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• CAGE analysis for non-small cell lung carcinoma

  Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed. To achieve this goal, we performed CAGE (Cap Analysis of Gene Expression) to quantify promoter activities on 97 frozen tissues from surgically resected lung cancers (22 SCC and 75 AD). The result was followed up by by immunohistochemical analysis (IHC) in an independent group.

  Study JGAS000070

• Hematopoietic Tet2 inactivation enhances the response to checkpoint blockade immunotherapy

  Somatic mutations inactivating TET2 are among the most common drivers of clonal hematopoiesis (CH). While TET2 inactivation is associated with monocyte-derived inflammation and improved chimeric antigen-receptor-T cell function, its impact on immunotherapy response is unknown. In murine models, hematopoietic Tet2 mutation enhanced the immune checkpoint blockade (ICB) response via the combined presence of phagocytes, CD4 and CD8 T cells. This effect was lost with myeloid- or T-cell restricted Tet2 inactivation, or in mice with 20% Tet2-mutant hematopoiesis. Mechanistically, in Tet2-mutant tumor-infiltrating leukocytes (TILs), ICB preferentially restricted cell states linked to tumor progression while inducing anti-tumor states. Tet2-mutant monocytes activated costimulatory programs, while Tet2-mutant T cells showed enhanced T cell memory signatures, alongside decreased exhaustion and regulatory phenotypes. This murine data was clinically relevant, since tumors from colorectal cancer and melanoma patients with TET2 driver mutation-CH (TET2-CH) showed enhanced immune infiltration, inflammation, and T cell activation. In melanoma patients treated with ICB, TET2-CH was associated with 6-fold greater odds of clinical benefit. Collectively, we demonstrate that hematopoietic Tet2 inactivation primes leukocytes for anti-tumor states associated with immunotherapy response and provides a potential biomarker for personalized therapy.

  Study EGAS50000001191

• Acute Respiratory Distress Network Early Versus Delayed Enteral Feeding to Treat People with Acute Lung Injury or Acute Respiratory Distress Syndrome (ARDSNet EDEN-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. Biospecimens: Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from ARDSNet-EDEN include bronchial lavage, plasma, DNA, and urine. Please note that use of biospecimens in genetic and non-genetic research is subject to a tiered consent. Objectives: To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days (VFDs) and decrease gastrointestinal intolerances compared with initial full enteral feeding. Background: Mechanically ventilated patients cannot eat normally and if not fed for long periods become malnourished. Because malnutrition is associated with poor outcomes in critically ill patients, artificial nutrition is often provided, especially in those with acute lung injury (ALI) and with expected longer duration of mechanical ventilation. When feasible, enteral nutrition targeting full caloric needs has been advocated over parenteral nutrition. However, feeding intolerance and common care practices often serve as practical barriers to reaching recommended goals. Although confounded by indication and severity of illness, several observational studies have shown improved clinical outcomes, including fewer infections, shorter duration of mechanical ventilation, and lower mortality for patients receiving a higher percentage of calculated caloric needs. Nonetheless, the best timing, formulation, and amount of enteral nutrition remain unknown. Participants: A total of 1,000 participants were enrolled. Design: Participants were randomized, stratified by site and presence of shock at enrollment, to receive either trophic or full enteral feeding for the first 6 days of mechanical ventilation. The initial 272 patients were also simultaneously randomized to a separate trial (the OMEGA study) comparing a nutritional supplement containing omega-3 fatty acids and antioxidants with an isocaloric, isovolemic control in a 2 × 2 factorial design.The designated feeding strategy was initiated within 6 hours of randomization and continued until death, extubation, or day 6. The care of mechanically ventilated patients still receiving enteral feedings after day 6 was managed according to the full feeding strategy in both groups. In extubated patients who then required reintubation, enteral nutrition was restarted and managed according to the study protocol.In the full-feeding group, enteral nutrition was initiated at 25 mL/h and advanced to goal rates as quickly as possible. Gastric residual volumes were checked every 6 hours while enteral feeding was increased. Patients randomized to the initial trophic-feeding group had enteral nutrition initiated at 10 mL/h (10-20 kcal/h) for the first 272 patients who also received the omega-3 or control supplement (240 mL volume per day). After the data and safety monitoring board stopped the OMEGA portion of the factorial design, the initial trophic feeding rate was changed to 20 kcal/h to approximate the calories that had been delivered in the OMEGA study. Gastric Residual Volumes (GRVs) were checked every 12 hours during trophic feeding. In patients randomized to trophic feeding, enteral nutrition was advanced to full-energy feeding rates following the same protocol used for the full-feeding group if they were still receiving mechanical ventilation at 144 hours. Conclusions: There was no difference between groups with regard to the primary end point, VFDs to day 28. There also were no differences in 60-day mortality, organ failure−free days, ICU-free days, or the incidence of infection between groups. Similarly, there were no differences between groups in VFDs or survival when analyzed by body mass index category or when subsets of patients with shock or more severe lung injury (acute respiratory distress syndrome) were examined.JAMA. 2012 Feb 22;307(8):795-803

