped group can be compared with one in which undisturbed, routine clinical care is carried out in patients taking the same drugs. Both arms will be followed for a year after being prescribed a targeted medication. Patients randomized into the intervention arm that are prescribed one or more of the 27 targeted index medication will receive pharmacogenomic testing using a custom micro-array measuring 43 Single nucleotide polymorphisms in 14 genes. The study is being conducted by the Indiana University School of Medicine and the Indiana University Institute of Personalized Medicine in collaboration with the Eskenazi and Indiana University Health Systems and will evaluate the economic and clinical outcomes associated with embedding a pharmacogenomics program in a system that serves as the primary health care safety-net in Indianapolis, Indiana. By successfully implementing a pharmacogenomics program and integrating it with the Electronic Health Record and Clinical Decision Support system, physicians will be able to optimize patient care by delivering tailored therapeutic decisions based on the patient's individual genetics.

  Study phs001701

• Phase 2 Study of Nivolumab and Entinostat in Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma

  The study was a single-center, open-label, phase II trial (registration no. NCT03250273) designed to evaluate the efficacy of entinostat in combination with nivolumab in patients with advanced pancreatic ductal adenocarcinoma (PDAC). The aim was to assess the objective response rate using RECIST v1.1 criteria as the primary endpoint. A total of 27 patients with advanced PDA were enrolled from November 2017 to November 2020. Their treatment involved a 14-day lead-in with entinostat monotherapy, followed by a combination with nivolumab. The study utilized several molecular technologies to assess immune profiles and tumor microenvironment (TME) changes: high-dimensional mass cytometry by time of flight (CyTOF), Luminex for chemokine analysis in plasma, multiplexed immunohistochemistry (mIHC), image cytometry-based quantification, bulk RNA sequencing analysis. The objective response rate (ORR) was 11% with three patients showing a partial response (PR). The median duration of response was 10.2 months. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 63% of patients, with the most common being decreased lymphocyte count, anemia, hypoalbuminemia, and hyponatremia. Gene expression analysis showed an enrichment in inflammatory response signaling pathways with the combination treatment. RNA sequencing data with clinical and demographic patient information will be available through dbGaP. For expression summaries, please refer to GEO submission GSE248014.

  Study phs003615

• Clinical Study of Intermittent Positive Pressure Breathing (IPPB-BioLINCC)

  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. Objectives: To evaluate the efficacy of long-term intermittent positive pressure breathing (IPPB) treatment when used as an adjunct to the overall care of ambulatory outpatients with chronic obstructive pulmonary disease. The evaluation compared the use of IPPB with use of a powered nebulizer.Participants: A total of 3218 participants were enrolled.Design: Multicenter randomized controlled clinical trial. Conclusions: Compliance with treatment, lung function, and quality of life were evaluated at regular intervals during follow-up, and records were kept of hospitalizations and vital status. Treatment compliance was less than optimal; only half of the participants used their devices for the prescribed amount of time or 10 minutes at least three times a day. Although this was disappointing, it was probably the best compliance that could be attained. There was no statistically significant difference between the treatment groups in mortality, rate and duration of hospitalizations, or change in lung function or life quality with time, overall or for clinically relevant subgroups. The trial group saw no advantage of IPPB over compressor nebulizer therapy and concluded that, if an advantage existed, it must be marginal.

  Study phs004010

• Genetic Markers of Caries Risk in Diverse Underserved Children: CIDR

  The study Predicting Caries Risk In Underserved Children, From Toddlers To The School-age Years In Primary Healthcare Settings, is a renewal of an initial project designed to develop a dental caries risk tool for use in primary medical and dental healthcare settings to identify high dental caries risk children, expanding from the toddler (1-4 years old, referred to as Stage 1 grant) to the school-age years (6-9 years old, referred to as Stage 2 grant); and to determine the relationships between dental caries risk profiles and dental caries disease patterns. 1326 children, 12 +/- 3 months of age, and their primary caregivers, were enrolled in the study. This cohort represents a diverse population, including ethnic and racial minorities and low socio-economic status groups. There are a total of six in-person visits (at child age 1, 2.5, 4, 6.5, 8 and 9.5 years), and at each one the primary caregiver (PCG) completes a dental caries risk questionnaire, and the child receives a detailed dental caries examination. Saliva samples were collected during the age 8 visit (2019-2020) from 1,059 racially and ethnically diverse individuals (543 children and 516 PCGs) for the purposes of human genetic testing, to study the genetics of dental caries experience of children and their primary caregivers.

  Study phs003280