  Study phs004168

• DETECT-A NGS Data Batch 4

  This batch is a subset of the full DETECT-A dataset, containing 25210 fastq files generated from 3040 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001015360

• DETECT-A NGS Data Batch 6

  This batch is a subset of the full DETECT-A dataset, containing 9 fastq files generated from 8 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001015458

• DETECT-A NGS Data Batch 5

  This batch is a subset of the full DETECT-A dataset, containing 12740 fastq files generated from 3211 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001015426

• DETECT-A NGS Data Batch 3

  This batch is a subset of the full DETECT-A dataset, containing 29294 fastq files generated from 3653 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001008597

• DETECT-A NGS Data Batch 2

  This batch is a subset of the full DETECT-A dataset, containing 498 fastq files generated from 71 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001008591

• DETECT-A NGS Data Batch 1

  This batch is a subset of the full DETECT-A dataset, containing 43963 fastq files generated from 3024 subjects. All sequencing was conducted using Illumina HiSeq 4000 and Illumina MiSeq platforms. Note that the division into batches follows no specific criteria and that the sequencing data for each subject has multiple files which may span multiple datasets. Thus, for a comprehensive analysis, it is recommended to request access to all datasets that comprise this study.

  Dataset EGAD00001008415

• Genome-Wide Characterization of Pancreatic Adenocarcinoma Patients Using Next Generation Sequencing

  In this study, we whole genome sequenced tumor/normal pairs from three pancreatic adenocarcinoma patients to separately characterize each patient with respect to somatic alterations. For 2 patients for whom tumor RNA was available, we also performed RNA sequencing to evaluate gene expression changes. While additional sequencing is needed to improve our understanding of the disease, the information acquired from this study contributes to our knowledge base on pancreatic cancer and helps to establish a foundation for identifying and developing more efficacious treatments for patients.

  Study phs000550

• DRIP-seq data for Molecular Characterization of ETMRs

  This dataset contains DRIP-seq data from 2 patients. DNA–RNA hybrids were extracted from tissue derived from ETMR patient-derived xenograft (PDX) models (BT183) that were treated using topotecan or saline as described previously27. Tumours were subsequently frozen and pelleted using ultracentrifugation. DNA–RNA hybrids were extracted as described previously using the same protocol that is applied for cultured cells21. DNA was extracted using proteinase K followed by phenol–chloroform extraction and ethanol precipitation. Subsequently the DNA was fragmented using the restriction enzymes HindIII, EcoRI, BsrGI, XbaI and SspI (New England Biolabs). Digested DNA was subsequently incubated with the anti-DNA–RNA hybrid anti- body S9.6 (Merck, MABE1095) and immunoprecipitated using agarose beads. Bound DNA–RNA hybrids were eluted and incubated with pro- teinase K and cleaned with an additional phenol–chloroform–ethanol extraction. The DNA was subsequently sonicated and sequenced using a Hiseq 2000 machine with a 50-bp single-read protocol. Each treat- ment condition was performed in duplicate and both RNase H and the input was included as negative controls resulting in 10 Fastq files.

  Dataset EGAD00001006219

• scRNA_seq_of_circulatory_immune_cells_from_Crohn_s_disease_patient_blood

  Whole blood from Crohn's disease patients with active inflammation in the terminal ileum was depleted of red blood cells and partially depleted of granulocytes before single cell sequencing using 10X genomics 3'v3 kit followed by Illumina sequencing (HS4000 and NovaSeq) 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 EGAS00001004150

• NHLBI TOPMed: Genome-Wide Association Study of Adiposity in Samoans

  The individuals sequenced here represent a small subset of the parent study (described below) and were carefully selected for the purpose of creating a Samoan-specific reference panel for imputation back into the parent study. The INFOSTIP algorithm of Gusev et. al. (2012) (PMID: 22135348) was used to optimally choose the individuals for sequencing. The research goal of the parent study (dbGaP ID phs000914) is to identify genetic variation that increases susceptibility to obesity and cardiometabolic phenotypes among adult Samoans using genome-wide association (GWAS) methods. DNA from peripheral blood and phenotypic information were collected from 3,119 adult Samoans, 23 to 70 years of age. The participants reside throughout the independent nation of Samoa, which is experiencing economic development and the nutrition transition. Genotyping was performed with the Affymetrix Genome-Wide Human SNP 6.0 Array using a panel of approximately 900,000 SNPs. Anthropometric, fasting blood biomarkers and detailed dietary, physical activity, health and socio-demographic variables were collected. We are replicating the GWAS findings in an independent sample of 2,500 Samoans from earlier studies. After replication of genomic regions and informative SNPs in those regions, we will determine sequences of the important genes, and determine the specific genetic variants in the sequenced genes that are associated with adiposity and related cardiometabolic conditions. We will also identify gene by environment interactions, focusing on dietary intake patterns and nutrients.

  Study phs000972

• Contextual and Health Behavior Effects on Epigenetic Aging Among Africans in the Family and Community Health Studies

  The Family and Community Health Studies (FACHS) is a longitudinal examination of health and health related behaviors in African American families. The original study cohort consisted of 867 African American parent-child dyads from Georgia and Iowa who were ascertained in cooperation with local school districts. The key inclusion criteria for participating in the study were the presence of an adolescent in the 5th grade (approximately 10-11 years old) who self-identified as African American (i.e., the Target) and the participation of a primary caretaker (PC) for the Target. The clinical and biological data included in this collection are from the Target (i.e., FACHS-T) portion of these studies of these African American parent-child dyads. The initial wave of behavioral assessments of the FACHS-T subjects was conducted in 1997-98 (Wave 1), with seven subsequent ascertainments, Wave 2 (1999–2000), Wave 3 (2002–2003), Wave 4 (2005–2006), Wave 5 (2007–2009), Wave 6 (2010–2011), Wave 7 (2014–2016) and Wave 8 (2019-2021). Full interviews were obtained at each wave of the study with the exact content of the wave varying as a function of developmental age. These interviews of the FACHS-T subjects collected a wide variety of data including the following: perceived discrimination; socioeconomic status; substance use exposure; common internalizing and externalizing disorders such as depression, substance use, and conduct disorder; school efficacy; peer support and perceived parenting practices. Biological sampling of the FACHS-T subjects was conducted at three time points. Saliva DNA was collected at Wave 5 while full phlebotomy was conducted at Waves 7 and 8. The genome wide methylation data listed below is derived from the whole blood DNA samples collected at Wave 8 and Wave 9. The genome wide genotyping data was determined using DNA from the Wave 7 samples. The clinical and biological data available herein are those from 309 FACHS-T subjects who participated in both Wave 7 and Wave 8, and who consented for deposition of their data in dbGAP.

  Study phs003723

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

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

  Study phs002062

• Genome-Wide Association Study of Amyotrophic Lateral Sclerosis in Finland

  The genetic etiology of amyotrophic lateral sclerosis (ALS) is not well understood. Finland has one of the highest incidence of ALS in the world, making it an ideal population for study. To identify genetic risk factors for this fatal neurodegenerative disease, we undertook a genome-wide association study of 405 Finnish patients diagnosed with ALS and 497 Finnish controls. Two loci that exceeded the Bonferroni threshold for genome-wide significance were identified. One was located on chromosome 21q22, corresponding to the known autosomal recessive D90A allele of the SOD1 gene. The other was detected on the short arm of chromosome 9, which had been previously identified in linkage studies of families with ALS. Together, these two loci account for most of the increased incidence of ALS observed in this population.

  Study phs000344

• NHLBI TOPMed: Heart and Vascular Health Study (HVH)

  Objectives The Heart and Vascular Health Study (HVH) is a case-control study of risk factors for the development of myocardial infarction (MI), stroke, venous thrombosis (VT), and atrial fibrillation (AF). The study setting is Group Health, an integrated health care delivery system in Washington State. Only VT cases and early-onset AF cases are included as part of TOPMed. Background The HVH study originated in 1988 with the examination of risk factors for MI. Over the ensuing years, the study has been funded by a series of grants which have added case subjects with stroke, VT, and AF. Study aims focused on the associations of medication use with cardiovascular events, and starting in 1997, the study aims expanded to include genetic associations with cardiovascular disease. Participants recruited in 2009 or later who provided blood samples for genetic analysis were asked for consent to deposit genetic and phenotypic data in dbGaP. Design As part of the HVH study, case subjects were identified by searching for ICD-9 codes consistent with MI, stroke, VT, or AF, and medical records were reviewed to confirm the diagnosis. Control subjects were identified at random from the Group Health enrollment and were matched to MI cases. All subjects have an index date. For cases, the index date was assigned as the date that the cardiovascular event (MI, stroke, VT, or AF) came to clinical attention. For controls, the index date was a random date within the range of the case index dates. For both cases and controls, information was collected from the inpatient and outpatient medical record, by telephone interview with consenting survivors, and from the Group Health pharmacy and laboratory databases. Consenting participants provided a blood specimen. Subjects Only VT and early-onset AF cases from HVH are included in TOPMed. Within the HVH study, VT and AF cases were diagnosed in both inpatient and outpatient settings, and only incident cases are eligible for inclusion in TOPMed. Genetic Research Genetic factors underlying cardiovascular disease are studied using DNA isolated from the blood samples. Phenotype data for HVH study participants are available through dbGaP phs001013.

  Study phs000993

• Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts

  Cancer-associated fibroblasts (CAFs) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although the extent of CAF heterogeneity has remained undefined. Here we employ single-cell RNA-sequencing to thoroughly characterize the neoplastic and tumor microenvironment content of human PDAC tumors. Six human PDAC tumor specimens from six patients were collected, and processed for single-cell RNA-sequencing analysis. Adjacent-normal pancreas tissue was also collected from two of the patients. Tumor samples were digested, and fluorescence-activated cell sorting was used to isolate viable cells. For one tumor sample, viable, CD45-negative, CD31-negative, and EpCAM-negative cells were also isolated to enrich for CAFs. The 10X Chromium platform was then used to isolate single cells for RNA-sequencing analysis. This work has demonstrated the differences in immune cell populations between adjacent-normal and tumor tissues, and identified subpopulations of epithelial cells and CAFs present in PDAC tumors. This high-throughput analysis is a resource to better understand the cell populations present in PDAC, and may ultimately aid in the development of more effective therapies for this deadly malignancy.

  Study phs001840

• Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE-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 The primary aim of the RESTORE clinical trial was to determine whether critically ill children managed with a nurse-implemented, goal-directed sedation protocol would experience fewer days of mechanical ventilation than participants receiving usual care. Background Ensuring the safety and comfort of critically ill infants and children supported by mechanical ventilation is integral to the practice of pediatric critical care. Although sedation therapy benefits young participants who cannot understand the imperative nature of invasive life-sustaining therapies, sedative use is also associated with untoward adverse effects. Specifically, opioids and benzodiazepines commonly used for pediatric sedation may impair bedside neurological assessment, depress spontaneous ventilation, and prolong mechanical ventilation. Over time, drug tolerance develops, which may precipitate iatrogenic withdrawal syndrome when sedation therapy is no longer necessary.Numerous studies in adult critical care support a minimal yet effective approach to sedation management. Sedation goals for mechanically ventilated adults have shifted from an unresponsive state to a calm, easily aroused, readily evaluated participant. Studies in adult participants evaluating targeted sedation, daily interruption and/or titration of sedation, pairing of spontaneous awakening with breathing, and no sedation have reported improved clinical outcomes, including decreased length of mechanical ventilation when compared with usual care. In contrast, few data inform sedation practices in pediatric critical care, and international studies describe significant practice variation. Given unique biobehavioral differences, knowledge generated in adult critical care may not translate to the care of critically ill children. The RESTORE study was conducted to test the effect of a nurse-implemented, goal-directed sedation protocol on clinical outcomes in pediatric participants with acute respiratory failure. Participants There was a total of 2,449 participants (mean age: 4.7 years; range: 2 weeks to 17 years). Design The RESTORE study was a cluster randomized clinical trial conducted in 31 US PICUs. Intervention PICUs (17 sites; 1,225 participants) used a protocol that included targeted sedation, arousal assessments, extubation readiness testing, sedation adjustment every 8 hours, and sedation weaning. Control PICUs (14 sites; 1,224 participants) managed sedation per usual care. The primary outcome variable was duration of mechanical ventilation. Conclusions Among children undergoing mechanical ventilation for acute respiratory failure, the use of a sedation protocol compared with usual care did not reduce the duration of mechanical ventilation. Exploratory analyses of secondary outcomes suggest a complex relationship among wakefulness, pain, and agitation (JAMA 2015; 313(4):379-89).

  Study phs003783

• Genomic Analyses in Neoadjuvant Immunotherapy-Treated Head and Neck Cancers

  This is a phase 2 multicenter interventional trial involving the preoperative (neoadjuvant) administration of pembrolizumab, an anti-programmed cell death protein-1 (anti-PD-1) agent, to patients with pathologically confirmed, surgically resectable advanced head and neck squamous cell carcinoma (HNSCC). Participating centers were Dana-Farber/Harvard Cancer Center, Alvin J. Siteman Cancer Center, Washington University and Memorial Sloan Kettering Cancer Center. The trial (NCT02296684) consisted of two cohorts: Cohort 1 enrolled and treated patients received one dose of pembrolizumab prior to surgical resection with curative intent, and adjuvant pembrolizumab was planned for patients with high risk pathological features (positive margins and/or extranodal extension) in the surgical specimen. Cohort 2 enrolled and treated patients received 2 doses of pembrolizumab prior to surgical resection with curative intent. Adjuvant treatment was not dictated by the trial protocol for Cohort 2. The primary endpoint was rate of at least 50% pathological tumor response (pTR), defined as the presence of tumor necrosis/keratinous debris in the tumor bed following neoadjuvant pembrolizumab. pTR was graded as follows: pTR0 (<10%), pTR1 (10-49%) and pTR2 (≥50%). Baseline, pre-treatment tumor biopsy and post-neoadjuvant pembrolizumab surgically resected tumor specimens were dissociated, and CD3+CD45+ cells were analyzed for T cell receptor (TCR) expression and 5' gene expression analysis using single cell sequencing technologies for a subset of patients.

  Study phs002864

• PCR-free shallow whole genome sequencing for chromosomal copy number detection from plasma of cancer patients is an efficient alternative to the conventional PCR-based approach

  Somatic copy number alterations (SCNAs) can be detected in tumor cell-free DNA (cfDNA) by shallow whole genome sequencing (sWGS). Polymerase chain reaction (PCR) is typically included in library preparations, but a PCR-free method could be an effective alternative for research and diagnostics. Peripheral blood samples (n=22) were collected in EDTA-containing tubes from non-small cell lung cancer patients (n=10) and healthy donors (n=12). PCR and PCR-free library preparations underwent sWGS and the following metrics were compared: mapping quality, proportion of duplicate reads, genome coverage, sequencing read length and copy number profiles. The PCR-free method was further evaluated on archived plasma samples (n=33) of varying pre-analytical quality collected in EDTA or lithium heparin tubes. Archived samples were from acute myeloid leukaemia (n=15) and B-cell lymphoma (n=18) patients. The percentage of unique reads was significantly higher for the 22 samples analysed by PCR-free (95.7%) compared to PCR (84%). PCR-free libraries from 33 archived samples produced data of a comparable quality, with 95.4% unique reads. All other evaluated metrics were highly comparable for PCR and PCR-free library preparations. We conclude that SCNA detection can be performed by PCR-free sWGS on cfDNA from cancer patients and is feasible for diagnostic and archival plasma collected in EDTA- or lithium heparin-containing tubes. Our results pave the way for an automated cfDNA workflow for cancer plasma samples.

  Study EGAS00001004692

• WGS data for EBiSC iPSC lines

  The European Bank for Induced Pluripotent stem cells (EBiSC) is designed to address the increasing demand by iPSC researchers for quality-controlled, disease-relevant research grade iPSC lines, data and cell services. In this study Whole Genome Sequencing was performed on a selection of lines from the project.

  Study EGAS50000000742

• The Surveillance Monitoring for ART Toxicities (SMARTT) and the Women and Infants Transmission Study (WITS)

  Zidovudine (ZDV) is a nucleoside reverse transcriptase inhibitor (NRTI) which competitively inhibits HIV reverse transcriptase and is incorporated into the viral DNA, resulting in DNA chain termination. It was the first approved antiretroviral medication used for preventing HIV transmission from mother to child. However, in vitro and animal studies have suggested genotoxicity of ZDV and no study has evaluated potential impact of in utero ZDV exposure using genomic sequencing technologies. In this study, we investigate markers of genomic damage detected in peripheral blood mononuclear cell samples obtained from 91 ZDV-exposed and, for comparison, 94 NRTI-unexposed HIV-uninfected children born to HIV-infected mothers during the first week after birth. We utilize high-throughput DNA sequencing (whole exome sequencing) and genotype array methods to comprehensively identify potential clonal somatic single nucleotide variants (SNVs) and large acquired copy number alterations (SCNAs) related to ZDV exposure.

  Study phs002061

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

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

  Dataset EGAD00001003769

• GATCI whole genome sequence data

  Sequence data in fastq format was aligned to the GRCh38 reference genome with BWA-MEM. Aligned sequence was preprocessed with GATK for Indel Realignment and Base Quality Score Recalibration. Duplicates were marked with Picard Mark Duplicates. Aligned sequence is in bam format. Details of the alignment can be found in the bam header

  Dataset EGAD00001005914